Conditions: Human Immunodeficiency Virus Type 1 (HIV-1)
Keywords: Antiretroviral agent Rilpivirine Cabotegravir FLAIR Human immunodeficiency virus
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 94
Healthy volunteers: no

Brief summary:
This study will assess the pharmacokinetics, safety, tolerability, maintenance of virological suppression and patient reported outcomes for participants receiving CAB and RPV LA injections following SC administration in the anterior abdominal wall SC tissue compared with IM administration in the gluteus medius muscle in adult participants living with HIV-1 infection in the FLAIR study (NCT02938520).

Detailed description:

Arms:
arm 1: Participants received an intramuscular (IM) injection of CAB LA 400 mg and RPV LA 600 mg on week -4 during the Screening phase. Participants then received a sub-cutaneous (SC) injection of CAB LA 400 mg + RPV LA 600 mg on Day 1 of Week 1, Week 4 and Week 8 (once in every 4 weeks (Q4W)) for a total of 12 weeks during the SC abdominal Injection Phase. 4 weeks later, participants returned to the clinic for an IM gluteal injection (at Week 12) of CAB LA 400 mg + RPV LA 600 mg during the Return to Gluteal Injection Phase and subsequent gluteal injection occurred after Q4W at Week 16.

Interventions: intervention 1: Cabotegravir - Injectable Suspension (CAB LA) intervention 2: Rilpivirine - Injectable Suspension (RPV LA)
Intervention descriptions: intervention 1: It is a sterile white to slightly pink suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. Each vial is for single-dose use containing a withdrawable volume of 2.0 mL, and does not require dilution prior to administration. CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection. intervention 2: It is a sterile white suspension containing 300 mg/mL of RPV as the free base. The route of administration is by intramuscular (IM) injection. Each vial contains a nominal fill of 2.0 mL, and does not require dilution prior to administration. RPV LA requires refrigeration and must be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection.

Protocol document:
Prot_000.pdf: 
Protocol
Main Study ID:  201584
Main Study Official Title: A Phase III, Randomized, Multicenter, Parallel-group, 
Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-
Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic 
Suppression Following Switch from an Integrase Inhibitor Single Tablet Regimen 
in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants
NCT ID for Main Study: NCT02938520
Sub-Study ID:  201584-001
Sub-Study Official Title:  An Amendment to the FLAIR Study to Evaluate the 
Pharmacokinetics, Safety, Tolerability, Maintenance of Virological Suppression 
and Patient Reported Outcomes for Participants Receiving Cabotegravir (CAB 200 
mg/mL) and Rilpivirine (300 mg/mL) Long-Acting Injections Following Sub-
cutaneous (SC) Administration in the Anterior Abdominal Wall SC Tissue 
Compared With Intramuscular (IM) Administration in the Gluteus Medius Muscle 
in Adult Participants Living With HIV-1 Infection in the FLAIR Study
NCT ID for Sub-Study: NCT05896748
Date of Document of Sub-Study: 28-Aug-2023 


TMF-16441767 
CONFIDENTIAL 
201584 
ViiV Healthcare group of companies 
 
Protocol Amendment 09 
 
1 
 
TITLE PAGE    
Protocol Title: A Phase III, Randomized, Multicenter, Parallel-group, Open-Label Study 
Evaluating the Efficacy, Safety, and Tolerability of Long-Acting Intramuscular 
Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following 
Switch from an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected 
Antiretroviral Therapy Naive Adult Participants 
 
Protocol Number: 201584 / Amendment 09 
Compound Number: GSK1265744 
Study Phase: Phase 3 
Sponsor Name and Legal Registered Address:  
This study is sponsored by ViiV Healthcare UK Limited. GlaxoSmithKline is supporting 
ViiV Healthcare in the conduct of this study.  
 
Sponsor Legal Registered Address (excluding US):  
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
 
US IND Sponsor Legal Registered Address: 
ViiV Healthcare Company 
410 Blackwell Street,  
Durham, NC 27701 
Telephone: +1 877 844 8872 
Fax number: + 1 919 237 9294 
 
In some countries, local law requires that the Clinical Trial sponsor is a local company 
legal entity.  In these instances, the appropriate company to be identified as Sponsor must 
be agreed with the global ViiV Healthcare clinical team and signed off by the Vice 
President, Global Research and Medical Strategy. 
 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual. 
 
Sponsor Signatory: 
Name:  
Sherene Min, MD, MPH 
Title:  
Vice President, Head of Clinical Development 
 
 
ViiV Healthcare  
 
Approval Date: 28 Aug 2023 
 


TMF-16441767 
CONFIDENTIAL 
201584 
ViiV Healthcare group of companies 
 
Protocol Amendment 09 
 
2 
 
 
 
Copyright 2022 ViiV Healthcare group of companies.  All rights reserved.  Unauthorized 
copying or use of this information is prohibited. 
 
 
Regulatory Agency Identifying Number(s):  
US IND: 109,678 
EudraCT #:  2016-001646-25 
 


TMF-16441767 
CONFIDENTIAL 
201584 
ViiV Healthcare group of companies 
 
Protocol Amendment 09 
 
3 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 09 
28 Aug 2023 
TMF-16441767 
Amendment 08 
21 October 2022 
TMF-15038148 
Amendment 07 
17-Jun-2022 
TMF-14728112 
Amendment 06 
05-Aug-2021 
TMF-13030701 
Amendment 05 
20-May-2020 
2015N248866_05 
Amendment 04 
24-Sep-2018 
2015N248866_04 
Amendment 03 
25-Jun-2018 
2015N248866_03 
Amendment 02 
19-Jul-2017 
2015N248866_02 
Amendment 01 
13-Dec-2016 
2015N248866_01 
Original Protocol (00) 
26-May-2016 
2015N248866_00 
 
Amendment 09 28 Aug 2023 
This amendment is considered to be substantial based on the criteria defined in EU 
Clinical Trial Regulation No 536/2014 of the European Parliament and the Council of the 
European Union.  
Overall Rationale for the Amendment 09:  
The primary purposes of this amendment are: 
• To update the Potential Risk of Clinical Significance of HSR when using 
integrase inhibitors, such as CAB. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4.6.1 Risk 
Assessment  
Updated the Summary of Data/Rationale for 
Risk for HSR that have been reported in 
association with integrase inhibitors.  
 
Updated the description of the cases reported 
to be associated with CAB. 
• 
Updated safety 
information 
from CAB IB 
v13 
supplement 2  
 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
4 
 
TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SYNOPSIS FOR STUDY 201584 ........................................................ 9 
1.1. 
Rationale ...................................................................................................... 9 
1.2. 
Objectives/Endpoints .................................................................................... 9 
1.3. 
Overall Design ............................................................................................ 13 
1.3.1. 
201584 (FLAIR) Study Schematic ................................................ 15 
1.4. 
Treatment Arms and Duration ..................................................................... 15 
1.5. 
Type and Number of Participants ................................................................ 22 
1.6. 
Analysis ...................................................................................................... 22 
2. 
INTRODUCTION .................................................................................................... 23 
2.1. 
Study Rationale .......................................................................................... 25 
2.2. 
Brief Background ........................................................................................ 26 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 29 
4. 
STUDY DESIGN .................................................................................................... 33 
4.1. 
Overall Design ............................................................................................ 33 
4.2. 
Treatment Arms and Duration ..................................................................... 36 
4.2.1. 
Screening Phase (Up to 35 days) ................................................ 36 
4.2.2. 
Induction Phase ........................................................................... 37 
4.2.3. 
Eligibility for the Maintenance Phase ........................................... 37 
4.2.4. 
Maintenance Phase (Day 1 to Week 100) .................................... 38 
4.2.5. 
Extension Phase .......................................................................... 39 
4.2.6. 
Long-Term Follow-Up Phase – IM Regimen only ......................... 42 
4.2.7. 
Dose Modifications / Permitted Treatment Substitutions .............. 43 
4.2.8. 
Independent Data Monitoring Committee ..................................... 44 
4.3. 
Type and Number of Participants ................................................................ 45 
4.4. 
Design Justification ..................................................................................... 45 
4.5. 
Dose Justification ........................................................................................ 47 
4.5.1. 
Oral Lead-In Phase ...................................................................... 47 
4.5.2. 
Long Acting Injectable for Maintenance Phase ............................ 49 
4.5.3. 
Modeling and Dose Simulations for CAB LA and RPV LA ............ 54 
4.6. 
Benefit:Risk Assessment ............................................................................ 58 
4.6.1. 
Risk Assessment ......................................................................... 61 
4.6.2. 
Other Clinically Relevant Information ........................................... 77 
4.6.3. 
Benefit Assessment ..................................................................... 77 
4.6.4. 
Overall Benefit:Risk Conclusion ................................................... 77 
5. 
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA ............. 77 
5.1. 
Inclusion Criteria ......................................................................................... 78 
5.2. 
Exclusion Criteria ........................................................................................ 80 
5.3. 
Screening/Baseline/Run-in Failures ............................................................ 83 
5.4. 
Withdrawal/Stopping Criteria....................................................................... 83 
5.4.1. 
Liver Chemistry Stopping Criteria ................................................ 86 
5.4.2. 
QTc Stopping Criteria .................................................................. 91 
5.4.3. 
Virologic Failure ........................................................................... 92 
5.4.4. 
Definition of Virologic Failure ....................................................... 92 
5.4.5. 
Managing Virologic Failure .......................................................... 92 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
5 
 
5.5. 
Participant and Study Completion ............................................................... 94 
6. 
STUDY TREATMENT ............................................................................................ 95 
6.1. 
Investigational Product and Other Study Treatment .................................... 95 
6.1.1. 
Cabotegravir (CAB) – Tablet ........................................................ 95 
6.1.2. 
Rilpivirine (RPV) - Tablet ............................................................. 96 
6.1.3. 
Cabotegravir – Injectable Suspension (CAB LA) .......................... 96 
6.1.4. 
Rilpivirine – Injectable Suspension (RPV LA) ............................... 96 
6.1.5. 
ABC/DTG/3TC STR - Tablet ........................................................ 97 
6.1.6. 
Dolutegravir (DTG) – Tablet ......................................................... 97 
6.2. 
Treatment Assignment ................................................................................ 97 
6.3. 
Dose and Administration ............................................................................. 98 
6.4. 
Blinding ..................................................................................................... 100 
6.5. 
Packaging and Labeling ............................................................................ 100 
6.6. 
Preparation/Handling/Storage/Accountability ............................................ 100 
6.6.1. 
Dosing Considerations for CAB LA + RPV LA ............................ 101 
6.7. 
Compliance with Study Treatment Administration ..................................... 102 
6.8. 
Protocol Permitted Substitutions ............................................................... 103 
6.8.1. 
Oral Bridging .............................................................................. 103 
6.9. 
Interruption of Study Treatment ................................................................ 104 
6.9.1. 
IM Dosing .................................................................................. 104 
6.9.2. 
Oral Dosing ................................................................................ 106 
6.10. 
Discontinuation of Study Treatment .......................................................... 107 
6.10.1. 
Discontinuation of ABC/DTG/3TC .............................................. 107 
6.10.2. 
Discontinuation of CAB LA or RPV LA ....................................... 107 
6.11. 
Treatment of Study Treatment Overdose .................................................. 107 
6.12. 
Treatment after the End of the Study ........................................................ 108 
6.13. 
Concomitant Medications and Non-Drug Therapies .................................. 108 
6.13.1. 
Prohibited Medications and Non-Drug Therapies ....................... 110 
6.14. 
Medical Devices ........................................................................................ 113 
7. 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 113 
7.1. 
Time and Events Table ............................................................................. 113 
7.2. 
Screening and Critical Baseline Assessments .......................................... 126 
7.2.1. 
Screening .................................................................................. 126 
7.2.2. 
Baseline Assessments ............................................................... 127 
7.3. 
Efficacy ..................................................................................................... 128 
7.3.1. 
Plasma HIV-1 RNA .................................................................... 128 
7.3.2. 
Lymphocyte Subsets, CD4+ and CD8+ ..................................... 128 
7.3.3. 
HIV Associated Conditions ........................................................ 128 
7.4. 
Safety ....................................................................................................... 128 
7.4.1. 
Clinical evaluations .................................................................... 128 
7.4.2. 
Laboratory Assessments ........................................................... 130 
7.4.3. 
Adverse Events (AEs) and Serious Adverse Events 
(SAEs) ....................................................................................... 132 
7.4.4. 
Medical Device Deficiencies ...................................................... 137 
7.4.5. 
Time Period for Detecting Medical Device Deficiencies ............. 137 
7.4.6. 
Follow-Up of Medical Device Deficiencies.................................. 137 
7.4.7. 
Prompt Reporting of Medical Device Deficiencies to 
Sponsor ..................................................................................... 137 
7.4.8. 
Regulatory Reporting Requirements for Medical Device 
Deficiencies ............................................................................... 138 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
6 
 
7.4.9. 
Toxicity Management ................................................................. 138 
7.4.10. 
Specific Toxicities / Adverse Event Management ....................... 140 
7.4.11. 
Suicidal Risk Monitoring ............................................................. 148 
7.4.12. 
Pregnancy ................................................................................. 149 
7.4.13. 
Physical Exams ......................................................................... 151 
7.4.14. 
Vital Signs .................................................................................. 152 
7.4.15. 
Electrocardiogram (ECG) ........................................................... 152 
7.5. 
Pharmacokinetics ..................................................................................... 152 
7.5.1. 
PK Sample Collection ................................................................ 152 
7.5.2. 
Rationale of PK Sampling Strategy ............................................ 154 
7.5.3. 
Sample Analysis ........................................................................ 155 
7.6. 
Biomarker(s) ............................................................................................. 155 
7.6.1. 
Biomarker Endpoints (Exploratory) ............................................ 155 
7.7. 
Genetics ................................................................................................... 155 
7.8. 
Viral Genotyping and Phenotyping ............................................................ 156 
7.8.1. 
HIV-1 pol Viral Genotyping and Phenotyping ............................. 156 
7.8.2. 
HIV-1 Exploratory Analysis ........................................................ 156 
7.9. 
Value Evidence and Outcomes ................................................................. 156 
7.9.1. 
Value Evidence and Outcomes Endpoints (Secondary) ............. 158 
7.9.2. 
Value Evidence and Outcomes Endpoints (Exploratory) ............ 159 
8. 
DATA MANAGEMENT ......................................................................................... 159 
9. 
STATISTICAL CONSIDERATIONS AND DATA ANALYSES ............................... 159 
9.1. 
Hypotheses ............................................................................................... 159 
9.2. 
Sample Size Considerations ..................................................................... 160 
9.2.1. 
Sample Size Assumptions ......................................................... 160 
9.2.2. 
Sample Size Sensitivity .............................................................. 163 
9.2.3. 
Sample Size Re-estimation or Adjustment ................................. 165 
9.2.4. 
Sample Size Considerations for Week 124 Extension 
Switch Analysis .......................................................................... 165 
9.3. 
Data Analysis Considerations ................................................................... 166 
9.3.1. 
Analysis Populations .................................................................. 166 
9.3.2. 
Treatment Comparisons ............................................................ 167 
9.3.3. 
Planned Analyses ...................................................................... 167 
9.4. 
Key Elements of Analysis Plan ................................................................. 168 
9.4.1. 
Primary Analyses ....................................................................... 168 
9.4.2. 
Secondary Analyses .................................................................. 170 
9.4.3. 
Pharmacokinetic Analyses ......................................................... 171 
9.4.4. 
Pharmacokinetic/Pharmacodynamic Analyses ........................... 172 
9.4.5. 
Viral Genotyping/Phenotyping Analyses .................................... 172 
9.4.6. 
Health Outcomes Analyses ........................................................ 172 
9.4.7. 
Other Analyses .......................................................................... 173 
10. STUDY GOVERNANCE CONSIDERATIONS ...................................................... 173 
10.1. 
Posting of Information on Publicly Available Clinical Trial Registers .......... 173 
10.2. 
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ...................................................................................... 173 
10.3. 
Quality Control (Study Monitoring) ............................................................ 174 
10.4. 
Quality Assurance ..................................................................................... 174 
10.5. 
Study and Site Closure ............................................................................. 175 
10.6. 
Records Retention .................................................................................... 175 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
7 
 
10.7. 
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication ............... 176 
10.8. 
Review Committee .................................................................................... 176 
10.8.1. 
Independent Data Monitoring Committee ................................... 176 
11. REFERENCES ..................................................................................................... 177 
12. APPENDICES ...................................................................................................... 181 
12.1. 
Appendix 1: Abbreviations and Trademarks .............................................. 181 
12.2. 
Appendix 2: Division Of AIDS Table For Grading The Severity Of 
Adult And Pediatric Averse Events Version 2.0, November 2014 .............. 186 
12.2.1. 
Reference .................................................................................. 223 
12.3. 
Appendix 3:  Liver Safety – Required Actions, Follow Up 
Assessments and Study Treatment Restart Guidelines ............................ 224 
12.4. 
Appendix 4: CDC Classification System for HIV-1 Infections (2014) ......... 228 
12.4.1. 
Reference .................................................................................. 229 
12.5. 
Appendix 5: Genetic Research ................................................................. 230 
12.6. 
Appendix 6: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events ............................................. 232 
12.6.1. 
Definition of Adverse Events ...................................................... 232 
12.6.2. 
Definition of Serious Adverse Events ......................................... 233 
12.6.3. 
Definition of Cardiovascular Events ........................................... 235 
12.6.4. 
Recording of AEs and SAEs ...................................................... 235 
12.6.5. 
Evaluating AEs and SAEs .......................................................... 236 
12.6.6. 
Reporting of SAEs to ViiV Healthcare / GSK .............................. 237 
12.7. 
Appendix 7:  Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 238 
12.7.1. 
Contraception Guidance ............................................................ 239 
12.7.2. 
Collection of Pregnancy Information .......................................... 240 
12.8. 
Appendix 8: Country Specific Requirements ............................................. 241 
12.8.1. 
United Kingdom (UK) ................................................................. 241 
12.8.2. 
Japan ......................................................................................... 241 
12.8.3. 
Russia ....................................................................................... 242 
12.9. 
Appendix 9:  COVID-19 Pandemic and Clinical Trial Continuity ................ 242 
12.9.1. 
Changes to Study Visits and Study Procedures ......................... 243 
12.9.2. 
Changes to Informed Consent ................................................... 243 
12.9.3. 
Permissible Use of Antiretroviral Therapy .................................. 244 
12.9.4. 
Direct-To-Patient (DTP) Shipment of Oral Study IP ................... 245 
12.9.5. 
COVID-19 Experimental Agents ................................................ 246 
12.9.6. 
COVID-19 Specific Data Capture ............................................... 246 
12.10. Appendix 10: Information and Guidance for Managing Pregnant 
Participants ............................................................................................... 248 
12.10.1. Collection of Pregnancy Information .......................................... 249 
12.10.2. Introduction ................................................................................ 249 
12.10.3. Benefit/Risk Assessment ........................................................... 250 
12.10.4. Clinical Considerations .............................................................. 253 
12.10.5. Study Assessments and Procedures: specific 
assessments for pregnant participants ....................................... 256 
12.10.6. References ................................................................................ 257 
12.11. Appendix 11: Device Deficiencies: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting in Medical Device 
Studies ..................................................................................................... 258 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
8 
 
12.11.1. Definition of Device Deficiency ................................................... 258 
12.11.2. Recording and Follow-Up of Device Deficiencies ....................... 258 
12.11.3. Reporting of Medical Device Deficiencies for Participants .......... 259 
12.11.4. Reporting of Medical Device Deficiencies for Associated 
Person ....................................................................................... 260 
12.12. Appendix 12: Sub-Cutaneous Administration PK Sub-Study 
Amendment .............................................................................................. 260 
12.12.1. Sub-Study Amendment Background .......................................... 261 
12.12.2. Sub-Study Amendment Rationale .............................................. 269 
12.12.3. Sub-Study Objectives and Endpoints ......................................... 274 
12.12.4. Sub-Study FLAIR Amendment Design ....................................... 277 
12.12.5. Sub-Study Time and Events Table............................................. 289 
12.12.6. Sub-Study Health Outcomes Questionnaires ............................. 294 
12.12.7. Sub-Study Treatment ................................................................. 295 
12.12.8. Sub-Study Data Management .................................................... 296 
12.12.9. Sub-Study Statistical Considerations and Data Analyses ........... 296 
12.12.10. Sub-Study Pharmacokinetics ..................................................... 299 
12.12.11. References ................................................................................ 300 
12.13. Appendix 13: Mitigation for Geopolitical Situation in Russia/Ukraine ......... 301 
12.13.1. Changes to Study Visits and Study Procedures ......................... 301 
12.13.2. Changes to Informed Consent ................................................... 302 
12.13.3. Permissible Use of Antiretroviral Therapy .................................. 302 
12.13.4. Direct To Patient (DTP) Shipments of Oral Study IP .................. 303 
12.14. Appendix 14:  Protocol Amendments ........................................................ 304 
12.14.1. Amendment 01 (All Countries) ................................................... 304 
12.14.2. Amendment 02 (All Countries) ................................................... 332 
12.14.3. Amendment 03 (All Countries) ................................................... 339 
12.14.4. Amendment 04 (All Countries) ................................................... 348 
12.14.5. Amendment 05 (All Countries) ................................................... 387 
12.14.6. Amendment 06 (All Countries) ................................................... 394 
12.14.7. Amendment 07 (All Countries) ................................................... 403 
12.14.8. Amendment 08 (All Countries) ................................................... 406 
12.14.9. Amendment 09 (All Countries) ................................................... 411 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
9 
 
1. 
PROTOCOL SYNOPSIS FOR STUDY 201584 
1.1. 
Rationale 
201584 (the First Long-Acting Injectable Regimen – FLAIR study) is being conducted to 
establish if human immunodeficiency virus type-1 (HIV-1) infected adult participants 
whose virus is virologically suppressed on an integrase inhibitor single tablet regimen 
(INI STR) will remain suppressed after switching to a two-drug intramuscular (IM) long-
acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV).  In this study, the INI 
STR will be limited to abacavir/dolutegravir/lamivudine (ABC/DTG/3TC).  This study is 
designed to demonstrate the non-inferior antiviral activity of switching to a two drug 
CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared 
to remaining on ABC/DTG/3TC over 48 weeks (4 weeks oral CAB + RPV, 44 weeks LA 
therapy).  201584 (FLAIR) will also allow for characterization of long-term antiviral 
activity, safety, and tolerability and participant satisfaction of the regimens through 
Week 96.  Additionally, participants randomized to continue ABC/DTG/3TC will be 
given an option to switch to LA therapy at Week 100.  Eligible participants (HIV-1 
ribonucleic acid [RNA] <50 c/mL at Week 96) would transition to LA dosing, beginning 
with the first IM CAB LA + RPV LA injections at either Week 100 (direct to injection) 
or Week 104b (following optional oral lead-in with CAB 30 mg and RPV 25 mg). 
201584 (FLAIR) is being conducted in parallel with the 201585 (ATLAS) study with the 
aim to pool data generated from the current study with study 201585, in order to evaluate 
key program objectives. 
1.2. 
Objectives/Endpoints 
Objectives 
Endpoints 
Primary 
To demonstrate the non-inferior antiviral 
activity of switching to intramuscular CAB LA + 
RPV LA every 4 weeks (monthly) compared to 
continuation of ABC/DTG/3TC over 48 weeks 
in HIV-1 antiretroviral naïve participants. 
• Proportion of participants with a ‘virologic 
failure’ endpoint as per FDA Snapshot 
algorithm at Week 48 (Missing, Switch, or 
Discontinuation = Failure, Intent-to-Treat 
Exposed [ITT-E] population). 
Secondary 
To demonstrate the antiviral and immunologic 
activity of switching to intramuscular CAB LA + 
RPV LA every 4 weeks (monthly) compared to 
continuation of ABC/DTG/3TC. 
• Proportion of participants with plasma 
HIV-1 RNA <50 copies/mL (c/mL) at 
Week 48 using the FDA Snapshot 
algorithm (Intent-to-Treat Exposed [ITT-E] 
population). 
• Proportion of participants with plasma 
HIV-1 RNA <200 c/mL at Week 48 using 
the FDA Snapshot algorithm (ITT-E 
population). 
• Proportion of participants with plasma 
HIV-1 RNA <200 c/mL and HIV-1 RNA 
<50 c/mL at Week 96 using the FDA 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
10 
 
Objectives 
Endpoints 
Snapshot algorithm (ITT-E population). 
• Proportion of participants with a ‘virologic 
failure’ endpoint as per FDA Snapshot 
algorithm at Week 96. 
• Proportion of participants with confirmed 
virologic failure at Week 48 and Week 96. 
• Absolute values and change from Baseline 
in plasma HIV-1 RNA (log10 copies/mL) at 
Week 48 and Week 96. 
• Absolute values and changes from 
Baseline in CD4+ cell counts over time 
including Week 48 and Week 96. 
• Incidence of disease progression (HIV-
associated conditions, acquired 
immunodeficiency syndrome [AIDS] and 
death). 
To evaluate the safety and tolerability of 
switching to CAB LA + RPV LA every 4 weeks 
(monthly) compared to continuation of 
ABC/DTG/3TC over time. 
• 
Incidence and severity of adverse events 
(AEs) and laboratory abnormalities over 
time including Week 48 and Week 96. 
• Proportion of participants who discontinue 
treatment due to AEs over time including 
Week 48 and Week 96. 
• 
Absolute values and changes in laboratory 
parameters over time including Week 48 
and Week 96. 
To evaluate the effects of CAB LA + RPV LA 
every 4 weeks on fasting lipids over time 
compared to continuation of ABC/DTG/3TC 
over time. 
• Change from Baseline in fasting lipids over 
time including Week 48 and Week 96. 
To assess the development of viral resistance 
in participants experiencing protocol-defined 
virologic failure. 
• Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV, 
and other on-study ART at Week 48 and 
Week 96. 
To characterize CAB and RPV concentrations 
and population pharmacokinetics (PK) and 
identify important determinants of variability. 
• Plasma PK parameters for CAB LA and 
RPV LA (when evaluable, Ctrough, 
concentrations post dose [~Cmax], and 
area under the curve [AUC]). 
• Demographic parameters including, but 
not limited to, age, sex, race, body weight, 
body mass index (BMI), and relevant 
laboratory parameters will be evaluated as 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
11 
 
Objectives 
Endpoints 
potential predictors of inter- and intra-
participant variability for pharmacokinetic 
parameters.   
To assess the acceptance of pain and injection 
site reactions following injections. 
• Change from Week 5 in Dimension scores 
(e.g., “Bother of ISRs”, “Leg movement”, 
“Sleep”, and “Injection Acceptance”) and 
individual item scores assessing pain 
during injection, anxiety before and after 
injection, willingness to be injected in the 
future and overall satisfaction with mode of 
administration over time using the 
Perception of iNjection questionnaire 
(PIN).  
• Proportion of participants considering pain 
and local reactions following injection to be 
extremely or very acceptable based on the 
acceptability score over time using the 
Perception of iNjection questionnaire 
(PIN). 
To assess treatment satisfaction of CAB LA + 
RPV LA compared to continuation of 
ABC/DTG/3TC. 
 
• Change from baseline in total “treatment 
satisfaction” score, and individual item 
scores of the HIV Treatment Satisfaction 
Questionnaire (status version) (HIVTSQs) 
at Week 4b, Week 24, Week 44, Week 96 
(or Withdrawal). 
• Change in treatment satisfaction over time 
(using the HIVTSQc change version 
[HIVTSQc]) at Week 48 (or Withdrawal). 
To assess degree of health-related quality of 
life (HR QoL). 
• Change from Baseline in HR QoL using 
the HIV/AIDS targeted quality of life 
questionnaire (HAT-QoL) short format 
Week 24, Week 48, Week 96 (or 
Withdrawal). 
To assess health status. 
• Change from Baseline in health status at 
Week 24, Week 48, and Week 96 (or 
Withdrawal) using the 12-item Short Form 
Survey (SF-12). 
To assess treatment acceptance. 
• Change from Baseline in treatment 
acceptance at Week 8, Week 24, 
Week 48, Week 96 (or Withdrawal) using 
the “General Acceptance” dimension of 
the Chronic Treatment Acceptance 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
12 
 
Objectives 
Endpoints 
(ACCEPT) questionnaire. 
To assess tolerability of injections. 
• Change from Week 4b in tolerability of 
injections at Week 5, Week 40, Week 41, 
and Week 96 using the Numeric Rating 
Scale (NRS) within the CAB LA + RPV LA 
arm. 
To evaluate the antiviral and immunologic 
effects, safety and tolerability, and 
development of viral resistance to CAB LA + 
RPV LA at Week 124 and over time for 
participants switching from ABC/DTG/3TC in 
the Extension Phase, with and without optional 
oral lead-in. 
• Proportion of participants with HIV-1 RNA 
≥ 50 c/mL at Week 124, with and without 
oral lead-in (FDA Snapshot algorithm, 
Extension Switch population). 
• Proportion of participants with plasma HIV-
1 RNA <50 c/mL and HIV-1 RNA 
<200 c/mL over time. 
• Proportion of participants with confirmed 
virologic failure over time. 
• Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB and 
RPV over time. 
• Absolute values and change from Baseline 
in CD4+ cell counts over time. 
• Incidence and severity of AEs and 
laboratory abnormalities over time. 
• Proportion of participants who discontinue 
treatment due to AEs over time. 
• Absolute values and change in laboratory 
parameters over time. 
To evaluate the pharmacokinetics of CAB and 
RPV in the setting of no oral lead-in for 
participants switching from ABC/DTG/3TC in 
the Extension Phase. 
• To evaluate plasma CAB and RPV 
concentrations over time (Week 100 
[direct to inject without oral lead-in] and 
Week 104 [both direct to inject and 
optional oral lead-in participants]) 
Exploratory 
To explore the effect of participant 
characteristics on the virologic and 
immunologic response of CAB LA and RPV LA 
compared to continuation of ABC/DTG/3TC. 
• Proportion of participants by patient 
subgroup(s) (e.g., by age, gender, BMI, 
race, HIV-1 subtype, Baseline CD4+) with 
Virologic Failure over time including Week 
48, and 96 using the Snapshot algorithm 
for the ITT-E population. 
• Proportion of participants by subgroup(s) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
13 
 
Objectives 
Endpoints 
(e.g. by age, gender, BMI, race, HIV-1 
subtype, Baseline CD4+) with plasma 
HIV-1 RNA <50 c/mL at Week 48 and 
Week 96. 
• Change from Baseline in CD4+ cell counts 
by subgroups at Week 48 and Week 96. 
To explore relationship(s) between plasma 
concentrations of CAB and RPV and 
pharmacodynamic endpoints. 
• Relationship between plasma PK 
concentrations and virologic, immunologic 
responses, and/or occurrence of adverse 
events [AEs] over time may be explored. 
To evaluate renal and bone biomarkers in 
participants receiving CAB LA and RPV LA 
compared to continuation of ABC/DTG/3TC 
over time. 
• Absolute values and change from Baseline 
in renal (in urine and blood) and bone (in 
blood) biomarkers over time including 
Week 48 and Week 96. 
To assess preference for CAB LA + RPV LA 
compared to oral antiretroviral (ARV) therapy 
using a single dichotomous preference 
question. 
• For participants randomized to the “CAB 
LA + RPV LA” arm, preference for CAB 
LA + RPV LA compared to oral ARV 
regimen, at Week 48. 
1.3. 
Overall Design 
201584 (FLAIR) is a 120-week Phase 3, multi-phase, randomized, open label, active-
controlled, multicenter, parallel-group, non-inferiority study in HIV-1, ART-naïve adult 
participants.  Participants who fulfill eligibility requirements will enroll into the Induction 
Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week [-20] to Day 1).  
Participants who have an HIV-1 RNA <50 c/mL at Week (-4) will be randomized (1:1) 
into the Maintenance Phase at Day 1 to either continue ABC/DTG/3TC or to discontinue 
ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg once daily.  
ABC/DTG/3TC dosing on Day 1 should occur after randomization to avoid overlap of 
regimens (in the event that the participant is assigned to the CAB LA + RPV LA 
treatment arm).  However, if the participant takes ABC/DTG/3TC prior to coming into 
the clinic, randomization and initiation of oral CAB and RPV should continue as planned 
for Day 1.  Participants who are not eligible to continue into the Maintenance Phase will 
be withdrawn from the study.  At the Week 4a visit, assessments (including e.g., clinical 
chemistries) will be performed.  At visit Week 4b, participants will return to the clinic, 
take the last dose of oral CAB + RPV, and receive the first CAB LA (600 mg) + RPV LA 
(900 mg) injections (within 2 hours of the final oral dose of CAB + RPV).  The Week 4b 
visit can be performed as soon as central laboratory results become available and safety 
parameters are reviewed.  The second and third IM injections (CAB LA 400 mg + RPV 
LA 600 mg) will be performed at Week 8 and Week 12.  There will be a one week dosing 
window for the second and third IM injections such that the second injections occur 
within the window of Week 7 to Week 8, but not later than Week 8, and the third 
injections occur within the window of Week 11 to Week 12, but no later than Week 12.  
Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur every 4 weeks 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
14 
 
(monthly) thereafter, with a ± 7 day dosing window being allowed (but not preferred).  In 
addition, starting at the Week 12 injections, the interval between injection visits should 
be limited to a maximum of 5 weeks.  If the length of time between injections exceeds, or 
is projected to exceed 5 weeks, the Medical Monitor must be contacted to discuss 
individual participant case management.   
Participants randomized to ABC/DTG/3TC during the Maintenance Phase will continue 
ABC/DTG/3TC for at least an additional 100 weeks.  Participants who successfully 
complete Week 100 (without meeting study defined withdrawal criteria and who remain 
virologically suppressed:  HIV-1 RNA <50 c/mL) will be given the option to switch to 
the LA arm in the Extension Phase or be withdrawn from the study. 
Any participant who receives at least a single dose of CAB LA and/or RPV LA and 
discontinues the CAB LA + RPV LA regimen for any reason must enter the 52-week 
Long-Term Follow-Up Phase (please refer to the Long Term Follow-up Phase – IM 
Regimen Only section of the synopsis for additional details).  Participants must remain on 
suppressive highly active antiretroviral therapy (HAART) for at least 52 weeks after the 
last dose of CAB LA and/or RPV LA. 
In order to achieve balance across the two treatment arms, randomization will be 
stratified by participants’ Baseline HIV-1 RNA (<100,000, ≥100,000 c/mL) and gender at 
birth.  The primary endpoint for the study is the proportion of participants who meet the 
Snapshot virologic failure criterion at Week 48.  The proportion of participants with 
plasma HIV-1 RNA <50 c/mL at Week 48 of maintenance treatment using the FDA 
Snapshot algorithm (Missing, Switch or Discontinuation = Failure, Intent-to-Treat 
Exposed [ITT-E] population) is a key secondary endpoint comparison. 
Assuming a 20% screen failure rate, sufficient ART-naïve participants will be screened 
(approximately 775) in order to ensure that a total of approximately 620 participants are 
enrolled at the beginning of the Induction Phase.  Assuming 7.5% of enrolled participants 
will not participate in the Maintenance Phase, this will ensure approximately 
570 participants continue into the Maintenance Phase.  The sample size of 285 per arm 
(at Day 1) is such that the study has approximately 97% power to demonstrate non-
inferiority in the proportion of participants with snaphot virologic failure at Week 48 
using an 6% margin, assuming a true 3% failure rate for CAB LA + RPV LA and a 2% 
failure rate for the ABC/DTG/3TC control arm and using a 2.5% one-sided alpha level. 
This sample size is primarly chosen so that the pooled analysis of data from this study 
and study 201585 (combined sample size of 570 per arm) will have 90% power to show 
non-inferiority for the proportion of participants with Snapshot virologic failure at 
Week 48 using a 4% non-inferiority margin, under the assumptions described above.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
15 
 
1.3.1. 
201584 (FLAIR) Study Schematic 
 
1.  
 
¥Subjects who withdraw from IM CAB LA + RPV LA must enter the 52 week Long Term Follow-Up 
Phase if the marketed product is not locally available.  
 
1.4. 
Treatment Arms and Duration 
Screening Phase (Up to 35 Days) 
Informed consent must be obtained prior to any study procedures, including any 
Screening assessment. 
All participants will complete the Screening Phase of up to 35 days prior to Baseline 
(Week [-20]) during which all clinical and laboratory assessments of eligibility must be 
performed and reviewed.  Participants may be re-screened once.  Participants who are 
enrolled into the trial and subsequently withdrawn from the study, for any reason, may 
not be re-screened.  Participants may be enrolled as soon as all eligibility requirements 
have been confirmed at the site. 
Induction Phase (Week [-20] to Day 1) 
Following the Screening Phase, eligible participants will be enrolled into the study and 
begin a 20 week Induction Phase on ABC/DTG/3TC.  Participants who have 
demonstrated tolerability to the Induction Phase regimen and with an undetectable HIV-1 
RNA (<50 c/mL) at the Week (-4) visit are eligible to enter the Maintenance Phase.  A 
single repeat HIV-1 RNA test to determine eligibility may be allowed ONLY after 
consultation with the Medical Monitor.  The retest should be scheduled as soon as 
possible as results of this retest must be available prior to the Day 1 visit.  Participants 
with HIV-1 RNA ≥400 c/mL at Week (-4) are not eligible to enter the Maintenance 
Phase, will not be allowed a repeat to determine eligibility, and will therefore be 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
16 
 
withdrawn from the study.  Note:  ABC/DTG/3TC dosing on Day 1 should occur after 
randomization to avoid overlap of regimens (in the event that the participant is assigned 
to the CAB LA + RPV LA treatment arm).  However, if the participant takes 
ABC/DTG/3TC prior to coming into the clinic, randomization and initiation of oral CAB 
and RPV should continue as planned for Day 1. 
Maintenance Phase (Day 1 to Week 100) 
At Day 1, the Maintenance Phase begins.  Eligible participants will be randomized 1:1 to 
either: 
• Oral CAB 30 mg + RPV 25 mg once daily for four weeks (participants will be 
assessed for safety and tolerability after four weeks).  At Week 4a, participants 
will have the assessments completed, including clinical chemistries.  At visit 
Week 4b, participants will return to the clinic, take the last dose of oral CAB + 
RPV, and receive the first CAB LA (600 mg) + RPV LA (900 mg) injections 
(within 2 hours of the final oral dose of CAB + RPV).  The Week 4b visit can be 
performed as soon as central laboratory results become available and safety 
parameters are reviewed.  The second and third IM injections (CAB LA 400 mg + 
RPV LA 600 mg) will be performed at Week 8 and Week 12.  There will be a one 
week dosing window for the second and third IM injections such that the second 
injections occur within the window of Week 7 to Week 8, but not later than 
Week 8), and the third injections occur within the window of Week 11 to 
Week 12, but no later than Week 12.  Subsequent injections (CAB LA 400 mg + 
RPV LA 600 mg) will occur every 4 weeks thereafter, with a (+ or -) 7 day dosing 
window, from the projected visit date, being allowed (but not preferred).  
Following the Week 12 injection, the interval between injection visits should be 
limited to a maximum of 5 weeks.  The Medical Monitor must be contacted if the 
length of time between injections exceeds, or is projected to exceed, 5 weeks. 
OR 
• Continue on the oral ABC/DTG/3TC initiated during the Induction Phase for at 
least an additional 100 weeks.  Participants who successfully complete Week 100 
(without meeting study defined withdrawal criteria and who remain virologically 
suppressed through Week 96:  HIV-1 RNA <50 c/mL) will be given the option to 
switch to the LA arm in the Extension Phase or be withdrawn from the study. 
• ABC/DTG/3TC dosing on Day 1 should occur after randomization to avoid 
overlap of regimens (in the event that the participant is assigned to begin oral 
CAB and RPV on Day 1).  However, if the participant takes ABC/DTG/3TC prior 
to coming into the clinic, randomization and initiation of oral CAB and RPV 
should continue as planned on Day 1. 
Randomization will be stratified by participants’ Baseline HIV-1 RNA (<100,000, 
≥ 100,000 c/mL) and gender at birth.  
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
17 
 
Extension Phase 
All eligible participants who transition into the Extension Phase will continue study 
treatment until CAB LA and RPV LA are either locally approved and commercially 
available, the participant no longer derives clinical benefit, the participant meets a 
protocol-defined reason for discontinuation or until development of either CAB LA or 
RPV LA is terminated.  Visits will continue to occur every 4 weeks. 
Participants not eligible to enter the Extension Phase will end their study participation 
(Week 100 will be the last study visit, no withdrawal visit needed).  Sites may be 
reimbursed for up to a one month supply of antiretroviral medication to facilitate 
transition to non-study ART for participants that do not qualify for the Extension Phase. 
Participants Entering from the CAB LA + RPV LA Arm 
All participants who successfully complete Week 100 of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase.   
Participants Entering from the ABC/DTG/3TC Arm 
Participants randomized to continue ABC/DTG/3TC will have the option to either 
continue study participation by switching to CAB LA + RPV LA in the Extension Phase, 
or to complete their study participation at Week 100.   
The transition from ABC/DTG/3TC to CAB LA + RPV LA within the Extension Phase 
can be completed with or without an oral lead-in prior to commencement of injectable 
treatment.  The oral lead-in decision will be made by the participant in consultation with 
the investigator and must be appropriately documented.  As participants approach the 
Week 100 visit, sites must ensure sufficient CAB and RPV supply are available to 
support the participant’s decision for transition to LA. 
Participants who choose to continue on to the Extension Phase will need to be assessed 
for eligibility to begin the CAB LA + RPV LA regimen.  Participants will continue on 
ABC/DTG/3TC while eligibility is being confirmed.   
All participants with an undetectable HIV-1 RNA (<50 c/mL) result from the Week 96 
visit are eligible to enter the Extension Phase.  A single repeat of HIV-1 RNA for any 
participant with a HIV-1 RNA ≥50 c/mL and < 400 c/mL at Week 96 must be performed.  
The retest should be scheduled as soon as possible (but no later than 4 weeks from the 
Week 96 visit).  Participants with a HIV-1 RNA <50 c/mL upon retest are eligible to 
enter the Extension Phase.  Participants with HIV-1 RNA ≥400 c/mL at Week 96 are not 
eligible to enter the Extension Phase, will not be allowed a repeat to determine eligibility, 
and will therefore be withdrawn from the study. 
Participants Transitioning Direct to Injection in the Extension Phase 
Central lab results and safety parameters from the Week 96 visit must be available and 
reviewed for participants who choose to transition direct to injection.  Participants with 
ongoing safety issues or laboratory abnormalities of clinical concern (e.g., Grade 3 or 
Grade 4 liver enzyme elevations), will require consultation and agreement with the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
18 
 
Medical Monitor prior to proceeding directly to injections in the Extension Phase.  
If a clinical chemistry retest is required based on Week 96 labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following 
Week 96).  Participants will remain on oral ABC/DTG/3TC until the Week 100 injection 
visit, and until any required Week 96 retest results are available for review. 
At Week 100, eligible participants will take the last dose of ABC/DTG/3TC (or DTG + 
2 NRTIs), and receive the first injections of CAB LA (600 mg) + RPV LA (900 mg) as 
initial loading doses.  Clinical chemistries will also be assessed at Week 100.  At 
Week 101, participants will return to the clinic for PK and safety assessments including 
clinical chemistries.  The second and third injections (CAB LA 400 mg + RPV LA 
600 mg) will be administered at Week 104a and Week 108.  There will be a one week 
dosing window for the second and third IM injections such that the second injections 
occur within the window of Week 103 to Week 104a, but not later than Week 104a, and 
the third injections occur within the window of Week 107 to Week 108, but no later than 
Week 108.  Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur 
every 4 weeks thereafter, from the projected visit date, with a (+ or -) 7 day dosing 
window being allowed (but not preferred).  Following the Week 108 injection, the 
interval between injection visits should be limited to a maximum of 5 weeks.  The 
Medical Monitor must be contacted if the length of time between injections exceeds, or is 
projected to exceed, 5 weeks. 
Participants Receiving Optional Oral Lead-In in the Extension Phase 
At Week 100, eligible participants who after discussion with the investigator, choose to 
receive the optional oral lead-in will initiate a 4 week lead-in of oral CAB 30 mg + oral 
RPV 25 mg once daily. It is not necessary to dose ABC/DTG/3TC on the day the 
participant begins the oral lead-in with CAB + RPV.  However, if the participant takes 
ABC/DTG/3TC prior to coming into the clinic, initiation of oral CAB and RPV should 
continue as planned.  Clinical chemistries will also be assessed at Week 100.  At Week 
104a, following the 4 week CAB + RPV oral lead-in, participants will have additional 
safety assessments including clinical chemistries.  In addition, central lab results and 
safety parameters from the Week 104a visit must be available and reviewed.  If a clinical 
chemistry retest is required based on Week 104a labs, the retest should be performed as 
soon as possible (and preferably no later than 7 days following Week 104a).  Participants 
will remain on oral CAB 30 mg + RPV 25 mg until the Week 104b injection visit, and 
until any required Visit 104a retest results are available for review.  An HIV-1 RNA 
sample will not be collected at Week 104a for participants receiving the optional oral 
lead-in, but will be obtained at the Week 104b visit to serve as the injection baseline viral 
load. 
At visit Week 104b, participants will return to the clinic, take the last dose of oral CAB + 
RPV, and receive the first CAB LA (600 mg) + RPV LA (900 mg) injections (within 
2 hours of the final oral dose of CAB + RPV).  The Week 104b visit can be performed as 
soon as central lab results from the Week 104a visit become available and safety 
parameters are reviewed.  The second and third injections (CAB LA 400 mg + RPV LA 
600 mg) will be administered at Week 108 and Week 112.  There will be a one week 
dosing window for the second and third IM injections such that the second injections 
occur within the window of Week 107 to Week 108, but not later than Week 108, and the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
19 
 
third injections occur within the window of Week 111 to Week 112, but no later than 
Week 112.  Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur 
every 4 weeks thereafter, from the projected visit date, with a (+ or -) 7 day dosing 
window being allowed (but not preferred).  Following the Week 112 injection, the 
interval between injection visits should be limited to a maximum of 5 weeks.  The 
Medical Monitor must be contacted if the length of time between injections exceeds, or is 
projected to exceed, 5 weeks. 
Long-Term Follow-Up Phase – IM Regimen only 
• Where the CAB LA + RPV LA marketed product is not locally available, any 
participant who receives at least a single dose of CAB LA and/or RPV LA and 
discontinues the CAB LA + RPV LA regimen for any reason must enter the LTFU 
Phase. The participant must remain on suppressive highly active antiretroviral therapy 
(HAART) for at least 52 weeks after the last dose of CAB LA and/or RPV LA in 
order to prevent the potential selection of INI- and/or non-nucleoside reverse 
transcriptase inhibitor (NNRTI)-resistant mutants. Investigators must discuss the 
choice of the follow-up HAART regimen with the Medical Monitor prior to 
initiating the new regimen with the participant. HAART therapy should be 
initiated within four weeks of the last injection. The LTFU Phase will begin the 
day of the last CAB LA and/or RPV LA dose and continue for 52 weeks. These 
participants will not complete a Withdrawal visit but will instead move directly into 
the LTFU Phase.  
 
• Where the CAB LA + RPV LA marketed product is locally available, only 
participants that discontinue the CAB LA + RPV LA regimen for safety-related 
reasons only. must enter the LTFU Phase. Participants must remain on suppressive 
HAART for at least 52 weeks after the last dose of LA and/or RPV LA in order to 
prevent selective pressure on HIV and the potential for selection of resistant mutants. 
Investigators must discuss the choice of the follow-up HAART regimen with the 
Medical Monitor prior to initiating the new regimen with the participant. 
HAART therapy should be initiated within four weeks of the last injection. The 
LTFU Phase will begin the day of the last CAB LA and/or RPV LA dose and 
continue for 52 weeks. These participants will not complete a Withdrawal visit but 
will instead move directly into the LTFU Phase. In addition, for participants who 
withdraw during the LTFU, the final visit will be considered the study withdrawal 
visit.  
 
• NOTE: Participants transitioning to CAB LA + RPV LA marketed product or 
alternative HAART (except due to safety-related reasons) do not need to enter the 
LTFU Phase. 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
20 
 
Long-Term Follow-Up Phase requirement 
Marketed product 
locally available 
Subject WD due to safety-
related reasons 
LTFU Phase required? 
No 
Yes 
Yes 
No 
Yes 
Yes 
Yes 
No 
No, but Safety FU visit required to 
assess potential safety issues 
occurred after the last injection 
 
Participants will be assessed with clinic visits at Months 1, 3, 6, 9 and 12.  Female 
participants of child bearing potential must continue to use adequate contraception 
methods for at least 52 weeks after the last injection.   
In order to assure that participants have access to HAART during the Long-Term Follow-
Up Phase, GlaxoSmithKline (GSK) may supply HAART regionally or reimbursement 
will be provided as needed during this phase.  The Long-Term Follow-Up Phase may be 
shortened at any time during the study for various reasons; e.g., better understanding of 
risks of development of resistance as CAB and RPV exposures decline, regulatory 
approval and commercial availability, end of study timings, etc. 
This phase is considered study participation and participants will be followed on study 
during this time.  A withdrawal visit is not required for participants who do not complete 
the Long-Term Follow Up Phase.  The participants’ last on study visit will be considered 
the withdrawal visit. 
 
Protocol Permitted Substitutions 
Participants who are HLA-B*5701 positive at the Screening visit are allowed to enter the 
study on DTG and an approved dual-nucleoside reverse transcriptase inhibitor (NRTI) 
backbone that does not contain abacavir (e.g. tenofovir/emtricitabine [TDF/FTC] or 
tenofovir alafenamide/emtricitabine [TAF/FTC]).  This regimen may be supplied 
regionally by GSK or reimbursement will be provided as needed.  
During the Induction Phase, prior to randomization into the Maintenance Phase at Day 1, 
one switch to an alternate approved background NRTI therapy is allowed for toxicity or 
tolerability management.  The date of a decision to switch the NRTI background therapy 
for toxicity or tolerability management must be documented in the electronic case report 
form (eCRF).  Switches of a background NRTI for any other reason are not permitted in 
the study.  Local prescribing information should be consulted for information regarding 
use of these medications.   
For consistency with prescribing information, dose reductions of lamivudine (or 
emtricitabine if used as alternate NRTI) are permitted as needed for creatinine clearance 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
21 
 
<50 mL/min (throughout the study).  No other dose reductions, modifications, or changes 
in the frequency of any components of any regimen will be allowed during the 
Maintenance and Extension Phases of the study.   
Following the Induction Phase, in exceptional circumstances, and in consultation with the 
Medical Monitor, Investigators may provide oral CAB and RPV as a short-term 
“bridging” strategy for participants who have begun CAB LA + RPV LA and who will 
miss a subsequent scheduled LA injection.  Should a participant need “oral bridging”, 
sites must contact the Medical Monitor for guidance on treatment strategies prior to a 
missed CAB LA + RPV LA dose.  Should a participant not notify the site in advance, the 
Medical Monitor must be contacted for further treatment guidance. 
Protocol waivers or exemptions are not allowed.  Therefore, adherence to the study 
design requirements are essential and required for study conduct. 
Study Completion 
Participants are considered to have completed the study if they satisfy one of the 
following:  
• Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including the Week 100 visit, and did not enter the Extension 
Phase; 
• Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including the Week 100 visit, and entered and completed the 
Extension Phase (defined as remaining on study until commercial supplies of 
CAB LA + RPV LA become locally available or development of CAB LA + RPV 
LA is terminated). 
Participants who withdraw from CAB LA + RPV LA and go into the Long-Term Follow 
Up Phase will be considered to have prematurely withdrawn from the study, even if they 
complete the 52 week follow-up phase. 
Independent Data Monitoring Committee 
An Independent Data Monitoring Committee (IDMC) will be instituted to ensure external 
objective medical and/or statistical review of efficacy and safety in order to protect the 
ethical interests and well-being of subjects and to protect the scientific validity of this 
study and study 201585.  
The IDMC will evaluate accumulating efficacy, tolerability and safety, and PK of 
CAB LA + RPV LA at predetermined times during the study.  An interim analysis will be 
performed for the IDMC to evaluate the efficacy/safety/PK of CAB LA + RPV LA prior 
to the final analysis.  Full details of the methods, timing, decision criteria and operating 
characteristics will be pre-specified in the IDMC Charter. 
An interim futility analysis will be performed with the intent of having approximately 
50% of participants reaching Week 24 and providing sufficient lead time to allow the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
22 
 
IDMC to review the data prior to any participants reaching the Week 48 visit.  A futility 
rule based on Bayesian posterior predictive probability approach will be applied to assess 
the probability that CAB LA + RPV LA injectable regimen demonstrate non-inferiority 
to the continued ABC/DTG/3TC arm given the partial data set.  The sponsor will remain 
blinded to this analysis. 
In addition, the IDMC may also continuously monitor the incidence of participants 
meeting the confirmed virologic failure criteria through Week 48 to ensure that 
participants are not being sub-optimally treated in the CAB LA + RPV LA arm. 
Full details of the analyses, estimated timing and the decision criteria that will be used to 
determine regimen performance will be pre-specified in the IDMC Charter. 
1.5. 
Type and Number of Participants 
The target population to be enrolled into the study is HIV-1 infected antiretroviral (ART) 
naïve participants. 
Assuming a 20% screen failure rate, sufficient ART-naïve participants will be screened 
(approximately 775) in order to ensure that a total of approximately 620 participants are 
enrolled at the beginning of the Induction Phase.  Assuming 7.5% of enrolled participants 
will not participate in the Maintenance Phase, this will ensure approximately 
570 participants continue into the Maintenance Phase.  Participants will be enrolled from 
multiple sites which may include sites in Canada, France, Germany, Italy, Japan, the 
Netherlands, Russia, South Africa, Spain, the United Kingdom, and the United States. 
Randomization will be stratified by participants’ Baseline HIV-1 RNA (<100,000, 
≥ 100,000 c/mL) and gender at birth. 
A goal of this study is to enroll approximately 20% women, who are typically under-
represented in clinical studies.  To provide sufficient data to determine whether either 
gender is correlated with treatment response, sites are expected to take into account 
gender in their screening strategies.   
Participants who prematurely discontinue from the study will not be replaced. 
1.6. 
Analysis 
The primary analysis at Week 48 will take place after the last participant has had their 
Week 48 viral load assessed, including a retest if required.  The primary analysis method 
for the proportion of participants defined as Snapshot virologic failures at Week 48 will 
be a Cochran-Mantel Haenszel test stratified by participants’ Baseline HIV-1 RNA 
(<100,000, ≥100,000 c/mL) and gender at birth.  A non-inferiority margin of 6% will be 
used for this comparison, where if the upper limit of the 95% confidence interval (CI) of 
the difference in failure rate between the two study arms is less than 6%, non-inferiority 
will be demonstrated. 
Assuming the true virologic failure rate is 3% for the CAB LA + RPV LA injectable 
regimen and 2% for the INI STR arm, this would provide approximately 97% to show 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
23 
 
non-inferiority at a 2.5% one-sided significance level.  If we observe a 2% failure rate for 
the INI STR arm, then non-inferiority would be declared if we observe a 5% or lower 
failure rate for the CAB LA + RPV LA arm (i.e. an observed treatment difference less 
than 3 percentage points for [CAB LA + RPV LA] – INI STR). 
A key secondary analysis will evaluate the proportion of responders (HIV-1 RNA 
<50 c/mL per Snapshot) at Week 48 using a Cochran-Mantel Haenszel test stratified by 
randomization stratification factors.  A non-inferiority margin of -10% will be used for 
this secondary comparison, where if the lower limit of the 95% confidence interval (CI) 
of the difference in responder rate between the two study arms is greater than -10%, non-
inferiority will be demonstrated.  Assuming true response rates for the CAB LA + RPV 
LA arm and current ART arm are both 87%, the sample size of 285 per arm will provide 
at least 94% power to show non-inferiority at a 2.5% one-sided significance level. 
In addition, the data from this study, together with data from a separate study, 201585, 
will be combined to assess non-inferiority using a 4% non-inferiority margin.  The 
combined sample size from both studies (570 pooled per arm) will provide 90% power, 
under the assumptions described above, to show non-inferiority for the proportion of 
participants with virologic failure (per FDA’s snapshot algorithm for assessing HIV-1 
RNA ≥ 50 c/mL) at Week 48. 
In descriptive analyses, antiviral response will be assessed according to the proportion of 
participants with and without oral lead-in who have HIV-1 RNA ≥50 c/mL at Week 124 
(i.e., 24 weeks from initiation of CAB LA + RPV LA at Week 100, ±6 week analysis 
window, using the FDA Snapshot algorithm), with corresponding 95% confidence 
interval.  No formal statistical comparison with respect to safety and efficacy outcomes 
will be performed.   
201584 (FLAIR) is being conducted in parallel with study 201585 (ATLAS) with the aim 
to pool data generated from the current study with study 201585, in order to evaluate key 
program objectives. 
2. 
INTRODUCTION 
Advances in antiretroviral therapies (ART) have led to significant improvements in 
morbidity and mortality among Human Immunodeficiency Virus (HIV)-infected persons, 
and has transformed HIV into a chronic manageable disease. Suppression of viral 
replication is the cornerstone of ART’s success and this in turn, is dependent on a 
participant’s ability to adhere to life-long therapy with 3 or more antiretrovirals (ARVs).  
Fixed-dose combinations (FDCs) have greatly advanced HIV treatment by allowing 
simplification of dosing and reducing pill burden.  Among regimens of comparable 
efficacy, physicians and HIV-1-infected participants who receive ART rate total pill 
burden, dosing frequency, and safety concerns among the greatest obstacles to achieving 
adherence. Incomplete adherence may lead to the emergence of drug-resistant virus that 
can lead to the loss of virologic control and reverse the benefits of ART.  Different HIV 
treatment modalities are being developed to help improve adherence and participant 
outcomes, and prevent the emergence of resistance and transmission of the virus.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
24 
 
There is also an increasing desire to develop nucleoside reverse transcriptase inhibitor 
(NRTI)-sparing regimens that avoid long-term NRTI-associated adverse drug reactions, 
including renal, hepatic, bone and cardiovascular toxicities.  In addition, while there are 
no currently approved two-drug regimens to maintain suppression, simplifying treatment 
has long been a goal to increase treatment compliance and improve the quality of life for 
participants with HIV. 
Cabotegravir (CAB) is a potent integrase inhibitor that possesses attributes that allow 
formulation and delivery as a long-acting (LA) parenteral product.  Rilpivirine (RPV), 
which can also be formulated as a LA product, is a diarylpyrimidine derivative and a non-
nucleoside reverse transcriptase inhibitor (NNRTI) with in vitro activity against wild type 
HIV-1 and select NNRTI-resistant mutants.  A two-drug combination therapy with CAB 
LA plus RPV LA may offer a better tolerability profile, as well as improved adherence 
and treatment satisfaction in virologically suppressed patients. 
To date, there are three integrase inhibitors approved in the US and EU for the treatment 
of HIV-infection: raltegravir (RAL) (Merck), elvitegravir (EVG) (Gilead), and 
dolutegravir (DTG) (ViiV Healthcare).  Two of these three (DTG, EVG) are currently 
available as components of a once daily single tablet regimen.  In April, 2015, the 
Department of Health and Human Services (DHHS) updated treatment guidelines to 
include five recommended choices for initial treatment of HIV infection.  Four of these 
five include integrase based therapy as the first line recommended regimen for ART-
naïve participants [DHHS, 2015]. 
DTG is a potent dual cation binding integrase inhibitor, exhibiting rapid reduction in viral 
load, best in class efficacy, and a high barrier to resistance.  DTG is a once daily, 
unboosted integrase inhibitor that has demonstrated sustained antiviral activity 
comparable or superior to standard of care in combination with dual NRTIs [Raffi, 2013; 
Walmsley, 2015].  In addition, due to its mechanism of metabolism, DTG lacks many of 
the frequent drug interactions associated with other medications commonly taken by 
HIV-positive patients.  To date, the efficacy, PK, safety and drug interaction potential of 
DTG has been evaluated in an extensive program of Phase 1 to 3B clinical trials 
[TIVICAY Prescribing Information, 2017].  DTG has also demonstrated significant 
improvements over the first marketed INI (RAL), including activity in the presence of 
integrase (IN)-resistant viruses and an improved dosing regimen (unboosted once daily 
administration) with similar or improved safety.  
Abacavir (ABC)/DTG/lamivudine (3TC) is a combination product of an INI and 
two NRTIs formulated into a fixed dose combination (FDC) single tablet regimen (STR) 
that offers the simplicity of a once-daily well-tolerated regimen, with a high genetic 
barrier for resistance.  It may be taken with or without food, and demonstrates few drug-
drug interactions in treatment-naïve participants.  
The overall objective of this study will be to demonstrate the non-inferior antiviral 
activity of switching to intramuscular CAB LA + RPV LA every 4 weeks compared to 
continuation of ABC/DTG/3TC over 48 weeks (44 weeks of LA maintenance treatment) 
in HIV-1 antiretroviral naïve participants. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
25 
 
2.1. 
Study Rationale 
The overall objective of the CAB LA + RPV LA clinical development program is to 
develop a highly effective, well tolerated two drug long-acting injectable regimen which 
has the potential to offer improved compliance, treatment convenience, and improved 
quality of life for individuals with HIV compared to current standard of care.  201584 
(FLAIR) is being conducted to establish if human immunodeficiency virus type-1 
(HIV-1) infected adult participants whose virus is virologically suppressed on an 
integrase inhibitor single tablet regimen (INI STR), will remain suppressed after 
switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir 
(CAB) and rilpivirine (RPV).  This study is designed to demonstrate the non-inferior 
antiviral activity of switching to a two drug CAB LA + RPV LA regimen every 4 weeks 
(monthly) compared to remaining on a single tablet integrase based regimen 
(ABC/DTG/3TC) over 48 weeks.  201584 (FLAIR) will also allow for characterization of 
long-term antiviral activity, safety, tolerability, and participant satisfaction of the 
regimens through Week 96.   
Additionally, participants initially randomized to continue ABC/DTG/3TC will have an 
option to switch to CAB LA + RPV LA at, or after, completion of the Week 100 visit.  
Amendment 04 of the FLAIR study will provide an opportunity to access an optional (vs 
mandatory) oral lead-in for these participants who transition to LA treatment at 
Week 100.  Eligible participants (HIV-1 RNA <50 c/mL at Week 96) would transition to 
LA dosing, beginning at either Week 100 (direct to injection) or Week 104b (following 
optional oral lead-in with CAB 30 mg and RPV 25 mg). 
Importantly, the oral lead-in during the early development program for CAB LA and 
RPV LA was instituted to minimize the risk of severe adverse drug reactions during LA 
dosing (e.g. acute hypersensitivity).  The 4 week oral lead-in allowed for an evaluation of 
any untoward adverse events and an assessment of safety labs prior to initiation of LA 
therapy.  To date, the principal safety risk identified with cabotegravir, following 3145 
exposures to drug (oral and/or LA), is suspected DILI, which has occurred in a few 
individuals, all of whom were receiving oral CAB.  The time to onset ranged between 
4 weeks and one year and manifested as asymptomatic elevations of ALT, without 
compromise to hepatic function.  Each participant fully recovered, with removal of 
investigational product, without hospitalization or intervention.  During the Phase 3 
ATLAS and FLAIR studies, no cases of DILI have been identified, during the oral lead-
in period, or following initiation of LA dosing.  There has been no evidence to date of a 
risk for clinically significant hepatotoxicity observed with cabotegravir.  Additionally, 
throughout the development program to date, no cases of severe drug hypersensitivity or 
severe drug allergy have been observed.  While the risk of idiosyncratic severe drug 
reactions cannot be fully excluded, the risk of occurrence is felt to be low, on the basis of 
safety data generated to date. 
Based on blinded, instream review of ongoing Phase 3 aggregate AE data (from FLAIR, 
and ATLAS) and of individual case reports (SAEs), no new, emerging, drug related 
safety issues have been identified within the four week oral lead-in dosing period (e.g., 
hypersensitivity, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS], 
severe drug induced liver injury [DILI]) that would have precluded participants from 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
26 
 
proceeding to CAB LA + RPV LA injections during the Maintenance Phase of the 
studies.  Additionally, review of accumulating data has not identified any new safety 
issues occurring on CAB LA + RPV LA that were otherwise predictable based on oral 
exposure experience. 
As a result of the accumulated safety data, which has been generated over the course of 
the Phase 1, 2 and 3 clinical studies, this amendment has been developed to generate 
safety, efficacy and PK data for the transition from oral ART to CAB LA + RPV LA 
without receiving an oral lead-in.  These data are intended to inform regulatory 
discussions around the safe and effective direct to inject dosing option with CAB LA + 
RPV LA.  The decision to dose with or without an oral-lead-in will be optional in this 
study, as elected by the study participant following informed consent discussions with the 
investigator. 
At Week 124, a descriptive analysis will be conducted to assess antiviral response (HIV-1 
RNA ≥50 c/mL) for participants who choose no oral lead-in.  No formal statistical 
comparison will be performed with respect to safety and efficacy outcomes at Week 124. 
Data from this optional oral lead in will provide valuable knowledge/insight into the 
evolution of the ‘direct to injection’ concept.  
2.2. 
Brief Background 
Various approaches to simplify a patient's antiretroviral therapy (ART) regimen, after 
achieving virologic suppression, have been studied.  Previous studies have evaluated 
switches to ritonavir-boosted PI monotherapy in virologically suppressed participants 
[Bierman, 2009 and Arribas, 2012].  While the data from these studies have shown both 
long-term non-inferiority and inferiority to continual Highly Active Antiretroviral 
Therapy (HAART), they suggest that simplifying from a three drug dual class regimen to 
a single boosted protease inhibitor may be a safe and effective option for the majority of 
participants studied who have effectively maintained virologic suppression.  
Other approaches have looked at two nucleoside reverse transcriptase inhibitors (NRTIs) 
with a ritonavir-boosted protease inhibitor (PI/r) compared to a PI/r + single NRTI.  In 
the OLE study, virologically suppressed (HIV-1 RNA <50 c/mL) HIV-1 infected 
participants receiving a lopinavir-ritonavir (LPV/r) + lamivudine (3TC) or emtricitabine 
(FTC) based NRTI regimen simplified to a dual regimen of LPV/r + 3TC or FTC.  The 
primary endpoint was the proportion of participants without virologic failure at Week 48.  
In a modified Intent to Treat (m-ITT) analysis, dual therapy with LPV/r + 3TC 
demonstrated non-inferiority efficacy and comparable safety to LPV/r + 2 NRTIs. 
[Arribas, 2015].   
Two Phase 2b studies (LAI116482 [LATTE] and 200056 [LATTE-2]) have been 
conducted with oral CAB and/or intramuscular (IM) CAB LA, evaluating an induction / 
maintenance simplification approach.  In LAI116482 (LATTE), participants were 
randomized to oral CAB 10, 30, or 60 mg + two nucleoside reverse transcriptase 
inhibitors (NRTIs) once daily compared to efavirenz (EFV) + 2 NRTIs.  The study 
enrolled and treated 243 participants, 181 of whom received one of the three regimens of 
CAB plus 2 NRTIs and 62 of whom received EFV 600 mg once daily plus 2 NRTIs.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
27 
 
Following 24 weeks of Induction therapy, participants receiving CAB who had achieved 
a HIV-1 RNA < 50 copies/mL (c/mL) simplified their ART regimen by discontinuing the 
NRTIs, initiating rilpivirine (RPV), and continuing on two drug ART (CAB + RPV).  A 
robust virologic response (HIV-1 RNA <50 c/mL) was observed across all CAB plus 
NRTI treatment groups by the end of the 24-week induction phase (CAB subtotal: 
156/181 [86%] vs EFV: 46/62 [74%] (ITT-E), with a shorter time to virologic 
suppression for the CAB groups compared with the EFV group (each p<0·001; log-rank 
test).  A planned Week 48 analysis (24 weeks of CAB + 2 NRTIs Induction, followed by 
24 weeks of CAB + RPV Maintenance) demonstrated that the proportion of participants 
with plasma HIV-1 RNA <50 c/mL (Snapshot algorithm), in each of the CAB plus RPV 
groups remained numerically higher than the EFV plus dual NRTI group at Week 48 
(CAB: 149 [82%] vs EFV: 44 [71%]).  Similar antiviral activity was observed across the 
three dosing arms of CAB in combination with RPV (10 mg:  80%; 30 mg: 80%; 60 mg:  
87%, ITT-E, MSD=F), which compared favourably to EFV 600 mg plus 2 NRTIs (71%; 
ITT-E, MSD=F).  
Following 72 weeks of two-drug maintenance therapy (Week 96), 137 (76%) of CAB 
plus RPV participants and 39 (63%) of EFV plus dual NRTI participants remained 
virologically suppressed (ITT-E, MSD=F).   
An efficacy analysis of the ITT-Maintenance Exposed (ITT-ME) population which 
excludes participants who did not enter the Maintenance Phase, and assessed the ability 
of the two-drug regimen to maintain viral suppression was also performed at Week 96.  
In this population, virologic response (HIV-1 RNA <50 c/mL) was high across all 
treatment arms at Week 96, demonstrating a comparable durability of virologic response 
between treatments (CAB: 137/160 [86%]; EFV: 39/47 [83%]) with numerically higher 
values observed for the CAB 30 mg (45/53 [85%]) and 60 mg (51/55 [93%]) groups 
compared with the 10 mg group (41/52 [79%]).   
The 200056 study (LATTE-2) evaluated a 20 week induction of HIV-1 RNA suppression 
with a three drug oral antiretroviral regimen consisting of CAB + ABC / 3TC Fixed Dose 
Combination (FDC) followed by randomization to a two-drug regimen consisting of 
intramuscular (IM) long-acting (LA) CAB LA + RPV LA compared to continuation of 
oral CAB + ABC / 3TC for the maintenance of HIV-1 RNA suppression.  A total of 309 
participants were enrolled and treated. 
During the Induction Period there was a rapid and sustained decline in HIV-1 RNA, with 
91% of participants (282/309) achieving HIV-1 RNA <50 c/mL through 20 weeks of 
therapy.  There was a single participant (with known compliance issues) with confirmed 
virologic failure during the Induction Period.  Virologic testing revealed no treatment 
emergent phenotypic or genotypic resistance in this participant. 
The primary endpoint for 200056 was the Week 32 proportion of participants with HIV-1 
RNA < 50 c/mL (Snapshot, Intent-to-Treat Maintenance Exposed population [ITT-ME]). 
Following virologic suppression on three drug oral therapy in the Induction Period, 
286 participants qualified to enter randomization at the Day 1 visit, and were 
subsequently randomized 2:2:1 onto every 4 week intramuscular (IM) injections with 
CAB LA + RPV LA (Q4W), every 8 week IM injections with CAB LA + RPV LA 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
28 
 
(Q8W) or continuation of oral CAB + NRTIs, respectively.  At the time of randomization 
at Day 1, participants entering one of the IM arms discontinued all oral ART.  Through 
32 weeks of two-drug maintenance therapy, 95% (Q8W) and 94% (Q4W) of participants 
on injectable dosing were virologic successes, compared to 91% of participants 
continuing three drug oral CAB + NRTIs, meeting pre-specified criteria for comparability 
between the dosing arms.  Through 32 weeks of Maintenance therapy, there was one 
participant each on Q8W and oral dosing with confirmed virologic failure (CVF), without 
any evolution of viral resistance.  The CVF on Q8W dosing occurred following an 
aberrant RPV injection, without measurable plasma RPV concentrations 4 weeks post 
dosing.   
Week 48 data was a secondary endpoint for 200056, and permitted the evaluation of the 
two-drug long-acting combinations’ ability to maintain the virologic suppression 
demonstrated at Week 32.  At Week 48, 92% (Q8W) and 91% (Q4W) of participants 
receiving injectable dosing had a sustained virologic response (HIV-1 RNA <50 c/mL) 
compared to 89% of participants continuing oral CAB + 2 NRTIs.  Although the 
proportion of participants with virologic success was similar for Q8W and Q4W dosing, 
the reason for Snapshot failure was different between the arms.  There were more 
Snapshot failures for virologic reasons on the Q8W arm (n=8, 7%) than in the Q4W arm 
(n=1, <1%), and more participants with no virologic data (discontinued due to AE or 
other reasons) on the Q4W arm (n=9, 8%) compared to the Q8W arm (n=1, <1%).   
Between Week 32 and Week 48, one additional participant (Q8W) had confirmed 
virologic failure.  This participant had a Baseline HIV-1 RNA of 444,489 c/mL.  At 
Week 48, the participant was a suspected virologic failure with HIV-1 RNA = 463 c/mL.  
Upon retest, ten days later, the virologic failure was confirmed with HIV-1 RNA of 
205 c/mL.  At the time of CVF, this participant had treatment emergent NNRTI 
resistance K103N, E138G, and E238T, with high level phenotypic resistance to 
delaviridine (>MAX), efavirenz (48 fold change [FC]), nevirapine (>Max), and 
rilpivirine (3.34 FC).  The fold change to etravirine (1.91) was below the lower 
cutoff.  Week 48 integrase genotype had the treatment emergent integrase resistance 
mutation Q148R, with accompanying resistance to raltegravir (29 FC), elvitegravir (138 
FC), and cabotegravir (6.06 FC).  The Week 48 sample was not resistant to dolutegravir 
(1.38 FC). 
Overall, AEs and clinical chemistries were similar to those observed in prior studies with 
CAB, without discernible trends between Q8W, Q4W, and oral.  Injections were well 
tolerated with two participants discontinuing due to injection tolerability through 48 
weeks (both on Q8W dosing).  The vast majority of injection site reactions were due to 
pain/discomfort with nearly all injection site reactions classified as mild (82%) or 
moderate (17%), with <1% of reactions classified as severe.  There was no discernible 
tolerability difference between Q4W (2 mL) dosing and Q8W (3 mL dosing).  The most 
common non-ISR AEs during the Maintenance Phase were nasopharyngitis (24%), 
headache (16%), and diarrhea (13%) on IM arms and nasopharyngitis (30%), headache 
(11%), and diarrhea (5%) on oral CAB.  Through Week 48, SAEs during the 
Maintenance Period occurred in 7% of participants randomized to CAB LA + RPV LA 
and 5% of participants randomized to remain on oral treatment, none were drug related.  
Based on the data from the Week 48 endpoint, Q4W dosing was chosen to progress for 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
29 
 
further clinical development. 
Long-acting two class therapy consisting of CAB LA + RPV LA as an IM regimen, has 
the benefit of being a NRTI-sparing regimen for long-term treatment of HIV infection 
which will avoid known NRTI-associated adverse drug reactions and long-term 
toxicities.  Additionally, a two-drug combination therapy with CAB LA plus RPV LA 
may offer a better tolerability and resistance profile, as well as improved adherence and 
treatment satisfaction in virologically suppressed participants improving the quality of 
life for people with living with HIV.   
201584 (FLAIR) is being conducted in parallel with study 201585 with the aim to pool 
data generated from the current study with study 201585, in order to evaluate key 
program objectives. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To demonstrate the non-inferior antiviral 
activity of switching to intramuscular CAB LA + 
RPV LA every 4 weeks compared to 
continuation of ABC/DTG/3TC over 48 weeks 
in HIV-1 antiretroviral naïve participants. 
• Proportion of participants with a ‘virologic 
failure’ endpoint as per FDA Snapshot 
algorithm at Week 48 (Missing, Switch or 
Discontinuation = Failure, Intent-to-Treat 
Exposed [ITT-E] population). 
Secondary 
To demonstrate the antiviral and immunologic 
activity of switching to intramuscular CAB LA + 
RPV LA every 4 weeks compared to 
continuation of ABC/DTG/3TC. 
• Proportion of participants with plasma HIV-
1 RNA <50 copies/mL (c/mL) at Week 48 
using the FDA Snapshot algorithm (Intent-
to-Treat Exposed [ITT-E] population). 
• Proportion of participants with plasma HIV-
1 RNA <200 c/mL at Week 48 using the 
FDA Snapshot algorithm (ITT-E 
population). 
• Proportion of participants with plasma HIV-
1 RNA <200 c/mL and HIV-1 RNA 
<50 c/mL at Week 96 using the FDA 
Snapshot algorithm (ITT-E population). 
• Proportion of participants with a ‘virologic 
failure’ endpoint as per FDA Snapshot 
algorithm at Week 96. 
• Proportion of participants with confirmed 
virologic failure at Week 48 and Week 96. 
• Absolute values and change from Baseline 
in plasma HIV-1 RNA at Week 48 and 
Week 96. 
• Absolute values and changes from 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
30 
 
Objectives 
Endpoints 
Baseline in CD4+ cell counts over time 
including Week 48 and Week 96. 
• Incidence of disease progression (HIV-
associated conditions, acquired 
immunodeficiency syndrome [AIDS] and 
death). 
To evaluate the safety and tolerability of 
switching to CAB LA + RPV LA every 4 weeks 
compared to continuation of ABC/DTG/3TC 
over time. 
• 
Incidence and severity of AEs and 
laboratory abnormalities over time 
including Week 48 and Week 96. 
• Proportion of participants who discontinue 
treatment due to AEs over time including 
Week 48 and Week 96. 
• 
Absolute values and changes in laboratory 
parameters over time including Week 48 
and Week 96. 
To evaluate the effects of CAB LA + RPV LA 
every 4 weeks on fasting lipids over time 
compared to continuation of ABC/DTG/3TC 
over time. 
• Change from Baseline in fasting lipids over 
time including Week 48 and Week 96. 
To assess the development of viral resistance 
in participants experiencing protocol-defined 
virologic failure. 
• Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV, 
and other on-study ART at Week 48 and 
Week 96. 
To characterize CAB and RPV concentrations 
and population pharmacokinetics and identify 
important determinants of variability. 
 
• Plasma PK parameters for CAB LA and 
RPV LA (when evaluable, Ctrough. 
concentrations post dose [~Cmax], and 
area under the curve [AUC]).   
• Demographic parameters including, but 
not limited to age, sex, race, body weight, 
body mass index, and relevant laboratory 
parameters will be evaluated as potential 
predictors of inter- and intra-participant 
variability for pharmacokinetic parameters.   
To assess the acceptance of pain and injection 
site reactions following injections. 
• Change from Week 5 in Dimension scores 
(e.g., “Bother of ISRs”, “Leg movement”, 
“Sleep”, and “Injection Acceptance”) and 
individual item scores assessing pain 
during injection, anxiety before and after 
injection, willingness to be injected in the 
future and overall satisfaction with mode of 
administration over time using the 
Perception of iNjection questionnaire 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
31 
 
Objectives 
Endpoints 
(PIN).  
• Proportion of participants considering pain 
and local reactions following injection to be 
extremely or very acceptable based on the 
acceptability score over time using the 
Perception of iNjection questionnaire 
(PIN). 
To assess degree of health-related quality of 
life (HR QoL). 
• Change from Baseline in HR QoL using 
the HIV/AIDS targeted quality of life 
questionnaire (HAT-QoL) short form at 
Week 24, Week 48, Week 96 (or 
Withdrawal). 
To assess treatment satisfaction of CAB LA + 
RPV LA compared to continuation of 
ABC/DTG/3TC. 
 
• Change from baseline in total “treatment 
satisfaction” score, and individual item 
scores of the HIV Treatment Satisfaction 
Questionnaire (status version) (HIVTSQs) 
at Week 4b, Week 24, Week 44, Week 96 
(or Withdrawal). 
• Change in treatment satisfaction over time 
(using the HIVTSQ change version 
[HIVTSQc]) at Week 48 (or Withdrawal). 
To assess health status. 
• Change from Baseline in health status at 
Week 24, Week 48, and Week 96 (or 
Withdrawal) using the 12-item Short Form 
Survey (SF-12). 
To assess treatment acceptance. 
• Change from Baseline in treatment 
acceptance at Week 8, Week 24, 
Week 48, Week 96 (or Withdrawal) using 
the “General Acceptance” dimension of 
the Chronic Treatment Acceptance 
(ACCEPT) questionnaire. 
To assess tolerability of injections. 
• Change from Week 4b in tolerability of 
injections at Week 5, Week 40, Week 41, 
and Week 96 using the Numeric Rating 
Scale (NRS) within the CAB LA + RPV LA 
arm. 
To evaluate the antiviral and immunologic 
effects, safety and tolerability, and viral 
resistance of CAB LA + RPV LA at Week 124 
and over time for participants switching from 
• Proportion of participants with HIV-1 RNA 
≥ 50 c/mL at Week 124, with and without 
oral lead-in (FDA Snapshot algorithm, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
32 
 
Objectives 
Endpoints 
ABC/DTG/3TC in the Extension Phase, with 
and without oral lead-in. 
Extension Switch population). 
• Proportion of participants with plasma HIV-
1 RNA <50 c/mL and HIV-1 RNA 
<200 c/mL over time. 
• Proportion of participants with confirmed 
virologic failure over time. 
• Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB and 
RPV over time. 
• Absolute values and change from Baseline 
in CD4+ cell counts over time. 
• Incidence and severity of AEs and 
laboratory abnormalities over time. 
• Proportion of participants who discontinue 
treatment due to AEs over time. 
• Absolute values and change in laboratory 
parameters over time. 
To evaluate the pharmacokinetics of CAB and 
RPV in the setting of no oral lead-in for 
participants switching from ABC/DTG/3TC in 
the Extension Phase. 
• To evaluate plasma CAB and RPV 
concentrations over time (Week 100 
[direct to inject without oral lead-in] and 
Week 104 [both direct to inject and 
optional oral lead-in participants]) 
Exploratory 
To explore the effect of participant 
characteristics on the virologic and 
immunologic response of CAB LA and RPV LA 
compared to continuation of ABC/DTG/3TC. 
• Proportion of participants by patient 
subgroup(s) (e.g., by age, gender, BMI, 
race, HIV-1 subtype, Baseline CD4+) with 
Virologic Failure over time including Week 
48, and 96 using the Snapshot algorithm 
for the ITT-E population. 
• Proportion of participants by subgroup(s) 
(e.g. by age, gender, BMI, race, HIV-1 
subtype, Baseline CD4+) with plasma HIV-
1 RNA <50 c/mL at Week 48 and Week 
96. 
• Change from Baseline in CD4+ cell counts 
by subgroups at Week 48 and Week 96. 
To explore relationship(s) between plasma 
concentrations of CAB and RPV and 
pharmacodynamic endpoints. 
• Relationship between plasma PK 
concentrations and virologic, immunologic 
responses, and/or occurrence of adverse 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
33 
 
Objectives 
Endpoints 
events [AEs] over time may be explored. 
To evaluate renal and bone biomarkers in 
participants receiving CAB LA and RPV LA 
compared to continuation of ABC/DTG/3TC 
over time. 
• Absolute values and change from Baseline 
in renal (in urine and blood) and bone (in 
blood) biomarkers over time including 
Week 48 and Week 96. 
To assess preference for CAB LA + RPV LA 
compared to oral antiretroviral (ARV) therapy 
using a single dichotomous preference 
question. 
• For participants randomized to the “CAB 
LA + RPV LA” arm, preference for CAB 
LA + RPV LA compared to oral ARV 
regimen, at Week 48. 
4. 
STUDY DESIGN 
4.1. Overall Design 
201584 (FLAIR) is a 120-week Phase 3, multi-phase, randomized, open label, active-
controlled, multicenter, parallel-group, non-inferiority study in HIV-1, ART-naïve adult 
participants.  Participants who fulfill eligibility requirements will enroll into the Induction 
Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week [-20] to Day 1).  
Participants who have an HIV-1 RNA <50 c/mL at Week (-4) will be randomized (1:1) 
into the Maintenance Phase at Day 1 to either continue ABC/DTG/3TC or to discontinue 
ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg once daily (to 
determine individual safety and tolerability prior to administration of CAB LA + RPV 
LA).  ABC/DTG/3TC dosing on Day 1 should occur after randomization to avoid overlap 
of regimens (in the event that the participant is assigned to the CAB LA + RPV LA 
treatment arm).  However, if the participant takes ABC/DTG/3TC prior to coming into 
the clinic, randomization and initiation of oral CAB and RPV should continue as planned 
for Day 1.  Participants who are not eligible to continue into the Maintenance Phase will 
be withdrawn from the study.  At the Week 4a visit, assessments (including e.g. clinical 
chemistries) will be performed as per the Time and Events Table (Table 5).  At the 
Week 4b visit, participants will return to the clinic, take the last dose of oral CAB + RPV, 
and receive the first CAB LA + RPV LA injections (within 2 hours of the final oral dose 
of CAB + RPV).  The Week 4b visit can be performed as soon as central laboratory 
results become available and safety parameters are reviewed.  If a retest is required based 
on Week 4a labs, the retest should be performed as soon as possible (and preferably no 
later than 7 days following Week 4a).  Participants will remain on oral CAB 30 mg + 
RPV 25 mg until the Week 4b injection visit, and until any required Visit 4a retest results 
are available for review. 
The visit schedule following the oral lead-in period will be based on timing of the first 
injection visit at Week 4b such that the Week 5 visit should be performed approximately 
7 days after the Week 4b visit.  The second and third IM injections (CAB LA 400 mg + 
RPV LA 600 mg) will be performed at Week 8 and Week 12.  There will be a one week 
dosing window for the second and third IM injections such that the second injections 
occur within the window of Week 7 to Week 8, but not later than Week 8), and the third 
injections occur within the window of Week 11 to Week 12, but no later than Week 12.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
34 
 
Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur every 4 weeks 
thereafter, with a ± 7 day dosing window being allowed (but not preferred).  In addition, 
starting at the Week 12 injection (third injection), the interval between injection visits 
should be limited to a maximum of 5 weeks.  If the length of time between injections 
exceeds, or is projected to exceed 5 weeks, the Medical Monitor must be contacted to 
discuss individual participant case management.   
Participants randomized to ABC/DTG/3TC during the Maintenance Phase will continue 
ABC/DTG/3TC for at least an additional 100 weeks.  Participants who successfully 
complete Week 100 (without meeting study defined withdrawal criteria and who remain 
virologically suppressed through Week 96:  HIV-1 RNA <50 c/mL) will be given the 
option to switch to the LA arm in the Extension Phase or be withdrawn from the study.  
The transition from ABC/DTG/3TC to CAB LA + RPV LA within the Extension Phase 
can be completed with or without an oral lead-in prior to commencement of injectable 
treatment.  The oral lead-in decision will be made by the participant in consultation with 
the investigator and must be appropriately documented. 
Where the CAB LA + RPV LA marketed product is not locally available, any participant 
who receives at least a single dose of CAB LA and/or RPV LA and discontinues the CAB 
LA + RPV LA regimen for any reason must enter the 52-week Long-Term Follow-Up 
Phase. Where CAB LA + RPV LA marketed product is locally available, only 
participants that discontinue the CAB LA + RPV LA regimen for safety-related reasons 
should enter the LTFU Phase. All participants must remain on suppressive highly active 
antiretroviral therapy (HAART) for at least 52 weeks after the last dose of CAB LA 
and/or RPV LA. 
In order to achieve balance across the two treatment arms, randomization will be 
stratified by participant’s Baseline HIV-1 RNA (<100,000, ≥100,000 c/mL) and gender at 
birth.  The primary endpoints for the study is the proportion of participants who meet the 
Snapshot virologic failure criteria at Week 48 (48 weeks of two drug maintenance 
treatment, 44 weeks of LA therapy).  The proportion of participants with plasma HIV-1 
RNA <50 c/mL at Week 48 using the FDA Snapshot algorithm (Missing, Switch or 
Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population) is a key 
secondary comparison.   
Approximately 620 subjects will be enrolled into the Induction Phase of the study. 
Assuming 7.5% of enrolled participants will not participate in the Maintenance Phase, 
this will ensure approximately 570 participants continue into the Maintenance Phase.  
The sample size of 285 per arm (at Day 1 randomization) is such that the study has 
approximately 97% power to demonstrate non-inferiority in the proportion of participants 
with snaphot virologic failure at Week 48 using an 6% margin, assuming a true 3% 
failure rate for CAB and a 2% failure rate for the ABC/DTG/3TC control arm and using a 
2.5% one-sided alpha level. 
An Independent Data Monitoring Committee (IDMC) will evaluate interim efficacy, 
tolerability and safety, and PK of CAB LA + RPV LA at predefined times during the 
study.  An interim futility analysis will be performed for the IDMC with the intent of 
having approximately 50% of participants reaching Week 24.  In addition, the IDMC 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
35 
 
may also monitor the incidence of participants meeting CVF criteria through Week 48 to 
ensure that participants are not being sub-optimally treated in the CAB LA + RPV LA 
arm.  Additional details are provided in Section 9.3.3, and in the IDMC charter, which is 
available upon request. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
36 
 
Figure 1 
201584 (FLAIR) Study Schematic 
 
1.  
 
¥Subjects who withdraw from IM CAB LA + RPV LA must enter the 52 week Long Term Follow-Up 
Phase if the marketed product is not locally available.  
4.2. 
Treatment Arms and Duration 
4.2.1. 
Screening Phase (Up to 35 days) 
Informed consent must be obtained prior to any study procedures, including any 
Screening assessment. 
All participants will complete the Screening phase of up to 35 days prior to Baseline 
(Week [-20]) during which all clinical and laboratory assessments of eligibility must be 
performed and reviewed.  All Screening results must be available prior to enrolment.  A 
single repeat of a procedure/lab parameter is allowed to determine eligibility (unless 
otherwise specified).  In exceptional circumstances only, if a repeat lab is required 
because a central lab result cannot be generated, local labs can be reviewed and approved 
by the Medical Monitor, for consideration of participant eligibility.  A repeat central lab 
will be submitted concurrently or at the next planned visit.  Similarly, if a central 
laboratory result cannot be generated for genotype/phenotype, a local result can be 
considered following review and approval by the study virologist. 
Participants not meeting all inclusion and exclusion criteria at initial screen may be re-
screened one time with a new participant number.  Participants who are enrolled into the 
trial and subsequently withdrawn from the study, for any reason, may not be re-screened.  
Participants may be enrolled as soon as all eligibility requirements have been confirmed 
at the site. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
37 
 
4.2.2. 
Induction Phase 
Following the Screening Phase, eligible participants will be enrolled into the study and 
begin a 20 week Induction Phase study on ABC/DTG/3TC (Week [-20] to Day 1). 
ABC/DTG/3TC dosing on Day 1 should occur after randomization to avoid overlap of 
regimens (in the event that the participant is assigned to the CAB LA + RPV LA 
treatment arm).  However, if the participant takes ABC/DTG/3TC prior to coming into 
the clinic, randomization and initiation of oral CAB and RPV should continue as planned 
on Day 1.  
4.2.3. 
Eligibility for the Maintenance Phase 
Participants with an undetectable HIV-1 RNA (<50 c/mL) at the Week (-4) visit are 
eligible to enter the Maintenance Phase.  A single repeat HIV-1 RNA test to determine 
eligibility may be allowed ONLY after consultation with the medical monitor.  
Participants with HIV-1 RNA ≥400 c/mL at Week (-4) are not eligible to enter the 
Maintenance Phase, will not be allowed a repeat to determine eligibility, and will 
therefore be withdrawn from the study. 
Result of HIV-1 RNA at Week (-4) 
Action 
<50 c/mL 
Begin Maintenance Phase at Day 1. 
≥50 c/mL but <400 c/mL 
Single repeat allowed only after consultation 
and approval from Medical Monitor. 
Single repeat <50 c/mL 
Begin Maintenance Phase at Day 1. 
Single repeat ≥50 c/mL 
Cannot begin Maintenance Phase and must 
be withdrawn from study; Complete withdrawal 
visit instead of Day 1. 
≥400 c/mL 
Cannot begin Maintenance Phase and must 
be withdrawn from study; Complete withdrawal 
visit instead of Day 1. 
 
Should a participant be allowed a repeat, results of this repeat must be available prior to 
Day 1, therefore the time needed for scheduling the visit, lab draws and lab analysis 
should be considered.   
The Medical Monitor may advise the site to withdraw a participant from the study prior 
to Week (-4) if the participant is unlikely to be eligible for the Maintenance Phase. 
Participants ineligible for the Maintenance Phase will be withdrawn.   
If the participant is ineligible for the Maintenance Phase, samples with a HIV-1 RNA 
>400 c/mL will be sent to a central laboratory for resistance testing and results provided 
to the Investigator once available. 
Sites may be reimbursed for up to a one month supply of antiretroviral medication to 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
38 
 
facilitate transition to non-study ART for participants that do not qualify for the 
Maintenance Phase. 
4.2.4. 
Maintenance Phase (Day 1 to Week 100) 
At Day 1, the Maintenance Phase begins.  Eligible participants will be randomized 1:1 to: 
• Oral CAB 30 mg + RPV 25 mg once daily for four weeks (participants will be 
assessed for safety and tolerability after four weeks).  At Week 4a, participants 
will have the assessments completed as per the Time and Events Table 
(Section 7.1.), including clinical chemistries.  At the Week 4b visit, participants 
will return to the clinic, take the last dose of oral CAB + RPV, and receive the 
first CAB LA (600 mg) + RPV LA (900 mg) injections (within 2 hours of the 
final oral dose of CAB + RPV).  The Week 4b visit can be performed as soon as 
central laboratory results from the Week 4a visit become available and safety 
parameters are reviewed.  If a retest is required based on Week 4a labs, the retest 
should be performed as soon as possible (and preferably no later than 7 days 
following Week 4a).  Participants will remain on oral CAB 30 mg + RPV 25 mg 
until the Week 4b injection visit, and until any required Visit 4a retest results are 
available for review.  The visit schedule following the oral lead-in period will be 
based on timing of the first injection visit at Week 4b such that the Week 5 visit 
should be performed approximately 7 days after the Week 4b visit.  The second 
and third IM injections (CAB LA 400 mg + RPV LA 600 mg) will be performed 
at Week 8 and Week 12.  There will be a one week dosing window for the second 
and third IM injections such that the second injections occur within the window of 
Week 7 to Week 8, but not later than Week 8), and the third injections occur 
within the window of Week 11 to Week 12, but no later than Week 12.  
Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur every 4 
weeks (monthly) thereafter, with a ± 7 day dosing window being allowed (but not 
preferred).  In addition, following the Week 12 injection, the interval between 
injection visits should be limited to a maximum of 5 weeks.  The Medical 
Monitor must be contacted if the length of time between injections exceeds, or is 
projected to exceed, 5 weeks.  The dosing window (±7 days) for injections after 
Week 12 is allowed, but also not preferred.   
OR 
• Continue on oral ABC/DTG/3TC initiated during the Induction Phase for at least 
an additional 100 weeks.  Participants who successfully complete Week 100 
(without meeting study defined withdrawal criteria and who remain virologically 
suppressed through Week 96:  HIV-1 RNA <50 c/mL) will be given the option to 
switch to the LA arm in the Extension Phase or be withdrawn from the study. 
• ABC/DTG/3TC dosing on Day 1 should occur after randomization to avoid 
overlap of regimens (in the event that the participant is assigned to the CAB LA + 
RPV LA treatment arm).  However, if the participant takes ABC/DTG/3TC prior 
to coming into the clinic, randomization and initiation of oral CAB and RPV 
should continue as planned on Day 1. 
If, in the opinion of the Investigator, a participant experiences a significant safety event 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
39 
 
while taking oral CAB or RPV, administration of the first injections will be determined 
ONLY in consultation with the Medical Monitor.  Any rash that is possibly related to 
study drug, and is present between Day 1 and Week 4b, must be discussed with the 
Medical Monitor prior to initiation of CAB LA or RPV LA (See Section 7.4.10.13). 
Participant randomization will be stratified by participants’ Baseline HIV-1 RNA 
(<100,000, ≥100,000 c/mL) and gender at birth.   
4.2.5. 
Extension Phase 
All eligible participants who transition into the Extension Phase will continue study 
treatment until CAB LA and RPV LA are either locally approved and commercially 
available, the participant no longer derives clinical benefit, the participant meets a 
protocol-defined reason for discontinuation or until development of either CAB LA or 
RPV LA is terminated.  Visits will continue to occur every 4 weeks. 
Participants not eligible to enter the Extension Phase will end their study participation 
(Week 100 will be the last study visit, no withdrawal visit needed).  Sites may be 
reimbursed for up to a one month supply of antiretroviral medication to facilitate 
transition to non-study ART for participants that do not qualify for the Extension Phase. 
4.2.5.1. 
Participants Entering from the CAB LA + RPV LA Arm 
All participants who successfully complete 100 weeks of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase.  See the Time and Events Table (Section 7.1) for more information. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
40 
 
4.2.5.2. 
Participants Entering from the ABC/DTG/3TC Arm 
Participants randomized to continue ABC/DTG/3TC will have the option to either 
continue study participation by switching to CAB LA + RPV LA in the Extension Phase, 
or to complete their study participation at Week 100 (no withdrawal visit needed).  The 
transition from ABC/DTG/3TC to CAB LA + RPV LA within the Extension Phase can 
be completed with or without an oral lead-in prior to commencement of injectable 
treatment.  The participant’s decision will be taken in consultation with the investigator 
and must be appropriately documented.  As participants approach the Week 100 visit, 
sites must ensure sufficient CAB and RPV supply are available to support the 
participant’s decision for transition to LA. 
Participants who choose to continue on to the Extension Phase will need to be assessed 
for eligibility to begin the CAB LA + RPV LA regimen.  Participants will continue on 
ABC/DTG/3TC while eligibility is being confirmed. 
All participants with an undetectable HIV-1 RNA (<50 c/mL) result from the Week 96 
visit are eligible to enter the Extension Phase.  A single repeat of HIV-1 RNA for any 
participant with a HIV-1 RNA ≥50 c/mL and < 400 c/mL at Week 96 must be performed. 
The retest should be scheduled as soon as possible (but no later than 4 weeks from the 
Week 96 visit).  Participants with a HIV-1 RNA <50 c/mL upon retest are eligible to 
enter the Extension Phase.  Participants with HIV-1 RNA ≥400 c/mL at Week 96 are not 
eligible to enter the Extension Phase, will not be allowed a repeat to determine eligibility, 
and will therefore be withdrawn from the study. 
Result of HIV-1 RNA at Week 96 
Action 
<50 c/mL 
Begin Extension Phase at Week 100 
≥50 c/mL but <400 c/mL 
Perform HIV-1 RNA retest as soon as possible 
(not later than 4 weeks). 
Single repeat <50 c/mL 
Begin Extension Phase at Week 100 
Single repeat ≥50 c/mL 
Cannot begin Extension Phase and must be 
withdrawn from study; Complete Week 100 
visit (no withdrawal visit required) 
≥400 c/mL 
Cannot begin Extension Phase and must be 
withdrawn from study; Complete Week 100 
visit (no withdrawal visit required) 
 
Participants Transitioning Direct to Injection in the Extension Phase:   
Central lab results and safety parameters from the Week 96 visit must be available and 
reviewed for participants who choose to transition directly to injections.  Participants 
with ongoing safety issues or laboratory abnormalities of clinical concern (e.g. Grade 3 or 
Grade 4 liver chemistry elevations) will require consultation and agreement with the 
Medical Monitor prior to proceeding directly to injections in the Extension Phase. 
If a clinical chemistry retest is required based on Week 96 labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
41 
 
Week 96).  Participants will remain on oral ABC/DTG/3TC until the Week 100 injection 
visit, and until any required Week 96 retest results are available for review. 
At Week 100, eligible participants will take the last dose of ABC/DTG/3TC (or DTG + 
2 NRTIs), and receive the first injections of CAB LA (600 mg) + RPV LA (900 mg) as 
initial loading doses.  Clinical chemistries will also be assessed at Week 100.  At 
Week 101, participants will return to the clinic for PK and safety assessments including 
clinical chemistries.  The second and third injections (CAB LA 400 mg + RPV LA 
600 mg) will be administered at Week 104a and Week 108.  There will be a one week 
dosing window for the second and third IM injections such that the second injections 
occur within the window of Week 103 to Week 104a, but not later than Week 104a, and 
the third injections occur within the window of Week 107 to Week 108, but no later than 
Week 108.  Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur 
every 4 weeks thereafter, from the projected visit date, with a (+ or -) 7 day dosing 
window being allowed (but not preferred).  Following the Week 108 injection, the 
interval between injection visits should be limited to a maximum of 5 weeks.  The 
Medical Monitor must be contacted if the length of time between injections exceeds, or is 
projected to exceed, 5 weeks. 
Participants Receiving Optional Oral Lead-In in the Extension Phase: 
As participants approach the Week 100 visit, sites must ensure sufficient oral CAB and 
RPV are available for participants who choose to use the oral lead-in. 
At Week 100, eligible participants who after discussion with the investigator, choose to 
receive the optional oral lead-in will initiate a 4 week lead-in of oral CAB 30 mg + oral 
RPV 25 mg once daily.  It is not necessary to dose ABC/DTG/3TC on the day the 
participant begins the oral lead-in with CAB + RPV.  However, if the participant takes 
ABC/DTG/3TC prior to coming into the clinic, initiation of oral CAB and RPV should 
continue as planned.  Clinical chemistries will be assessed at Week 100.  At Week 104a, 
following the 4 week CAB + RPV oral lead-in, participants will have additional safety 
assessments including clinical chemistries as per the Time and Events Table 
(Section 7.1).  In addition, central lab results and safety parameters from the Week 104a 
visit must be available and reviewed before the Week 104b visit.  If a clinical chemistry 
retest is required based on Week 104a labs, the retest should be performed as soon as 
possible (and preferably no later than 7 days following Week 104a).  Participants will 
remain on oral CAB 30 mg + RPV 25 mg until the Week 104b injection visit, and until 
any required Visit 104a retest results are available for review. 
At Week 104b visit, participants will return to the clinic, take the last dose of oral CAB + 
RPV, and receive the first CAB LA (600 mg) + RPV LA (900 mg) injections (within 
2 hours of the final oral dose of CAB + RPV).  The Week 104b visit can be performed as 
soon as central lab results from the Week 104a visit become available and safety 
parameters are reviewed.  The second and third injections (CAB LA 400 mg + RPV LA 
600 mg) will be administered at Week 108 and Week 112.  There will be a one week 
dosing window for the second and third IM injections such that the second injections 
occur within the window of Week 107 to Week 108, but not later than Week 108, and the 
third injections occur within the window of Week 111 to Week 112, but no later than 
Week 112.  Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
42 
 
every 4 weeks (monthly) thereafter, from the projected visit date, with a (+ or -) 7 day 
dosing window being allowed (but not preferred).  Following the Week 112 injection, the 
interval between injection visits should be limited to a maximum of 5 weeks.  If the 
length of time between injections exceeds, or is projected to exceed 5 weeks, the Medical 
Monitor must be contacted to discuss individual participant case management. 
4.2.6. 
Long-Term Follow-Up Phase – IM Regimen only 
• Where the CAB LA + RPV LA marketed product is not locally available, any 
participant who receives at least a single dose of CAB LA and/or RPV LA and 
discontinues the CAB LA + RPV LA regimen for any reason must enter the LTFU 
Phase. The patient must remain on suppressive highly active antiretroviral therapy 
(HAART) for at least 52 weeks after the last dose of CAB LA and/or RPV LA in 
order to prevent the potential selection of INI- and/or NNRTI-resistant mutants. 
Investigators must discuss the choice of the follow-up HAART regimen with the 
Medical Monitor prior to initiating the new regimen with the participant. 
HAART therapy should be initiated within four weeks of the last injection. The 
LTFU Phase will begin the day of the last CAB LA + RPV LA dose and continue for 
52 weeks. These participants will not complete a Withdrawal visit but will instead 
move directly into the LTFU Phase as per the Time and Events Table (Section 7.1). 
 
• Where CAB LA + RPV LA marketed product is locally available, only participants 
that discontinue the CAB LA + RPV LA regimen for safety-related reasons 
included in Section 5.4 must enter the LTFU Phase. Participants must remain on 
suppressive HAART for at least 52 weeks after the last dose of CAB LA and/or RPV 
LA in order to prevent selective pressure on HIV and the potential for selection of 
resistant mutants. Investigators must discuss the choice of the follow-up HAART 
regimen with the Medical Monitor prior to initiating the new regimen with the 
patient. HAART therapy should be initiated within four weeks of the last 
injection. The LTFU Phase will begin the day of the last CAB LA and/or RPV LA 
dose and continue for 52 weeks. These participants will not complete a Withdrawal 
visit but will instead move directly into the LTFU Phase. In addition, for participants 
who withdraw during the LTFU, the final visit will be considered the study 
withdrawal visit.  
 
• NOTE: Participants transitioning to CAB LA + RPV LA marketed product or 
alternative HAART (except due to safety-related reasons) do not need to enter the 
LTFU Phase. 
Long-Term Follow-Up Phase requirement 
Marketed product 
locally available 
Subject WD due to safety-
related reasons 
LTFU Phase required? 
No 
Yes 
Yes 
No 
Yes 
Yes 
Yes 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
43 
 
Marketed product 
locally available 
Subject WD due to safety-
related reasons 
LTFU Phase required? 
No 
No, but Safety FU visit required to 
assess potential safety issues 
occurred after the last injection 
 
Participants will be assessed with clinic visits at Months 1, 3, 6, 9 and 12. Female 
participants of child bearing potential must continue to use adequate contraception 
methods for at least 52 weeks after the last injection.   
In order to assure that participants have access to HAART during the Long-Term Follow-
Up Phase, GSK may supply HAART regionally or reimbursement will be provided as 
needed during this phase.  As participants approach the end of the Long-Term Follow-Up 
Phase (e.g. Prior to Month 12 visit), investigative sites and/or participants must make 
alternative arrangements for independent access of the participant’s continued HAART 
off / post study. 
The Long-Term Follow-Up Phase may be shortened at any time during the study for 
various reasons, e.g. better understanding of risks of development of resistance as CAB 
and RPV exposures decline, regulatory approval and commercial availability, end of 
study timings, etc. 
This phase is considered study participation and participants will be followed on study 
during this time.  A withdrawal visit is not required for participants participating in the 
Long-Term Follow-Up Phase.  The participants’ last on study visit will be considered the 
withdrawal visit. 
4.2.7. 
Dose Modifications / Permitted Treatment Substitutions 
Participants who are HLA-B*5701 positive at the Screening visit are allowed to enter the 
study on DTG and an approved dual-NRTI backbone that does not contain abacavir (e.g. 
tenofovir/emtricitabine [TDF/FTC] or tenofovir alafenamide/emtricitabine [TAF/FTC]).  
This regimen may be supplied regionally by GSK or reimbursement will be provided as 
needed.  
During the Induction Phase, prior to randomization into the Maintenance Phase at Day 1, 
one switch to an alternate approved background NRTI therapy is allowed for toxicity or 
tolerability management.  The date of a decision to switch the NRTI background therapy 
for toxicity or tolerability management must be documented in the eCRF.  Switches of a 
background NRTI for any other reason are not permitted in the study.  Local prescribing 
information should be consulted for information regarding use of these medications. 
A short term bridging supply for participants on the CAB LA + RPV LA arm may be 
permitted following discussion with the Medical Monitor (see Section 6.8.1). 
For consistency with prescribing information, dose reductions of lamivudine (or 
emtricitabine if used as alternate NRTI) are permitted in the context of renal insufficiency 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
44 
 
(throughout the study), e.g. as needed for creatinine clearance <50 mL/min.   
If a dose reduction of lamivudine, a component of TRIUMEQ, is required for participants 
with creatinine clearance less than 50 mL/min, the individual entities should be used (e.g. 
DTG tablets, ABC tablets, 3TC tablets as separate medications, with dosing consistent 
with prescribing information).  DTG can be provided centrally through the study.  Single 
entity products will need to be sourced locally and can be reimbursed by the Sponsor as 
needed.  Lamivudine (3TC) dose reduction will be allowed throughout the study, and is 
not considered to be a “switch to an alternative approved background NRTI therapy”, but 
rather an alignment with prescribing information to maintain consistent 3TC plasma 
exposure for participants with renal insufficiency. 
No other dose reductions, modifications, or changes in the frequency of any components 
of any regimen will be allowed during the Maintenance and Extension Phases of the 
study. 
Please refer to Appendix 9 in Section 12.9. for study management information during the 
COVID-19 pandemic. 
Protocol waivers or exemptions are not allowed.  Therefore, adherence to the study 
design requirements are essential and required for study conduct. 
4.2.8. 
Independent Data Monitoring Committee 
An Independent Data Monitoring Committee (IDMC) will be instituted to ensure external 
objective medical and/or statistical review of efficacy and safety in order to protect the 
ethical interests and well-being of subjects and to protect the scientific validity of this 
study (201584) and study 201585.  
An IDMC will evaluate accumulating efficacy, tolerability / safety, and PK of CAB LA + 
RPV LA at predetermined times during the study.  An interim futility analysis will be 
performed with the intent of having approximately 50% of participants reaching Week 24 
and providing sufficient lead time to allow the IDMC to review the data prior to any 
participants reaching the Week 48 visit.  A futility rule based on Bayesian posterior 
predictive probability approach will be applied to assess the probability that CAB LA + 
RPV LA injectable regimen demonstrate non-inferiority to the continued ABC/DTG/3TC 
arm given the partial data set.  The Sponsor will remain blinded to this analysis.   
In addition, the IDMC may also monitor the incidence of participants meeting confirmed 
virologic failure criteria through Week 48 to ensure that participants are not being sub-
optimally treated in the CAB + RPV arm. 
Additional ad hoc analyses may be scheduled if needed.   
Full details of the analyses, estimated timing and the decision criteria that will be used to 
determine regimen performance will be pre-specified in the IDMC Charter. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
45 
 
4.3. 
Type and Number of Participants 
Assuming a 20% screen failure rate, sufficient ART-naïve participants will be screened 
(approximately 775) in order to ensure that a total of approximately 620 participants are 
enrolled at the beginning of the Induction Phase.  Assuming 7.5% of enrolled participants 
will not participate in the Maintenance Phase (based on the rate of withdrawals observed 
during the Induction Period of study 200056), 620 participants enrolled into the Induction 
Phase will ensure approximately 570 participants continue into the Maintenance Phase.  
Participants will be enrolled from multiple sites which may include sites in Canada, 
France, Germany, Italy, Japan, the Netherlands, Russia, South Africa, Spain, the UK, and 
the US. 
Randomization will be stratified by participants’ Baseline HIV-1 RNA (<100,000, 
≥ 100,000 c/mL) and gender at birth. 
A goal of this study is to enroll approximately 20% women who are typically under-
represented in clinical studies.  To provide sufficient data to determine whether either 
gender is correlated with treatment response, sites are expected to take into account 
gender in their screening strategies.  Enrolment may be allowed to continue at select sites 
in order to reach targets in key study populations. 
Participants who prematurely discontinue from the study will not be replaced. 
4.4. 
Design Justification 
The design of this study (1:1 randomized, open-label, active-controlled, multicenter, 
parallel group, non-inferiority study) is well established for confirming the non inferiority 
of an investigational agent compared with an active comparator and is generally accepted 
by regulatory authorities as rigorous proof of antiviral activity.  The primary endpoint, 
proportion of participants with virologic failure per Snapshot algorithm at Week 48 is the 
FDA recommended endpoint for switch design studies (Center for Drug Evaluation and 
Research, Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs 
for Treatment, 2015). 
Various approaches to simplify a participant's antiretroviral therapy (ART) regimen, after 
achieving virologic suppression, have been studied.  Previous studies have evaluated 
switches to ritonavir-boosted PI monotherapy therapy in virologically suppressed 
participants [Bierman, 2009 and Arribas, 2012].  While the data from these studies have 
shown both long-term non-inferiority and inferiority to continual Highly Active 
Antiretroviral Therapy (HAART), they suggest that simplifying from a three drug dual 
class regimen to a single boosted protease inhibitor may be a safe and effective option for 
the majority of participants studied who have effectively maintained virologic 
suppression.  
In addition, the 200056 (LATTE-2) clinical trial, evaluated a different simplification 
approach and served as proof of concept for 201584 (FLAIR).  In 200056, HIV-1 RNA 
suppression was induced with a three drug antiretroviral regimen consisting of CAB + 
ABC/3TC FDC, and then participants transitioned to a two-drug two-class regimen 
consisting of CAB LA + RPV LA for the maintenance of HIV-1 RNA suppression.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
46 
 
Through 32 weeks on two-drug maintenance therapy, 95% (Q8W) and 94% (Q4W) of 
participants on injectable dosing were virologic successes by snapshot, compared to 91% 
of participants continuing three drug oral CAB + NRTIs, meeting pre-specified criteria 
for comparability between the dosing arms.  During the Maintenance Period, there was 
one protocol confirmed virologic failure (CVF) on Q8W dosing and one CVF on oral 
dosing, without any evolution of resistance.  The CVF on Q8W dosing occurred 
following an aberrant RPV injection, without measurable RPV concentrations 4 weeks 
post dosing.  Overall AEs and clinical chemistries, were in line with those observed in 
prior studies with CAB, without discernible trends between Q8W, Q4W, and 
oral.  Injections were well tolerated with two participants discontinuing due to injection 
tolerability through 32 weeks (both on Q8W dosing).  The vast majority of injection site 
reactions were due to pain/discomfort with nearly all injection site reactions classified as 
mild (82%) or moderate (17%), with <1% of reactions classified as severe.  There was no 
discernible tolerability difference between Q4W (2 mL) dosing and Q8W (3 mL dosing).   
The Week 48 data demonstrated similar virologic success between the Q4W and Q8W 
arms, with 92% (Q8W) and 91% of participants remaining suppressed (HIV-1 
RNA <50 c/mL) compared to 89% of participants continuing oral CAB + 2 NRTIs.  
Although the proportion of participants with virologic success was similar for Q8W and 
Q4W dosing, there were more Snapshot failures for virologic reasons on the Q8W arm 
(7%) compared to the Q4W arm (<1%), and more participants with Snapshot failure for 
non-virologic reasons (discontinued due to AE or other reasons) on the Q4W arm (8%) 
compared to the Q8W arm (<1%).  Additionally, between Week 32 and Week 48, one 
additional participant (Q8W) had confirmed virologic failure, with treatment emergent 
NNRTI (K103N, E138G, and E238T) and integrase (Q148R).  See Section 2 for 
additional information on this participant. 
On the basis of these 200056 data, Q4W dosing was selected to progress into Phase 3 for 
further clinical development. 
The open-label design for 201584 (FLAIR) best suits the objectives of this study.  A 
double-blind, double-dummy design for this study would result in an increased pill 
burden in all participants, a requirement for placebo injections across the comparator 
arms, elevated risk of oral ART non-adherence in participants receiving placebo 
injections, limitations to patient reported preference data comparing injectable and oral 
ART, as well as considerable trial design complexities. 
A blinded design is also complicated by the requirement for an oral lead-in, in the CAB 
LA + RPV LA arm only.  Blinding the oral lead-in would require additional placebo pills 
for 5 weeks in the ART continuation arm, that otherwise would not be required.   
In addition to study design challenges, the impact of blinding in both studies carries the 
potential risk of oral regimen non-compliance, in participants on the ART continuation 
arm, who may believe that they are receiving active drug via injection (and therefore 
possibly increased risk of HIV transmission to uninfected partners).  The additional risk 
of inadvertent non-adherence to oral ART outweighs any benefits that may be gained 
through a blinded design.  
Importantly, a key objective for the planned Phase 3 studies is to understand the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
47 
 
acceptability and patient reported preferences to this novel injectable regimen, relative to 
daily oral standard of care (SOC) ART.  An unblinded study design supports collection of 
participant preference data in a way that would not be possible if a double-blind, double-
dummy design were implemented. 
Due to the complexities, limitations and risks of blinding each switch study, both Phase 3 
studies are planned as open label studies.   
4.5. 
Dose Justification 
4.5.1. 
Oral Lead-In Phase 
During the oral lead-in phase of this study, oral formulations of CAB and RPV will be 
co-administered to confirm tolerability in each participant prior to possible IM dosing 
with CAB LA and RPV LA.  Data from study LAI116181 [GlaxoSmithKline Document 
Number 2011N130484_00] have demonstrated that there is no clinically relevant drug-
drug interaction following repeat oral administration of CAB with RPV.  The 
combination of oral RPV (25 mg once daily) and CAB (10, 30 or 60 mg once daily) has 
been administered to HIV-infected participants in both LATTE and LATTE-2 (oral lead-
in).  In the present study, the approved recommended dose of RPV 25 mg once daily will 
be used in combination with CAB 30 mg once daily.  The oral dose of CAB was selected 
based on observed safety and efficacy from the Phase 2b LATTE study.   
CAB has demonstrated good short-term safety/tolerability and antiviral activity as 
monotherapy following oral administration of 5 mg and 30 mg once daily.  LAI116482 
(LATTE) is a Phase 2b, dose-ranging study (randomized 1:1:1 to CAB 10 mg, 30 mg, or 
60 mg) which evaluated the long-term efficacy and safety of a two-drug, two-class, once 
daily combination of CAB + RPV in HIV-infected, treatment-naïve adult participants 
compared to efavirenz (EFV) 600 mg once daily with two NRTIs.  Following a 24-week 
phase of induction of virologic suppression using CAB + 2 NRTIs, the regimen was 
simplified to oral CAB + RPV once daily for an additional 72-weeks (total comparative 
study duration of 96 weeks).  The results of this study also informed the Phase 2b study 
(200056, LATTE-2) with intramuscular CAB LA and RPV LA.   
Comparable efficacy, safety and tolerability were observed across all three CAB doses at 
the early dose selection and confirmation visits at Week 16 and 24 in LATTE.  
Additionally, the proportion of participants who achieved the primary endpoint of HIV-1 
RNA <50 c/mL (Missing, Switch, Discontinuation=Failure [MSDF] algorithm) at 
Week 48 (24 weeks on Maintenance) remained consistently high across the CAB dose 
arms (≥80%) with a low rate of confirmed virologic failure (Table 1).   Across all dose 
arms, CAB achieved similar efficacy at Week 24 of Induction when co-administered with 
2 NRTIs and at Week 96 when co-administered with RPV 25 mg once daily (72 weeks 
on Maintenance).   Rates of virologic suppression through Week 96 (Maintenance) on the 
two drug regimen remained similar to that attained through Week 24 (Induction) on 
three-drug ART.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
48 
 
Table 1 
LAI116482:  Proportion (95% CI) of Participants with Plasma HIV-1 
RNA <50 c/mL at Key Visits- Snapshot (MSDF) Analysis (ITT-E 
Population) 
 
 
Visit 
 
CAB 
10 mg 
N=60 
CAB 
30 mg 
N=60 
CAB 
60 mg 
N=61 
CAB 
Subtotal 
N=181 
EFV  
600 mg 
 
Week 16 
n (%) 
54 (90) 
50 (83) 
53 (87) 
157 (87) 
46 (74) 
95%CI 
Proportion 
(82, 98) 
(74, 93) 
(78, 95) 
(82, 92) 
(63, 85) 
Week 24 
n (%) 
52 (87) 
51 (85) 
53 (87) 
156 (86) 
46 (74) 
95%CI 
Proportion 
(78, 95) 
(76, 94) 
(78, 95) 
(81, 91) 
(63, 85) 
Week 48 
n (%) 
48 (80) 
48 (80) 
53 (87) 
149 (82) 
44 (71) 
95%CI 
Proportion 
(70, 90) 
(70, 90) 
(78, 95) 
(77, 88) 
(60, 82) 
a. 
CAB was administered with two NRTIs during the 24 week Induction Period. 
b. 
95% CIs are normal approximation confidence intervals. 
CAB was well tolerated across all doses studied and none of the doses met pre-defined 
safety stopping criteria.  A good safety and tolerability profile with a low discontinuation 
rate due to AEs was observed in all three dose arms with no significant dose-dependent 
trends in safety parameters.   
Although CAB 30 mg was already selected based on short-term efficacy and safety 
through Week 24, the observed durability of viral suppression through 96 weeks, across 
all doses, provides further support for selection of the CAB 30 mg dose for Phase 3.  In 
addition, the 30 mg dose achieves trough CAB plasma concentrations that are greater 
than mean CAB plasma concentrations observed following CAB LA dosing which allows 
an adequate assessment of safety and tolerability prior to transitioning to the long-acting, 
Maintenance Phase of the study.   
CAB has low risk of causing or being a victim of drug-drug interactions, and therefore, 
the selected 30 mg dose can be safely used with most common concomitant medications 
without dose adjustment.  CAB exposures are not impacted by the presence of food; 
however, given that it will be co-administered with RPV, which requires food for optimal 
absorption, the recommended intake of oral CAB in the Phase 3 studies is with food at 
the same time as RPV.   
Overall, the efficacy and safety data from the LATTE study, CAB LA dose simulations 
detailed in Section 4.5.2, and limited drug-drug interaction potential support selection of 
the CAB 30 mg dose for once daily administration with the recommended approved dose 
of RPV 25 mg once daily during the oral lead-in phase of this study.   
The oral lead-in for participants randomized to the ABC/DTG/3TC arm who choose to 
receive CAB LA + RPV LA during the Extension Phase of the study is optional.  Without 
oral lead-in dosing, CAB LA and RPV LA achieve concentrations following their initial 
injections similar to induction doses of their respective efficacious oral products.  Oral 
ABC/DTG/3TC administered up to and including the day of the initial CAB LA + RPV 
LA injections will provide additional exposure to active antiviral agents during the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
49 
 
transition from oral to LA treatment (e.g., exposure that would replace oral CAB + RPV 
exposure). 
4.5.2. 
Long Acting Injectable for Maintenance Phase 
During the Maintenance and Extension Phases of this study, CAB LA and RPV LA will 
be co-administered as two separate IM injections at each dosing visit.  A CAB LA and 
RPV LA every 4 week dosing regimen has been selected for evaluation in Phase 3.   
The safety and efficacy of a 2-drug regimen with CAB and RPV for maintenance of 
virologic suppression was established in LATTE, as detailed in Section 4.5.1, and 
informed the Phase 2b study (LATTE-2) with CAB LA and RPV LA.  Study 200056 
(LATTE-2) is an ongoing, Phase 2b dose-ranging study evaluating the long-term efficacy 
and safety of a two-drug, two-class combination of CAB LA + RPV LA given every 
4 weeks (Q4W) or every 8 weeks (Q8W), as compared to an oral three-drug regimen, for 
maintenance of virologic suppression in HIV-infected, treatment-naive adults.  The first 
phase of the LATTE-2 study was a 20 week Induction Period (16 weeks of oral CAB + 
2 NRTIs, 4 weeks of CAB + 2 NRTIs + oral RPV).  Subjects who were eligible to 
continue into the Maintenance Period were then randomized (2:2:1) to receive IM 
injections of CAB LA every 4 weeks (800 mg Day 1 then 400 mg Q4W) or every 
8 weeks (800 mg Day 1, 600 mg Week 4, 600 mg Week 8, then 600 mg Q8W) in 
combination with IM RPV LA every 4 weeks (600 mg Day 1 then 600 mg Q4W) or 
every 8 weeks (900 mg Day 1, 900 mg Week 8, then 900 mg Q8W), respectively, or 
continue on their triple ART regimen.  
The Q4W dosing strategy was selected for further investigation in Phase 3 based on the 
efficacy, safety and tolerability at Week 48, and compared to oral.  Thus, the results from 
LATTE-2 provide the basis for the LA dosing strategy in the present study. 
The proportion of subjects who achieved the primary endpoint of HIV-1 RNA <50 c/mL 
(Missing, Switch, Discontinuation=Failure [MSDF] algorithm) by Week 32 was 
consistently high across both Q4W and Q8W dosing strategies (≥94%) with one subject, 
randomized to the Q8W regimen and one subject in the oral treatment arm, with protocol-
defined virologic failure during LA therapy.  At Week 32, Snapshot failure rate was 4% 
(n=5) for the Q8W Arm and <1% (n=1) for the Q4W Arm.  Although the Snapshot 
success rate at Week 48 was similar between treatment arms, the rate of Snapshot failures 
at Week 48 increased to 7% (n=8) for the Q8W Arm but remained at <1% (n=1) for the 
Q4W Arm (Table 2).  Refer to Section 2.2 for additional information on LATTE-2 data. 
Table 2 
LATTE-2:  Proportion (95% CI) of Subjects with Plasma HIV-1 RNA 
<50 c/mL at Week 48 - Snapshot (MSDF) Analysis (ITT-E Population) 
Outcome 
Q8W IM 
N=115 
n (%) 
Q4W IM 
N=115 
n (%) 
Q8W+Q4W 
N=230 
n (%) 
CAB 30 
mg 
N=56 
n (%) 
Virologic Success, n (%) 
106 (92) 
105 (91) 
211 (92) 
50 (89) 
Virologic Failure, n (%) 
8 (7) 
1 (<1) 
9 (4) 
1 (2) 
Data in window not below 
6 (5) 
1 (<1) 
7 (3) 
0 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
50 
 
Outcome 
Q8W IM 
N=115 
n (%) 
Q4W IM 
N=115 
n (%) 
Q8W+Q4W 
N=230 
n (%) 
CAB 30 
mg 
N=56 
n (%) 
threshold 
Discontinued for lack of efficacy 
1 (<1) 
0 
1 (<1) 
1 (2) 
Discontinued for other reason 
while not below threshold 
1 (<1) 
0 
1 (<1) 
0 
No Virologic Data 
1 (<1) 
9 (8) 
10 (4) 
5 (9) 
Discontinued due to AE or Death 
0 
6 (5) 
6 (3) 
2 (4) 
Discontinued for Other Reasons 
1 (<1) 
3 (3) 
4 (2) 
3 (5) 
CAB LA and RPV LA were both well tolerated resulting in a low discontinuation rate 
due to AEs, including injection site reaction (ISR) related AEs, with no significant trends 
in safety parameters in either the Q8W or Q4W dosing regimens. 
Due to the increased Snapshot failure rate at Week 48 for the Q8W Arm, a Q4W dosing 
strategy was selected for further evaluation in Phase 3.  To allow some flexibility, with 
the exception of Week 8 and Week 12, a one-week window (on each side) around the 4-
weekly dosing regimen can be allowed without anticipated impact on the safety or 
efficacy of the regimen.  For Week 8 and Week 12, there is only a minus one week 
window such that injections should be administered no later than Week 8 and Week 12. 
For CAB LA, steady-state mean CAB pre-dose concentrations following Q4W dosing 
remain between the oral CAB 10 mg and 30 mg once daily mean trough concentrations, 
both doses found to be safe and efficacious in the LATTE study.  For RPV LA, steady-
state mean RPV pre-dose concentrations following Q4W dosing are comparable with the 
range of exposures following oral RPV 25 mg once daily observed to be safe and 
efficacious in pivotal Phase 3 studies.  Maintenance Phase PK data in LATTE-2 are 
summarized for both regimens of CAB LA (Table 3, Figure 2) and RPV LA (Table 4, 
Figure 3). 
 
Table 3 
Summary of Observed CAB PK Parameters following Repeat Dose 
Administration of Cabotegravir LA to HIV-infected Subjects  
(LATTE-2) 
Cohort 
Plasma CAB PK Parametera 
AUC(0-τ)b 
(µg.h/mL) 
Cmaxc 
(µg/mL) 
Individual  
Average C0d 
(µg/mL) 
tmaxe 
(d) 
Week 24 
Week 40 
Week 
24 
Week 
40 
Week 
24 
Week 
40 
Week 
24 
Week 
40 
Q4W 
(n=115) 
1858 
(1719, 
2007) 
[37] 
2017 
(1847, 
2203) 
[41] 
3.50  
(3.2, 
3.8) 
[39] 
3.50 
(3.3, 
3.8) 
[37] 
2.35 
(2.2, 
2.5) 
[32] 
2.56 
(2.4, 
2.7) 
[32] 
6.9 
(0 – 29) 
6.9  
(0 – 28) 
Q8W 
(n=115) 
3037 
  (2786, 
3027  
(2762, 
3.55 
(3.2, 
3.33 
(3.1, 
1.43 
(1.3, 
1.49 
(1.4, 
6.9  
(0 – 59) 
7.0  
(0 –  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
51 
 
Cohort 
Plasma CAB PK Parametera 
AUC(0-τ)b 
(µg.h/mL) 
Cmaxc 
(µg/mL) 
Individual  
Average C0d 
(µg/mL) 
tmaxe 
(d) 
Week 24 
Week 40 
Week 
24 
Week 
40 
Week 
24 
Week 
40 
Week 
24 
Week 
40 
3310) 
[42] 
3322) 
[47] 
3.9) 
[56] 
3.6) 
[47] 
1.6) 
[54] 
1.6) 
[42] 
57) 
Oral)f  
(n=50) 
------ 
------ 
------ 
------ 
4.51 
(4.1, 
5.0) 
[37] 
4.54  
(4.1, 
5.0) 
[38] 
------ 
------ 
a. 
Geometric mean (95% CI) [CVb%] 
b. 
AUC(0-τ) = AUC(Week 24 to Week 28) for Q4W regimen (n=84), and AUC(Week 24 to Week 32) for Q8W 
regimen (n=86) or AUC(Week 40 to Week 44) for Q4W (n=80) and AUC(Week 40 to Week 48) for Q8W regimen 
(n=93). 
c. 
Cmax:  Q4W:  between Week 24 and Week 28 (n=97) or Week 40 and Week 44 (n=95);  Q8W:  between 
Week 24 to Week 32 (n=98) or Week 40 and Week 48 (n=104). 
d. 
Individual Average C0 Week 24 observed using troughs at Week 20, Week 24, Week 28 and Week 32 for the 
Q4W arm (n=108) and at Week 24, and Week 32 for Q8W arm (n=100) and Individual Average C0 Week 40 using 
troughs at Week 40, Week 44, and Week 48 for Q4W (n=98) and Week 16, Week 24, Week 32, Week 40 and 
Week 48 for Q8W (n=112). 
e. 
Tmax presented as median (range) in days, (Week 24 to Week 32:  n=97 Q4W arm, n=98, Q8W arm; Week 40 to 
Week 48:  n=95 Q4W, n=104 Q8W). 
f. 
Oral comparator arm combined troughs at Day 1, predose and at Week 32 ± Week 48. 


T M F -1 6 4 4 1 7 6 7  
C O N FI D E N TI A L  
2 0 1 5 8 4  
 
 
Pr ot o c ol A m e n d m e nt 0 9  
 
5 2  
 
Fi g ur e 2 
M e a n ( S D) O b s er v e d C o n c e ntr ati o n -Ti m e D at a f oll o wi n g C A B L A 
Q 8 W a n d Q 4 W a n d C τ (f oll o wi n g C A B 3 0 m g Or al O n c e D ail y a ) 
t hr o u g h W e e k 4 8 ( L A T T E-2)  
 
a.  
Or al C A B 3 0 m g o nc e d aily a d mi nist er e d f or f o ur w e eks pri or t o first i nj ecti o n.  
T a bl e 4 
S u m m ar y of O b s er v e d R P V P K P ar a m et er s f oll o wi n g R e p e at D o s e 
A d mi ni str ati o n of R P V L A t o HI V -i nf e ct e d S u bj e ct s ( L A T T E-2)  
C o h ort  
Pl a s ma R P V P K Par a met er a 
A U C( 0 -τ)b 
( n g. h/ m L) 
C m a x c 
( n g/ m L) 
I n di vi d u al 
A v er a g e C 0 d 
( n g/ m L) 
t m a xe 
( d) 
W e e k 24  
W e e k 40  
W e e k 
2 4  
W e e k 
4 0  
W e e k 
2 4  
W e e k 
4 0  
W e e k 
2 4  
W e e k 
4 0  
Q 4 W  
( n = 1 1 5) 
6 1 30 9  
( 5 6 7 24, 
6 6 26 4) 
[ 3 7] 
7 1 10 6  
( 6 5 3 54, 
7 7 36 6) 
[ 3 9] 
1 0 3  
( 9 4, 
1 1 4) 
[ 4 9] 
1 2 7  
( 1 1 8, 
1 3 6) 
[ 3 6] 
7 7. 2  
( 7 2, 
8 3)  
[ 3 5] 
9 2. 1  
( 8 7, 
9 8)  
[ 3 2] 
6. 9 9  
( 0-
2 9)  
6 0. 
( 0-
2 8)  
Q 8 W 
( n = 1 1 5) 
9 6 19 6  
( 8 7 2 86, 
1 0 60 1 5) 
[ 4 8] 
1 1 61 6 0  
( 1 0 8 18 9, 
1 2 47 1 9) 
[ 3 5] 
1 0 4  
( 9 5, 
1 1 4) 
[ 4 7] 
1 2 1  
( 1 1 1, 
1 3 1)  
[ 4 2] 
4 9. 3  
( 4 6, 
5 3)  
[ 4 1] 
6 3. 2  
( 5 9, 
6 8)  
[ 3 5] 
7. 0 0  
( 0-
5 7)  
6 0. 
( 0-
5 9)  
a.  
G e o m etric m e a n ( 9 5 % CI) [ Cv b %]  
b.  
A U C( 0 -τ) = A U C( W e ek 2 4 t o W e ek 2 8) f or Q 4 W r e gi m e n ( n = 8 4), a n d A U C( W e ek 2 4 t o W e ek 3 2) f or Q 8 W 
r e gi m e n ( n = 8 6) or A U C( W e ek 4 0 t o W e ek 4 4) f or Q 4 W  ( n = 8 0) a n d A U C( W e ek 4 0 t o W e ek 4 8) f or Q 8 W r e gi m e n 
( n = 9 2) vi a n o n-c o m p art m e nt al P K a n alysis 
c. 
C m ax:  Q 4 W: b et w e e n W e ek 2 4 a n d W e ek 2 8 ( n = 9 6) or W e ek 4 0 a n d W e ek 4 4 ( n = 9 4); Q 8 W: b et w e e n W e ek 2 4 
t o W e ek 3 2 ( n = 9 7) or W e ek 4 0 a n d W e ek 4 8 ( n = 1 0 4) 
d.  
I n divi d u al Av er a g e C 0 W e ek 2 4 o bs erv e d usi n g tr o u g hs at W e ek 2 4, W e ek 2 8 a n d W e ek 3 2 f or t h e Q 4 W ar m 
 
W e e k
0 1 
4 
8
1 2 
1 6 
2 0 
2 42 5 
2 8 
3 2
3 2 
3 6 
4 04 1 
4 4 
4 8
4 8
Pl a s m a C A B ( g/ m L)
0. 1
1
1 0
8 0 0 m g I M L D, 6 0 0 m g I M W 4, W 8 a n d Q 8 W
8 0 0 m g I M L D, 4 0 0 m g I M Q 4 W
3 0 m g P O Q D
P A-I C 9 0 ( 0. 1 6 6 g/ m L)
1 0 m g P O Q D C  ( L A T T E, 1. 3 5g/ m L)


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
53 
 
(n=104) and at Week 24, and Week 32 for Q8W arm (n=101); Individual Average C0 Week 40 using troughs at 
Week 36, Week 40, Week 44, and Week 48 for Q4W (n=102) and Week 40 and Week 48 for Q8W (n=100) 
e. 
Tmax presented as median (range), (Week 24 to Week 32: n=96 Q4W arm, n=97 Q8W arm; Week 40 to Week 
48:  n=94 Q4W, n=104 Q8W) 
Figure 3 
Mean (SD) Observed Concentration-Time Data following RPV LA 
Q8W and Q4W and Cτ (following RPV 25 mg Oral Once Dailya) 
through Week 48 (LATTE-2) 
 
a. 
Oral RPV 25 mg once daily administered for four weeks prior to first injection. 
 
The Q4W dosing schedule for both CAB LA and RPV LA have been optimized for the 
present study.  In LATTE-2, the Q4W dosing regimen for CAB LA included a 1st dose of 
800 mg (two 2 mL injections) at Day 1, followed by 400 mg IM Q4W starting at Week 4.  
For RPV LA in LATTE-2, the Q4W treatment arm was 600 mg IM Q4W from Day 1.  
This specific schedule from the LATTE-2 Q4W dosing regimens for both compounds 
was modified for Phase 3 to align dosing for both compounds and minimize the number 
of injections needed.  Both observed and model predicted CAB concentrations indicated 
that the loading dose strategy could be optimized while maintaining plasma 
concentrations during the early phase at levels associated with good efficacy and safety; 
i.e., by lowering the first CAB LA loading dose from 800 mg to 600 mg.  This change 
reduces the number of injections to a single 3-mL injection for the first CAB LA 
injection (Week 4b in this protocol).  For RPV LA, modeling and simulation indicates 
that a 900 mg IM loading dose (one 3 mL injection) on Day 1 rather than a 600 mg IM 
first dose brings RPV plasma concentrations closer to steady-state values during the early 
phase.  The dosing schedule in the protocol includes a 4 week oral lead-in beginning at 
Day 1.  Therefore, the timing in the Time and Events Table translates to the following:  
Day 1, Week 4, and Q4W thereafter = Study Week 4b, Week 8, and Q4W thereafter, 
Week
0 1
4
8
12
16
20
2425
28
32
32
36
4041
44
48
48
Plasma RPV (ng/mL)
10
100
1000
900mg IM Q8W
600mg IM Q4W
25mg PO QD
PA-IC90 (12ng/mL)
25mg PO QD (LATTE, 70ng/mL)


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
54 
 
respectively.  
 
In summary, a modified Q4W regimen that aligns the dosing of CAB LA + RPV LA to 
one injection of each compound at each visit, was selected for Phase 3.  The first 
injections of CAB LA and RPV LA will be administered as 3 mL each, at doses of 
600 mg and 900 mg, respectively.  Subsequent injections of CAB LA and RPV LA will 
be 2 mL each, at doses of 400 mg and 600 mg, respectively (see also Section 4.5.3).  
4.5.3. 
Modeling and Dose Simulations for CAB LA and RPV LA 
Modeling and simulation was used to provide confidence in the selected regimen, inform 
the injection loading dose strategy, flexibility around dosing windows, and the use of the 
oral bridging strategy. 
4.5.3.1. 
CAB LA 
For CAB LA, the model included data from 416 subjects who received CAB LA as single 
or repeat administration, with approximately 50% of data obtained from 200056 
(LATTE-2), approximately 20% from 201120 (CAB LA PrEP study), and approximately 
30% from Phase 1 studies.  The simulation of the predicted median (90% prediction 
interval [PI]) CAB concentration-time profile based on the population PK model is 
shown in Figure 4.  The lower bound of the PI remains approximately at or above 4x PA-
IC90 throughout dosing.  At steady state, 98% of the population is predicted to achieve 
trough concentrations above 4x PA-IC90, and 88% is predicted to achieve trough 
concentrations above the geometric mean trough following the 10 mg oral dose in 
LATTE of 1.35 µg/mL (8x PA-IC90).   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
55 
 
Figure 4 
Simulated* Median (90% Prediction Interval [PI]) CAB Plasma 
Concentrations versus Time for the CAB LA Q4W Regimen (600 mg 
IM Day 1, then 400 mg IM Q4W thereafter^) 
 
a. 
* Note: current simulations based on interim plasma concentration dataset 
b. 
^Study Time and Events include a 4 week oral lead in.  Therefore, Day 1 = day of first injections (Week 4b study 
visit); Week 4 = second injections (Week 8 study visit) 
c. 
Medium dashed line at 1.35 µg/mL corresponds to the geometric mean Ctrough concentration following oral CAB 
10 mg once daily (LATTE) and is equivalent to 8x PA-IC90  
d. 
Dotted line at 0.664 µg/mL corresponds to 4x PA-IC90  
e. 
Long dashed line at 0.166 µg/mL corresponds to the PA-IC90. 
 
At steady state, a one week delay in dosing of the Q4W regimen results in approximately 
15% reduction in median CAB trough.  With this delay, 95% are predicted to remain 
above 4x PA-IC90, and 79% are predicted to remain above the 10 mg oral target (Figure 
5).  Simulations including delays greater than one week have been explored (not shown), 
with <70% of subjects remaining above the 10 mg oral target.  Therefore, a 1-week delay 
is the maximum allowed per the protocol.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
56 
 
Figure 5 
Impact of 1-week Delay in Dosing at Steady State (Week 40 delayed 
to Week 41) on Simulated* Median (90% PI) CAB Plasma 
Concentrations versus Time for the CAB LA Q4W regimen (600 mg 
IM Day 1, then 400 mg IM Q4W thereafter^) 
 
a. 
* Note: current simulations based on interim plasma concentration dataset 
b. 
^Study Time and Events include a 4 week oral lead in.  Therefore, Day 1 = day of first injections (Week 4b study 
visit); Week 4 = second injections (Week 8 study visit) 
Medium dashed line at 1.35 µg/mL corresponds to the geometric mean Cτ following oral CAB 10 mg once daily  
(LATTE) and is equivalent to 8x PA-IC90  
Dotted line at 0.664 µg/mL corresponds to 4x PA-IC90  
Long dashed line at 0.166 µg/mL corresponds to the PA-IC90. 
4.5.3.2. 
RPV LA 
The Q4W regimen for this study was selected based on LATTE-2 safety and efficacy 
data as described above and supported by modeling and simulation of pharmacokinetic 
data obtained following administration of RPV LA in healthy participants (Phase 1 
studies C158 and LAI115428 [GlaxoSmithKline Document Number 2011N112455_03]) 
and in HIV-infected participants (Phase 2 study LATTE-2), with the majority of the data 
coming from 200056 (LATTE-2).  
The predicted median (90% PI) steady-state Cτ for the proposed regimen is 86.8 ng/mL 
(45.6 – 168 ng/mL) (Figure 6).  With this regimen, >99% of participants remain above 
the 5th percentile of steady state trough values following oral RPV 25mg (corresponding 
to 2x the PA-IC90).  With a loading dose of 900 mg RPV LA on Day 1, the anticipated 
median RPV Cτ at Week 4 is 42 ng/mL, with >98% of participants above the RPV PA-
IC90. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
57 
 
Figure 6 
Simulated* Median (90% PI) RPV Plasma Concentrations versus 
Time Profile for the RPV LA Q4W regimen (900 mg IM Day 1, then 
600 mg IM Q4W thereafter^) 
 
a. 
* Note: current simulations based on interim plasma concentration dataset 
b. 
^Study Time and Events include a 4 week oral lead in.  Therefore, Day 1 = day of first injections (Week 4b study 
visit); Week 4 = second injections (Week 8 study visit)  
c. 
Horizontal line at 72 ng/mL corresponds to median Cτ following oral RPV 25mg once daily in LATTE-2 (oral lead-
in) and is similar to median RPV Cτ in other studies in HIV-infected patients (LATTE, ECHO/THRIVE) 
 
At steady-state, a one week delay in dosing for the Q4W regimen is predicted to result in 
a median steady-state Cτ that remains above the median trough for RPV 25 mg (Figure 
7).  This supports allowance of some flexibility in the dosing regimen. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
58 
 
Figure 7 
Impact of 1-week Delay in Dosing at Steady State (Week 40 delayed 
to Week 41) on Simulated* Median (90% PI) RPV Plasma 
Concentrations versus Time for RPV LA Q4W dosing regimen 
(900 mg IM Day 1 and then 600 mg IM Q4W thereafter^) 
 
a. 
*Note: current simulations based on interim plasma concentration dataset 
b. 
^Study Time and Events include a 4 week oral lead in.  Therefore, Day 1 = day of first injections (Week 4b study 
visit); Week 4 = second injections (Week 8 study visit) 
c. 
Horizontal line at 72 ng/mL corresponds to median Cτ following oral RPV 25 mg once daily in LATTE-2 (oral lead-
in) and is similar to median RPV Cτ in other studies in HIV-infected patients (LATTE, ECHO/THRIVE) 
4.6. 
Benefit:Risk Assessment 
Summaries of findings from both clinical and non-clinical studies conducted with oral 
and CAB LA or RPV LA can be found in the Investigator Brochures (GlaxoSmithKline 
Document Number RH2009/00003/07; RPV IB, 2017). 
Oral RPV is an approved medicinal product and detailed information on its benefit/risk 
profile together with any risk mitigation measures are described in product labeling 
(Edurant Prescribing Information, 2018).   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
59 
 
ABC/DTG/3TC is an established regimen that has been in clinical use for several years 
and has an established benefit/risk profile described in detail in the DTG IB 
(GlaxoSmithKline Document Number RM2007/00683/11) and respective country 
product labels (TRIUMEQ Prescribing Information, 2018). 
A potential safety issue related to neural tube defects in infants born to women with 
exposure to dolutegravir (DTG) at the time of conception has been recently identified as 
noted below: 
Potential Risk 
of Clinical 
Significance 
Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (IP) [ABC/DTG/3TC, DTG] 
Refer to DTG IB and country product labels for additional information 
DTG: Neural 
tube defects 
A preliminary analysis of an ongoing birth 
outcome surveillance study in Botswana 
involving women exposed to dolutegravir 
(DTG) identified four cases (as of May 
2018) of neural tube defects in 426 infants 
born to mothers who were exposed to 
DTG-containing regimens from the time of 
conception. In the same study, no infant 
born to a women who started DTG during 
pregnancy had a neural tube defect, out of 
2,824 women. A causal relationship of 
these events to the use of DTG has not 
been established. The incident rate of 
neural tube defects in the general 
population ranges from 0.5-1 cases per 
1,000 live births. As neural tube defects 
occur within the first 4 weeks of fetal 
development (at which time the neural 
tubes are sealed) this potential risk would 
concern women exposed to DTG at the 
time of conception and in early pregnancy. 
Recently updated data (April 2020) for this 
birth outcome study showed that among 
women who were on DTG when they 
became pregnant, 7/3,591 neural tube 
defects (NTD) occurred (0.19%). In 
comparison, NTDs were identified in 
21/19,361 (0.11%) women delivering on 
any non-DTG antiretrovirals. There was 
not a significant difference in the number 
of neural tube defects between births to 
women taking DTG and those taking other 
non-DTG antiretroviral treatments (0.09% 
difference).  
1. A female subject is eligible to 
participate if she is not pregnant, 
not lactating, and, if she is a 
female of reproductive potential, 
agrees to follow one of the 
options listed in the Modified List 
of Highly Effective Methods for 
Avoiding Pregnancy in Females 
of Reproductive Potential (FRP) 
(see Section 12.7.1.) from 30 
days prior to the first dose of 
study medication and for at least 
30 days after discontinuation of 
all oral study medications, and 
for at least 52 weeks after 
discontinuation of CAB LA and 
RPV LA. 
2. Women who are breastfeeding 
or plan to become pregnant or 
breastfeed during the study are 
excluded; 
3. Females of reproductive 
potential are reminded re: 
pregnancy avoidance and 
adherence to contraception 
requirements at every study 
visit. 
4. Pregnancy status is monitored 
at every study visit 
5. In Russia, women who become 
pregnant or who desire to 
become pregnant while in the 
study will have study treatment 
discontinued and will be 
withdrawn from the study.  
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
60 
 
The most significant toxicity associated with ABC is the well-characterized drug-related 
hypersensitivity reaction (HSR).  Studies have shown that carriage of the HLA-B*5701 
allele is associated with a significantly increased risk of a HSR to ABC.  In the 
prospective study CNA106030 (PREDICT-1), the use of pre-therapy screening for the 
presence of HLA-B*5701 and subsequently avoiding ABC in HLA-B*5701 positive 
participants, significantly reduced the incidence of clinically suspected ABC HSR from 
7.8% (66 of 847) to 3.4% (27 of 803) (p<0.0001).  In clinical studies EPZ108859 
(ARIES) and CNA109586 (ASSERT), 0.8% (4/515) and 3.1% (6/192) of participants 
who were HLA-B*5701 negative and who received ABC developed a clinically suspected 
ABC HSR, respectively. 
In any participant treated with ABC, the clinical diagnosis of suspected HSR (as detailed 
in the Local Country Prescribing Information) must remain the basis of clinical decision 
making.  Regardless of HLA-B*5701 status, it is important to permanently discontinue 
ABC and not re-challenge with ABC (i.e., TRIUMEQ, ZIAGEN, EPZICOM / KIVEXA 
or TRIZIVIR) if a HSR cannot be ruled out on clinical grounds, due to the potential for a 
severe or even fatal reaction. 
A detailed clinical description of this reaction (including the type and severity of events 
that can occur on re-challenge or reintroduction following ABC interruption for non-HSR 
reasons) and guidance regarding its management are included in the Local Country 
Prescribing Information for TRIUMEQ (or EPZICOM if TRIUMEQ is not available 
within country).   
Mitigation for ABC HSR:  Every potential participant will be screened for the carriage 
of the HLA-B*5701 allele.  Participants who are HLA-B*5701 positive at the Screening 
visit are allowed to enter the study on a dual-NRTI backbone that does not contain 
abacavir (see Section 6.8).  
The following section outlines the risk assessment and mitigation strategy for CAB and 
RPV in this protocol. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
61 
 
4.6.1. 
Risk Assessment 
Oral CAB and CAB LA (GSK1265744 / GSK1265744 LA) 
Since CAB exposure in humans with or without HIV infection is limited, the clinical safety profile in humans has yet to be fully 
elucidated.  The following risks have primarily been identified during routine preclinical testing and/or in the clinical trial experience to 
date and are considered of potential relevance to clinical usage in the context of this protocol.  Additional information about the clinical 
experience to date and possible risks associated with treatment using CAB can be found in the Summary of Data and Guidance for the 
Investigator section of the IB. 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Drug Induced Liver Injury 
(DILI) 
Less than 1% of participants in the CAB program to 
date have developed transaminitis (elevated liver 
transaminases characterised by predominant ALT 
elevation).  In some of these participants’ transient 
transaminitis were explained by acute hepatitis C 
infection and whilst a small number of others did not 
have alternative explanations, suggesting a mild 
form of DILI without hepatic dysfunction which 
resolved upon withdrawal of treatment with CAB.  
 
• Exclusion criteria as described in Section 5.2 
will prohibit participants with significant 
liver impairment based on screening liver 
chemistry including transaminases (ALT and 
AST) as well on prior medical history.  
Participants with a history of chronic liver 
disease with ongoing inflammation and/or 
fibrosis will have additional confirmatory 
assessments to confirm suitability for entry 
into the study. A 4-week oral lead-in period 
was implemented at the beginning of this 
study, where all participants will receive oral 
CAB prior to the administration of CAB LA 
to determine individual safety and 
tolerability.  During the Extension Phase of 
the study, following review of available oral 
lead-in and Maintenance Phase safety data, 
the protocol was amended to allow an 
optional oral lead-in for the participants 
transitioning from ABC/DTG/3TC to CAB 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
62 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
LA+RPV LA. 
• Liver transaminases (ALT and AST) will be 
closely monitored throughout this study 
(refer to Time & Events Table) and the liver 
chemistry stopping criteria will be adopted as 
described in Section 7.4.10.1 of this protocol. 
Participants will be withdrawn from CAB 
treatment where no compelling alternative 
cause is identified and DILI is suspected. 
• Participants who develop ALT ≥3 times ULN 
while on study must consult with Medical 
Monitor prior to initiation or continuation of 
CAB LA.   
• All instances of liver transaminase elevations 
of Grade 2 and above will be followed to 
resolution.  Participants withdrawn from 
CAB treatment due to meeting liver 
chemistry stopping criteria will be regularly 
monitored both clinically and using liver 
chemistries to determine progress towards 
resolution of the liver event. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
63 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Injection Site 
Reactions (ISRs) 
 
Clinical, experience to date has demonstrated ISRs 
occur in the majority of exposed participants treated 
with CAB LA but are generally mild (Grade 1) or 
moderate (Grade 2) and include events of pain, 
tenderness, erythema, or nodule formation of several 
days duration (median duration for individual events 
<1 week).  ISRs may occur more than once in an 
individual participant receiving multiple injections. 
Although some Grade 3 ISRs were reported, the 
majority of ISRs have not, to date, been associated 
with an excess of participants’ withdrawal. 
None of the ISRs reported to date was serious and no 
clinically significant complications were reported. 
• Administration advice to minimize risk of 
poor administration technique giving rise to 
injection site reactions.  Advice on care, 
monitoring, natural course, and treatment of 
ISRs given in study documentation  
• Advice will be given to participants on care 
of injection site on day/days immediately 
post administration, use of analgesia, 
compresses where appropriate. 
• Participants will be closely monitored for 
ISRs particularly for signs of pain, 
tenderness, infections, erythema, swelling, 
induration, or nodules (granulomas or cysts) 
throughout the study.   
• Complications of ISRs such as infections 
(abscess, cellulitis) and collections of fluid 
requiring drainage will be monitored. 
• Specialist dermatology consultation will be 
sought if warranted for individual 
participants. 
Hypersensitivity 
Reactions (HSR) 
Hypersensitivity reactions have been reported in 
association with integrase inhibitors. These reactions 
were characterized by rash, constitutional findings, 
and sometimes, organ dysfunction, including liver 
• The risk of developing a hypersensitivity 
reaction post administration of CAB LA was  
minimized at the start of the study by the use 
of a mandatory 4-week oral lead-in of CAB 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
64 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
 
injury.  
The cases which have been reported in association 
with CAB have predominantly presented with 
angioedema and urticaria. While a causal association 
with more severe or systemic hypersensitivity 
reactions has not been identified with CAB to date, 
there remains a theoretical risk of such reactions 
with or without hepatic symptoms. The long 
exposures anticipated after CAB LA injection may 
complicate the management of a drug 
hypersensitivity reaction, were it to occur. 
 
to determine individual safety and tolerability 
prior to the introduction of CAB LA.  During 
the Extension Phase of the study, following 
review of available oral lead-in and 
Maintenance Phase safety data, the protocol 
was amended to allow an optional oral lead-
in for the participants transitioning from 
ABC/DTG/3TC to CAB LA+RPV LA. 
• Clinical assessments, laboratory tests 
(including liver transaminases) and vital 
signs will be performed throughout this study 
(refer to Time & Events Table).  Results from 
these assessments may aid early detection of 
HSR. 
• Oral CAB will be withdrawn immediately for 
cases with suspected HSR during the oral 
lead-in phase.  During oral and CAB LA 
treatment, any HSR reactions that occur 
would be managed supportively 
Effects in pregnancy 
seen in non-clinical 
studies 
In animal reproduction studies, CAB when 
administered to rats at >30 times the systemic 
exposure at the maximum recommended oral human 
dose (MRHD) of 30 mg during organogenesis 
through delivery, had adverse effects on labor and 
delivery that may be related to a delay in the onset of 
parturition, resulting in increased fetal mortality 
• Pregnant females are excluded from 
enrolment in this study and women of 
childbearing potential (WOCBP) are required 
to adopt highly reliable means of 
contraception during participation and 
throughout the long term follow up phase of 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
65 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
(stillbirths) and neonatal deaths immediately after 
birth. 
A delay in the onset of parturition, increased 
stillbirths and neonatal deaths were observed in a rat 
pre- and postnatal development study at greater than 
30 times the exposure at the recommended human 
dose (RHD). No evidence of adverse developmental 
outcomes was observed with oral cabotegravir in rats 
or rabbits (greater than 30 times or similar to 
(approximately 0.7 times) the exposure at the RHD, 
respectively) given during organogenesis.  
The clinical significance of these findings in humans 
is unknown. 
For pregnant participants remaining in the study, 
refer to Appendix 10 for additional data regarding 
CAB and pregnancy. Not applicable in Russia. 
this study following exposure to CAB LA. 
• WOCBP are also required to undergo regular 
pregnancy testing throughout study conduct. 
Pregnant participants who remain in the 
study do not need pregnancy testing for the 
duration of the pregnancy.  
• Participants who become pregnant during the 
study may remain in the study provided all 
protocol defined pregnancy related 
assessments, procedures and documentation 
are completed, and a pregnancy specific ICF 
addendum is signed by the participant. Not 
applicable in Russia. Details regarding 
management of pregnant participants are 
found in Appendix 10.  
• In Russia, women who become pregnant or 
who desire to become pregnant while in the 
study will have study treatment discontinued 
and will be withdrawn from the study. 
Potential effects in 
females exposed to 
dolutegravir during 
conception and early 
pregnancy 
A preliminary analysis of an ongoing birth outcome 
surveillance study in Botswana involving women 
exposed to dolutegravir (DTG), a different molecule 
in the same integrase class of medications as CAB, 
identified four cases (as of May 2018) of neural tube 
defects in 426 infants born to mothers who were 
• Pregnant females are excluded from 
enrolment in clinical trials of CAB at this 
time and women of childbearing potential 
(WOCMP) are required to adopt highly 
reliable means of contraception during 
participation and throughout the long term 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
66 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
exposed to DTG-containing regimens from the time 
of conception. In the same study, no infant born to a 
woman who started DTG during pregnancy had a 
neural tube defect, out of 2,824 women. A causal 
relationship of these events to the use of DTG has 
not been established. The incidence of neural tube 
defects in the general population ranges from 0.5-1 
cases per 1,000 live births. As neural tube defects 
occur within the first 4 weeks of fetal development 
(at which time the neural tubes are sealed) this 
potential risk would concern women exposed to 
DTG at the time of conception and in early 
pregnancy. Recently updated data (April 2020) for 
this birth outcome study showed that among women 
who were on DTG when they became pregnant, 
7/3591 neural tube defects (NTD) occurred (0.19%). 
In comparison, NTDs were identified in 21/19,361 
(0.11%) women delivering on any non-DTG 
antiretrovirals. There was not a significant difference 
in the number of neural tube defects between births 
to women taking DTG and those taking other non-
DTG antiretroviral treatments (0.09% difference).  
The clinical relevance of either of these findings in 
relation to CAB use is unknown.  
follow up phase of the studies after exposure 
to CAB LA.  
• WOCBP also undergo regular pregnancy 
testing throughout study conduct.  
• Pregnant participants who remain in the 
study do not need pregnancy testing for the 
duration of the pregnancy. It should be noted 
that CAB concentration could remain for 
prolonged periods despite discontinuation of 
CAB LA.  
• Participants who become pregnant during the 
study may remain in the study, provided that 
all protocol defined pregnancy related 
assessments, procedures and documentation 
are completed and a pregnancy specific ICF 
addendum is signed by the participant. Not 
applicable in Russia. Details regarding 
management of pregnant participants is found 
in Appendix 10. 
• In Russia, women who become pregnant or 
who desire to become pregnant while in the 
study will have study treatment discontinued 
and will be withdrawn from the study. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
67 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Development of 
Resistance following 
discontinuation of 
CAB LA 
 
Residual concentrations of CAB would remain in the 
systemic circulation of participants for prolonged 
periods (more than 1 year in some participants, 
GlaxoSmithKline Document Number 
2016N269422_00, Study 201120) despite stopping 
treatment (e.g. for tolerability issues or treatment 
failure).  
Participants discontinuing CAB LA regimen may be 
at risk for developing HIV-1 resistance to CAB 
many weeks after discontinuing injectable therapy.  
 
• Alternative oral HAART regimens will be 
prescribed within four weeks after 
participants stop CAB LA.  This would be 
anticipated to result in rapid resuppression of 
HIV-1 RNA thus minimizing of the risk of 
emergent resistance. 
 
• The Sponsor will continue to monitor 
participants in this study who discontinue a 
LA regimen for a minimum of 52 weeks 
from the time of the last LA administration. 
Drug-Drug 
Interactions (DDIs) 
For a complete listing of permitted and prohibited 
concurrent medications for CAB and CAB LA, refer 
to Section 6.13. 
CAB and CAB LA should not be co-administered 
with the following medicinal products, as significant 
decreases in CAB plasma concentrations may occur 
(due to UGT enzyme induction), which may result in 
loss of therapeutic effect of CAB. 
- 
the anticonvulsants carbamazepine, 
oxcarbazepine, phenobarbital, phenytoin 
• All participants will be informed of 
prohibited medications throughout the study 
and updates provided as needed via the 
informed consent. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
68 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
- 
the antimycobacterials rifampicin, 
rifampin, rifapentine, rifabutin  
- 
St John’s wort (Hypericum perforatum). 
Chronic use of oral glucocorticoids must be avoided; 
however, short treatment courses (for example, 
21 days or less) and topical, inhaled or intranasal use 
of glucocorticoids will be allowed. 
Residual concentrations of CAB could remain in the 
systemic circulation of participants who stopped 
treatment (e.g. for tolerability issues or treatment 
failure) for prolonged periods (months).   
Participants discontinuing a LA regimen may be at 
risk for developing DDIs many weeks after 
discontinuing injectable therapy.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
69 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Inadvertent 
Intravenous Injection 
(Accidental 
Maladministration) 
As with any intramuscular injection, it is possible 
that CAB LA can be inadvertently administered 
intravenously instead of intramuscularly resulting in 
higher than expected concentrations of CAB.  This 
could be due to administrator error, improper 
injection technique and / or improper needle length 
used based on body type. 
The clinical consequences of overdose with CAB are 
currently unknown. HIV-1 viral suppression may not 
be effective following accidental maladministration. 
• Training will be provided to all sites on 
proper injection technique.   
• Should IM maladministration be suspected at 
any time (e.g., suspected under or overdose 
or inadvertent IV dosing), a PK sample, post 
dose ECG, vital signs or any other supportive 
testing may be obtained at the discretion of 
the investigator, and the Medical Monitor 
notified.   
• Laboratory samples for safety parameters and 
HIV-1 RNA will be closely monitored in all 
participants.  Additionally, 2 hour post dose PK 
samples will be obtained at a few timepoints 
(Week 4b; Week 48; Week 96; Week 104b 
[participants transitioning from ABC/DTG/3TC]) for 
determination of CAB concentration and possible 
pharmacokinetic correlation with safety 
parameters such as ECG changes and virologic 
response.  Additionally, an unscheduled PK 
sample may be drawn approximately 2 hours post 
dosing for future evaluation of CAB 
concentrations. 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
70 
 
ORAL RPV 
For safety and risk mitigation for oral RPV refer to the RPV prescribing information [Edurant Prescribing Information, 2018].   
 
RPV LA 
Information about the clinical experience to date and possible risks associated with treatment using RPV LA can be found in the Summary 
of Data and Guidance for the Investigator section of the IB.  Systemic reactions following RPV LA injections have been observed in 
clinical trials. These occur infrequently (in less than 0.5% of participants) and typically begin to resolve within minutes of the injection 
however, some participants required supportive care. Where timely PK data was available, high RPV PK plasma concentrations have been 
observed which may have resulted from an accidental partial IV injection of RPV The following risks are considered to be of specific 
clinical relevance in the context of IM use: 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Injection Site Reactions 
Clinical, experience to date has demonstrated ISRs occur in 
the majority of exposed participants treated with RPV LA but 
are generally mild (Grade 1) or moderate (Grade 2) and 
include events of pain, tenderness, erythema, or nodule 
formation of several days duration (median duration for 
individual events <1 week).  ISRs may occur more than once 
in an individual participant receiving multiple injections. 
Although some Grade 3 ISRs were reported, the majority of 
ISRs have not, to date, been associated with an excess of 
participants’ withdrawal due to ISRs. 
 
 
• Administration advice to minimize 
risk of poor administration 
technique giving rise to injection 
site reactions.  Advice on care, 
monitoring, natural course, and 
treatment of ISRs given in study 
documentation. 
• Advice to participants on care of 
injection site on day/days 
immediately post administration, 
use of analgesia, compresses where 
appropriate. 
• Participants will be closely 
monitored for ISRs particularly for 
signs of pain, tenderness, 
infections, erythema, swelling, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
71 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
induration, or nodules (granulomas 
or cysts) throughout the study.   
• Complications of ISRs such as 
infections (abscess, cellulitis) and 
collections of fluid requiring 
drainage will be monitored. 
• Specialist dermatology consultation 
will be sought if warranted for 
individual participants. 
Rash 
 
Some observations of rash with oral RPV have been reported 
in clinical studies executed to date (the majority are Grade 1 
or Grade 2).  
Severe skin and hypersensitivity reactions have been reported 
during the postmarketing experience, including cases of Drug 
Reaction with Eosinophilia and Systemic Symptoms 
(DRESS), with oral RPV containing regimens.  While some 
skin reactions were accompanied by constitutional symptoms 
such as fever, other skin reactions were associated with organ 
dysfunctions, including elevations in hepatic serum 
biochemistries. 
 
• At the beginning of this study, RPV 
LA administration was preceded by 
a four week oral RPV lead-in to 
evaluate safety and tolerability in 
individual participants.  During the 
Extension Phase of the study, 
following review of available oral 
lead-in and Maintenance Phase 
safety data, the protocol was 
amended to allow an optional oral 
lead-in for the participants 
transitioning from ABC/DTG/3TC 
to CAB LA+RPV LA. 
• Participants with a Grade 1 or 2 
rash will be allowed to continue 
treatment , depending on the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
72 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
clinical judgment of the 
investigator. 
• Participants experiencing a grade 3 
or 4 rash should discontinue their 
ART medication and will be 
withdrawn from the study. 
• All rash events should be assessed 
with special attention to systemic 
symptoms, laboratory 
abnormalities, or mucosal 
involvement.  Close clinical follow-
up, including follow-up of 
laboratory abnormalities, and 
appropriate medical intervention, 
including referral to dermatologist 
as appropriate, should be instituted 
for these events; daily follow-up is 
recommended for 5 days from the 
onset of the event to monitor for 
progression of the event. 
Development of 
Resistance 
 
Residual concentrations of RPV can remain in the systemic 
circulation of participants who stopped treatment (e.g. for 
tolerability issues or treatment failure) for more than one year 
in some participants [McGowan, 2016].   
 
 
• Alternative oral HAART regimens 
will be prescribed within four 
weeks after participants stop RPV 
LA.  This would be anticipated to 
result in rapid resuppression of 
HIV-1 RNA thus minimizing of the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
73 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Participants discontinuing a LA regimen may be at risk for 
developing resistance to RPV many weeks after discontinuing 
injectable therapy. 
risk of emergent resistance. 
• The Sponsor will continue to 
monitor participants in this study 
who discontinue a LA regimen for a 
minimum of 52 weeks from the 
time of the last LA administration. 
Drug-Drug Interactions 
(DDIs) 
For a complete listing of permitted and prohibited concurrent 
medications for RPV and RPV LA, refer to Section 6.13. 
RPV and RPV LA should not be co-administered with the 
following medicinal products, as significant decreases in RPV 
plasma concentrations may occur (due to CYP3A enzyme 
induction), which may result in loss of therapeutic effect of 
RPV LA. 
- 
the anticonvulsants carbamazepine, 
oxcarbazepine, phenobarbital, phenytoin 
- 
the antimycobacterials rifampicin, rifapentine, 
rifabutin 
- 
the glucocorticoid systemic dexamethasone, 
except as a single dose treatment 
- 
St John’s wort (Hypericum perforatum). 
Of note, evidence to date indicates that clinically relevant 
DDIs with RPV LA and other antiretrovirals are unlikely to 
occur. 
Residual concentrations of RPV could remain in the systemic 
• All participants will be informed of 
prohibited medications throughout 
the study and updates provided as 
needed via informed consent. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
74 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
circulation of participants who stopped treatment (e.g. for 
tolerability issues or treatment failure) for prolonged periods 
(months). 
Participants discontinuing a LA regimen may be at risk for 
developing resistance to RPV many weeks after discontinuing 
injectable therapy.  
Inadvertent 
Intravenous Injection 
(Accidental 
Maladministration) 
As with any intramuscular injection, it is possible that RPV 
LA can be inadvertently administered intravenously instead 
of intramuscularly resulting in higher than expected 
concentrations of RPV.  This could be due to administrator 
error, improper injection technique and / or improper needle 
length used based on body type.   
The clinical consequences of overdose with RPV LA are 
currently unknown.  HIV-1 viral suppression may not be 
effective following accidental maladministration. 
 
Systemic reactions following RPV LA injections have been 
observed in clinical trials. These occur infrequently (in less 
than 0.5% of participants) and typically begin to resolve 
within minutes of the injection, however, some participants 
required supportive care. Where timely PK data was 
available, high RPV PK plasma concentrations have been 
observed which may have resulted from an accidental partial 
IV injection of RPV. 
• Training will be provided to all 
sites on proper injection technique.   
• Should IM maladministration be 
suspected at any time (e.g. 
suspected under or overdose or 
inadvertent IV dosing), a PK 
sample, post dose ECG monitoring 
and vital signs or any other 
supportive testing may be obtained 
at the discretion of the investigator, 
and the Medical Monitor notified. 
• Laboratory samples for safety 
parameters and HIV-1 RNA will be 
closely monitored in all 
participants.  Additionally, 2 hour 
post dose PK samples will be 
obtained at a few timepoints (Week 
4b; Week 48; Week 96; Week 104b 
[participants transitioning from 
ABC/DTG/3TC]) for determination 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
75 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
 
of RPV concentration and possible 
pharmacokinetic correlation with 
safety parameters such as ECG 
changes and virologic response.  
Additionally, an unscheduled PK 
sample may be drawn 
approximately 2 hours post dosing 
for future evaluation of RPV 
concentrations. 
Study Procedures 
Risks of complications 
from venipuncture for 
blood sampling 
Complications from with venipuncture include swelling, 
bleeding, bruising and infection  
• These risks will be minimized using 
current standard of care techniques 
for venipuncture. 
Risks of ECG pad 
removal 
Participants will be required to have ECG tracings recorded 
periodically throughout the study. 
Some discomfort and rash may occur where the ECG pads are 
removed. 
• ECGs will be conducted by 
appropriately trained personnel and 
effort made to minimise contact time 
for application of the pads. 
Other 
Risk of Treatment 
Failure 
This study employs a novel maintenance approach to the 
treatment of HIV-1 infection.  Following virologic 
suppression, participants will be transitioned off of a 3 drug 
ART regimen to a 2 drug LA ART regimen that remains 
experimental.  CAB and RPV have demonstrated antiviral 
activity in the Phase 2b studies LAI116482 (oral two drug 
• HIV-1 RNA will be closely 
monitored throughout the study.  
 
• Plasma samples will be collected 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
76 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
treatment) and 200056 (two drug LA treatment).   
Doses of the CAB LA and RPV LA have been selected to 
achieve exposures that are expected to maintain virologic 
efficacy on the basis of available data with the oral 
formulations and LA data from 200056.   
Due to administration error, it is possible that a participant 
could receive an inadequate dose of CAB LA or RPV LA.  
Sub-therapeutic concentrations of either CAB LA or RPV LA 
could lead to virologic failure and possibly the development 
of resistance.   
throughout the Maintenance Phase 
for determination of CAB and RPV 
concentration and possible 
pharmacokinetic correlation with 
virologic response.   
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
77 
 
4.6.2. 
Other Clinically Relevant Information 
Additional details concerning safety observations from clinical studies and for which a 
causal association has not been established or which are of minimal clinical significance 
may be found in the Investigator’s Brochure (please refer to Section 6 of the IB: 
‘Summary of Data and Guidance for the Investigator.’) 
Adverse Events of Special Interest: 
Seizure: 
A small number of seizure cases have been reported following CAB administration (less 
than 1% of all those receiving CAB in clinical studies). . These cases have had alternative 
explanations for their occurrence.  Overall, there is not convincing evidence that 
cabotegravir exposure may be causally associated with seizure or with reduction of 
seizure threshold, due to the low frequency of reports, the confounders present in the 
cases received to date and lack of any pre-clinical signal or identified plausible 
mechanism.  However, seizure and seizure-like events are considered as AEs of special 
interest for CAB.   Subjects with recent history of, or recent treatment for seizure will be 
excluded from study participation. Report any cases of seizure or seizure like events 
immediately. 
4.6.3. 
Benefit Assessment 
The antiviral activity of CAB against HIV-1 has been well established through Phase 2 
and Phase 3 studies.  RPV is an established antiviral agent against HIV-1 in treatment 
naive participants, with long term durability (>96 weeks in Phase 3 and >240 weeks in 
Phase 2b). 
Participants receiving CAB LA + RPV LA are anticipated to benefit from maintenance of 
virological suppression using LA agents.  Participants randomized to an arm containing 
CAB LA + RPV LA will have Q4W dosing without the need to take concomitant daily 
oral therapy.  Adherence in these participants is expected to be improved and will be 
directly observed.  Efficacy of the two-drug regimen, as IM agents, has been 
demonstrated through Week 96 of this study and the ongoing 200056 and 201585 studies 
.  .  The reduction in ART, and the discontinuation of NRTIs, may offer long term safety 
and tolerability benefits in these participants. 
4.6.4. 
Overall Benefit:Risk Conclusion 
Taking into account the measures taken to minimize risk to participants participating in 
this study, the potential risks identified in association with the CAB + RPV are justified 
by the anticipated benefits that may be afforded to study participants switching to a Long-
Acting, NRTI-sparing regimen. 
5. 
SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA 
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the investigational product or other study treatment 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
78 
 
that may impact participant eligibility is provided in the current Investigator Brochures 
for CAB (GlaxoSmithKline Document Number RH2009/00003/07) and RPV (RPV IB, 
2017), and the RPV product label (Edurant Prescribing Information, 2018).  Information 
for ABC/DTG/3TC or DTG is provided in the current DTG IB (GlaxoSmithKline 
Document Number: RM2007/00683/11) and US or country product label (TRIUMEQ 
Prescribing Information, 2018; TIVICAY Prescribing Information, 2017). 
5.1. 
Inclusion Criteria 
Deviations from inclusion criteria are not allowed because they can potentially jeopardise 
the scientific integrity of the study, regulatory acceptability or participant safety.  
Therefore, adherence to the criteria as specified in the protocol is essential. 
In general, participants screened for this study must: 
• be able to understand and comply with protocol requirements, instructions, and 
restrictions,  
• be likely to complete the study as planned,  
• understand the long term commitment to the study, 
• and be considered appropriate candidates for participation in an investigative 
clinical trial with oral and intramuscularly injectable medications (e.g., no active 
substance abuse, acute major organ disease). 
Laboratory results from the central laboratory services provided by this trial will be used 
to assess eligibility.  A single repeat of a procedure / lab parameter is allowed to 
determine eligibility (unless otherwise specified).  In exceptional circumstances only, if a 
repeat lab is required because a central lab result cannot be generated, local labs can be 
reviewed and approved by the Medical Monitor, for consideration of participant 
eligibility.  A repeat central lab will be submitted concurrently or at the next planned 
visit.  Similarly, if a central laboratory result cannot be generated for 
genotype/phenotype, a local result can be considered following review and approval by 
the study virologist. 
Participants are allowed to re-screen for this study one time.  This will require a new 
participant number. 
The following are study specific eligibility criteria unless stated otherwise.  In addition 
to these criteria, Investigators must exercise clinical discretion regarding selection of 
appropriate study participants, taking into consideration any local treatment 
practices or guidelines and good clinical practice (GCP).  All participants must be 
considered appropriate candidates for initiation of antiretroviral therapy in 
accordance with local treatment guidelines. 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
79 
 
Participants eligible for enrolment in the study must meet all of the following criteria: 
AGE 
1. HIV-1 infected, ART-naive men or women aged 18 years or greater at the time of 
signing the informed consent. 
TYPE OF PARTICIPANT AND DIAGNOSIS INCLUDING DISEASE SEVERITY  
2. HIV-1 infection as documented by Screening plasma HIV-1 RNA ≥1000 c/mL; 
3. Antiretroviral-naïve (≤ 10 days of prior therapy with any antiretroviral agent 
following a diagnosis of HIV-1 infection).  Any previous exposure to an HIV 
integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be 
exclusionary. 
SEX 
4. Female Participants: 
A female participant is eligible to participate if she is not pregnant at Screening and 
first day of Induction Phase (as confirmed by a negative serum human chorionic 
gonadotrophin [hCG] test), not lactating, and at least one of the following conditions 
applies: 
 
a. 
Non-reproductive potential defined as: 
• Pre-menopausal females with one of the following: 
• Documented tubal ligation 
• Documented hysteroscopic tubal occlusion procedure with follow-up 
confirmation of bilateral tubal occlusion  
• Hysterectomy 
• Documented Bilateral Oophorectomy 
• Postmenopausal defined as 12 months of spontaneous amenorrhea [in 
questionable cases a blood sample with simultaneous follicle stimulating 
hormone (FSH) and estradiol levels consistent with menopause (refer to 
laboratory reference ranges for confirmatory levels)].  Females on hormone 
replacement therapy (HRT) and whose menopausal status is in doubt will be 
required to use one of the highly effective contraception methods if they wish 
to continue their HRT during the study.  Otherwise, they must discontinue HRT 
to allow confirmation of post-menopausal status prior to study enrolment. 
b. Reproductive potential and agrees to follow one of the options listed in the 
Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of 
Reproductive Potential (FRP) (see Appendix 7.) from 30 days prior to the first dose 
of study medication, throughout the study, and for at least 30 days after 
discontinuation of all oral study medications and for at least 52 weeks after 
discontinuation of CAB LA and RPV LA. 
The investigator is responsible for ensuring that participants understand how to 
properly use these methods of contraception. 
ALL participants in the study should be counseled on safer sexual practices including 
the use and benefit/risk of effective barrier methods (e.g., male condom) and on the 
risk of HIV transmission to an uninfected partner. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
80 
 
INFORMED CONSENT 
5. Capable of giving signed informed consent as described in Section 6.2 which 
includes compliance with the requirements and restrictions listed in the consent form 
and in this protocol. 
OTHER 
6. French participants: In France, a participant will be eligible for inclusion in this 
study only if either affiliated to or a beneficiary of a social security category. 
5.2. 
Exclusion Criteria 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardise the scientific integrity of the study, regulatory acceptability or participant 
safety.  Therefore, adherence to the criteria as specified in the protocol is essential. 
A participant will not be eligible for inclusion in this study if any of the following criteria 
apply: 
Exclusionary Medical Conditions  
1. Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed 
during the study. 
2. Any evidence at Screening of an active Centers for Disease and Prevention Control 
(CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not 
requiring systemic therapy or historic or current CD4+ cell count <200 cells/mm3 
are not exclusionary (local guidelines dictate). 
3. Participants with known moderate to severe hepatic impairment. 
4. Any pre-existing physical or mental condition (including substance abuse disorder) 
which, in the opinion of the Investigator, may interfere with the participant’s ability 
to comply with the dosing schedule and/or protocol evaluations or which may 
compromise the safety of the participant. 
5. Participants determined by the Investigator to have a high risk of seizures, 
including participants with an unstable or poorly controlled seizure disorder.  A 
participant with a prior history of seizure may be considered for enrolment if the 
Investigator believes the risk of seizure recurrence is low.  All cases of prior 
seizure history should be discussed with the Medical Monitor prior to enrolment.  
6. Participant who, in the investigator's judgment, poses a significant suicide risk.  
Participant’s recent history of suicidal behavior and/or suicidal ideation should be 
considered when evaluating for suicide risk. 
7. The participant has a tattoo or other dermatological condition overlying the gluteus 
region which may interfere with interpretation of injection site reactions. 
8. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at 
Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody 
(anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV DNA as follows: 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
81 
 
Exclusionary Medical Conditions  
• Participants positive for HBsAg are excluded; 
• Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg 
status) and positive for HBV DNA are excluded.   
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for 
anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. 
9. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not 
be excluded, however Investigators must carefully assess if therapy specific for 
HCV infection is required; participants who are anticipated to require HCV 
treatment prior to Week 48 of the Maintenance Phase must be excluded.  HCV 
treatment on study may be permitted post Week 48, following consultation with the 
Medical Monitor.   
Participants with HCV co-infection will be allowed entry into Phase 3 studies if: 
• Liver enzymes meet entry criteria. 
• HCV Disease has undergone appropriate work-up, HCV is not advanced, and 
will not require treatment prior to the Week 48 visit.  Additional information 
(where available) on participants with HCV co-infection at screening should 
include results from any liver biopsy, fibroscan, ultrasound, or other fibrosis 
evaluation, history of cirrhosis or other decompensated liver disease, prior 
treatment, and timing/plan for HCV treatment.   
• In the event that recent biopsy or imaging data is not available or is 
inconclusive, the Fib-4 score will be used to verify eligibility.   
• 
A Fib-4 score > 3.25 is exclusionary  
• 
Fib-4 scores 1.45 – 3.25 requires Medical Monitor consultation. 
Fibrosis 4 Score Formula:  
(Age x AST) / (Platelets x (√ALT)) 
10. Unstable liver disease (as defined by any of the following:  presence of ascites, 
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or 
persistent jaundice), known biliary abnormalities (with the exception of Gilbert's 
syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per 
investigator assessment).   
11. History of liver cirrhosis with or without hepatitis viral co-infection. 
12. Ongoing or clinically relevant pancreatitis. 
13. All participants will be screened for syphilis (rapid plasma reagin 
[RPR]).  Participants with untreated syphilis infection, defined as a positive RPR 
without clear documentation of treatment, are excluded.  Participants with a 
positive RPR test who have not been treated may be rescreened at least 30 days 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
82 
 
Exclusionary Medical Conditions  
after completion of antibiotic treatment for syphilis. 
14. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, 
or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or 
penile intraepithelial neoplasia; other localized malignancies require agreement 
between the investigator and the study Medical Monitor for inclusion of the 
participant prior to enrolment. 
15. Any condition which, in the opinion of the Investigator, may interfere with the 
absorption, distribution, metabolism or excretion of the drug or render the 
participant unable to receive study medication. 
16. History or presence of allergy or intolerance to the study drugs or their components 
or drugs of their class.  In addition, if heparin is used during PK sampling, 
participants with a history of sensitivity to heparin or heparin-induced 
thrombocytopenia must not be enrolled. 
17. Current or anticipated need for chronic anti-coagulation. 
18. Alanine aminotransferase (ALT) ≥3 times ULN.   
19. Clinically significant cardiovascular disease, as defined by history/evidence of 
congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery 
bypass grafting (CABG) surgery or percutaneous transluminal coronary 
angioplasty (PTCA) or any clinically significant cardiac disease. 
CONCOMITANT MEDICATIONS 
20. Exposure to an experimental drug and/or experimental vaccine within 28 days or 
5 half-lives of the test agent, or twice the duration of the biological effect of the test 
agent, whichever is longer, prior to the first dose of IP. 
21. Treatment with any of the following agents within 28 days of Screening: 
• radiation therapy 
• cytotoxic chemotherapeutic agents 
• tuberculosis (TB) therapy, with the exception of treatment of latent TB with 
isoniazid 
• Immunomodulators that alter immune responses (such as chronic systemic 
corticosteroids, interleukins, or interferons).  Note: Participants using short-
term (e.g. ≤21 day) systemic corticosteroid treatment; topical, inhaled or 
intranasal corticosteroids are eligible for enrolment. 
22. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening. 
23. Treatment with any agent, except recognized ART as allowed above, with 
documented activity against HIV-1 within 28 days of the first dose of IP. 
24. Use of medications which are associated with Torsades de Pointes (See SPM for a 
list of relevant medications). 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
83 
 
Exclusionary Medical Conditions  
DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA 
25. Any evidence of primary resistance to NNRTIs (except for K103N which is 
allowed), or any known resistance to INIs from historical resistance test results 
(International AIDS Society [ IAS]-USA, 2015).  Note:  re-tests of Screening 
genotypes are allowed only at the discretion of the study virologist. 
26. Participants who are HLA-B*5701 positive and are unable to use an NRTI 
backbone that does not contain abacavir (participants who are HLA-B*5701 
positive may be enrolled if they use a NRTI backbone that does not contain 
abacavir; HLA-B*5701 positive participants may be excluded from the study if 
local provision of an alternate NRTI backbone is not possible). 
27. Any verified Grade 4 laboratory abnormality.  A single repeat test is allowed 
during the Screening Phase to verify a result. 
28. Any acute laboratory abnormality at Screening, which, in the opinion of the 
Investigator, would preclude the participant’s participation in the study of an 
investigational compound. 
29. Participant has estimated creatinine clearance <50 mL/min/1.73m2 via the Chronic 
Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey, 2009). 
30. Participation in other interventional studies is generally not permitted, however for 
eligible subjects in South Africa, co-enrolment in the AIDS Clinical Trial Group 
(ACTG) interventional study (A5392) could be exceptionally permitted after 
review and approval by the Medical Monitor. 
5.3. 
Screening/Baseline/Run-in Failures 
Screen failures are defined as participants who consent to participate in the clinical trial 
but are never subsequently enrolled or randomized.  In order to ensure transparent 
reporting of screen failure participants, meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements, and respond to queries from Regulatory 
authorities, a minimal set of screen failure information is required including 
Demography, Screen Failure details, Eligibility Criteria, and Serious Adverse Events (see 
Section 7.4.3.6). 
5.4. 
Withdrawal/Stopping Criteria 
Participants permanently discontinuing study treatments prior to Week 100 are 
considered to be withdrawn from the study treatments.  Similarly, participants 
permanently discontinuing participation from the Extension Phase prior to  the CAB LA 
+ RPV LA marketed product being locally available are considered to be withdrawn from 
the study treatments, and will move directly into the Long-Term Follow-Up Phase. 
Participants permanently discontinuing participation from the Long-Term Follow-Up 
Phase are considered to be withdrawn from the study treatments and from the study. 
Participants who enter the Extension Phase but permanently discontinue participation in 
the Extension Phase when the CAB LA + RPV LA marketed product is locally available 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
84 
 
must enter the Long Term Follow-Up Phase if they withdraw from the study due to 
safety-related reasons only. 
A participant may withdraw consent and discontinue participation in this study at any 
time.  The Investigator may also, at their discretion, discontinue the participant from 
participating in this study at any time (e.g., safety, behavioral or administrative reasons).  
If a participant withdraws from the study, he/she may request destruction of any samples 
taken, and the investigator must document this in the site study records.  Participants who 
are withdrawn from the study will not be replaced. 
All participants who discontinue prematurely from the study, irrespective of arm, will be 
asked for additional information to establish the reason for withdrawal. 
Participants are not obligated to state the reason for withdrawal.  However, the reasons 
for withdrawal, or failure to provide a reason, must be documented by the Investigator on 
the Completion/Withdrawal section of the electronic case report form (eCRF).  Every 
effort should be made by the Investigator to follow-up participants who withdraw from 
the study.  
Participants may have a temporary interruption to their study treatment for management 
of toxicities. 
Reasons for study withdrawal may include: 
• 
Adverse event / Serious adverse event 
• 
Protocol deviation 
• 
Intolerability of injections 
• 
Participant lost to follow-up 
• 
Participant withdrew consent 
• 
Investigator discretion 
• 
Participant or investigator non-compliance 
• 
Termination of the study by the Sponsor 
• 
At the request of the participant, Investigator, GSK, or ViiV Healthcare 
• 
The participant requires concurrent prohibited medications during the course of the 
study.  The participant may remain in the study if, in the opinion of the Investigator 
and the Medical Monitor, such medication will not interfere with the conduct or 
interpretation of the study or compromise the safety of the participant. 
Participants must be withdrawn from the study for any of the following reasons: 
• 
Participants who are not eligible to continue into the Maintenance Phase. 
• 
Participants who are not eligible, or do not wish to continue on to the Extension 
Phase. 
• 
Participants who cannot or do not wish to continue on to the Long-Term Follow Up 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
85 
 
Phase. 
• 
Confirmed virologic failure. 
• 
In Russia, pregnancy (intrauterine), regardless of termination status of the pregnancy. 
(If receiving CAB LA + RPV LA, the participant would discontinue LA study 
treatment and continue to be followed up in the LTFU phase. 
• 
Participant requires a second switch or a dose adjustment of any component of the 
ABC/DTG/3TC (with exception of dose reduction for renal insufficiency as noted in 
Section 4.2.7).  A substitution for NRTI backbone is allowed at Screening, e.g. 
ABC/3TC to TDF/FTC or TAF/FTC for participants who are HLA-B*5701 positive. 
During the Induction Phase, prior to randomization into the Maintenance Phase at 
Day 1, one switch to an alternate approved background NRTI therapy is allowed for 
toxicity or tolerability management.   
• 
Participant requires substitution or dose reduction of CAB LA or RPV LA (oral 
bridging supply and potential for a second loading dose may be permissable 
following discussion with the Medical Monitor). 
• 
Grade 4 clinical AE or toxicity in the absence of compelling evidence that the AE is 
not causally related to the IP. 
• 
Liver toxicity where Stopping Criteria are met and no compelling alternative cause is 
identified (See Section 5.4.1). 
• 
Renal toxicity is met and no compelling alternate cause is identified. 
• 
Participant has a Grade 3 or higher rash or Grade 2 rash with evidence of systemic 
involvement. 
• 
The following QT criteria: 
• 
Corrected QT interval (QTc) >550 msec considered causally related to IP (See 
Section 5.4.2). 
This criterion must be based on the average QTc value of triplicate ECGs.  For example, 
if an ECG demonstrates a prolonged QT interval, obtain two more ECGs over a brief 
Phase, and then use the averaged QTc values of the three ECGs to determine whether the 
participant should be discontinued from the study.   
Efficacy data for participants withdrawing from the study will be considered evaluable up 
to the point at which they are withdrawn using the same criteria for evaluability as for 
participants who complete the study. 
Safety data for all participants who receive any amount of study drug, including 
participants who withdraw from the study, will be included in evaluations of safety. 
If a participant is prematurely or permanently withdrawn from the study, the procedures 
described in the Time and Events Table (Table 5) for the in-clinic Withdrawal visit are to 
be performed.  An in-clinic Follow-Up visit will be conducted 4 weeks after the last dose 
of study medication for participants with ongoing AEs, and serious adverse events 
(SAEs) related & not related to study drug and also any laboratory abnormalities that are 
considered to be AEs or potentially harmful to the participant, at the last on-study visit.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
86 
 
All data from the Withdrawal visit will be recorded, as they comprise an essential 
evaluation that should be done prior to discharging any participant from the study.    
Where the CAB LA + RPV LA marketed product is not locally available, any participant 
who receives at least a single dose of CAB LA and/or RPV LA and discontinues the CAB 
LA + RPV LA regimen for any reason must enter the 52-week Long-Term Follow-Up 
Phase.  
Where CAB LA + RPV LA marketed product is locally available, only participants that 
discontinue the CAB LA + RPV LA regimen for safety-related reasons must enter the 
LTFU Phase.  
All participants must remain on suppressive highly active antiretroviral therapy 
(HAART) for at least 52 weeks after the last dose of CAB LA and/or RPV LA. 
The following actions must be taken in relation to a participant who fails to attend the 
clinic for a required study visit: 
• 
The site must attempt to contact the participant and re-schedule the missed visit as 
soon as possible.  
• 
The site must counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the participant wishes to and/or should 
continue in the study.  
• 
In cases where the participant is deemed ‘lost to follow-up’, the investigator or 
designee must make every effort to regain contact with the participant (where 
possible, 3 telephone calls and if necessary a certified letter to the participant’s last 
known mailing address or local equivalent methods). These contact attempts should 
be documented in the participant’s medical record.  
• 
Should the participant continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost to 
Follow-up”.  
5.4.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology (in alignment with the FDA 
premarketing clinical liver safety guidance).   
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf 
IP will be stopped if any of the following liver chemistry criteria are met: 
• ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin, bilirubin 
fractionation required). 
• 
NOTE: serum bilirubin fractionation should be performed if testing is available.  
If testing is unavailable, sites should evaluate the presence of detectable urinary 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
87 
 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver 
injury.  If testing is unavailable and a participant meets the criterion of total 
bilirubin ≥ 2xULN, then the event meets liver stopping criteria. 
• ALT ≥8xULN. 
• ALT ≥3xULN (if Baseline ALT is < ULN) with symptoms or worsening of acute 
hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, or eosinophilia, OR; 
• ALT ≥3x Baseline ALT with symptoms or worsening of acute hepatitis or 
hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, or eosinophilia. 
• ALT ≥5xULN and <8xULN that persists ≥2 weeks (with bilirubin <2 ULN & no 
signs or symptoms of acute hepatitis or hypersensitivity). 
• ALT ≥5xULN but <8xULN and cannot be monitored weekly for >2 weeks. 
5.4.1.1. 
Liver Chemistry Stopping Criteria, Participant Management and Follow-
Up 
Participants who develop ALT ≥5xULN must be followed weekly until resolution or 
stabilization (ALT <5xULN on 2 consecutive evaluations). 
When any of the liver chemistry stopping critera is met, do the following: 
• Immediately hold IP.  If receiving LA therapy, do not administer another 
injection until approval is received from the ViiV Safety and Labelling 
Committee. 
• Report the event to the Medical Monitor within 24 hours of learning its 
occurrence (Section 7.4.3.4, Table 7). 
• Complete the liver event eCRF and SAE eCRF, where applicable, (see 
Section 7.4.3.4). 
• Complete the liver imaging and/or liver biopsy eCRFs if these tests are 
performed. 
• Perform liver event follow up assessments (described below), and monitor the 
participant until liver chemistries resolve, stabilize, or return to Baseline values as 
described below. 
• Make every reasonable attempt to have participants return to clinic within 24 
hours for repeat liver chemistries, liver event follow up assessments (see below), 
and close monitoring. 
• A specialist or hepatology consultation is recommended. 
• Monitor participants twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilize or return to within Baseline values. 
Make every attempt to carry out the liver event follow up assessments described below: 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
88 
 
• Viral hepatitis serology including: 
o Hepatitis A immunoglobulin M (IgM) antibody; 
o Hepatitis B surface antigen (HBsAg) and Hepatitis B Core Antibody (IgM); 
o Hepatitis C RNA; 
o Hepatitis E IgM antibody; 
o Cytomegalovirus IgM antibody; 
o Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); 
• Syphilis screening; 
• Drugs of abuse screen including alcohol; 
• Serum acetaminophen test (APAP adduct test).  The site must contact GSK when 
this test is required.  Please refer to the central laboratory manual. 
• Blood sample for pharmacokinetic (PK) analysis, obtained within 60 hours of last 
dose.  Record the date/time of the PK blood sample draw and the date/time of the 
last dose of investigational product prior to blood sample draw on the eCRF.  If 
the date or time of the last dose is unclear, provide the participant’s best 
approximation.  If the date/time of the last dose cannot be approximated OR a PK 
sample cannot be collected in the time period indicated above, do not obtain a PK 
sample.  Instructions for sample handling and shipping are in the SPM. 
• Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH); 
• Fractionated bilirubin, if total bilirubin is greater than 1.5xULN; 
• Obtain complete blood count with differential to assess eosinophilia; 
• Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver kidney 
microsomal antibodies, and quantitative total immunoglobulin G (IgG or gamma 
globulins); 
• Liver imaging (ultrasound, magnetic resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver disease; complete Liver Imaging and/or Liver 
Biopsy eCRF forms; 
• Record the appearance or worsening of clinical symptoms of hepatitis, or 
hypersensitivity, fatigue, decreased appetite, nausea, vomiting, abdominal pain, 
jaundice, fever, or rash as relevant on the AE report form; 
• Record use of concomitant medications, acetaminophen, herbal remedies, other 
over the counter medications, or putative hepatotoxins, on the concomitant 
medications report form.   
• Record alcohol use on the liver event alcohol intake case report form. 
5.4.1.2. 
Liver Event Adjudication Committee 
A liver safety panel will be used to evaluate all subjects who meet liver stopping criteria. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
89 
 
Uniform sets of data and standards for adjudication will be applied across cases to inform 
outcomes. 
Full details of the analyses, estimated timing and the decision criteria will be pre-
specified in an Adjudication Committee Charter. 
5.4.1.3. 
Liver Chemistry Stopping Criteria – Restart 
Participants who meet liver toxicity stopping criteria should not be retreated with 
investigational product unless an exemption has been approved by the ViiV Safety and 
Labeling Committee (VSLC).  The guideline for Restart approved by the VSLC, which is 
maintained as a separate document (See Section 12.3, Appendix 3) must be followed. 
5.4.1.4. 
General Guidance Restart 
• The definition restart is not always clear cut in medical practice. Restarts should 
be limited to cases in which there is clear evidence that the underlying cause of 
the liver event is not related to study drug.  
• For long-acting agents, a restart may actually be continuation of therapy rather 
than a true re-start due to the timeframe between dose administration relative to 
decision making on allowing a restart. 
• If protocol defined stopping criteria for liver chemistry elevations are met 
(Section 5.4.1), study drug must be stopped. Participants who meet liver 
chemistry stopping criteria should not be retreated with investigational product 
unless an exemption has been approved by the VSLC.  The guideline for Restart 
approved by the VSLC, which is maintained as a separate document must be 
followed. 
• If the restart is approved by the VSLC in writing, the participant must be provided 
with a clear description of the possible benefits and risks of drug administration, 
including the possibility of recurrent, more severe liver injury or death.  
• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• The participant must also provide signed informed consent specifically for the IP 
restart. Documentation of informed consent must be recorded in the study chart. 
• Study drug must be administered at the dose specified by the VSLC. 
• Participants approved by the VSLC for restart of IP must return to the clinic once 
a week for liver chemistry tests for a minimum of one month and thereafter for as 
long as clinically indicated and then laboratory monitoring may resume as per 
protocol. Longer durations of close monitoring may be required for long-acting 
IP. 
Drug Restart 
“Drug restart” can be approved by the VSLC for defined non-drug-induced liver injury 
if no evidence of: 
• 
immunoallergic injury /HLA association with injury 
• 
alcoholic hepatitis 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
90 
 
Study drug must be held while labs and evaluation are completed to assess diagnosis. 
 
If participant meets liver chemistry stopping criteria do not restart the participant with 
study treatment unless: 
• ViiV Healthcare Safety and Labelling Committee (VSLC) approval is granted, 
• Ethics and/or IRB approval is obtained, if required, and 
• Separate consent for treatment restart is signed by the participant. 
Refer to 12.3for full guidance. 
Background 
• Restarts should be limited to cases in which there is clear evidence that the 
underlying cause of the liver event is not related to study drug.  
• For long-acting agents, a restart may actually be continuation of therapy rather 
than a true re-start due to the timeframe between dose administration relative to 
decision making on allowing a restart. 
• If protocol defined stopping criteria for liver chemistry elevations are met 
(Section 12.3), study drug must be stopped. Subjects who meet liver chemistry 
stopping criteria should not be retreated with investigational product unless an 
exemption has been approved by the VSLC.  The algorithm for restart is 
described in Section 12.3 and summarised in Figure 9. 
• If the restart is approved by the VSLC in writing, the subject must be provided 
with a clear description of the possible benefits and risks of drug administration, 
including the possibility of recurrent, more severe liver injury or death.  
• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• The subject must also provide signed informed consent specifically for the IP 
restart. Documentation of informed consent must be recorded in the study chart. 
• Study drug must be administered at the dose specified by the VSLC. 
• Subjects approved by the VSLC for restart of IP must return to the clinic once a 
week for liver chemistry tests for a minimum of one month and thereafter for as 
long as clinically indicated and then laboratory monitoring may resume as per 
protocol. Longer durations of close monitoring may be required for long-acting 
IP. 
Refer to Section 12.3for full guidance.  
Drug Restart Following Transient Resolving Liver Events Not Related to IP 
Approval by the VSLC for drug restart or additional IM administration can be considered 
where: 
• Abnormalities in liver chemistries have a clear underlying cause (e.g., biliary 
obstruction, hypotension, acute viral hepatitis) and liver chemistries have 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
91 
 
significantly improved. . 
• If definitive non-study drug related diagnosis, restart will be considered once ALT 
<3x ULN (for participants with baseline ALT <1.5x ULN) or <3x baseline ALT 
value (for participants with baseline ALT >1.5x UNL). 
• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• If restart of drug or continuation of LA dosing is approved by the VSLC in 
writing, the participant must be provided with a clear description of the possible 
benefits and risks of drug administration, including the possibility of recurrent, 
more severe liver injury or death. 
• The participant must also provide signed informed consent specifically for the 
restart.  Documentation of informed consent must be recorded in the study chart. 
• Study drug must be administered at the dose specified by the VSLC. 
Participants approved by the VSLC for restarting or re-dosing IP must return to the clinic 
once a week for liver chemistry tests for a minimum of one month and thereafter for as 
long as clinically indicated and then laboratory monitoring may resume as per protocol.  
If protocol defined stopping criteria for liver chemistry elevations are met, study drug 
must be stopped. 
See Section 12.3, Appendix 3 for full guidance. 
5.4.2. 
QTc Stopping Criteria 
A participant who has a QTc interval >550 msec considered causally related to IP will be 
withdrawn from the study.  The QTc should be based on averaged QTc values of 
triplicate electrocardiograms obtained over a brief (e.g., 5 to 10 minute) recording period.   
If an alternative cause of the QT prolongation is determined (e.g., participant receiving 
drug known to cause prolonged QT or TdP), the IP may be restarted (or continued) after 
consultation and agreement with the Medical Monitor.  
The same QT correction formula must be used for each individual participant to 
determine eligibility for and discontinuation from the study.  This formula may not be 
changed or substituted once the participant has been enrolled. 
• 
For example, if a participant is eligible for the protocol based on QTcB, then 
QTcB must be used for discontinuation of this individual participant as well. 
• 
Once the QT correction formula has been chosen for a participant’s eligibility, 
the same formula must continue to be used for that participant for all QTc data 
being collected for data analysis.  Safety ECGs and other non-protocol specified 
ECGs are an exception.   
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
92 
 
5.4.3. 
Virologic Failure 
Following randomization into the Maintenance Phase, no changes, or intensification of 
ART will be permitted prior to protocol-defined virologic failure (one switch allowed 
during Induction Phase for toxicity / tolerability management – See Section 6.8).  Only 
plasma HIV-1 RNA values determined by the central laboratory will be used to assess 
virologic failure.  Baseline plasma HIV-1 RNA is the assessment completed on the first 
day of the Induction Phase.  The definition of confirmed virologic failure does not apply 
to participants in the Long-Term Follow-Up Phase.  These participants will be followed 
for the potential emergence of virologic resistance only.  
5.4.4. 
Definition of Virologic Failure 
For the purposes of clinical management in this study, virologic failure is defined as any 
of the following: 
• Non-response as indicated by a less than a 1.0 log10 copies/mL decrease in plasma 
HIV-1 RNA after 4 weeks of starting the Induction Phase, which is subsequently 
confirmed, unless the plasma HIV-1 RNA is < 400 c/mL (Induction Phase 
criteria). 
• Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 
c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the 
lowest HIV-1 RNA value is ≥ 200 c/mL (Induction Phase criteria). 
• Rebound as indicated by two consecutive plasma HIV-1 RNA levels ≥ 200 c/mL 
after prior suppression to < 200 c/mL.  
5.4.5. 
Managing Virologic Failure 
Inadequate adherence is a common cause for virologic failure, and should be explored as 
a first step in the management of study participants (e.g., at the first indication of 
inadequate virologic response or rebound). 
5.4.5.1. 
HIV-1 RNA Blips 
HIV-1 RNA “blips” are not usually associated with subsequent virologic failure [DHHS, 
2015].  Although the implications of persistent HIV-1 RNA levels between the lower 
level of detection and <200 c/mL are unclear, the risk of emerging resistance is believed 
to be relatively low.   
Participants with transient increases in HIV-1 RNA (‘blips’ HIV-1 RNA <200 c/mL) are 
not considered suspected virologic failures and do not require a change in therapy.   
Participants who have a HIV-1 RNA ≥ 50 c/mL and <200 c/mL at key analysis 
timepoints (Week 48, Week 96) must return to the clinic as soon as possible (but no more 
than 4 weeks from the Week 48 or Week 96 visit) for a repeat HIV-1 RNA test, such that 
the result falls within the same analysis window. 
In order to better characterize HIV-1 RNA ‘blips,’ if there is a known reason / 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
93 
 
explanation for the blip (e.g. immunization, allergies, etc), the study team should be 
notified of the reason and case context. 
If the Investigator has concerns regarding persistent low level viremia (HIV-1 RNA 
≥50 c/mL and <200 c/mL), the Medical Monitor should be contacted to discuss 
participant management.  Following discussion with the Medical Monitor, additional 
viral load testing may be performed between visits to determine the appropriate 
participant disposition for the next scheduled visit (e.g. if additional injections should be 
administered). 
5.4.5.2. 
Suspected Virologic Failure 
Upon notification that a participant’s HIV-1 RNA plasma level meets any of the 
definitions of suspected virologic failure, the Investigator should confirm the definition is 
met by initiating a repeat of the HIV-1 RNA assessment.   
The following guidelines should be followed for scheduling confirmatory HIV-1 RNA 
testing in an effort to avoid false-positive results:  
• Confirmatory testing should be scheduled 2 to 4 weeks following resolution of 
any intercurrent illness, during which time the participant should receive full dose 
of all IP. 
• Confirmatory testing should be scheduled at least 4 weeks following any 
immunization, during which time the participant should receive full dose of all IP. 
• If therapy is interrupted* due to toxicity management, non-compliance, or other 
reasons, confirmatory testing should be scheduled 2 to 4 weeks following 
resumption of full dose of all IP. 
• The participant should have received full dose of IP for at least 2 weeks at the 
time confirmatory plasma HIV-1 RNA testing is done. 
*Note:  treatment interruption guidelines above may not apply for participants on CAB 
LA + RPV LA treatment.  The study team should be contacted to discuss any treatment 
interruptions for participants meeting the definition of virologic failure. 
In addition, the Investigator should query the participant regarding intercurrent illness, 
recent immunization, or interruption of therapy.   
Sites should contact the Medical Monitor to discuss individual participants, 
whenever necessary. 
5.4.5.3. 
Confirmed Virologic Failure 
Participants who have confirmed virologic failure must be discontinued from the 
Induction, Maintenance or Extension Phase of the study.  However, participants who 
have received at least one dose of CAB LA or RPV LA prior to confirming virologic 
failure will remain in the study on oral HAART in the Long-Term Follow Up Phase (see 
Section 4.2.6). 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
94 
 
A plasma sample from the suspected virologic failure visit as well as the first day of the 
Induction Phase (Baseline) will be sent for genotypic and phenotypic resistance testing 
and the result made known to the Investigator when available.  A plasma sample from the 
confirmation visit will be obtained for storage.  This sample may be used for possible 
future analyses; e.g., for genotypic and phenotypic analyses of participants who 
experience virologic failure. 
5.5. 
Participant and Study Completion 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition.  
Participants are considered to have completed the study if they satisfy one of the 
following:  
• Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including the Week 100 visit, and did not enter the Extension 
Phase; 
• Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including the Week 100 visit, and entered and completed the 
Extension Phase (defined as remaining on study until commercial supplies of 
CAB LA + RPV LA become locally available or development of CAB LA + RPV 
LA is terminated). 
Participants who withdraw from CAB LA + RPV LA and go into the Long-Term Follow 
Up Phase will be considered to have prematurely withdrawn from the study, even if they 
complete the 52 week follow-up phase. 
Safety Follow Up Visit: 
In addition to the 52 week Long-Term Follow-Up Phase required for participants 
randomized to CAB LA + RPV LA, an in-clinic or telephone Follow-Up visit will be 
conducted as described below.  
1. Where marketed CAB LA + RPV LA is locally available: Safety Follow Up 
Visit is required for subjects completing the study (regardless of whether subjects 
are transitioning to CAB LA + RPV LA marketed product or alternative 
HAART). It should be conducted approximately 2-4 weeks after the last dose of 
IP to assess HIV associated conditions, AEs, Concomitant medications, ISR AEs 
after the last injection and the plan to transition to marketed product. This visit 
may be conducted in person or by telephone. Ensure that relevant eCRF forms 
(including the Conclusion Visit) are updated/completed. 
2. Where marketed CAB LA + RPV LA is not yet locally available: 
a. Safety Follow Up Visit should be conducted approximately 2-4 weeks 
after the last dose of IP and may be conducted in person or by telephone. 
Ensure relevant eCRF forms (including the Conclusion Visit) are 
updated/completed. This visit is only required if the subject: 
i. Has ongoing AEs, SAEs related and not related to study drug and 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
95 
 
also any laboratory abnormalities that are considered to be AEs or 
potentially harmful to the participant, at the last on-study visit 
AND 
ii. Is not planning to attend additional study visits after the last IP 
injection (i.e. Withdrawal visit, Long Term Follow Up visits) 
where the ongoing AEs/SAEs/lab abnormalities can be assessed.  
b. Safety Follow Up Visit is not required if the subject enters the Long Term 
Follow Up Phase. Note: If the first LTFU visit after the last injection is 
scheduled more than 3 months after the last dose of IP, please consult the 
Medical Monitor to advise if the Safety Follow Up Visit is still required. 
6. 
STUDY TREATMENT 
6.1. 
Investigational Product and Other Study Treatment 
The term ‘study treatment’ is used throughout the protocol to describe any combination 
of products received by the participant as per the protocol design.  Study treatment may 
therefore refer to the individual study treatments or the combination of those study 
treatments. 
In this study, investigational product (IP) refers to oral ABC/DTG/3TC single tablet 
regimen (or alternately DTG), oral CAB, and CAB LA, which will be supplied by GSK 
and oral RPV and RPV LA which will be supplied by Janssen Pharmaceuticals.  The dual 
NRTI background therapy that is administered with single entity DTG is not considered 
IP. 
The contents of the labels will be in accordance with all applicable regulatory 
requirements. 
Under normal conditions of handling and administration, investigational product is not 
expected to pose significant safety risks to site staff.  Take adequate precautions to avoid 
direct eye or skin contact and the generation of aerosols or mists.  Notify the monitor of 
any unintentional occupational exposure.  A Material Safety Data Sheet (MSDS) 
describing the occupational hazards and recommended handling precautions will be 
provided to site staff if required by local laws or will otherwise be available from GSK 
upon request. 
Investigational product must be stored in a secure area under the appropriate physical 
conditions for the product.  Access to and administration of the investigational product 
will be limited to the investigator and authorised site staff.  Investigational product must 
be dispensed or administered only to participants enrolled in the study and in accordance 
with the protocol.  For further details on IP storage, access, and administration refer to 
SPM. 
6.1.1. 
Cabotegravir (CAB) – Tablet 
CAB is manufactured by GSK and is formulated as white to almost white oval shaped 
film coated 30 mg tablets for oral administration, packaged in high density polyethylene 
(HDPE) bottles with desiccant and child-resistant closure that include an induction seal.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
96 
 
CAB tablets will be packaged in bottles of 30 tablets.  Participants must keep all IP in its 
original pack container.  GSK will notify sites if and when data are available to support 
the use of pill boxes.  CAB tablets are to be stored according to the product label. 
CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline 
cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-
coat.  The white film-coating contains hypromellose, titanium dioxide and polyethylene 
glycol. 
6.1.2. 
Rilpivirine (RPV) - Tablet 
RPV [Edurant Prescribing Information, 2018) is provided by Janssen Research & 
Development, LLC, a division of Janssen Pharmaceuticals as 25 mg tablets that are off-
white, round, biconvex, film-coated and debossed on one side with “TMC” and the other 
side with “25”.  RPV is manufactured by Janssen -Cilag S.p.A, Latina, Italy.  RPV will 
be provided as globally marketed product, including US and the European Union.  RPV 
will be overlabeled and packaged in bottles of 30 tablets.  RPV tablets are to be stored 
according to the product label. 
Each tablet contains 27.5 mg of rilpivirine hydrochloride, which is equivalent to 25 mg of 
RPV.  Each tablet also contains the inactive ingredients croscarmellose sodium, lactose 
monohydrate, magnesium stearate, polysorbate 20, povidone K30 and silicified 
microcrystalline cellulose.  The tablet coating contains hypromellose 2910 6 mPa.s, 
lactose monohydrate, PEG 3000, titanium dioxide and triacetin. 
6.1.3. 
Cabotegravir – Injectable Suspension (CAB LA) 
CAB LA is manufactured by GSK and is a sterile white to slightly pink suspension 
containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) 
injection.  The product is packaged in a 3 mL USP Type I glass vial with a 13 mm gray 
stopper and aluminium seal.  Each vial is for single-dose use containing a withdrawable 
volume of 2.0 mL, and does not require dilution prior to administration.  CAB LA 
injectable suspension is to be stored according to the product label. 
CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 
3350, mannitol, and water for injection. 
6.1.4. 
Rilpivirine – Injectable Suspension (RPV LA) 
RPV LA (also named JNJ-16150108-AAA), 300 mg/mL Extended Release Suspension 
for Injection (G001), is provided by Janssen Research & Development, LLC, a division 
of Janssen Pharmaceuticals as a sterile white suspension containing 300 mg/mL of RPV 
as the free base.  The route of administration is by intramuscular (IM) injection.  RPV LA 
is packaged in a single use 4 mL USP Type I glass vial with a 13 mm grey stopper and 
aluminium seal.  Each vial contains a nominal fill of 2.0 mL, and does not require 
dilution prior to administration.  RPV LA injectable suspension should be stored 
according to the product label and should be protected from light. 
RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
97 
 
monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water 
for injection. 
6.1.5. 
ABC/DTG/3TC STR - Tablet 
ABC/DTG/3TC STR is manufactured by GSK.  Each film-coated tablet contains abacavir 
sulphate equivalent to 600 mg of abacavir, dolutegravir sodium equivalent to 50 mg 
dolutegravir, and 300 mg of lamivudine.  ABC/DTG/3TC tablets are purple, biconvex, 
oval, debossed with “572 Tri” on one side.  ABC/DTG/3TC will be packaged in bottles 
of 30 tablets.  ABC/DTG/3TC should be stored and dispensed in the original container, 
protected from moisture, are packaged with a desiccant which should not be removed.  
ABC/DTG/3TC tablets are to be stored according to the product label. 
The inactive ABC/DTG/3TC tablet ingredients include D-mannitol, magnesium stearate, 
microcrystalline cellulose, povidone, and sodium starch glycolate.  The tablet film-
coating contains the inactive ingredients iron oxide black, iron oxide red, macrogol/PEG, 
polyvinyl alcohol – part hydrolyzed talc, and titanium oxide. 
6.1.6. 
Dolutegravir (DTG) – Tablet 
Dolutegravir is manufactured by GSK and will be provided to participants who are HLA-
B*5701 positive (to be used in combination with 2 NRTIs).  DTG 50 mg tablets are 
yellow, round, biconvex, film-coated tablets.  The tablets contain 52.62 mg dolutegravir 
sodium salt, which is equivalent to 50 mg dolutegravir free acid.  Each tablet is debossed 
with “SV 572” on one side and “50” on the other side.   The tablets are packaged into 
high density polyethylene (HDPE) bottles with induction seals and child-resistant 
closures.  Each bottle contains 30 tablets and a desiccant.  DTG tablets are to be stored 
according to the product label. 
Each tablet of DTG also contains the following inactive ingredients: D-mannitol, 
microcrystalline cellulose, povidone K29/32, sodium starch glycolate, and sodium stearyl 
fumarate.  The tablet film-coating contains the inactive ingredients iron oxide yellow, 
macrogol/PEG, polyvinyl alcohol-part hydrolyzed, talc, and titanium dioxide. 
6.2. 
Treatment Assignment 
Informed consent must be obtained prior to any study procedures, including Screening 
visit activities.  Participants will be assigned to study treatment in accordance with the 
randomization schedule.  The randomization schedule, including stratification, will be 
generated using the GSK validated randomization software RANDALL NG.  The 
randomization schedule is comprised of a series of blocks, with equal treatment 
allocation within each block, which are shared across centres via central randomization. 
Given the open-label study design, central randomization was used to eliminate selection 
bias due to foreknowledge of randomized treatment.  With central randomization, 
knowledge at a site of the randomized treatment group for previous subjects does not 
predict which treatment group will be assigned to the next randomized subject.   
At the beginning of the Maintenance Phase, randomization and study treatment 
assignment will be facilitated by the interactive response technology (IRT) through the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
98 
 
central Randomization and Medication Ordering System Next Generation (RAMOS NG).   
Following confirmation of fulfilment of eligibility to continue into the Maintenance 
Phase, study site personnel will be required to register participants using RAMOS NG for 
assignment of a unique identifier (designating the participant’s randomization code and 
treatment sequence assignment) for each participant participating in the study.  A unique 
treatment number will be assigned for each participant participating in the study. 
Participants will be randomized in a 1:1 ratio to CAB LA + RPV LA or to remain on 
ABC/DTG/3TC through Week 100, in accordance with the computer generated 
randomization schedule.  Randomization will be stratified by participants’ Baseline 
HIV-1 RNA (<100,000, ≥100,000 c/mL) and gender at birth.  In addition, RAMOS NG 
will facilitate the initial supply and subsequent resupply of IP to study sites. 
6.3. 
Dose and Administration 
At Day 1 (beginning of Maintenance Phase), participants will be randomly assigned to 
receive treatment with CAB LA + RPV LA or to remain on ABC/DTG/3TC.  
ABC/DTG/3TC dosing on Day 1 should occur after randomization to avoid overlap of 
regimens (in the event that the participant is assigned to the CAB LA + RPV LA 
treatment arm).  However, if the participant takes ABC/DTG/3TC prior to coming into 
the clinic, randomization and initiation of oral CAB and RPV should continue as planned 
on Day 1. Regardless of treatment arm assignment, the investigator should instruct all 
participants on the importance of treatment adherence.  This study has an open-label 
design.  Following is a table of dosing and administration for all treatment arms: 
Induction Phase (Week [-20] to Day 1) – All Subjects 
Week (-20) to Day 1 
(1 tablet once daily) 
Take 1 tablet ABC 600 mg / DTG 50 mg / 3TC 300 mg once 
daily with or without food 
*Take Day 1 dose after randomization. 
Maintenance Phase (Day 1 to Week 100) 
CAB LA + RPV LA Arm  
Oral Lead-in 
Day 1 to Week 4b 
(2 tablets once daily) 
Take 1 tablet CAB 30 mg once daily. 
Take 1 tablet RPV 25 mg once daily. 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injection (Loading Dose) – Week 4b^ 
Week 4b^ 
(two 3 mL injections once) 
Receive last dose of oral CAB + RPV 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
99 
 
Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
Receive RPV LA 900 mg given as 1 X 3 mL IM injection  
Maintenance Injections – Every 4 Weeks following Week 4b 
Week 8 to Week 100 
(two 2 mL injections every 4 
weeks) 
Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
ABC/DTG/3TC Once Daily Arm* 
Day 1 to Week 100 
(1 tablet once daily) 
Take 1 tablet ABC 600 mg / DTG 50 mg / 3TC 300 mg once 
daily with or without food 
*Take Day 1 dose after randomization. 
Extension Phase (Week 100 through End of Study)  
CAB LA + RPV LA Arm – continue IM dosing Every 4 Weeks+ 
ABC/DTG/3TC Arm (Transition to CAB LA + RPV LA)* - Optional Oral Lead-In 
Dosing If Using Optional Oral Lead-In 
Week 100 to Week 104b 
(2 tablets once daily) 
Take 1 tablet CAB 30 mg once daily. 
Take 1 tablet RPV 25 mg once daily. 
 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injection (Loading Dose) – Week104b^ - Optional Oral Lead-In 
Week 104b^ 
(two 3 mL injections once) 
Receive last dose of oral CAB + RPV 
 
Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
Receive RPV LA 900 mg given as 1 X 3 mL IM injection  
Maintenance Injections – Every 4 Weeks following Week 104b – Optional Oral Lead-In 
Week 108 forward 
(two 2 mL injections every 4 
weeks) 
Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
 
Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
ABC/DTG/3TC Arm (Transition to CAB LA + RPV LA)* 
Direct to Inject Dosing - if Not Using Oral Lead-In 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
100 
 
First Injection (Loading Dose) – Week100^ - No Oral Lead-In 
Week 100^ 
(two 3 mL injections once) 
Receive last dose of oral ABC/DTG/3TC 
Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
Receive RPV LA 900 mg given as 1 X 3 mL IM injection 
Maintenance Injections – Every 4 Weeks following Week 100 – No Oral Lead-In 
Week 104a forward 
(two 2 mL injections every 4 
weeks) 
Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
 
Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
a. 
+until locally approved and commercially available, the participant no longer derives clinical benefit, the 
participant meets a protocol-defined reason for discontinuation or until development of CAB LA or RPV LA is 
terminated. 
b. 
*Participants randomized to ABC/DTG/3TC will be given an option to switch to CAB LA + RPV LA (or be 
discontinued from the study) at Week 100.  If the participant decides not to continue participation in the study, 
arrangements for off-study ART should be made in advance of this Week 100 visit. 
c. 
^See Section 6.6.1 for Dosing Considerations for CAB LA + RPV LA 
The CAB + RPV oral regimen should be administered together once daily at 
approximately the same time each day with a meal.   
6.4. 
Blinding 
This will be an open-label study and therefore no blinding is required.  No study 
summary data, according to actual randomized treatment groups, will be available to 
sponsor staff prior to the planned Week 48 analysis.  
6.5. 
Packaging and Labeling 
The contents of the label will be in accordance with all applicable regulatory 
requirements. 
6.6. 
Preparation/Handling/Storage/Accountability 
In accordance with local regulatory requirements, the investigator, institution, or the head 
of the medical institution (where applicable) is responsible for study treatment 
accountability, reconciliation, and record maintenance (i.e. receipt, reconciliation and 
final disposition records).  The amount of IP dispensed and/or administered to study 
participants, the amount returned by study participants, and the amount received from and 
returned to GSK must be documented. 
Only participants enrolled in the study may receive study treatment and only authorized 
site staff may supply or administer study treatment.  All study treatments must be stored 
in a secure environmentally controlled and monitored (manual or automated) area in 
accordance with the labelled storage conditions with access limited to the investigator 
and authorized site staff. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
101 
 
IP accountability will be evaluated using pill counts of unused IP for participants 
receiving oral treatment (ABC/DTG/3TC [or alternate DTG], oral CAB, oral RPV).  Pill 
counts will not be done for the dual NRTIs taken with DTG, as these will not be provided 
centrally.  IP accountability will be conducted each time the participant receives a 
new/refill supply of IP, when the participant completes oral CAB and RPV (including 
oral bridging supply), and through the Withdrawal visit, study completion, or Week 104b 
of the Extension Phase.   
IP accountability for participants receiving CAB LA + RPV LA will be performed at the 
‘vial’ level (e.g. correct number of vials were used for each injection).  There may be a 
small amount of solution remaining in the vial which does not require quantification.  
Used vials may be discarded at the site once accountability is complete. 
Product accountability records must be maintained throughout the course of the study. 
• 
Under normal conditions of handling and administration, IP is not expected to pose 
significant safety risks to site staff.  Take adequate precautions to avoid direct eye or 
skin contact and the generation of aerosols or mists.  In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or GSK study 
contact. 
• 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK. 
• 
Further guidance and information for final disposition of unused study treatment are 
provided in the SPM.  
• 
Please refer to Appendix 9 in Section 12.9. for study management information 
during the COVID-19 pandemic. 
6.6.1. 
Dosing Considerations for CAB LA + RPV LA 
Vials of CAB LA and RPV LA are each supplied as a suspension and need no further 
dilution or reconstitution.  Since RPV LA requires refrigeration, sites should allow the 
vial to come to approximately room temperature prior to injecting.  Sites should gently 
invert the vials a few times to re-suspend sediments and allow bubbles to subside, and 
then use a syringe to withdraw the required volume of suspension for IM injection.   
All injections must be given intramuscularly in the gluteus medius.  Sites may use their 
discretion as to where in the gluteus muscle each injection is given according to 
individual participant circumstance.  If possible, CAB and RPV injections should be 
given on different sides of the body (e.g. left or right gluteus medius), or spaced 
approximately 2 cm from one another, from the site of any previous injection or any 
injection site reaction.  The time, side, and location of injections will be captured in the 
eCRF.   
IM injections should be administered at a 90 degree angle into the gluteus medius muscle 
using a needle of appropriate gauge and length (recommended 1.5” 23 gauge needle for 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
102 
 
CAB LA and a 1.5” 23 gauge needle for RPV LA in most participants).  The needle 
should be long enough to reach the muscle mass and prevent study drug from seeping 
into subcutaneous tissue, but not so long as to involve underlying nerves, blood vessels, 
or bone.  Variable needle lengths and/or needles with different gauge (CAB LA: 21 to 
25 gauge; RPV LA: 21 to 23 gauge) are permitted if needed to accommodate individual 
body type.  Longer needle lengths may be required for participants with higher body 
mass indexes (BMIs, example > 30), to ensure that injections are administered 
intramuscularly as opposed to subcutaneously.  BMI, needle gauge and length used will 
be collected in the eCRF. Additional details of the injection device used by sites for IM 
administration, including, but not limited to functional performance, may also be 
collected within the eCRF. 
At the Week 4b visit, participants should be dosed with the loading dose IM regimen 
(CAB LA 600 mg + RPV LA 900 mg) within 2 hours of taking the last oral CAB + RPV 
dose where possible.  The same should apply to participants switching from the oral 
regimen to an IM regimen at Week 104b. 
Should IM maladministration, specifically overdose or inadvertent IV dosing, be 
suspected at any time, the participant will stay onsite for approximately 2 to 3 hours post 
dose for safety monitoring.  An ECG will be performed at approximately 2 hours post 
dose.  The Medical Monitor will be notified in the event of a suspected 
maladministration.   
In the event of suspected intravenous administration, a PK sample will also be drawn 
approximately 2 hours post dose for evaluation of CAB and RPV plasma concentrations. 
Appropriate, confirmation of successful IM administration will also be captured in the 
eCRF.  
Additional dosing instructions and considerations can be found in the SPM. 
6.7. 
Compliance with Study Treatment Administration 
IP accountability will be evaluated using pill counts of unused IP (CAB and RPV tablets 
at the end of oral dosing [including bridging supply], and ABC/DTG/3TC [or alternate 
DTG]).  This assessment will be conducted each time the participant receives a supply of 
oral study medication.  These data will be recorded in the participant’s eCRF.  Treatment 
start and stop dates will also be recorded in the eCRF. 
When participants are dosed with CAB LA and RPV LA at the site, they will receive IM 
injections directly from the investigator or designee, under medical supervision.  The date 
and time of each injection of CAB LA and RPV LA administered in the clinic will be 
recorded in the source documents.  These data will be recorded in the participant’s eCRF.  
The dose of study treatment and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study treatment.   
IP accountability (e.g. pill counts) will not be assessed for alternate NRTIs taken with 
single entity DTG, or during the Long-Term Follow-Up Phase. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
103 
 
Due to the long acting nature of the CAB LA and RPV LA, it will be imperative that the 
participant is compliant with dosing visits.  As part of the screening and participant 
selection process, Investigators must discuss with potential participants the long-term 
commitments for the study, and the importance of adhering to treatment regimens. 
Investigators must have plans in place for adherence counselling for both treatment arms.   
6.8. 
Protocol Permitted Substitutions 
Participants who are HLA-B*5701 positive at the Screening visit are allowed to enter the 
study on DTG and an approved dual-NRTI backbone that does not contain abacavir (e.g. 
TDF/FTC or TAF/FTC).  This regimen may be supplied regionally by GSK or 
reimbursement will be provided as needed.  
During the Induction Phase, prior to randomization into the Maintenance Phase at Day 1, 
one switch to an alternate approved background NRTI therapy is allowed for toxicity or 
tolerability management.  The date of a decision to switch the NRTI background therapy 
for toxicity or tolerability management must be documented in the eCRF.  Switches of a 
background NRTI for any other reason are not permitted in the study.  Local prescribing 
information should be consulted for information regarding use of alternative background 
medications.   
For consistency with prescribing information, dose reductions of lamivudine (or 
emtricitabine if used as alternate NRTI) are permitted throughout the study in the context 
of renal insufficiency, e.g. as needed for creatinine clearance <50 mL/min  (See 
Section 4.2.7. for additional information). 
No other dose reductions, modifications, or changes in the frequency of any components 
of any regimen will be allowed during the Maintenance and Extension Phases of the 
study.   
Please refer to Appendix 9 in Section 12.9. for study management information during the 
COVID-19 pandemic. 
Protocol waivers or exemptions are not allowed.  Therefore, adherence to the study 
design requirements are essential and required for study conduct. 
6.8.1. 
Oral Bridging 
In exceptional circumstances, to address pre-planned missed CAB LA + RPV LA dosing 
visits, following consultation with the Medical Monitor, Investigators may provide daily 
oral CAB 30 mg and RPV 25 mg as a short-term “bridging” strategy for subjects who 
have begun CAB LA + RPV LA and who will miss a subsequent scheduled LA injection.  
In certain circumstances (e.g., prior to steady state dosing and following a >4 week oral 
bridge) repeating the loading doses of CAB IM and RPV IM may be required.  Should a 
subject require “oral bridging”, sites must contact the Medical Monitor for guidance with 
treatment and dosing strategies prior to a missed CAB LA + RPV LA dose.   
Please refer to Appendix 9 in Section 12.9. for study management information during the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
104 
 
COVID-19 pandemic. 
6.9. 
Interruption of Study Treatment 
IP may be interrupted at the discretion of the Investigator in the event of an AE, 
according to the severity of the AE. 
If one or more antiretroviral medications is held due to toxicity or adverse events, all 
antiretroviral medications must be held to reduce the risk of development of resistance 
taking into account both the length of the planned interruption and the pharmacokinetic 
half-life of each antiretroviral of the regimen, in a way to minimize the risk of 
development of resistance. 
It is important to note that keeping to the participant’s visit schedule is a very 
important component to the study.   
Note: All decisions regarding dose interruption / resumption must be discussed with 
the Medical Monitor in advance. 
6.9.1. 
IM Dosing 
Participants receiving CAB LA and RPV LA are anticipated to be at high risk for 
development of virologic resistance if ART is interrupted.  The time period during which 
participants are at risk for development of virologic resistance may be determined by the 
period between when drug levels fall below therapeutic values and when they fall below 
levels which exert selective pressure on HIV.  This time period will vary by ART agent 
and is dependent upon effective concentration, inhibitory concentration and half-life. 
Plasma concentrations of both LA drugs may be measurable for more than one year in 
some participants following IM injections.  Any interruption in IM dosing should be 
discussed with the Medical Monitor.  Investigators should ensure that the participant 
initiates alternative highly active ART (e.g. in the Long-Term Follow-Up Phase) to 
minimize the risk of developing resistance as concentrations of CAB and RPV decline 
over time. 
IM dosing is expected to occur during the week in which the participant’s projected visit 
falls (as according to the date of the first injections [Week 4b]).  The first injections of 
CAB LA (600 mg) and RPV LA (900 mg) are administered at Week 4b (can be 
performed as soon as lab results from Week 4a become available).  The second and third 
IM injections (CAB LA 400 mg + RPV LA 600 mg) will be performed at Week 8 and 
Week 12.  There will be a one week dosing window for the second and third IM 
injections such that the second injections occur within the window of Week 7 to Week 8, 
but not later than Week 8, and the third injections occur within the window of Week 11 to 
Week 12, but no later than Week 12.  Subsequent injections (CAB LA 400 mg + RPV 
LA 600 mg) will occur every 4 weeks thereafter, with a (+ or -) 7 day dosing window, 
from the projected visit date, being allowed (but not preferred).  In addition, following 
the Week 12 injections, time between injection visits should be limited to a maximum of 
5 weeks.  The Medical Monitor must be contacted if the length of time between injections 
exceeds, or is projected to exceed 5 weeks.  For the duration of the study, the injection 
visit schedule should be maintained according to the first IM injections given at Week 4b. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
105 
 
At one-week post dose visits (Week 5, Week 41, and Week 101), there is no defined visit 
window, rather visits should occur approximately one week from the last injection. 
• Dosing may occur without consultation from the Medical Monitor if performed 
within the (+ or -) 7 day window.   
• Any request for the visit/dosing to occur outside of the allowed window must be 
discussed and agreed with the Medical Monitor prior to dosing.  In the event of a 
late dose, a revised dosing schedule for subsequent dosing may be required and 
will be communicated to the site staff at the time of approval for continued 
dosing.  Temporary switch to oral dosing of CAB and/or RPV may be an option 
based on individual participant circumstance as described in Section 6.8.   
• See the SPM for scheduling guidance and further information and examples. 
Note: All decisions regarding dose interruption/ resumption must be discussed with 
the Medical Monitor in advance. 
Transition from ABC/DTG/3TC to IM Dosing into the Extension Phase: 
Participants who were randomized to ABC/DTG/3TC and are eligible to enter the 
Extension Phase will transition to IM dosing at or after Week 100.  The transition from 
ABC/DTG/3TC to CAB LA + RPV LA can be completed with or without an oral lead-in 
prior to commencement of injectable treatment.  The participant decision will be taken in 
consultation with the investigator and appropriately documented.  In order to ensure no 
interruption in study treatment, the transition into Extension should be performed as 
follows: 
Participants Transitioning Directly to Injections in the Extension Phase:   
Central lab results and safety parameters from the Week 96 visit must be available and 
reviewed for participants who choose to transition direct to injection.  If a clinical 
chemistry retest is required based on Week 96 labs, the retest should be performed as 
soon as possible (and preferably no later than 7 days following Week 96).  Participants 
will remain on oral ABC/DTG/3TC until the Week 100 injection visit, and until any 
required Week 96 retest results are available for review. 
At Week 100, eligible participants will take the last dose of ABC/DTG/3TC (or DTG + 
2 NRTIs), and receive the first injections of CAB LA (600 mg) + RPV LA (900 mg) as 
initial loading doses.  Clinical chemistries will also be assessed at Week 100.  At 
Week 101, participants will return to the clinic for PK and safety assessments including 
clinical chemistries.  The second and third injections (CAB LA 400 mg + RPV LA 
600 mg) will be administered at Week 104a and Week 108.  There will be a one week 
dosing window for the second and third IM injections such that the second injections 
occur within the window of Week 103 to Week 104a, but not later than Week 104a, and 
the third injections occur within the window of Week 107 to Week 108, but no later than 
Week 108.  Subsequent injections (CAB LA 400 mg + RPV LA 600 mg) will occur 
every 4 weeks thereafter, from the projected visit date, with a (+ or -) 7 day dosing 
window being allowed (but not preferred).  Following the Week 108 injection, the 
interval between injection visits should be limited to a maximum of 5 weeks.  The 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
106 
 
Medical Monitor must be contacted if the length of time between injections exceeds, or is 
projected to exceed, 5 weeks. 
Participants Receiving Optional Oral Lead-In in the Extension Phase: 
At Week 100, eligible participants who after discussion with the investigator, choose to 
receive the optional oral lead-in will begin a 4 week lead-in of oral CAB 30 mg + oral 
RPV 25 mg once daily.  It is not necessary to dose ABC/DTG/3TC on the day the 
participant begins the oral lead-in with CAB + RPV.  However, if the participant takes 
ABC/DTG/3TC prior to coming into the clinic, initiation of oral CAB and RPV should 
continue as planned. 
At Week 104a, assessments including clinical chemistries will be performed.  At 
Week 104b, participants will return to clinic, take the last dose of oral CAB + RPV, and 
receive the first injections of CAB LA (600 mg) + RPV LA (900 mg) (within 2 hours of 
the final oral dose of CAB + RPV).  The Week 104b visit can be performed as soon as 
lab results from Week 104a become available.  The second and third IM injections (CAB 
LA 400 mg + RPV LA 600 mg) will be performed at Week 108 and Week 112.  There 
will be a one week dosing window for the second and third IM injections such that the 
second injections occur within the window of Week 107 to Week 108, but not later than 
Week 108, and the third injections occur within the window of Week 111 to Week 112, 
but no later than Week 112.  Subsequent injections (CAB LA 400 mg + RPV LA 
600 mg) will occur every 4 weeks (monthly) thereafter, with a (+ or -) 7 day dosing 
window, from the projected visit date, being allowed (but not preferred).  In addition, 
following the Week 112 injections, time between injection visits should be limited to a 
maximum of 5 weeks.  The Medical Monitor must be contacted if the length of time 
between injections exceeds, or is projected to exceed 5 weeks.  For the duration of the 
study, the injection visit schedule should be maintained according to the first IM 
injections given at Week 104b. 
6.9.2. 
Oral Dosing 
Visits for participants on the oral dosing arm are expected to occur as projected according 
to the Baseline visit.  There is a (+ or -) 3 day visit window, from the projected visit date 
(for all oral dosing in the Induction, Maintenance, and Extension Phases of the study).  
However, the number of tablets dispensed should be considered when scheduling the next 
visit. 
Any interruption in therapy (scheduling conflicts, life circumstances, etc) during any oral 
dosing period that is greater than 7 consecutive days must be discussed with the Medical 
Monitor prior to resumption of therapy.  The Medical Monitor must be contacted upon 
site staff becoming aware of resumption in therapy, if therapy was resumed without prior 
approval. 
Visits for participants in the Long Term Follow Up are expected to occur as projected 
according to the last injection.  There is no calendar defined visit window in the Long 
Term Follow Up Phase.   
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
107 
 
6.10. 
Discontinuation of Study Treatment 
Participants unable to manage drug toxicity or tolerate investigational product must have 
IP discontinued. 
6.10.1. 
Discontinuation of ABC/DTG/3TC 
In the event of a discontinuation of an ABC-containing product for any reason, re-
initiation of this drug should be undertaken with caution.  Health care providers should 
obtain a complete history of the events surrounding the discontinuation of the ABC-
containing product.  If there are symptoms consistent with a hypersensitivity reaction, 
ABC must not be reinitiated.  If there is no evidence of a prior reaction, the participant 
may restart treatment with the ABC-containing product.  The participant and health care 
provider must be aware of the possibility of a rapid-onset hypersensitivity reaction upon 
reinitiation of ABC, which may be life-threatening or fatal, and the participant must be 
able to, if necessary, receive prompt medical evaluation (see also Section 7.4.10.12). 
6.10.2. 
Discontinuation of CAB LA or RPV LA 
 Where the CAB LA + RPV LA marketed product is not locally available, any participant 
who receives at least a single dose of CAB LA and/or RPV LA and discontinues the CAB 
LA + RPV LA regimen for any reason must enter the 52-week Long-Term Follow-Up 
Phase.  
Where CAB LA + RPV LA marketed product is locally available, only participants that 
discontinue the CAB LA + RPV LA regimen for safety-related reasons must enter the 
LTFU Phase.  
All participants must remain on suppressive highly active antiretroviral therapy 
(HAART) for at least 52 weeks after the last dose of CAB LA and/or RPV LA. (see 
Section 4.2.6.). 
6.11. 
Treatment of Study Treatment Overdose 
For this study, any tablet intake exceeding a total daily dose of CAB 30 mg will be 
considered an overdose.  For participants receiving oral RPV, any dose exceeding a total 
daily dose of 25 mg will be considered an overdose.  For participants receiving 
ABC/DTG/3TC, any tablet intake exceeding the protocol defined daily number of tablets 
(one tablet daily) will be considered an overdose.  For participants receiving DTG + 
NRTIs, any tablet count exceeding the marketed dose in local prescribing information 
will be considered an overdose. 
For CAB LA and RPV LA, any single dose in excess of the studied doses will be 
considered an overdose.   
Should IM maladministration, specifically overdose or inadvertent IV dosing, be 
suspected at any time, the participant will stay onsite for approximately 2 to 3 hours post 
dose for safety monitoring.  An ECG will be performed approximately 2 hours post dose.  
The Medical Monitor will be notified in the event of a suspected maladministration.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
108 
 
In the event of suspected intravenous administration, a PK sample will also be drawn 
approximately 2 hours post dose for evaluation of CAB and RPV plasma concentrations. 
For the purposes of this study, an overdose is not an AE (refer to Section 12.6.1) unless it 
is accompanied by a clinical manifestation associated with the overdose.  If the clinical 
manifestation presents with serious criteria, the event is a SAE (see Section 12.6.2). 
If an overdose occurs and is associated with an adverse event requiring action, all study 
medications must be temporarily discontinued until the adverse event resolves.  
The Investigator should use clinical judgement in treating overdose, as GSK is unable to 
recommend specific treatment. 
In the event of an overdose the investigator or treating physician should: 
1. contact the Medical Monitor immediately. 
2. closely monitor the participant for adverse events (AEs)/serious adverse events 
(SAEs) and laboratory abnormalities until IP can no longer be detected systemically 
(number of days will vary by compound – Medical Monitor / study team can advise). 
3. obtain a plasma sample for pharmacokinetic (PK) analysis if possible within 2 days 
from the date of the last dose of study treatment if requested by the Medical Monitor 
(determined on a case-by-case basis). 
4. document the quantity of the excess dose as well as the duration of the overdosing in 
the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant (see Section 4.2.7 for information regarding dose modifications). 
6.12. 
Treatment after the End of the Study 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition, whether or not GSK is providing 
specific post-study treatment. 
6.13. 
Concomitant Medications and Non-Drug Therapies 
Participants should be advised to notify their investigator of any current or proposed 
concomitant medication, whether prescribed or over-the-counter, because of the potential 
drug:drug interactions between such treatments and the study drugs.  The investigator 
should evaluate any potential drug:drug interactions at every visit, including reviewing 
the most current version of the investigator brochures, the U.S and/or local prescribing 
information for RPV, and ABC/DTG/3TC (or DTG + NRTIs), especially if any new 
concomitant medications are reported by participants.  All concomitant medications, 
blood products, and vaccines taken during the study will be recorded in the eCRF.  The 
minimum requirement is that the drug name, route, and the dates of administration are to 
be recorded. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
109 
 
Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study (except prohibited medications described in 
Section 6.13.1).  Chemoprophylaxis for HIV-associated conditions is encouraged, if 
appropriate, at the discretion of the participant and their physician.   
Because non-HIV vaccines may cause a temporary increase in the level of plasma HIV-1 
RNA, it is highly recommended that a vaccine, if necessary, be given during or 
immediately after a scheduled visit after all laboratory tests have been drawn.  This 
approach will minimize the risk of non-specific increases in the level of plasma HIV-1 
RNA at the next scheduled assessment. 
Other IM injectables (with exceptions below) are permitted but must be administered 
away from the site of IP administration if possible (should be spaced 2 cm or more away 
from site of IP injection). 
Antacid and H2 Antagonist Use: 
While both oral CAB and RPV have dosing requirements with antacid products 
containing divalent cations, only oral RPV has requirements for dosing with H2 
antagonists.  Since co-administration of oral CAB and RPV is required in this study, the 
most restrictive dosing requirements must be taken into consideration.  
CAB oral administration only:  Antacid products containing divalent cations (e.g., 
aluminium, calcium, and magnesium) must be taken at least 2 hours before or at least 4 
hours after CAB. 
Concurrent administration of multivitamins is acceptable. 
Oral RPV administration only:   
• Antacid products containing divalent cations (e.g., aluminium, calcium, and 
magnesium) must be taken at least 2 hours before or at least 4 hours after RPV. 
• H2-Receptor antagonists (e.g. cimetidine, famotidine, nizatidine, ranitidine) may 
cause significant decreases in RPV plasma concentrations.  H2-antagonists must 
be taken at least 12 hours before or at least 4 hours after taking RPV. 
• RPV should not be co-administered with proton pump inhibitors, such as 
esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole. 
Administration of clarithromycin, erythromycin and telithromycin is not recommended 
with RPV due to possible increase in plasma concentration of RPV due to CYP3A 
enzyme inhibition.  Where possible, alternatives such as azithromycin should be 
considered. 
Drugs that cause Torsade de Pointes (TdP) should be used with caution when taking 
rilpivirine (see SPM for list of drugs associated with TdP). 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
110 
 
ABC/DTG/3TC:  DTG should be administered 4 hours before or 6 hours after taking 
antacid or laxative products or sucralfate containing polyvalent cations (e.g., aluminum 
and magnesium) or calcium supplements.  Proton pump inhibitors and H2-Receptor 
antagonists (e.g. cimetidine, famotidine, nizatidine, ranitidine) may be used in place of 
antacids with no dosing restrictions.  Iron supplements can be taken with DTG provided 
that all three are taken together with a meal.  Under fasting conditions, DTG should be 
given 2 hours prior to OR 6 hours after iron supplements. 
Metformin concentrations may be increased by DTG.  For participants starting metformin 
after DTG, titrate as recommended in local prescribing information for DTG and monitor 
glucose control.  If starting DTG after metformin, consider dose reduction of metformin 
as needed if glucose is well controlled. 
Clinical monitoring is recommended for participants taking methadone as methadone 
maintenance therapy may need to be adjusted in some participants. 
Approved hormonal contraception may be administered. However, the investigator 
should consult local prescribing information for guidance on the use of hormonal 
contraceptives with background ART as some antiretrovirals have clinically significant 
drug interactions with these products. 
Please refer to the local prescribing information for other drugs that should be used with 
caution, require dose adjustment, or increased clinical monitoring if taken with 
ABC/DTG/3TC. 
DTG + 2 NRTIs:  For participants who are HLA-B*5701 positive and are receiving 
DTG +alternate NRTI background therapy or who have switched to alternate NRTI 
background therapy during the Induction Phase for tolerability, refer to local prescribing 
information for details regarding concurrent therapies. 
6.13.1. 
Prohibited Medications and Non-Drug Therapies 
The following concomitant medications or therapies are not permitted at any time during 
the study: 
• 
HIV immunotherapeutic vaccines are not permitted at any time during the study.  
• 
Other experimental agents, antiretroviral drugs not otherwise specified in the 
protocol, cytotoxic chemotherapy, or radiation therapy may not be administered 
(see Section 5.2).  
• 
Systemically administered immunomodulators (such as interleukin and interferon 
agents) are prohibited (a list of examples is provided in the SPM).  This includes 
topical agents with substantial systemic exposure and systemic effects.   Use of 
topical imiquimod is permitted.    
• 
Acetaminophen (paracetamol) cannot be used in participants with acute viral 
hepatitis (James, 2009). 
• 
Chronic use of systemic (oral or parenteral) glucocorticoids must be avoided due 
to the immunosuppressive effect and potential decreases in RPV plasma 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
111 
 
concentrations; however, short treatment courses with oral prednisone/ 
prednisolone/methylprednisolone (e.g. adjunctive treatment of pneumocystis 
pneumonia with 21 days of tapering prednisone) are allowed.  A single dose of 
systemic dexamethasone is permitted, but more than a single dose in a treatment 
course may cause a significant decrease in RPV plasma concentration and is 
prohibited.  Topical, inhaled or intranasal use of glucocorticoids will be allowed.   
• 
Hepatitis C infection therapy is prohibited during the Induction and Maintenance 
Phase before the Week 48 primary endpoint, and interferon-based HCV therapy is 
prohibited throughout the entire study.  Options for treatment of hepatitis C 
should be discussed with the Medical Monitor prior to initiation of therapy. 
Note: Any prohibited medications that decrease CAB or RPV concentrations should be 
discontinued for a minimum of four weeks or a minimum of three half-lives (whichever 
is longer) prior to the first dose and any other prohibited medications should be 
discontinued for a minimum of two weeks or a minimum of three half-lives (whichever is 
longer) prior to the first dose. 
For additional information on concurrent therapies and interactions suspected to be 
relevant to other antiretroviral therapy used during the study (e.g. ABC/DTG/3TC), 
please consult the current DTG Investigator brochure and local prescribing information. 
Concurrent with CAB and/or RPV 
For participants receiving either formulation of CAB and/or RPV, the following 
medications could significantly decrease the levels of CAB and/or RPV due to enzyme 
induction and therefore must not be administered concurrently:  
• Carbamazepine 
• Oxcarbazepine 
• Phenobarbital  
• Phenytoin 
• Rifabutin 
• Rifampicin / Rifampin 
• Rifapentine 
• St. John’s wort (Hypericum perforatum) 
Concurrent with RPV 
In addition, participants must discontinue the following (or change to an allowable 
alternative) while receiving treatment with RPV: 
• Oral RPV:  proton pump inhibitors, such as esomeprazole, lansoprazole, 
omeprazole, pantoprazole, rabeprazole; 
• Both Oral and RPV LA:  systemic dexamethasone (more than a single dose). 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
112 
 
If the participant cannot discontinue use or change to an allowable alternative while 
receiving treatment with RPV, the participant should not be randomized into the study. 
Please refer to the current RPV Investigator brochure and local prescribing information 
for other drugs that are prohibited, should be used with caution, require dose adjustment, 
or increased clinical monitoring if taken with oral RPV. 
Concurrent with either CAB LA or RPV LA 
In addition, for participants receiving CAB LA and RPV LA, use of anticoagulation 
agents for greater than 14 days is prohibited, with the exception of the use of 
anticoagulation for DVT prophylaxis (e.g., postoperative DVT prophylaxis) or the use of 
low dose aspirin (daily doses ≤325mg).  Systemic anticoagulation (including prophylaxis 
doses) on the day of an IM injection should be avoided. 
Concurrent with ABC/DTG/3TC 
The following medications or their equivalents may cause decreased concentrations of 
DTG.  Therefore, the following medications must not be administered concurrently with 
DTG: 
• 
Carbamazepine 
• 
Oxcarbazepine 
• 
Phenobarbital 
• 
Phenytoin 
• 
Rifampin  
• 
Rifapentine  
• 
St. John’s wort (Hypericum perforatum) 
Dofetilide and pilsicainide are prohibited as DTG may inhibit their renal tubular secretion 
resulting in increased dofetilide/pilsicainide concentrations and potential for toxicity. 
Note:  Any prohibited medication that decrease DTG concentrations should be 
discontinued for a minimum of four weeks or a minimum of three half-lives (whichever 
is longer) prior to the first dose.  Any other prohibited medication should be discontinued 
for a minimum of two weeks or a minimum of three half-lives (whichever is longer) prior 
to the first dose. 
Please refer to the current DTG IB and local prescribing information for other drugs that 
should be used with caution, require dose adjustment, or increased clinical monitoring if 
taken with ABC/DTG/3TC (or DTG with alternate NRTI background therapy). 
Concurrent with DTG + NRTIs 
In addition to the prohibited medications noted for DTG above (as a component of 
ABC/DTG/3TC), for participants who are HLA-B*5701 positive and who are receiving 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
113 
 
DTG + alternate NRTI background therapy, refer to the current DTG IB and local 
prescribing information for details regarding concurrent therapies. 
6.14. 
Medical Devices 
The medical devices to be used in this study are: vial adaptor, syringe and needle. 
Instructions for medical device use are provided in the Study Reference Manual. 
All device deficiencies, (including malfunction, use error and inadequate labeling) shall 
be documented, and reported by the investigator throughout the clinical investigation (see 
12.11) and appropriately managed by the sponsor. 
7. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns.  Therefore, adherence to the study design requirements, including those 
specified in the Time and Events Table, are essential and required for study conduct. 
This section lists the procedures and parameters of each planned study assessment.  The 
exact timing of each assessment is listed in the Time and Events Table Section 7.1. 
The following points must be noted:  
• 
If assessments are scheduled for the same nominal time, THEN the assessments 
should occur in the following order: 
1. 12-lead ECG 
2. vital signs 
3. blood draws 
• 
Note: The timing of the assessments should allow the blood draw to occur at the 
exact nominal time. 
• 
The timing and number of planned study assessments may be altered during the 
course of the study based on newly available data to ensure appropriate 
monitoring. 
• 
The change in timing or addition of time points for any planned study 
assessments must be documented in a Note to File which is approved by the 
relevant study team member and then archived in the study sponsor and site 
study files, but this will not constitute a protocol amendment.  
• 
The IRB/IEC will be informed of any safety issues that require alteration of the 
safety monitoring scheme or amendment of the Informed Consent Form.  
7.1. 
Time and Events Table 
Please refer to Appendix 9 in Section 12.9. for study management information during the 
COVID-19 pandemic. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
114 
 
Note:  While some assessments included in the Time and Events Table are conducted less 
frequently following the primary endpoint (Week 48), IM injections for participants 
randomized to CAB LA + RPV LA (and for participants who switch to CAB LA + RPV 
LA during the Extension Phase) will continue to be administered Q4W.  Beginning at 
Week 112, the schedule of assessments for participants continuing in the Extension Phase 
from the CAB LA + RPV LA arm will be modified to collect clinical chemistries, HIV-1 
RNA, and CD4+ cell count every 12 weeks.  
Participants originally randomized to ABC/DTG/3TC at Day 1, who choose to continue 
into the Extension Phase and transition to CAB LA + RPV LA, will have all assessments 
noted in the Time and Events table below performed Q4W through Week 124.  
Beginning at Week 124, the schedule of assessments for these participants transitioning 
from ABC/DTG/3TC into the Extension Phase will be modified to collect clinical 
chemistries, HIV-1 RNA, and CD4+ cell count every 12 weeks as noted in the Time and 
Events schedule below. 
From Week 124 forward, all participants (from both originally randomized treatment 
arms), will have the same schedule of events (same visits, same assessments, same time 
frame). 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
115 
 
Table 5 
201584 (FLAIR) Time and Events Table 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
Clinical and Other Assessments 
Written Informed 
Consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Verification 
(Inclusion / 
Exclusion 
Criteria) 
X 
X 
 
 
X
b 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
b 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical Historyc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication 
History / Prior 
ART History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom 
Directed 
X 
X 
X X X X 
X 
X X X X X X X X X X X X 
X 
X 
X X 
X 
X X 
X X X 
X 
X 
X 
 
X 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
116 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
Physical Exam 
and Medical 
Assessment d 
Weight, BMI, and 
Height e 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X  
 
 
 
X  
 
 
 
X 
 
 
Cardiovascular 
Risk Assessment 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs (BP, 
HR, 
temperature) f 
X 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X  
 
 
 
X 
 
 
12-Lead ECG g 
X 
X 
pr
e-
do
se 
x3 
 
 
 
X 
X 
 
X
g 
 
 
 
 
 
 
X
g 
 
 
 
 
 
X 
 
 
 
 
X  
 
 
 
X 
 
 
CDC 
Classification 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
117 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
HIV Associated 
Conditions 
 
 
X X X X 
X 
X X X X X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
X X X 
X 
X 
X 
X 
X 
AE and SAE 
Assessment, 
Con Meds 
X 
h 
X 
X X X X 
X 
X X X X X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
X X X 
X 
X 
X 
X 
X 
ISR Assessment 
(LA Arm Only) 
 
 
 
 
 
 
 
 
X X X X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
X X X 
X 
X 
X 
X 
X  
If 
appli-
cable 
Columbia 
Suicide Severity 
Rating Scale 
(eC-SSRS) i 
X 
X 
 
 
X X 
X 
 
X  
X X X X 
 
X 
 
 
X W7
2 
W84 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Clinical 
Chemistry  
and Hematology 
X 
X 
X X X X 
X 
X 
 
 
X X X X 
 
X X X X 
X 
 
X 
X 
 
X 
X 
 
X X 
 
X 
X 
 
X 
Rapid Plasma 
Reagin (RPR) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
118 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
Pregnancy 
Testingj 
S 
U 
S S S S 
U S U  
S S S S 
 
S S S S 
S 
S 
S 
S 
Uj 
 
S 
S 
U S S 
S - 
Q4
W 
 
S 
 
S 
HIV-1 RNA and 
sample for 
storagek  
Xk 
X 
X X X X 
X 
 
X  
X X X X 
 
X S
k 
X X 
X 
 
X 
S
k 
 
X 
 
X X X 
 
X 
X 
 
X 
CD4+  
X 
X 
X X X X 
X 
 
X  
X X X X 
 
X 
 
X X 
X 
 
X 
 
 
 
 
X X X 
 
X 
X 
 
X 
CD8+ 
 
X 
 
 
X 
 
X 
 
X  
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X  
 
 
 
X 
 
 
Urinalysisl  
 
X 
 
 
 
 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Fasting Lab 
Assessments:  
Glucose, 
Cholesterol 
(Total, HDL and 
LDL) and 
Triglycerides m 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X  
 
 
 
X
O 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
119 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
Hepatitis B 
(HBsAg), Anti-
HBc, and Anti-
HBsAG 
 
Hepatitis C  
(anti-HCV Ab) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA-B*5701 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PT/PTT/INR 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Renal and Bone 
marker analytes 
(blood/urine)n 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Peripheral Blood 
Mononuclear 
Cells (PBMCs) o 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Genetic Samplep 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
120 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
Pharmacokinetics (CAB + RPV only) 
PK Sample  
(S)= Storage 
sample 
 
 
 
 
 
 
 
 
X
v 
w 
X
t  
v 
X X X X X
v 
X
v 
X X X 
S 
 
X
v 
X 
X 
v 
X 
v 
 
X
v 
w 
S 
 
 
 
X 
 
S 
Investigational Products 
Oral CAB and 
Oral RPV 
Dispensation  
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
x 
O
LI 
O
nl
y 
 
 
Xx 
OLI 
Onl
y 
 
 
 
 
 
 
 
 
ABC/DTG/3TC 
Dispensation (or 
DTG alternate) 
 
X 
X X X
q 
r 
 
X 
X 
 
 
X X X X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study Treatment 
Accountability  
(pill counts) 
 
 
X X X
r 
X 
X 
X X
u 
 
X X X X 
 
X 
 
X 
 
X 
 
X 
X 
O
LI 
O
 
 
X 
OLI 
Onl
y 
X
u 
 
 
 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
121 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
nl
y 
IM Study 
Treatment 
Administration – 
Q4W throughout 
Maintenance and 
Extension Phase 
 
 
 
 
 
 
 
 
X  
X X X X 
 
X X X X 
X 
X 
X 
X 
 
X 
X 
X
s 
X X 
X – 
co
nt 
do
s-
ing 
Q4
W 
 
 
 
 
Patient Reported Outcomesz 
HAT-QoL (short 
form) 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
SF-12 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
ACCEPT 
 
 
 
 
 
 
X 
 
 
 
W
8 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
HIVTSQ(s) 
 
 
 
 
 
 
X 
 
X  
 
X 
 
W
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
122 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
4
4 
HIVTSQ(c) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
PIN (LA Arm 
Only)aa 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
NRS (LA Arm 
Only) 
 
 
 
 
 
 
 
 
X X 
 
 
 
W
4
0 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Preference (LA 
Arm Only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Follow Up Visit (for subjects completing the study, whether transitioning to CAB LA + RPV LA marketed product or alternative HAART) and Safety Follow Up Visit (for subjects 
withdrawing from the study) are required as described in Section 5.5 
Direct to Inject:  Participants transitioning into the Extension Phase who do not use the optional CAB + RPV oral lead-in beginning at Week 100. 
Oral Lead-In:  Participants transitioning into the Extension Phase who do use the optional CAB + RPV oral lead-in beginning at Week 100. 
LA Arm:  Participants who were originally randomized to CAB LA + RPV LA at Day 1. 
Switch Arm:  All participants who transition into the Extension Phase from ABC/DTG/3TC (or DTG + 2 NRTI’s) at Week 100 – e.g., both direct to inject and oral lead-in participants.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
123 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
a. 
Complete all Screening assessments within 35 days.  Participants may begin the Induction Phase as soon as all Screening assessments are complete.  Participants may be 
rescreened once and will be assigned a new participant number. 
b. 
Confirmation of eligibility to enter the Maintenance Phase (Section ), eligibility to enter the Extension Phase (Section ). 
c. 
Collect full routine medical history plus (report at Baseline visit): HIV risk factors (may be collected at a later study visit), cardiovascular risk factors (assessments include 
smoking status and history, family history of cardiac events), recent [≤6 months] illicit drug use, intravenous drug use, gastrointestinal disease, metabolic, psychiatric, renal 
and neurologic disorders. 
d. 
Physical exams should be conducted as part of normal routine clinical care but data will not be collected in the eCRF. Medical assessments include any decisions the study 
staff must make for participant management and / or care.  
e. 
Height collected at Baseline only. 
f. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
g. 
A 12-lead ECG will be performed after resting in a semi-supine position for at least 5 minutes.  Perform ECG at Baseline (Week [-20]) in triplicate prior to dosing.  For 
subjects randomized to CAB LA + RPV LA, at Week 4b and Week 48, a second ECG will be obtained approximately 2 hours after the last injection and just prior to the 2 
hour post dose PK sampling. 
h. 
Collect SAEs at Screen only if associated to study participation. 
i. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  During the Maintenance Phase, the eC-SSRS will be administered at each Q4W visit through the 
Week 48 primary endpoint, and then followed by Q12W assessments for CAB LA + RPV LA arm, thereafter through Week 96 (LA:  Week 60, 72, 84, 96).  The 
ABC/DTG/3TC arm will have assessments at Week 72 and Week 96).  Preferably completed at the beginning of the visit following administration of other patient reported 
questionnaires required prior to injections. 
j. 
Conduct pregnancy tests for only women of childbearing potential at every visit throughout the study, including Q4W during the Extension Phase.  Remind females of 
reproductive potential of the need to avoid pregnancy while in study and adherence to the study’s contraception requirements.  A negative urine pregnancy test is required 
prior to beginning the Induction Phase (Week [-20]), on Day 1 (preferably prior to randomization), and at Week 4b (or Week 104b for subjects transitioning from 
ABC/DTG/3TC) prior to the first injection. Serum pregnancy test can substitute for urine pregnancy test if locally required, but must be appropriately timed to confirm 
pregnancy status prior to e.g. randomization and first IM administration. S=Serum/U=Urine. 
k. 
Plasma for storage will be used: to determine genotypic eligibility at Screen, for possible future analyses, as back- up in case samples are lost or damaged in transit to the 
lab and for genotypic and phenotypic analyses in cases of virologic failure.  HIV-1 RNA will not be collected for analysis at Week 52 and Week 100 (Week 48 or Week 96 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
124 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
retest will be captured as unscheduled visit).  Plasma for storage will be collected at Week 52 and Week 100. 
l. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; and urine phosphate. 
m. Overnight fast is preferred; however, a minimum of a 6 hour fast is acceptable. 
n. 
Blood sample for renal and bone biomarker assessments: Renal: Cystatin C; Retinol Binding Protein (RBP); Bone: bone specific alkaline phosphatase, procollagen type 1-
N-propeptide, type 1 collagen cross-linked C-telopeptide, osteocalcin, 25 hydroxy-Vitamin D 
o. 
Whole blood/Peripheral Blood Mononuclear Cell collection samples may be used for virologic analyses as described in Section .  PBMCs will be collected at Day 1, Week 
96, Withdrawal visits. 
p. 
Informed consent for genetic research must be obtained before sample collection.  Sample may be collected at any visit after signing informed consent, but preferably at the 
Week [-20] visit. 
q. 
Instruct participants to continue to take the ABC/DTG/3TC regimen until Day 1 of the Maintenance Phase.  Participants will be randomized at Day 1 to continue on 
ABC/DTG/3TC arm or begin oral CAB + oral RPV.  Day 1 dosing should occur after randomization to determine defined treatment for the Maintenance Phase. 
r. 
Remind participants of the potential change in study treatment and visit frequency beginning at Day 1. 
s. 
Visit Week 104b is only required for participants transitioning from the ABC/DTG/3TC arm. 
t. 
The Week 5 visit should be performed approximately 7 days after the first injections at Week 4b (3 to 10 day window allowed). 
u. 
For oral CAB + RPV only. 
v. 
Take PK samples pre-dose.  At Week 4b (and Week 104b for participants transitioning to LA from ABC/DTG/3TC using the optional oral lead-in), the pre-dose PK sample 
should be taken after review of the PK diary and prior to the final oral CAB + RPV dose.  A sample will be also be taken at Week 4b, Week 48, and Week 96 (and Week 100 
[direct to inject] or Week 104b [using CAB + RPV oral lead-in]), approximately 2 hours post-injections.  The Week 5, Week 41, and Week 101 visit can be performed at any 
time from 3 to 10 days after the Week 4b, Week 40, and Week 100 injection, respectively. PK samples at Week 5, Week 41, and Week 101 can be taken at any time during 
the visit. 
w. Participants should take the last dose of oral CAB+RPV at Week 4b (and Week 104b for participants transitioning to LA from ABC/DTG/3TC if using the optional oral lead-
in) in the clinic after PK sampling. Participants should take the last dose of ABC/DTG/3TC at Week 100 if transitioning directly to injections at Week 100.  Injections should 
be administered within 2 hours of the last oral dose where possible. 
x. 
For participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC only. 
y. 
Safety Follow Up Visit (for subjects completing the study, whether transitioning to CAB LA + RPV LA marketed product or alternative HAART) and Safety Follow Up Visit (for 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
125 
 
Procedures 
Screening a 
Induction Phase 
by Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
Withdrawal 
Safety Follow-Up Y 
Long-Term Follow-Up 
Baseline (-20) 
(-16)
(-12 -8)
(-4)
WDy 
Day 1 
4a
4b – LA arm
5t – LA arm
8, 12, 16, 20
24
28, 32, 36 
40, 44
41 – LA arm
48
52 - LA Arm 
56
60 – LA Arm
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm 
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm
104a LA and Oral Lead-In 
Arm
104b - Oral Lead-In Arm
108
112, 116, 120,124 
ABC/DTG/3TC S it h A
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA 
Arm) or 124 (Switch Arm)j
subjects withdrawing from the study) are required as described in Section 5.5 
z. 
With the exception of the NRS questionnaire, patient reported questionnaire/surveys are recommended to be administered at the beginning of the visit before any other 
clinical assessments are conducted, and prior to completion of the eCSSRs assessments.  Only conduct questionnaires/surveys at Withdrawal if occurring prior to Week 96 
(The NRS will not be collected at Withdrawal). 
aa. The PIN, Preference, and NRS questionnaires are to be administered only to participants receiving CAB LA + RPV LA injections. The NRS should be collected 30 to 60 
minutes post-injection (and at Week 5 and Week 41, one week post-injections) - the participant should record the maximum level of pain experienced with the most recent 
injections. 
Note: BMI- Body mass Index, BP – Blood pressure, HR – Heart Rate, HDL – High Density Lipoprotein, LDL – Low Density Lipoprotein, PT – Prothrombin Time / PTT – Partial 
Thromboplastin Time / INR – International Normalized Ratio 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
126 
 
7.2. 
Screening and Critical Baseline Assessments 
Written informed consent must be obtained from each potentially eligible participant by 
study site personnel prior to the initiation of any Screening procedures as outlined in this 
protocol.  The consent form must have been approved by the Institutional Review Board 
(IRB) /Independent Ethics Committee (IEC).  After signing an informed consent, 
participants will complete Screening assessments to determine participant eligibility.  
Each participant being screened for study enrolment evaluation will be assigned a 
participant number at the Screening visit.  This number will be given sequentially in 
chronological order of participant presentation according to a numeric roster provided by 
GSK. 
Participants must be counseled on the practice of safer sexual practices including the use 
of effective barrier methods (e.g. male condom/spermicide) and the length of time in 
which they are required for participation in this study as part of the eligibility process. 
7.2.1. 
Screening 
All participants will complete the Screening phase of up to 35 days prior to Baseline 
(Week [-20]) during which all clinical and laboratory assessments of eligibility must be 
performed and reviewed.  All Screening results must be available prior to enrolment.  A 
single repeat of a procedure/lab parameter is allowed to determine eligibility (unless 
otherwise specified).   
Eligibility criteria must be carefully assessed at the Screening visit and confirmed at the 
first Induction Phase visit prior to enrolment.  Participants may enroll and begin the 
Induction Phase as soon as all Screening assessments are complete and the results are 
available and documented.   
Laboratory results from the central laboratory services provided by this trial will be used 
to assess study eligibility.  A single repeat of a procedure / lab parameter is allowed to 
determine eligibility (unless otherwise specified).  In exceptional circumstances only, if a 
repeat lab is required because a central lab result cannot be generated, local labs can be 
reviewed and approved by the Medical Monitor, for consideration of participant 
eligibility.  A repeat central lab will be submitted concurrently or at the next planned 
visit.   
Each participant screened will be assigned a participant number.  Participants not meeting 
all inclusion and exclusion criteria at initial screen may be re-screened one time with a 
new participant number.  Participants who are enrolled into the trial and subsequently 
withdrawn from the study for any reason may not be rescreened. 
At Screening, samples for HIV-1 genotypic and phenotypic resistance testing and plasma 
HIV-1 RNA measurement will be obtained. If a central laboratory result cannot be 
generated for Screening genotype/phenotype, a local result can be considered following 
review and approval by the study virologist. 
Physical exams should be conducted as part of normal routine clinical care but will not be 
collected systematically in the eCRF.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
127 
 
Participants infected with hepatitis B virus (HBV) will not be enrolled in the study.  
Evidence of HBV infection is based on the results of testing at Screening for hepatitis B 
surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface 
antibody (anti-HBs), and HBV DNA.  HBV DNA will only be performed for participants 
with positive anti-HBc and negative HBsAg and negative anti-HBs (past and/or current 
evidence). 
Participants with an anticipated need for HCV therapy prior to Week 48 of the 
Maintenance Phase of the study must not be enrolled into this study, as HCV therapy may 
include the prohibited medication interferon.  The length of this study should be 
considered when assessing the potential need for therapy. 
All participants will be screened for syphilis (rapid plasma reagin [RPR]) at Screening.  
Participants with untreated syphilis infection, defined as a positive RPR without clear 
documentation of treatment, are excluded.  Participants with a positive RPR test who 
have not been treated may be rescreened at least 30 days after completion of antibiotic 
treatment for syphilis.  Participants with a serofast RPR result despite history of adequate 
therapy and no evidence of re-exposure may enrol after consultation with the Medical 
Monitor. 
The electronic Columbia Suicidality Severity Rating Scale (eC-SSRS) (see Section 
7.4.11) assessed at the Screening visit will assess the participant’s lifetime risk (any 
suicidal ideation, behavior, etc occurring over the participant’s lifetime).  A positive alert 
is not necessarily exclusionary, rather a means to assess overall risk. 
7.2.2. 
Baseline Assessments 
Participants will have “Baseline” assessments completed at the beginning of the 
Induction Phase (Week [-20] visit). 
Any changes to the eligibility parameters must be assessed and any results required must 
be available and reviewed prior to enrolment (e.g. urine pregnancy test for women of 
child bearing potential). 
HIV-1 genotypic resistance testing and plasma HIV-1 RNA measurement results from 
Screening must be available prior to the Baseline visit. 
In addition to a full routine medical history and current medical conditions, more detailed 
information will be collected for some disease processes such as: 
• cardiovascular risk factors (assessments will include height, weight, blood 
pressure, smoking status and history, pertinent medical conditions [e.g., 
hypertension, diabetes mellitus], and family history of premature cardiovascular 
disease);  
• history of illicit drug use [e.g. cocaine, heroin, and methamphetamine use]); 
• intravenous drug use history; 
• gastrointestinal disease (e.g. GI bleeding, PUD, etc); 
• metabolic (e.g. Type I or II diabetes mellitus); 
• psychiatric (e.g. depression); 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
128 
 
• renal (e.g. nephrolithiasis, nephropathy, renal failure); and, 
• neurologic disorders (e.g. history of seizures). 
7.3. 
Efficacy 
7.3.1. 
Plasma HIV-1 RNA 
Plasma for quantitative HIV-1 RNA will be collected according to the Time and Events 
schedule (Section 7.1).  Methods to be used may include but are not limited to the Abbott 
RealTime HIV-1 Assay lower limit of detection (LLOD) 40 c/mL.  In some cases (e.g., 
where the HIV-1 RNA is below the lower limit of detection for a given assay) additional 
exploratory methods will be used to further characterize HIV-1 RNA levels. 
7.3.2. 
Lymphocyte Subsets, CD4+ and CD8+ 
Lymphocyte subsets will be collected for assessment by flow cytometry (total 
lymphocyte counts, percentage and absolute CD4+ and CD8+ lymphocyte counts, ratios) 
according to Time and Events schedule (Section 7.1) and Laboratory Assessments 
(Section 7.4.2). 
7.3.3. 
HIV Associated Conditions 
HIV-associated conditions will be recorded as per Time and Events schedule 
(Section 7.1).  HIV-associated conditions will be assessed according to the 2014 CDC 
Revised Classification System for HIV Infection in Adults (see Section 12.4).   
7.4. 
Safety 
7.4.1. 
Clinical evaluations 
Planned time points for all safety assessments are listed in the Time and Events Table 
(Section 7.1).  Additional time points for safety tests (such as vital signs, physical exams 
and laboratory safety tests) may be added during the course of the study based on newly 
available data to ensure appropriate safety monitoring. 
The following clinical evaluations will be performed according to the Time and Events 
schedule: 
• 
Monitoring and recording of all AEs and SAEs.  Additional information on the Time 
Period and Frequency of Detecting AEs and SAEs is provided in Section 7.4.3.1. 
• 
Physical exams should be conducted as part of normal routine clinical care but will 
not be collected systematically in the eCRF.  Abnormalities noted during any exam 
must be recorded in the eCRF (e.g., in the current medical conditions or AE logs). 
• 
Height and weight will be measured and recorded.  Height collected on the first day 
of the Induction Phase only. 
• 
Vital signs will include systolic and diastolic blood pressure and heart rate collected 
after resting for about 5 minutes.  Temperature will also be collected. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
129 
 
• 
Past medical history, family history, social history, medication history.  Targeted 
history on cardiovascular risk (smoking history, family and personal history). 
• 
HIV-associated conditions will be recorded. 
• 
Electrocardiogram:  A 12-lead ECG will be performed in a semi-supine position 
after resting for about 5 minutes.  At the first day of the Induction Phase, ECGs 
should be performed in triplicate prior to first dose.  At Week 4b and Week 48 of the 
Maintenance Phase, a 2 hour post dose ECG will be performed for participants 
randomized to CAB LA + RPV LA.  The same QT correction formula must be used 
for each individual participant to determine eligibility for and discontinuation from 
the study.  This formula may not be changed or substituted once the participant has 
been enrolled.  An ECG machine that automatically calculates the heart rate and 
measures PR, QRS, QT, and QTc intervals is preferred, and these calculated 
numbers can be used for reporting purposes.  Otherwise, an appropriately qualified 
ECG reader must interpret the results.  The same interpreter should assess all ECGs 
for each participant.  Regardless, each ECG should be reviewed by a qualified ECG 
reader.  The qualified ECG reader will make the non-calculated ECG interpretations. 
• 
Regular monitoring of hematology, blood chemistry, urinalysis and fasting glucose 
and lipids (parameters to be tested listed below).   
• 
Periodic assessment of glucose, and bone and renal markers. 
• 
Pregnancy testing: 
• 
A negative urine pregnancy test is required prior to initiation of IP at the 
beginning of the Induction Phase, prior to the first dose of CAB LA or RPV LA, 
or as required by the Medical Monitor following a treatment interruption(s).  If 
serum testing is required locally, the results should be available prior to the visit 
where urine testing is indicated per the Time and Events Schedule (Section 7.1). 
• 
Participants who are enrolled in the study and have a positive pregnancy test 
during the course of the study will be allowed to remain in the study, provided a 
pregnancy specific ICF addendum is signed by the participant. No IP can be 
continued (oral or LA) in any pregnant participant until the benefit/risk 
assessment is discussed with the participant and the pregnancy specific ICF 
addendum has been signed. See details in Appendix 10. Not applicable in 
Russia. 
• 
Pregnant participants who remain in the study do not need pregnancy testing during 
the study, for the duration of their pregnancy. Not applicable in Russia. 
• 
Evaluation and documentation of all concomitant medications and blood products.  
• 
Injection Site Reactions (ISRs) will be assessed clinically during the Maintenance 
and Extension Phase for the following:  
• 
Pain, tenderness, pruritis, warmth, bruising, discoloration, infections, rash, 
erythema, swelling, induration, and nodules (granulomas or cysts).   
• 
A clinical assessment (using Division of Acquired Immunodeficiency Syndrome 
[DAIDS] grading scale) should be performed both before and after an injection 
to identify resolving and new ISRs.  All injection site reactions are considered 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
130 
 
adverse events.  The clinical assessment and interpretation of any ISR will be 
documented in the ISR AE eCRF.   
• 
Columbia Suicide Severity Rating Scale (eC-SSRS) will be assessed as per the Time 
and Events Schedule (see Section 7.1 and Suicidal Risk Monitoring Section 7.4.11). 
Any appropriately qualified site personnel (e.g., Investigator, sub-Investigator, or study 
coordinator/nurse) can perform assessments. 
7.4.2. 
Laboratory Assessments 
All protocol required laboratory assessments, as defined in the Time and Events Schedule 
(see Table 5), must be performed by the central laboratory.  Laboratory assessments must 
be conducted in accordance with the Central Laboratory Manual and Protocol Time and 
Events Schedule.  Laboratory requisition forms must be completed and samples must be 
clearly labelled with the participant number, protocol number, site/centre number, and 
visit date.  Details for the preparation and shipment of samples will be provided by the 
central laboratory.  Reference ranges for all safety parameters will be provided to the site 
by the central laboratory. 
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification) the results must be recorded in the eCRF.  Local laboratory services may 
be used to verify pending laboratory parameters only after consultation and agreement 
with the study team. 
Refer to the lab manual for appropriate processing and handling of samples to avoid 
duplicate and/or additional blood draws. 
Labs will be automatically graded by the central lab according to the DAIDS toxicity 
scales (See Section 12.2 “Division of AIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events”). 
For fasting laboratory assessments, an overnight fast is preferred; however, a minimum of 
a 6 hour fast is acceptable. 
Following are the lab parameters to be assessed as per the Time and Events Schedule (see 
Section 7.1): 
Table 6 
Safety Laboratory Assessments 
Hematology 
Platelet count  
Automated WBC differential: 
RBC count 
Neutrophils 
WBC count (absolute)  
Lymphocytes 
Hemoglobin 
Monocytes 
Hematocrit 
Eosinophils 
MCV 
Basophils 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
131 
 
Clinical Chemistry 
BUN 
Potassium 
AST  
Total bilirubina 
Creatinine 
Chloride 
ALT  
Albumin  
Glucosec 
Total CO2 
Alkaline phosphatase 
Creatine phosphokinase 
Sodium 
Lipase 
Phosphate (inorganic 
phosphorus) 
Creatinine clearanceb 
Fasting Lipid Paneld 
Total cholesterol 
HDL cholesterol 
LDL cholesterol 
Triglycerides 
Other Tests 
Plasma HIV-1 RNAe 
CD4+ and CD8+ cell counts [CD4/CD8 ratio]f 
Peripheral Blood Mononuclear Cells (PBMCs):  Day 1, Week 96, Withdrawal only 
Hepatitis B (HBsAg), anti-HBc, anti-HBsAg, and hepatitis C antibody (Screening)g 
Rapid Plasma Reagin (RPR) (Screening and Baseline) 
HLA-B*5701 (Screening only) 
Prothrombin Time (PT)/International Normalized Ratio (INR)/ Partial Thromboplastin Time (PTT) 
Pregnancy test for women of childbearing potentialh 
Follicle stimulating hormone (FSH) and estradiol (only in instances when postmenopausal status 
is questionable) 
Urinalysis, urine albumin/creatinine ratio, and urine protein/creatinine ratio, urine phosphate 
Genetic Sample  
Renal biomarkers including Cystatin-C (blood), Retinol Binding Protein (RBP, blood/urine)i 
Bone biomarkers including: Bone-specific alkaline phosphatase, procollagen type 1 N-
propeptide, type 1 collagen cross-linked C-telopeptide, osteocalcin, 25 hydroxy-Vitamin Di 
1. MCV = mean corpuscular volume, RBC = red blood cells, WBC = white blood cells, BUN = Blood urea 
nitrogen, AST=aspartate aminotransferase, ALT = alanine aminotransferase, CO2 = carbon dioxide, HDL = 
high density lipoprotein, LDL = low density lipoprotein, HBsAg = hepatitis B virus surface antigen, PT/INR = 
prothrombin time/international normalized ratio 
a. 
Direct bilirubin will be reflexively performed for all total bilirubin values >1.5 × ULN. 
b. 
Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) [Levey, 2009]. 
c. 
For fasting glucose assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments. 
d. 
For fasting lipids assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments. 
e. 
For participants meeting virologic withdrawal criteria, plasma samples will be analyzed in attempt to obtain 
genotype/phenotype data.  HIV-1 RNA will not be collected for analysis at Week 52 and Week 100 (Week 48 
or Week 96 retest will be captured as unscheduled visit).  Plasma for storage will be collected at Week 52 and 
Week 100. 
f. 
CD8+ cells will only be reported at Baseline (Week [-20]), Week (-4), Day 1, Week 4b, Week 24, Week 48, 
Week 96, and Withdrawal.  Additionally, participants transitioning from the ABC/DTG/3TC arm to CAB LA + 
RPV LA will have CD8+ at Week 104b. 
g. 
HBV DNA will only be performed for participants with a positive anti-HBc, negative HBsAg, and negative anti-
HBs (past and / or current evidence). 
h. 
Urine pregnancy test/ serum pregnancy test will be performed according to the Time and Events Table (Table 
5).  
i. 
Since the intention is to utilize these biomarker data for research purposes, the sponsor will not be reporting 
the results of these assessments to the investigator, except for 25 hydroxy-vitamin D. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
132 
 
7.4.3. 
Adverse Events (AEs) and Serious Adverse Events (SAEs) 
The investigator and their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE.  
The definitions of an AE or SAE can be found in Section 12.6, Appendix 6. 
Please refer to Appendix 9 in Section 12.9. for study management information during the 
COVID-19 pandemic. 
Reporting of medical device deficiencies are covered in Appendix 11.  
7.4.3.1. 
Time Period and Frequency for collecting AE and SAE information 
• 
Any SAEs assessed as related to study participation (e.g., protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a ViiV/GSK 
product will be recorded from the time a participant consents to participate in the 
study up to and including any follow-up contact.  
• 
AEs will be collected from the start of Study Treatment until the follow-up 
contact (see Section 7.4.3.3), at the timepoints specified in the Time and Events 
Table (Section 7.1). 
• 
All AEs and SAEs associated with medical device deficiencies for associated 
persons (i.e. healthcare professionals) will be collected.  The associated person 
will be provided with a safety reporting information and an authorisation letter, as 
indicated in Section 7.4.4. 
• 
Medical occurrences that begin prior to the start of study treatment but after 
obtaining informed consent may be recorded on the Medical History/Current 
Medical Conditions section of the eCRF. 
• 
All SAEs will be recorded and reported to GSK within 24 hours, as indicated in 
Section 12.6. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study 
participants.  However, if the investigator learns of any SAE, including a death, at 
any time after a participant has been discharged from the study, and he/she 
considers the event reasonably related to the study treatment or study 
participation, the investigator must promptly notify GSK. 
NOTE: The method of recording, evaluating and assessing causality of AEs and SAEs 
plus procedures for completing and transmitting SAE reports to GSK are provided in 
Section 12.6, Appendix 6. 
7.4.3.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.  Appropriate questions include: 
• 
“How are you feeling?”  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
133 
 
• 
“Have you had any (other) medical problems since your last visit/contact?”  
• 
“Have you taken any new medicines, other than those provided in this study, since 
your last visit/contact?”  
7.4.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  All SAEs, and non-serious AEs of special 
interest (as defined in 7.4.10) will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the participant is lost to follow-
up (as defined in Section 5.4).  Further information on follow-up procedures is given in 
Appendix 6. 
7.4.3.4. 
Prompt Reporting of Serious Adverse Events and Other Events 
SAEs, pregnancies, and liver function abnormalities meeting pre-defined criteria will be 
reported promptly by the investigator to the Medical Monitor as described in Table 7 
once the investigator determines that the event meets the protocol definition for that 
event.  Any seizure or suspected seizure should be reported in an expedited manner, as 
noted in Table 7. 
Criteria for liver chemistry stopping and follow-up criteria are in Section 5.4.1.  
Additional information for reporting cardiovascular and death events is included in 
Section 7.4.3.7 and Section 7.4.3.8, respectively. 
Table 7 
Reporting of Serious Adverse Events and Other Events 
 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
All SAEs 
24 hours 
“SAE” data 
collection tool 
24 hours 
Updated “SAE” data 
collection tool 
 
Cardiovascular or 
death event 
Initial and 
follow-up 
reports to be 
completed 
when the 
cardiovascular 
event or death 
is reported  
“CV events” and/or 
“death” data 
collection tool(s) if 
applicable 
 
Initial and follow-up 
reports to be 
completed when 
the cardiovascular 
event or death is 
reported 
Updated “CV events” 
and/or “death” data 
collection tool(s) if 
applicable 
 
Pregnancy 
24 hours 
“Pregnancy 
Notification Form” 
Within 24 hours of 
investigator 
awareness of 
pregnancy 
outcome 
“Pregnancy Follow-
up Form” 
Seizure or suspected 
seizure 
24 hours 
eCRF 
24 hours 
eCRF 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
134 
 
 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
Suspected ABC HSR 
in participants 
randomized to the STR 
arm or receiving an 
oral ABC-containing 
regimen during the 
Long-Term Follow-Up 
Phasea 
1 week 
ABC HSR eCRF 
1 week 
Updated ABC HSR 
eCRF 
ALT≥3×ULN and 
bilirubin≥2×ULN 
(>35% direct) (or 
ALT≥3×ULN) 
24 hoursb 
“SAE” data 
collection tool. 
“Liver Event eCRF” 
and “Liver Imaging” 
and/or “Liver 
Biopsy” eCRFs, if 
applicablec 
24 hours 
Updated “SAE” data 
collection tool/“Liver 
Event” documentsc 
ALT≥5×ULN that 
persists ≥2 weeks  
24 hoursb 
Liver Event eCRFc  
24 hours  
Updated Liver Event 
eCRFc 
ALT ≥8×ULN  
24 hoursb 
Liver Event eCRFc 
24 hours  
Updated Liver Event 
eCRFc 
ALT ≥3×ULN (if 
baseline ALT is <ULN) 
or ALT ≥3 fold 
increase from baseline 
value with appearance 
or worsening of 
symptoms of hepatitis 
or hypersensitivity 
24 hoursb 
Liver Event eCRFc 
24 hours  
Updated Liver Event 
eCRFc 
a. 
ABC HSR eCRF only required if event meets one of the ICH E2A definitions of seriousness. 
b. 
GSK must be contacted at onset of liver chemistry elevations to discuss participant safety. 
c. 
Liver event documents (i.e., “Liver Event eCRF” and updates, “Liver Imaging eCRF” and/or “Liver Biopsy 
eCRF”, as applicable) should be completed as soon as possible. 
SAE reporting to GSK via electronic data collection tool 
• 
Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the Medical Monitor. 
• 
Site will enter the serious adverse event data into the electronic system as soon as it 
becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) will be taken off-line to prevent the entry of new data or changes to 
existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
135 
 
taken off-line, the site can report this information on a paper SAE form or to the 
Medical Monitor by telephone. 
• 
Contacts for SAE receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information Page and in the Study Reference 
Manual. 
• 
The investigator will be required to confirm review of the SAE causality by ticking 
the ‘reviewed’ box at the bottom of the eCRF page within 72 hours of submission of 
the SAE. 
The method of recording, evaluating, and follow-up of AEs and SAEs plus procedures 
for completing and transmitting SAE reports to the Medical Monitor are provided in the 
SPM.  Procedures for post study AEs/SAEs are provided in the SPM. Primary and 
secondary Medical Monitor/SAE contact information is provided at the beginning of this 
protocol on the Sponsor/Medical Monitor Contact Information Page and in the Study 
Reference Manual. 
7.4.3.5. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
Disease-related events (DREs) or outcomes listed in the CDC Classification System for 
HIV-1 Infections (Section 12.4) can be serious/life threatening and will be recorded on 
the HIV-Associated Conditions eCRF page if they occur.  However, these individual 
events or outcomes, as well as any sign, symptom, diagnosis, illness, and/or clinical 
laboratory abnormality that can be linked to any of these events or outcomes are not 
reported to GSK as AEs and SAEs even though such event or outcome may meet the 
definition of an AE or SAE, unless the following conditions apply: 
• 
The investigator determines that the event or outcome qualifies as an SAE under part 
‘f’ of the SAE definition (see Section 12.6.2), or 
• 
The event or outcome is in the investigator’s opinion of greater intensity, frequency 
or duration than expected for the individual participant, or 
• 
The investigator considers that there is a reasonable possibility that the event was 
related to treatment with the investigational product, or 
• 
Death occurring for any reason during a study, including death due to a disease-
related event, will always be reported promptly. 
• 
Lymphomas and invasive cervical carcinomas are excluded from this exemption; 
they must be reported as SAEs even if they are considered to be HIV-related. 
If any of the above conditions is met then record the DRE on the SAE page rather 
than the HIV Associated Conditions eCRF page and report promptly (i.e., expedited 
reporting, see Section 7.4.3.4) to GSK. 
7.4.3.6. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to GSK of SAEs related to study treatment (even 
for non- interventional post-marketing studies) is essential so that legal obligations and 
ethical responsibilities towards the safety of participants and the safety of a product under 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
136 
 
clinical investigation are met.  
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation.  GSK will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) and investigators. 
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
7.4.3.7. 
Cardiovascular Events 
Investigators will be required to fill out event specific data collection tools for the 
following AEs and SAEs:   
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular (CV) events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• 
Revascularisation 
This information should be recorded in the specific cardiovascular eCRF within one week 
of when the AE/SAE(s) are first reported.  The CV CRFs are presented as queries in 
response to reporting of certain CV MedDRA terms. 
7.4.3.8. 
Death Events 
In addition, all deaths will require a specific death data collection tool to be completed.  
The death data collection tool includes questions regarding cardiovascular (including 
sudden cardiac death) and noncardiovascular death. 
This information should be recorded in the specific death eCRF within one week of when 
the death is first reported. 
The Death CRF is provided immediately after the occurrence or outcome of death is 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
137 
 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
7.4.4. 
Medical Device Deficiencies 
The vial adaptor, syringe and needles used in the study are classed as medical devices by 
the US Food and Drug Administration (FDA). To fulfil regulatory reporting obligations 
worldwide, the investigator is responsible for the detecting and documentation of events 
meeting the definitions of device deficiency that occur during the study with such 
devices. 
The definition of a medical device deficiency can be found in Appendix 11. 
NOTE: Medical device deficiencies associated with an SAE will be reported together 
with an SAE form. AEs associated with a medical device deficiency must be documented 
in the eCRF.  
7.4.5. 
Time Period for Detecting Medical Device Deficiencies 
• Medical device deficiencies that result in an incident will be detected, 
documented and reported during all periods of the study in which the medical 
device is used. 
• If the investigator learns of any device deficiency at any time after a participant 
has been discharged from the study, and such device deficiency is considered 
reasonably related to a medical device provided for the study, the investigator will 
notify the sponsor within 24 hours. 
• Medical device deficiencies and any associated AE/SAEs for associated persons 
(i.e. healthcare professionals) will be collected.  The associated person will be 
provided with a safety reporting information and authorization letter. 
• The method of documenting Medical Device Incidents is provided in Appendix 
11. 
7.4.6. 
Follow-Up of Medical Device Deficiencies 
• Follow-up applies to all participants, including those participants who discontinue 
study treatment or the study, and associated persons. 
• The investigator is responsible for ensuring that follow-up includes any 
supplemental investigations as indicated to elucidate the nature and/or causality of 
the deficiency. 
• New or updated information will be recorded on the original completed form with 
all changes signed and dated by the investigator. 
7.4.7. 
Prompt Reporting of Medical Device Deficiencies to Sponsor 
• Device deficiencies will be reported to the sponsor within 24 hours after the 
investigator determines that the event meets the protocol definition of a device 
deficiency. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
138 
 
• The medical device deficiency report form will be sent to the sponsor by email. 
• The sponsor will be the contact for the receipt of device deficiency reports. 
7.4.8. 
Regulatory Reporting Requirements for Medical Device 
Deficiencies 
The investigator will promptly report all deficiencies occurring with any medical device 
used for CAB + RPV in the study, as described in 12.11in order for the sponsor to fulfil 
the legal responsibility to notify appropriate regulatory authorities and other entities 
about certain safety information relating to medical devices being used in clinical studies.  
The investigator, or responsible person according to local requirements (e.g., the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/IEC. 
7.4.9. 
Toxicity Management 
Adverse events that occur during the trial should be evaluated by the Investigator and 
graded according to the Division of AIDS (DAIDS) toxicity scales (See Section 12.2 
“Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events”).  Additional information regarding detecting, documenting and reporting AEs 
and SAEs are available in Section 7.4.3 and Section 12.6. 
7.4.9.1. 
Treatment Interruption Due to an Adverse Event 
IP may be interrupted at the discretion of the Investigator and according to the severity of 
the AE.  If one or more antiretroviral medications is held due to toxicity or adverse 
events, all antiretroviral medications must be held to reduce the risk of development of 
resistance taking into account both the length of the planned interruption and the 
pharmacokinetic half-life of each antiretroviral of the regimen, in a way to minimize the 
risk of development of resistance. 
No toxicity-related dose reductions of IP will be allowed.  IP should be restarted as soon 
as medically appropriate; in general, for oral dosing, this should be no longer than 14 
days after discontinuation (unless Grade 3 or 4 toxicities persist).  Any interruption in 
therapy during the Maintenance Phase, oral dosing, of greater than 7 consecutive days 
must be discussed with and agreed by the Medical Monitor prior to resumption of 
therapy.  The Medical Monitor must be contacted upon becoming aware of resumption in 
therapy, if therapy was resumed without prior approval (Section 6.9).  IM dosing is 
expected to occur during the week in which the participant’s projected visit falls (as 
according to the date of the first injection visit [Week 4b]).  An additional (+ or -) 
7 day window, from the projected visit date, is allowable from the third injections 
forward for IM dosing but not preferred.  Any interruption outside of this guidance 
MUST be discussed with the Medical Monitor prior to reinitiating IM IP (see 
Section 6.9.1). 
Guidance is provided below on general participant management and IP interruptions 
based on the severity of the AE.  Information regarding permitted substitutions \ is 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
139 
 
provided in Section 6.8.  All changes in the IP regimen must be accurately recorded in the 
participant’s eCRF. 
Note: For participants receiving an ABC-containing product as part of the background 
regimen, in the event of a discontinuation of ABC for any reason, reinitiation of this drug 
should be undertaken with caution. The investigator should obtain a complete history of 
the events surrounding the discontinuation of the ABC-containing product, evaluate for 
the possibility of a clinically suspected HSR, and initiate participant management as 
outlined in the Local Country Prescribing Information, regardless of a participant’s HLA-
B*5701 status.  Screening for the presence of HLA-B*5701 is recommended prior to 
reinitiating treatment with ABC-containing products in participants of unknown HLA-
B*5701 status who have previously tolerated ABC. 
7.4.9.2. 
Grade 1 or Grade 2 Toxicity/Adverse Event 
Participants who develop a Grade 1 or Grade 2 AE or toxicity may continue IP at the 
discretion of the Investigator. (NOTE: See Section 7.4.10 “Specific Toxicities/Adverse 
Event Management” for exceptions to this guideline).  Participants who choose to 
withdraw from study due to a Grade 1 or 2 AE should have study withdrawal and follow-
up evaluations completed. 
Participants who develop ALT ≥3 times ULN while on study must consult with 
Medical Monitor prior to initiation or continuation of CAB LA and RPV LA. 
7.4.9.3. 
Grade 3 Toxicity/Adverse Event 
Participants who develop a Grade 3 AE or toxicity should be managed as follows: 
• If the Investigator has compelling evidence that the Grade 3 AE or toxicity has 
not been caused by IP, dosing may continue after discussion with the Medical 
Monitor. 
• Participants who develop a Grade 3 AE or toxicity, which the Investigator 
considers related or possibly related to the IP, should have the IP withheld and be 
rechecked each week until the AE returns to Grade 2.  Once the AE is Grade ≤2, 
IP may be re-started.  
• Should the same Grade 3 AE recur within 28 days in the same participant, the IP 
should be permanently discontinued and the participant withdrawn from study.  
• Participants experiencing Grade 3 AEs requiring permanent discontinuation of IP 
should be followed weekly until resolution of the AE and to have withdrawal 
study evaluations completed.  A follow-up visit should be performed 2-4 weeks 
after the last dose of IP.  Any participant receiving at least one dose of CAB LA 
and /or RPV LA who discontinue IP / Withdraw will initiate treatment with 
HAART and enter the Long-Term Follow-Up Phase for 52 weeks of follow up.  
• Participants with Grade 3 asymptomatic laboratory abnormalities should be 
investigated for all potential non-drug related causes, and, following discussion 
with the Medical Monitor, may continue IP if the Investigator has compelling 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
140 
 
evidence that the toxicity is not related to IP, with the exception of liver chemistry 
stopping criteria (See Section 7.4.10.1).  Isolated Grade 3 lipid abnormalities do 
not require withdrawal of IP. 
7.4.9.4. 
Grade 4 Toxicity/Adverse Event 
• Participants who develop a Grade 4 AE or toxicity must have IP permanently 
discontinued.  However, if the Investigator has compelling evidence that the AE is 
not causally related to the IP, dosing may continue after discussion with and 
assent from the Medical Monitor.  Participants should be rechecked each week 
until the AE returns to Grade 2. 
• Participants experiencing Grade 4 AEs requiring permanent discontinuation of IP 
should be followed weekly until resolution of the AE and encouraged to complete 
the withdrawal and follow-up study evaluations as noted above.  Any participant 
receiving at least one dose of CAB LA and /or RPV LA who discontinue IP / 
Withdraw will initiate treatment with HAART and enter the Long-Term Follow-
Up Phase for 52 weeks of follow up.  
• Participants with Grade 4 asymptomatic laboratory abnormalities should be 
investigated for all potential non-drug related causes, and, following discussion 
with the Medical Monitor, may continue therapy if the Investigator has 
compelling evidence that the toxicity is not related to IP, with the exception of 
liver chemistry stopping criteria (See Section 7.4.10.1).  An in-clinic follow-up 
visit will be performed approximately 2-4 weeks after the last dose of study 
medication if AEs, SAEs, or laboratory abnormalities considered potentially 
harmful to the participant are ongoing at the last on-study visit.  Isolated Grade 4 
lipid abnormalities do not require withdrawal of IP. 
7.4.10. 
Specific Toxicities / Adverse Event Management 
General guidelines for the management of specific toxicities that are considered to be 
associated with treatment of HIV infected participants are provided below.  
Participants who permanently discontinue study drug for reasons of toxicity should be 
followed weekly until resolution of the AE and encouraged to complete the withdrawal 
and Follow-up study evaluations as noted in Section 7.4.3.3. 
7.4.10.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry threshold stopping criteria have been designed to assure participant 
safety and to evaluate liver event etiology during administration of IP and the follow-up 
period.  
For a complete listing of stopping and follow-up criteria refer to Section 5.4.1.  
Additional guidance on restart can be found in Section 5.4.1.3 and Section 12.3, 
Appendix 3. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
141 
 
7.4.10.2. 
Diarrhea 
Participants with Grade 1 or 2 diarrhea may continue study treatment without 
interruption. Participants with diarrhea of any toxicity grade may be treated 
symptomatically with anti-motility agents; however, the recommended daily dose of the 
chosen anti-motility agent must not be exceeded.  If symptoms persist or get worse on the 
recommended daily dose of the chosen anti-motility agent then the anti-motility agent 
must be discontinued and consultation made with the Medical Monitor. 
For participants with Grade ≥3 diarrhea that is unresponsive to the recommended dose of 
the anti-motility agents and for which an alternative etiology (e.g., infectious diarrhea) is 
not established, the treatment with the anti-motility agent and IP must be interrupted until 
resolution of diarrhea to Grade ≤2 or Baseline, after which IP and background ART may 
be resumed after discussion and agreement with the Medical Monitor.  If Grade ≥3 
diarrhea recurs within 28 days upon the resumption of IP, the IP should be permanently 
discontinued and the participant withdrawn from the study.  Any participant receiving at 
least one dose of CAB LA and /or RPV LA who discontinue IP / Withdraw will initiate 
treatment with HAART and enter the Long-Term Follow-Up Phase for 52 weeks of 
follow up. 
If loperamide is used for treatment of diarrhea, local prescribing information should be 
followed with respect to dose and frequency of administration.  Loperamide dosing 
should not exceed local prescribing information. 
7.4.10.3. 
Hypertriglyceridemia / Hypercholesterolemia 
Samples for lipid measurements must be obtained in a fasted state according to the Time 
and Events Table (Section 7.1).  Participants who experience asymptomatic triglyceride 
or cholesterol elevations may continue to receive IP.  Clinical management of 
participants with hypertriglyceridemia/hypercholesterolemia should not be based upon 
non-fasting samples (obtained in the fed state).  A confirmatory fasting triglyceride 
and/or cholesterol level should be obtained prior to the institution of medical therapy for 
hyperlipidemia.  Isolated Grade 3 and Grade 4 lipid abnormalities do not require 
withdrawal of IP. 
Please see the Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular 
Disease Focus Group [Dube, 2003] for full discussion of management of hyperlipidemia 
in the context of HIV therapy. 
7.4.10.4. 
Seizures 
A small number of seizure cases have been reported following CAB administration (less 
than 1% of all those receiving CAB in clinical studies). These cases have had alternative 
explanations for their occurrence. 
ViiV Healthcare has reviewed these cases in detail and does not believe they constitute a 
reasonable likelihood of causation associated with CAB. This assessment is supported by 
the lack of preclinical signal, class effect or known CNS mechanism, the relatively low 
frequency of seizures relative to expected rates in both healthy and HIV positive 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
142 
 
participants and clinical cofounders in each case. The Sponsor considers the risk of 
developing seizures on the study as being no higher than that of the rest of the HIV-1 
infected population.  
Seizures that occur on study should be managed according to the local guidelines on 
emergency seizure management which may include treatment with benzodiazepines, 
general supportive treatment, exclusion of metabolic and toxicological abnormalities 
using laboratory tests, and septic workup and excluding underlying structural 
abnormalities with neuroimaging. 
Where seizures occur, the Sponsor would like to better characterize these occurrences to 
enable systematic analyses. 
Investigators are requested to document and report seizure or possible seizure events 
promptly (within 24 hours of learning of the event) to the Sponsor for evaluation and 
onward reporting.  Data should be documented on the appropriate eCRF page. 
7.4.10.5. 
Creatine Phosphokinase (CPK) Elevation 
A Grade 3 or higher elevation in CPK should result in a repeat assessment within 2 to 4 
weeks to ensure the result is transient or due to exercise and will not require a change in 
study treatment.  A history regarding use of drugs known to cause increase of CPK (such 
as statins) physical activity or exercise preceding the CPK evaluation should be obtained.  
Grade 4 elevations in CPK should have a repeat assessment after the participant has 
abstained from exercise for >24 hours.  For persistent Grade 4 CPK elevations that are 
considered possibly or probably related to the IP, IP should be discontinued and the 
participant withdrawn from the study.  Any participant receiving at least one dose of 
CAB LA and /or RPV LA who discontinue IP will initiate treatment with HAART enter 
the Long-Term Follow-Up Phase for 52 weeks of follow up. 
7.4.10.6. 
Lipase Elevations and Pancreatitis 
Participants with asymptomatic Grade 1 or 2 elevations in lipase may be followed closely 
for the development of symptoms. 
Participants with asymptomatic Grade ≥3 elevations in lipase that are considered possibly 
or probably related to IP should have IP interrupted until serum lipase returns to 
Grade ≤2.  The lipase assay should be repeated within 2 weeks of any Grade ≥3 result.  
Participants with persistence of Grade ≥3 lipase in the absence of other diagnoses or 
reoccurrence of lipase elevation (at Grade ≥2) following reintroduction of IP should 
permanently discontinue IP. 
Participants with a confirmed diagnosis of clinical pancreatitis that is considered possibly 
or probably related to IP should have IP held.  After complete resolution of the episode, 
participants may be re-challenged with IP after discussion with the Medical Monitor, 
only if the Investigator has compelling evidence that the event was not caused by IP.  
Upon re-challenge, lipase determinations should be performed every 2 weeks for at least 
6 weeks after re-initiation of treatment.  With any elevation of lipase of Grade ≥2 or any 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
143 
 
recurrence of symptoms, the participant should discontinue IP and be withdrawn from 
study. 
Any participant receiving at least one dose of CAB LA and /or RPV LA who discontinue 
IP / Withdraw will initiate treatment with HAART and enter the Long-Term Follow-Up 
Phase for 52 weeks of follow up. 
7.4.10.7. 
Decline in Renal Function 
Participants who experience an increase in serum creatinine from Baseline of 
45 micromoles/liter (µMol/L) (or 0.5 milligrams/deciliter [mg/dL]) should return for a 
confirmatory assessment within 2 to 4 weeks.  A urinalysis and urine albumin/creatinine 
and urine total protein/albumin ratios should also be done at this confirmatory visit.  If 
the creatinine increase is confirmed, the investigator should contact the Medical Monitor 
to discuss additional follow-up and medical management. 
Participants who have a decline in the estimated GFR (using the CKD-EPI method) of 
>50% from Baseline must return for a confirmatory assessment as soon as possible 
[Levey, 2009].  A urinalysis and urine albumin/creatinine and urine protein/creatinine 
ratios should also be done at this confirmatory visit.  If the estimated GFR has declined 
by >50% (confirmed), then study drug should be withheld and the investigator should 
contact the Medical Monitor to discuss the rationale for restarting study drugs (if 
appropriate).  Consideration for confounding factors (e.g., background therapy, other 
medications, dehydration, concurrent conditions) should be taken into account, and a 
nephrology consult may be obtained.   
Proximal Renal Tubule Dysfunction 
Proximal Renal Tubule Dysfunction (PRTD) is defined as: 
• Confirmed rise in serum creatinine of ≥0.5 mg/dL from Baseline AND serum 
phosphate <2.0 mg/dL 
• Either of the above accompanied by any two of the following: 
• Glycosuria (≥250 mg/dL) in a non-diabetic 
• Low serum potassium (<3 mEq/L) 
• Low serum bicarbonate (<19 mEq/L) 
Participants meeting criteria for PRTD must return for a confirmatory assessment within 
2 weeks of diagnosis.  A urinalysis should also be performed at the time of the 
confirmatory assessment.  If PRTD is confirmed participants should have study drug 
withheld and the investigator should contact the Medical Monitor to discuss the rationale 
for restarting study drugs (if appropriate).  Consideration for confounding factors (e.g., 
NRTI backbone, other medications, dehydration, concurrent conditions) should be taken 
into account, and a nephrology consult may be obtained.  If study drug is reinitiated, it 
should have been withheld for no more than 4 weeks.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
144 
 
7.4.10.8. 
Proteinuria 
Participants with an abnormal urine microalbumin/creatinine ratio (>0.3 mg/mg, 
>300 mg/g or >34 mg/mmol) that represents a change from Baseline and no associated 
increase in creatinine, should have a repeat spot urine microalbumin/creatinine ratio 
performed within 2 to 4 weeks.  If confirmed, then consideration should be made for 
additional evaluation after consultation with the Medical Monitor. Additional evaluation 
may include a 24 hr urine protein and creatinine measurement and nephrology referral. 
Participants with an abnormal urine albumin/creatinine ratio (>0.3 mg/mg, 300 mg/g 
or>34 mg/mmol and representing a change from Baseline) and a serum creatinine 
increase >45 µMol/L (or 0.5 mg/dL) should have confirmation of both results within 2 
weeks.  If confirmed, the Medical Monitor should be immediately contacted.  Further 
management should be agreed between the investigator and Medical Monitor. 
7.4.10.9. 
QTc Prolongation 
Participants with an average QTc interval > 550 msec from three or more tracings 
separated by at least 5 minutes should have IP discontinued.  These criteria are based on 
an average QTc value of triplicate ECGs.  If an ECG demonstrates a prolonged QT 
interval, obtain 2 more ECGs over a brief period (~5-10 minutes) and use the averaged 
QTc values of the 3 ECGs to determine whether the participant should be discontinued 
from the study.  If an alternative cause of the QT prolongation is determined (e.g., 
participant receiving drug known to cause prolonged QT or TdP), then IP may be 
restarted after consultation with and agreement by the Medical Monitor.  
7.4.10.10. Injection Site Reactions (ISRs) 
Injection site reactions will be managed through investigator assessment throughout the 
study.  All ISRs that are either serious, Grade 3 or higher or persisting beyond 2 weeks 
must be discussed with the Medical Monitor to determine etiology and assess appropriate 
continued study participation.   
• 
Digital photographs may be documented, where possible, on all participants who 
have an injection site reaction, with observable findings, that is either serious or 
Grade 3 or higher, or that persist beyond 2 weeks.  Dermatology will be 
consulted on all participants who have an injection site reaction considered 
serious, Grade 3 or above, or if clinically significant and persistent beyond 
30 days and others if the Investigator or Medical Monitor feels it is medically 
necessary. 
Details regarding photo collection and any other follow up will be given by the Medical 
Monitor at the time of assessment. 
ISR discomfort can be managed symptomatically (e.g. cold/warm compress, 
acetaminophen, ibuprofen) if the reaction is interfering with the participant’s ability to 
perform activities of daily living.  The required intervention should be documented on the 
appropriate eCRF page. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
145 
 
7.4.10.11. Allergic Reaction 
Participants may continue IP for Grade 1 or 2 allergic reactions at the discretion of the 
Investigator.  The participant should be advised to contact the Investigator immediately if 
there is any worsening of symptoms or if further systemic signs or symptoms develop. 
Antihistamines, topical corticosteroids, or antipruritic agents may be prescribed.  
Participants with Grade ≥3 allergic reactions that are considered to be possibly or 
probably related to the IP should permanently discontinue the IP regimen and the 
participant should be withdrawn from the study.  Participants should be treated as 
clinically appropriate and followed until resolution of the AE. 
Participants in the ABC/DTG/3TC arm who are receiving ABC as part of their NRTI 
background regimen should be evaluated for the possibility of a clinically suspected ABC 
hypersensitivity reaction (HSR) and managed appropriately as outlined in the local 
prescribing information for ABC. 
Any participant receiving at least one dose of CAB LA and /or RPV LA who discontinue 
IP / Withdraw will initiate treatment with HAART and enter the Long-Term Follow-Up 
Phase for 52 weeks of follow up. 
7.4.10.12. Abacavir Hypersensitivity Reaction (ABC HSR) 
The most significant toxicity associated with ABC is the well-characterized drug-related 
hypersensitivity reaction (HSR).  A detailed clinical description of this reaction 
(including the type and severity of events that can occur on re-challenge or reintroduction 
following ABC interruption for non-HSR reasons) and guidance regarding its 
management are included in the Local Country Prescribing Information for TRIUMEQ.  
Investigators must familiarize themselves with this information on ABC HSR in the 
Local Country Prescribing Information for each of these products prior to initiating 
participants on ABC therapy. 
Studies have shown that carriage of the HLA-B*5701 allele is associated with a 
significantly increased risk of a HSR to ABC. In the prospective study CNA106030 
(PREDICT-1), the use of pre-therapy screening for the presence of HLA-B*5701 and 
subsequently avoiding ABC in HLA-B*5701 positive participants, significantly reduced 
the incidence of clinically suspected ABC HSR from 7.8% (66 of 847) to 3.4% (27 of 
803) (p<0.0001). In clinical studies EPZ108859 (ARIES) and CNA109586 (ASSERT), 
0.8% (4/515) and 3.1% (6/192) of participants who were HLA-B*5701 negative and who 
received ABC developed a clinically suspected ABC HSR, respectively. 
In any participant treated with ABC, the clinical diagnosis of suspected HSR (as 
detailed in the Local Country Prescribing Information) must remain the basis of 
clinical decision making. Regardless of HLA-B*5701 status, it is important to 
permanently discontinue ABC and not re-challenge with ABC (i.e., TRIUMEQ, 
ZIAGEN, EPZICOM/KIVEXA or TRIZIVIR) if a HSR cannot be ruled out on 
clinical grounds, due to the potential for a severe or even fatal reaction. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
146 
 
Essential Participant Information 
With reference to Local Country Prescribing Information and the ‘Participant Information 
and Consent Form’, Investigators must ensure that participants are fully informed 
regarding the following information on the hypersensitivity reaction prior to commencing 
ABC therapy: 
• 
Participants must be made aware of the possibility of a hypersensitivity reaction to 
abacavir that may result in a life-threatening reaction or death and that the risk of a 
hypersensitivity reaction is increased in individuals who are HLA-B*5701 positive. 
• 
Participants must also be informed that HLA-B*5701 negative individuals can also 
experience abacavir hypersensitivity reaction. Therefore, ANY participant who 
develops signs or symptoms consistent with a possible hypersensitivity reaction to 
abacavir MUST CONTACT their doctor IMMEDIATELY. 
• 
Participants who are hypersensitive to abacavir should be reminded that they must 
never take any abacavir containing medicinal products (e.g. TRIUMEQ, ZIAGEN, 
EPZICOM / KIVEXA or TRIZIVIR) again, regardless of their HLA-B*5701 status. 
• 
In order to avoid restarting abacavir, participants who have experienced a 
hypersensitivity reaction should be asked to return any remaining TRIUMEQ, 
EPZICOM / KIVEXA tablets to the Investigator or site staff. 
• 
Participants, who have stopped abacavir for any reason, and particularly due to 
possible adverse reactions or illness, must be advised to contact their doctor before 
restarting TRIUMEQ, EPZICOM / KIVEXA as more severe symptoms may recur 
within hours and may include life-threatening hypotension and death. 
• 
Each participant should be reminded to read the Package Leaflet included in the 
TRIUMEQ, EPZICOM / KIVEXA pack. They should be reminded of the importance 
of removing the Alert Card included in the pack, and keeping it with them at all 
times.  
Reporting of Hypersensitivity Reactions 
If a clinically suspected case of HSR to ABC meets one of the International Conference 
on Harmonization (ICH), 1994 definitions of seriousness listed in Section 12.6.2 then, in 
addition to reporting the case as an SAE, the ABC HSR eCRF should also be completed 
within one week of the onset of the hypersensitivity reaction.  Clinically suspected cases 
of HSR to ABC that do not meet criteria as an SAE can be recorded as an AE. 
7.4.10.13. Rash Without ABC HSR Symptoms 
Rash including serious skin reactions such as Stevens-Johnson Syndrome, Toxic 
Epidermal Necrolysis, Erythema Multiforme or rash with significant liver 
dysfunction:  
Participants should be instructed to contact the Investigator as soon as possible if they 
develop a rash on study. 
Participants who develop rash of any grade should be evaluated for the possibility of an 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
147 
 
ABC HSR or a serious skin reaction such as Stevens - Johnson syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) or Erythema Multiforme. SJS, TEN and Erythema 
Multiforme have been reported very rarely in participants taking ABC-containing 
products.  These participants generally do not have the cluster of additional symptoms 
(e.g., gastrointestinal and respiratory) that characterize the ABC HSR, but they do have 
features typical of these serious skin reactions. 
If a serious skin reaction develops, ABC (and / or all other concurrent medication(s) 
suspected in the Investigators causality assessment) should be discontinued, and the 
participant should not be re-challenged with any ABC-containing medicinal product (i.e., 
TRIUMEQ, ZIAGEN, TRIZIVIR, EPZICOM or KIVEXA). 
As many products other than abacavir also cause rash and/or serious skin reactions, all 
other medicinal products that the participant is receiving should also be reviewed and 
discontinued as appropriate. 
The following guidance is provided for clinical management of participants who 
experience rash alone in the absence of accompanying diagnosis of ABC HSR, systemic 
or allergic symptoms or signs of mucosal or target lesions. 
Mild to moderate rash is an expected adverse reaction for DTG-containing ART.  
Episodes generally occur within the first ten weeks of treatment, rarely require 
interruptions or discontinuations of therapy and tend to resolve within two to three weeks.  
No instances of serious skin reaction, including Stevens-Johnson Syndrome (SJS), toxic 
epidermal necrolysis (TEN) and erythema multiforme, have been reported for DTG in 
clinical trials.  For further characterization of HSR and rash observed with DTG-
containing ART, please see the current version of the DTG IB [GlaxoSmithKline 
Document Number RM2007/00683/11] or local prescribing information. 
Rash is an adverse drug reaction (ADR) for RPV.  In clinical trials, most rashes emerged 
during the first 4 weeks of treatment, were transient, and usually mild (Grade 1) to 
moderate (Grade 2).  There were no Grade 4 rashes and none were serious.  Treatment-
related Grade 3 rash was reported in 0.1% of participants in the RPV group.  Treatment-
related rash led to permanent discontinuation in 0.1% of participants in the RPV group.  
No cases of erythema multiforme, SJS or TEN have been reported during clinical 
development of RPV. 
Participants with an isolated Grade 1 rash may continue study drug at the Investigator’s 
discretion.  The participant should be advised to contact the Investigator immediately if 
there is any worsening of the rash, if any systemic signs or symptoms appear, or if 
mucosal involvement develops. 
Participants may continue study drug for an isolated Grade 2 rash.  However, study drug 
(and all other concurrent medication(s) suspected in the Investigators causality 
assessment) should be permanently discontinued for any Grade ≥2 rash that is associated 
with an increase in ALT.  The participant should be advised to contact the physician 
immediately if rash fails to resolve (after more than two weeks), if there is any worsening 
of the rash, if any systemic signs or allergic symptoms develop, or if mucosal 
involvement develops. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
148 
 
Participants should permanently discontinue study drug [and all other concurrent 
medication(s) suspected in the Investigators causality assessment] for an isolated Grade 3 
or 4 rash, except where the etiology of the rash has been definitively diagnosed as NOT 
attributable to study drug (see below), and the participant should be withdrawn from the 
study.  Participants should be treated as clinically appropriate and followed until 
resolution of the AE.  Every effort should be made to collect as much information as 
possible about the evolution of the event and any relationship with potentially related 
medical events (e.g., viral infection) or start of concomitant medication. 
The rash and any associated symptoms should be reported as adverse events and 
appropriate toxicity ratings should be used to grade the events (based on DAIDS toxicity 
gradings – see Section 12.2, Appendix 2). 
However, if the etiology of the rash has been definitively diagnosed as being unrelated to 
study drug and due to a specific medical event or a concomitant infection or a 
concomitant non-study medication, routine management should be performed and 
documentation of the diagnosis provided.  In this situation, the study drug should be 
continued.  
Participants in the ABC/DTG/3TC arm who are receiving ABC as part of their regimen 
should be evaluated for the possibility of a clinically suspected ABC HSR and managed 
appropriately as outlined in the local prescribing information for ABC. 
Any rash that is possibly related to study drug, and is present between Day 1 and 
Week 4b, must be discussed with the Medical Monitor prior to initiation of CAB LA 
or RPV LA. 
Any participant receiving at least one dose of CAB LA and /or RPV LA who discontinue 
IP / Withdraw will initiate treatment with HAART and enter the Long-Term Follow-Up 
Phase for 52 weeks of follow up. 
7.4.11. 
Suicidal Risk Monitoring 
Participants with HIV infection may occasionally present with symptoms of depression 
and/or suicidal ideation or behavior.  In addition, there have been some reports of 
depression, suicidal ideation and behavior (particularly in participants with a pre-existing 
history of depression or psychiatric illness) in some participants being treated with INIs, 
including ABC/DTG/3TC.  Additionally, depression and anxiety has been reported in 
some participants being treated with RPV.  Therefore, it is appropriate to monitor and 
closely observe participants prospectively, before and during treatment, for suicidal 
ideation and / or behavior, or any other unusual changes in behavior.  It is recommended 
that the Investigator consider mental health consultation or referral for participants who 
experience signs of suicidal ideation or behavior. 
Participants presenting with new onset/treatment emergent depression should be advised 
to contact the investigator immediately if symptoms of severe acute depression (including 
suicidal ideation/attempts) develop, because medical intervention and discontinuation of 
the study medication may be required. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
149 
 
Assessment of treatment-emergent suicidality will be monitored during this study using 
the electronic version of the Columbia Suicide-Severity Rating Scale (eC-SSRS).  The 
definitions of behavioral suicidal events used in this scale are based on those used in the 
Columbia Suicide History Form [Posner, 2007].  Questions are asked on suicidal 
behavior, suicidal ideation, and intensity of ideation.  Screening visit questions will be in 
relation to lifetime experiences and current experiences (within the past 2 months) and all 
subsequent questioning in relation to the last assessment.  The eC-SSRS is to be 
administered as a participant completed questionnaire specified in the Time and Events 
Table (Section 7.1).  The eC-SSRS will be conducted electronically by telephone or by 
computer/tablet connected to the internet. 
Additionally, the investigator will collect information using the Possible Suicidality-
Related AE (PSRAE) eCRF form in addition to the Adverse Event (non-serious or 
Serious Adverse Events) eCRF form on any participant that experiences a possible 
suicidality-related adverse event while participating in this study.  This may include, but 
is not limited to, an event that involves suicidal ideation, a preparatory act toward 
imminent suicidal behavior, a suicide attempt, or a completed suicide.  The investigator 
will exercise his or her medical and scientific judgment in deciding whether an event is 
possibly suicide-related.  PSRAE forms should be completed and reported to ViiV/GSK 
within one week of the investigator diagnosing a possible suicidality-related adverse 
event.  All sites should have a plan in place for managing risk of and possible suicide 
related events. 
7.4.12. 
Pregnancy 
7.4.12.1. 
Pregnancy Testing 
Women of childbearing potential must have a negative pregnancy test at Screening, 
Baseline (Week [-20]), the first Induction Phase visit (Day 1), and Week 100 (if no oral 
lead-in is used) or Week 104b (if using CAB and RPV oral lead-in) for women 
transitioning into the Extension Phase from the ABC/DTG/3TC arm (prior to 
administration of first CAB LA and / or RPV LA injections).  Pregnancy testing will also 
be conducted as per the Time and Events Table (Table 5) and at anytime during the trial 
when pregnancy is suspected. 
If pregnancy is confirmed, a discussion with the pregnant study participant assessing the 
benefit/risk assessment of continuing in the study will be undertaken. If, after this 
discussion, the participant would like to continue in the study, this will be allowed, 
provided the pregnant participant signs the pregnancy specific ICF addendum. See 
Appendix 10 for details.  
Pregnant participants who remain in the study do not need pregnancy testing during the 
study, for the duration of their pregnancy. 
Additionally, the Medical Monitor may request that a urine pregnancy test be performed 
in the event of a treatment interruption greater than 7 days.  
Not applicable in Russia. In Russia, women who become pregnant or who desire to 
become pregnant while in the study will have study treatment discontinued and will enter 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
150 
 
the LTFU phase. 
7.4.12.2. 
Rationale for Continued Use in Pregnancy 
Additional data regarding the use of CAB + RPV LA during pregnancy and management 
of pregnant participants remaining in the study are found in Appendix 10.  
The use of CAB + RPV LA during pregnancy may offer unique benefits. It is well 
documented that treatment adherence challenges to oral therapy exists both in the peri-
partum and post-partum periods with LA dosing offering a unique opportunity to 
overcome such adherence challenges. LA therapy may also help with nausea (50% mild 
to moderate) or hyperemesis (2%) that is frequently see, especially during the first 
trimester of gestation.  
Participants on LA dosing who become pregnant will have exposures throughout 
pregnancy due to the long half-life and PK tail of CAB/RPV. Prior to this protocol 
amendment, pregnant participants would have been withdrawn from the study, and 
initiated on an alternative oral ART regimen. Alternative regimens consist of either 2 or 3 
antiretrovirals to protect the life of the mother and for the prevention of MTCT. This 
regimen, combined with the long half-life and PK tail of CAB/RPV would potentially 
expose the fetus to additional ARVs during gestation (in some cases upwards of 5 
antiretrovirals). 
Given the risk/benefit ratio for CAB + RPV LA dosing in WOCBP coupled with 
concerns of increasing fetal exposure to several additional antiretrovirals upon participant 
withdrawal, this amendment to the protocol will allow pregnant participants to remain in 
the study after a pregnancy specific ICF addendum is signed by the participant.  
Not applicable in Russia. In Russia, women who become pregnant or who desire to 
become pregnant while in the study will have study treatment discontinued and will enter 
the LTFU phase. 
7.4.12.3. 
Time Period for Collecting Pregnancy Information 
Pregnancy information will be collected after the start of the Induction Phase until the last 
follow-up assessment.  This includes the entirety of the Long-Term Follow-Up Phase. 
Pregnant study participants who consent to remain in the study while pregnant will 
continue to have all clinical assessments (with the exception of pregnancy tests) 
performed as per the Time and Events Table (Section 7.1), including the collection of 
additional PK samples for CAB and RPV. See Appendix 10 for details. Not applicable in 
Russia. 
Pregnant participants who have received at least one dose of CAB LA or RPV LA and do 
not continue in the study during pregnancy will enter the Long-Term Follow-Up Phase of 
the study and will be monitored for 52 weeks after the last dose of CAB + RPV LA. 
Moreover, an alternative oral HAART will be initiated, at the discretion of the PI and in 
discussion with the Medical Monitor.   If a participant becomes pregnant within 52 weeks 
of the last dose of study drug, the participant should notify the study site. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
151 
 
 
7.4.12.4. 
Action to be Taken if Pregnancy Occurs 
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form.  The investigator should inform GSK within 24 hours of learning of 
the pregnancy and should follow the procedures outlined in Appendix 7. 
Pregnant participants who elect to continue in the study and receive CAB + RPV LA 
must sign a pregnant specific ICF addendum. Cabotegravir and rilpivirine are detected in 
systemic circulation for up to 12 months or longer after discontinuing injections of CAB 
+ RPV LA; therefore, consideration should be given to the potential for fetal exposure 
during pregnancy and should be discussed between the study participant and the study PI.  
Participants who become pregnant during the study and elect to continue in the study and 
receive CAB + RPV LA will have additional PK samples collected to monitor CAB LA 
and RPV LA exposure throughout the pregnancy (see Appendix 10) and at the time of 
delivery.    
Participants in Russia who become pregnant during the study may not elect to continue in 
the study and receive CAB + RPV LA. They must discontinue LA study treatment and 
enter the LTFU phase.  
The pregnancy must be followed up to determine outcome (including premature 
termination) and status of mother and child(ren).  Pregnancy complications and elective 
terminations for medical reasons must be reported as an AE or SAE.  Spontaneous 
abortions must be reported as SAEs. 
Any SAE occurring in association with a pregnancy brought to the investigator’s 
attention after the participant has completed the study and considered by the investigator 
as possibly related to the study treatment, must be promptly reported to ViiV/GSK. 
GSK’s central safety department will also forward this information to the Antiretroviral 
Pregnancy Registry. The international registry is jointly sponsored by manufacturers or 
licensees of ARV products. Additional information and a list of participating 
manufacturers/licensees are available from http://apregistry.com. 
7.4.13. 
Physical Exams 
• 
A complete physical examination will include, at a minimum, assessment of the 
Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.  Height 
and weight will also be measured and recorded as per the Time and Events Table 
in Section 7.1.  
• 
A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). 
• 
The site of IM injection administration should be assessed at every visit for signs 
of any possible reaction.  See Section 7.4.10.10 for additional information. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
152 
 
• 
Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
7.4.14. 
Vital Signs 
• 
Vital signs will be measured in semi-supine position after 5 minutes rest and will 
include temperature, systolic and diastolic blood pressure and heart rate.  These 
will be recorded as per the Time and Events Table in Section 7.1. 
7.4.15. 
Electrocardiogram (ECG) 
• 
A 12-lead ECG will be performed in a semi-supine position.  At the first day of 
the Induction Phase, ECGs should be performed in triplicate prior to first dose.  At 
Week 4b and Week 48 of the Maintenance Phase, a 2 hour post dose ECG will be 
performed for participants randomized to CAB LA + RPV LA.  An ECG machine 
that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals is preferred, and these calculated numbers can be used for reporting 
purposes.  Otherwise, an appropriately qualified ECG reader must interpret the 
results.  The same interpreter should assess all ECGs for each participant for the 
site.  Regardless, each ECG should be reviewed by a qualified ECG reader.  The 
qualified ECG reader will make the non-calculated ECG interpretations.  Refer to 
the Time and Events Table for collection timepoints (Table 5).  Refer to 
Section 5.4.2 for [QTc] withdrawal criteria and additional [QTc] readings that 
may be necessary. 
7.5. 
Pharmacokinetics 
Plasma samples for determination of CAB and RPV concentrations will be collected 
throughout the Maintenance Phase and for the participants transitioning from the 
ABC/DTG/3TC arm in the Extension Phase of the study as noted in Table 8.  Additional 
samples will be collected for storage during the Long-Term Follow Up Phase.  Samples 
(blood and plasma) for determination of RPV concentrations will be protected from light 
at all times, from sampling collection through analysis. 
Pregnant participants will have additional PK samples collected for the duration of the 
pregnancy. See Appendix 10 for details. Not applicable in Russia. 
7.5.1. 
PK Sample Collection 
Blood samples for evaluation of CAB (2 mL each) and RPV (2 mL each) plasma 
concentrations will be collected from all participants randomized to receive CAB + RPV 
as described in Table 8.   
At Week 4b (and Week 104b for participants using the oral CAB + RPV lead-in and 
transitioning into the Extension Phase from the ABC/DTG/3TC arm), PK samples must 
be collected within the window of 20 to 28 hours after the oral dose of CAB + RPV was 
taken the day prior to the clinic visit.   
Participants will be expected to complete a PK dosing diary card noting the date and time 
of the last three oral doses of IP prior to the scheduled clinic visits at Week 4b (or 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
153 
 
Week 104b if transitioning into Extension Phase from ABC/DTG/3TC).  The information 
from the diary card will be recorded in the eCRF.  Additionally, dosing information on 
the clinic day, including dosing and the actual date and time of the PK samples, must be 
recorded on the eCRF.  Participants will take their final dose of oral CAB + RPV in the 
clinic at Week 4b (or Week 104b) after the pre-dose PK sample collection. 
PK concentrations will be summarized, sources of variability examined, and used to 
explore potential exposure-response relationships. 
The timing of PK samples may be altered and/or PK samples may be obtained at 
additional time points to ensure thorough PK monitoring.   
Table 8 
CAB and RPV Plasma Pharmacokinetic Sample Schedule 
Group 
Analytea 
Sample Times Relative to Dose 
IM 
CAB 
Pre-Dose:  Week 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 96, 100, 108, Withdrawal 
2 Hours Post Dose:  Week 4b, Week 48, Week 96 
1 Week Post Doseb:  Week 5 and Week 41 
PK samples for storage only: 
Pre-dose: Week 64, 72, 80, and 88 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
RPV 
Pre-Dose:  Week 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 96, 100, 108, Withdrawal 
2 Hours Post Dose:  Week 4b, Week 48, Week 96 
1 Week Post Doseb:  Week 5 and Week 41 
PK samples for storage only: 
Pre-dose: Week 64, 72, 80, and 88 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
ABC/DTG/3TC 
Arm Transitioning 
to CAB LA + RPV 
LA at Week 100 
(participants 
using CAB + RPV 
oral lead-in) 
CAB 
Pre-Dose:  Week 104b, Week 108 (for storage), 
Withdrawal 
2 Hours Post Dose:  Week 104b 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
RPV 
Pre-Dose:  Week 104b, Week 108 (for storage), 
Withdrawal 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
154 
 
Group 
Analytea 
Sample Times Relative to Dose 
2 Hours Post Dose:  Week 104b 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
ABC/DTG/3TC 
Arm Transitioning 
to CAB LA + RPV 
LA at Week 100 
(Direct to Inject - 
participants not 
using CAB + RPV 
oral lead-in) 
CAB 
Pre-Dose:  Week 104a, Week 108 (for storage), 
Withdrawal 
2 Hours Post Dose:  Week 100 
1 Week Post Doseb:  Week 101 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
RPV 
Pre-Dose:  Week 104a, Week 108 (for storage), 
Withdrawal 
2 Hours Post Dose:  Week 100 
1 Week Post Doseb:  Week 101 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
1. 
PK visit window and sample collection: Pre-dose visits (from projected visit date): ±3 days (1st injection), 
minus 7 days (2nd and 3rd injection), and± 7 days (4th and all subsequent injections); Sample Collection:  Pre-
dose at Week 4b (and Week 104b for participants transitioning from ABC/DTG/3TC Arm using oral lead-in):  20 
to 28 hours after the last oral dose of CAB and RPV was taken; 2 hours post dose: ±one hour; one week post 
dose visits: 3 to 10 days post injection. 
a. 
Each analyte in individual collection tube. 
b. 
Samples taken at Week 5, Week 41, and Week 101 may be collected from 3 to 10 days after Week 4b, 
Week 40, and Week 100, respectively.  These samples may be collected at anytime during those visits.   
If a participant withdraws from the study, a PK sample should be collected as early as 
practically possible (i.e. at the withdrawal visit or on the day the withdrawal decision was 
made). 
Samples for determination of RPV will be protected from light until analyzed.  
Additional details concerning handling of PK samples, labeling and shipping directions 
will be supplied in the central laboratory manual. 
7.5.2. 
Rationale of PK Sampling Strategy 
Blood sampling for CAB and RPV concentrations will be performed during the 
Maintenance Phase of the study to evaluate PK in HIV infected participants.  The 
proposed PK visits and sampling scheme at each visit presented in Table 8 is based on 
consideration of available PK data to support interim and final PK and 
PK/Pharmacodynamic (PD) analysis planned in this study. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
155 
 
7.5.3. 
Sample Analysis 
7.5.3.1. 
CAB Sample Analysis 
Plasma analysis for CAB concentration determination will be performed under the 
control of Platform Technology and Science (PTS), GSK, the details of which will be 
included in the SPM.  Concentrations of CAB will be determined in plasma samples 
using the currently approved bioanalytical methodology.  Raw data will be archived at 
the bioanalytical site (detailed in the SPM). 
Once the plasma has been analyzed for CAB any remaining plasma may be analyzed for 
other compound-related metabolites and the results reported under a separate PTS, GSK 
protocol.  No human DNA analysis will be performed on these samples. 
7.5.3.2. 
RPV Sample Analysis 
Plasma RPV analysis will be performed under the control of Janssen R&D. 
Concentrations of RPV will be determined in plasma samples using the currently 
approved bioanalytical methodology.  Raw data will be archived at the bioanalytical site. 
Once the plasma has been analysed for RPV any remaining plasma may be used by the 
sponsor for further exploratory work on pharmacokinetics, metabolites, plasma protein 
binding, protein analysis, and biochemistry.  No human DNA analysis will be performed 
on these samples. 
7.6. 
Biomarker(s) 
Blood and urine are being collected to perform renal and bone biomarker assessments as 
outlined in the Time and Events Table (Table 5).  Renal biomarkers include Cystatin C 
(blood), and Retinol Binding Protein (RBP, blood/urine), urine albumin/creatinine ratio, 
urine protein/creatinine ratio, urine phosphate and serum creatinine.  Bone biomarkers 
(blood) include bone-specific alkaline phosphatase, procollagen type 1 N-propeptide, 
type 1 collagen cross-linked C-telopeptide, osteocalcin, 25 hydroxy-Vitamin D.  Since 
the intention is to utilize these biomarkers for research purposes, the Sponsor will not be 
reporting the results of these assessments to the investigator except for 25 hydroxy-
vitamin D.  
7.6.1. 
Biomarker Endpoints (Exploratory) 
• 
Change from Baseline in renal and bone biomarkers at Week 48 and Week 96. 
• 
Change from Baseline over time in eGFR using cystatin C and other renal 
biomarkers during the Maintenance Phase. 
7.7. 
Genetics 
Information regarding genetic research is included in Appendix 5. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
156 
 
7.8. 
Viral Genotyping and Phenotyping 
Whole venous blood samples will be obtained from each participant to provide “plasma 
for storage samples” and PBMCs according to the Time and Events Schedule in 
Section 7.1 (for potential viral genotypic and phenotypic analyses).  
Details concerning the handling, labeling and shipping of these samples will be supplied 
separately.  Genotypic and phenotypic analyses may be carried out by Monogram 
Biosciences using, but not limited to, their Standard Phenosense and GenoSure testing 
methods for protease (PRO) and reverse transcriptase (RT), or with their GeneSeq 
Integrase and PhenoSense Integrase assays. 
For Screening virologic evaluations, only viral genotype will be analyzed and this will be 
performed through the central laboratory. 
7.8.1. 
HIV-1 pol Viral Genotyping and Phenotyping 
At Screening, samples will be collected for HIV-1 RT and PRO genotype using a 
genotype assay and results will be provided to the Investigator to assist in the 
determination of participant eligibility. 
Participants experiencing confirmed virologic failure will have plasma samples tested for 
HIV-1 PRO and RT genotype and phenotype and HIV-1 integrase genotype and 
phenotype from both Baseline samples and from samples collected at the time of 
suspected virologic failure; these results will be reported to the Investigator as soon as 
available to provide guidance for election of a switch regimen. 
7.8.2. 
HIV-1 Exploratory Analysis 
Additional exploratory analyses for HIV-1 pol resistance may include viral genotyping 
and/or phenotyping on a representative subset of Baseline samples or virologic analysis 
on stored plasma samples from other time points.  Analyses for HIV-1 resistance may, be 
carried out on peripheral blood mononuclear cell (PBMC) samples collected at Day 1 and 
Week 96 (or Withdrawal visit if prior to Week 96) and/or on stored plasma samples from 
other relevant time points.  These analyses may also include but are not limited to 
additional viral genotyping and/or phenotyping, as well as other virologic evaluations 
such as linkage and minority species analyses, super low HIV-1 RNA quantitation and 
measurement of viral replicative capacity.  HIV-1 integrase genotype and phenotype will 
also be determined on the last on-treatment isolates from all participants who have HIV-1 
RNA ≥200 c/mL regardless of confirmatory HIV-1 RNA. 
7.9. 
Value Evidence and Outcomes 
Health outcomes assessments will be conducted according to the Time and Events Table 
(Table 5).  Assessments are recommended to be administered with an electronic site pad 
or paper instrument at the beginning of the visit prior to collection of blood for analysis 
and other scheduled assessments with the exception of the NRS (administered post 
injection).   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
157 
 
The 12-item Short Form Health Survey (SF-12) is a measure that describes the degree of 
general health status and mental health distress [Ware, 1995].  The SF-12 contains 12 
items and it is derived from the Medical Outcomes Study 36-Item Short Form Health 
Survey.  
 
The original HIVTSQ included 10 items and underwent two stages of psychometric 
validation (Woodcock, 2001; Woodcock, 2006).  Recently, the HIVTSQ was adapted to 
include injectable treatment for HIV following a qualitative study with HIV participants 
in five European countries.  The adaptation of the HIVTSQ included two additional items 
related to the mode of administration (ie: long acting intramuscular injection).  These are: 
• Item 11:  How easy or difficult have you been finding your treatment to be 
recently? 
• Item 12:  How satisfied are you with the amount of discomfort or pain involved 
with your present form of treatment? 
Psychometric analyses from three datasets (one from the UK, one from the USA, and one 
from the LATTE-2 trial) reveal that the addition of two items in the original version of 
the HIVTSQ is suitable and does not reduce the overall validity of the questionnaire.  The 
current study will be using the HIVTSQs (status version) and the revised HIVTSQc 
(change version) of this recently developed HIVTSQ 12-item questionnaire.  The 
HIVTSQ 12-item questionnaire retains the option of calculating the total score as if it 
only had the original 10 items (as the original 10 items are included in the HIVTSQ 12).  
In addition, it allows for calculation of an 11-item scale score including the 
“easy/difficult” item (item-11).  The “pain/discomfort” item (item-12) will be included in 
the questionnaire as a stand-alone item to evaluate potentially painful injectables.  These 
measures will assess change in treatment satisfaction over time (in the same subjects) and 
compare current satisfaction with previous treatment satisfaction, from an earlier time 
point. 
The Perception of Injection (PIN) questionnaire explores the bother of pain at the 
injection site and ISR, anxiety before and after injection, willingness to receive an HIV 
injectable treatment the following visit and satisfaction with the mode of treatment 
administration of individuals receiving injection and perceptions of individuals associated 
with receiving injections.  The PIN questionnaire was derived from the Vaccines' 
Perception of Injection (VAPI) questionnaire (Chevat, 2009), and adapted for HIV-
infected participants who will receive the CAB LA and RPV LA regimen.  This measure 
contains 21 items that measure pain at injection site, local site reactions, impact on 
functioning and willingness to pursue injectable treatment outside of a clinical trial.  
Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 
always equated with the most favorable perception of the injection, and 5 the most 
unfavorable. 
The ACCEPT questionnaire is a generic medication acceptance measure assessing how 
participants weigh advantages and disadvantages of long-term medications (Marant, 
2012).  ACCEPT may be a predictor of participants' future adherence to and/or 
persistence with their treatment.  While the ACCEPT questionnaire consists of 25 items 
that capture six dimensions, only the three questions that focus on general acceptance of 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
158 
 
study medication will be used in this study. 
The HIV/AIDS Targeted Quality of Life (HAT-QoL) instrument [Holmes, 1998] 
originally contained 42 items, grouped into nine dimensions, assessing overall function 
and well-being.  For the purposes of this study, a shorter version adapted from the 
original version will be used.  This shorter version contains 14 items grouped into the 
three following dimensions: “life satisfaction”, “disclosure worries” and “HIV 
medication”.  All items use a “past 4 weeks” timeframe and a Likert response scale from 
1= “all of the time’’ to 5= “none of the time”. 
The Numeric Rating Scale (NRS) is a segmented numeric version of the visual analog 
scale (VAS) in which a respondent selects a whole number (0 to 10 integers) that best 
reflects the intensity of his/her post-injection pain.  The NRS is anchored by 0 
representing “No pain” and 10 representing “Extreme pain”. 
The “Preference” question will contain a single item exploring whether participants 
prefer the CAB LA + RPV LA injectable treatment or the current oral ART regimen. 
Qualitative interviews may also be conducted regarding the subject’s experience on the 
injection regimen.  This would be conducted under a separate IRB/IEC approved consent.  
Participation in the interviews would be voluntary. 
7.9.1. 
Value Evidence and Outcomes Endpoints (Secondary) 
• 
Change from Week 5 in Dimension scores (e.g., “Bother of ISRs”, “Leg movement”, 
“Sleep”, and “Injection Acceptance”) and individual item scores assessing pain 
during injection, anxiety before and after injection, willingness to be injected in the 
future and overall satisfaction with mode of administration over time using the 
Perception of iNjection questionnaire (PIN).  
• 
Proportion of participants considering pain and local reactions following injection to 
be extremely or very acceptable based on the acceptability score over time using the 
Perception of iNjection questionnaire (PIN). 
• 
Change from baseline in total “treatment satisfaction” score, and individual item 
scores of the HIVTSQs at Week 4b, Week 24, Week 44, Week 96 (or Withdrawal). 
• 
Change in treatment satisfaction over time (using the HIVTSQc) at Week 48 (or 
Withdrawal). 
• 
Change from Baseline in treatment acceptance at Weeks 8, 24, 48, 96 (or Withdrawal 
from the study) using the “General acceptance” dimension of the Chronic Treatment 
Acceptance (ACCEPT) questionnaire. 
• 
Change from Baseline in health status at Weeks 24, 48, 96 (or Withdrawal) using the 
12-item Short Form Survey (SF-12). 
• 
Change from Baseline in HR QoL (using the HAT-QoL short form) at Weeks 24, 48, 
96 (or Withdrawal from the study). 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
159 
 
• 
Change from Week 4b in the tolerability of injections (using the NRS) at Weeks 5, 
40, 41, 96. 
7.9.2. 
Value Evidence and Outcomes Endpoints (Exploratory) 
• The “Preference” question will be assessed at Week 48 (primary analysis) in 
participants randomized to the “CAB LA and RPV LA” arm to explore participant 
preference between CAB LA + RPV LA injectable regimen and ARV regimen. 
8. 
DATA MANAGEMENT 
• 
For this study participant data will be entered into GSK defined eCRFs, 
transmitted electronically to GSK or designee and combined with data provided 
from other sources in a validated data system. 
• 
Management of clinical data will be performed in accordance with applicable 
GSK standards and data cleaning procedures to ensure the integrity of the data, 
e.g., removing errors and inconsistencies in the data. 
• 
Adverse events and concomitant medications terms will be coded using MedDRA 
(Medical Dictionary for Regulatory Activities) and an internal validated 
medication dictionary, GSKDrug. 
• 
eCRFs (including queries and audit trails) will be retained by GSK, and copies 
will be sent to the investigator to maintain as the investigator copy.  Participant 
initials will not be collected or transmitted to GSK according to GSK policy. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process including systems used can be found in the 
study Data Management Plan. 
• 
Please refer to Appendix 9 in Section 12.9. for study management information 
during the COVID-19 pandemic. 
 
9. 
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES 
9.1. 
Hypotheses 
This study is designed to show that the antiviral effect of oral ABC/DTG/3TC followed 
by intramuscular CAB LA + RPV LA regimen is non-inferior to continuation of 
ABC/DTG/3TC at Week 48 of maintenance treatment.  Non-inferiority in the proportion 
of participants with virologic failure at Week 48 (per FDA’s snapshot algorithm for 
assessing HIV-1 RNA ≥ 50 c/mL) can be concluded if the upper bound of a two-sided 
95% confidence interval for the difference in failure rates between the two treatment 
arms (CAB – ABC/DTG/3TC) is less than 6%. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
160 
 
If fla is the failure rate on CAB LA + RPV LA and fc is the failure rate on comparator arm 
then the hypotheses can be written as follows: 
H0: fla – fc ≥6%   
H1: fla – fc < 6% 
9.2. 
Sample Size Considerations 
9.2.1. 
Sample Size Assumptions 
This study will randomize approximately 285 participants per arm.  Assuming the true 
virologic failure rate is 3% for the CAB LA + RPV LA injectable regimen and 2% for the 
continuation of ABC/DTG/3TC arm, a non-inferiority margin of 6%, and a 2.5% one-
sided significance level, this would provide approximately 97% power to show non-
inferiority for the proportion of participants with virologic failure (per FDA’s snapshot 
algorithm for assessing HIV-1 RNA ≥ 50 c/mL) at Week 48.   
This sample size of 285 participants per arm will also provide at least 90% power to show 
non-inferiority in the proportion of participants with plasma HIV-1 RNA <50 c/mL (per 
FDA’s Snapshot algorithm) at Week 48 over a range of true response rates, on the basis 
of a -10% non-inferiority margin and 2.5% one-sided significance level (see Table 13).  
Assuming true response rates for the CAB LA + RPV LA arm and ABC/DTG/3TC arm 
were both 87%, the power is at least 94% to show non-inferiority for this key secondary 
endpoint. 
In addition, the data from this study, together with data from a separate study, 201585, 
will be combined to assess non-inferiority using a 4% non-inferiority margin.  The 
combined sample size from both studies (570 pooled per arm) will provide 90% power, 
under the assumptions described above, to show non-inferiority for the proportion of 
participants with virologic failure (per FDA’s snapshot algorithm for assessing HIV-1 
RNA ≥ 50 c/mL) at Week 48. 
9.2.1.1. 
Rationale for non-inferiority margin 
The selection of the non-inferiority margins in a switch study comparing regimens (rather 
than individual component drugs) is exclusively informed by clinical judgment (and 
practical considerations) since regimen efficacy over placebo will be obvious – if the 
regimen efficacy were no better than placebo virtually all subjects would show virologic 
failure.  While this implies that any non-inferiority margin would be justifiable 
statistically, it would not be justifiable clinically to accept more than a 4 to 6 percent 
increase in the rate of virologic failure relative to standard-of-care regimen(s). 
The non-inferiority margin of 6% is chosen in consideration of the FDA’s 2015 guidance 
document (Center for Drug Evaluation and Research, Human Immunodeficiency Virus-1 
Infection: Developing Antiretroviral Drugs for Treatment, 2015) which is the most 
current regulatory guidance from either the EMA or FDA and includes specific 
recommendations regarding switch studies. It suggests that margins in the neighborhood 
of 4% are clinically tolerable, with typical observed rates of virological failure ranging 
from 1 to 3%. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
161 
 
As this study (201584) and study 201585 are not sufficiently powered to rule out 4% 
virologic failure in excess, the 6% margin chosen in each study can be viewed as defining 
criteria for assessing the consistency / acceptability of the study-specific results prior to 
integration of the studies in the pooled analysis.  Assuming an observed control failure 
rate of 2%, then non-inferiority would be shown in an individual study using a 6% 
margin if the observed CAB LA+RPV LA failure rate was less than 5% (that is, if the 
observed treatment difference was less than 3 percentage points).  Accordingly, if the 
individual studies are successful in ruling out a 6% margin, the observed results are 
expected to be similar and reasonable to integrate for the purposes of the primary efficacy 
assessment based on the pooled analysis.  In addition, a virologic failure rate in this range 
may be clinically tolerable given the CAB LA + RPV LA regimen may offer important 
advantages over standard 3-drug oral regimens such as better tolerability, as well as 
improved adherence and treatment satisfaction in virologically suppressed subjects.  
Therefore, 6% is considered to be a reasonable non-inferiority margin for the individual 
studies, with a more stringent 4% margin applied for the pooled analysis. 
9.2.1.2. 
Assumption for Virologic Failure Rate at Week 48 (Primary Endpoint) 
Control Arm 
The Snapshot response and failure rates observed in five recent stable switch studies are 
displayed in Table 9, all of which enrolled participants with at least 6 months of prior 
therapy.  To inform the failure rates for early switch studies with INI-based regimens, for 
which no known relevant studies exist, the difference in snapshot failure rates between 
Week 48 and Week 96 observed in recent treatment naive studies with INI- based 
regimens are displayed in Table 10.  These differences provide approximate predictions 
of the failure rates that may be observed for early switch studies enrolling participants 
with 48 weeks of prior initial therapy.  Taken together, these data suggest that a 
reasonable assumption for the true failure rate for the ABC/DTG/3TC control arm is 2%, 
with no clear signal of differential failure rates between early and stable switch studies. 
Table 9 
Snapshot Analysis Outcomes in Recent Stable Switch Studies 
Week 48 
Study 
Treatment Arm 
HIV-1 RNA 
<50 c/mL 
Virologic 
Failure  
SPIRITa,b 
RPV/FTC/TDF 
89% 
8/317 (2.5%) 
STRATEGY-PIc 
QUAD 
94% 
2/290 (<1%) 
 
PI + FTC/TDF 
87% 
2/139 (1%) 
STRATEGY-NNRTId 
QUAD 
93% 
3/290 (1%) 
 
NNRTI + FTC/TDF 
88% 
1/143 (<1%) 
GS-292-0109e 
E/C/F/TAF 
97% 
10/959 (1%) 
 
TDF-based regimen f 
93% 
6/477 (1%) 
Week 24 
STRIIVING 
DTG + ABC/3TC STR 
85% 
1% 
 
Current ART  
88% 
1% 
a. 
Participants in the PI/r +2 NRTIs arm were switched to RPV/FTC/TDF at Week 24 and 
therefore Week 48 response data are not available. 
b. 
[Palella, 2014] 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
162 
 
c. 
[Arribas, 2014] 
d. 
[Pozniak, 2014] 
e. 
[Martinez, 2010] 
f. 
E/C/F/TDF or EFC/FTC/TDF or ATV+ FTC/TDF  
 
Table 10 
Snapshot Virologic Failure Rates with INI-based Regimens in 
Treatment Naive Participants 
Study 
Regimen 
Week 48 
Week 96 
Change 
SINGLE 
DTG/ABC/3TC 
21/414 (5%) 
42/414 (10%) 
+5% 
SPRING-2 
DTG + ABC/3TC or 
TDF/FTC 
20/411 (5%) 
22 /411 (5%) 
+0.5% 
FLAMINGO 
DTG + ABC/3TC or 
TDF/FTC 
15/242 (6%) 
19/242 (8%) 
+2% 
236-0102 
E/C/F/TDF 
25/348 (7.2%) 
6%  
-1% 
236-0103 
E/C/F/TDF 
19/353 (5.4%) 
24/353 (6.8%) 
+2% 
292-
0104/0111 
E/C/F/TAF 
4% 
5% 
+1% 
 
E/C/F/TDF 
4% 
4% 
0% 
 
CAB LA + RPV LA arm 
To inform the failure rate for the CAB LA + RPV LA arm, the Snapshot virologic failure 
rates from the Phase 2b CAB studies are displayed in Table 11 for the Intent-to-Treat 
Exposed population.  Eligible participants included in the ITT-ME population had HIV-1 
RNA <50 c/mL prior to receiving maintenance therapy at Day 1 for LATTE-2 and 
Week 24 for LATTE.   
For LATTE, 9% (7%, excluding 1 participant classified as failure due to ART changes 
during the Induction Phase) of participants previously suppressed at Week 20 to Week 24 
were classified as virologic failures at Week 72 (48 weeks of maintenance treatment with 
oral CAB + RPV).   
For LATTE-2, 4% of participants randomized to CAB LA + RPV LA regimens (pooled) 
were classified as virologic failures after 48 weeks of maintenance treatment.  
Furthermore, while the failure rate was <1% at Week 48 for Q4W, there was noted 
variation in the snapshot failure rate overtime, ranging between 0% to 3.5% through 
Week 48 for Q4W.  These results suggests a conservative assumption for the true failure 
rate for the CAB LA + RPV LA Q4W arm of 3%, even though there is no clinical 
rationale to suggest that the failure rate is truly higher for the CAB LA + RPV LA 
regimen compared to the control regimen. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
163 
 
Table 11 
Snapshot Analysis Outcomes for Phase 2b CAB Studies (Intent-to-
Treat Maintenance Exposed Population) 
Week 48 
Study 
Maintenance Treatment Arm 
HIV-1 RNA 
<50 c/mL 
Virologic Failure 
LATTE-2 (ITT-ME) a 
CAB LA + RPV LA Q8W (N=115) 
92% 
8/115 (7%) 
 
CAB LA + RPV LA Q4W (N=115) 
91% 
1/115 (<1%) 
 
Oral CAB + 2 NRTIs (N=56) 
89%  
1/56 (2%) 
 
Pooled LA 
92% 
6/230 (4%) 
Week 72  
LATTE (ITT-ME) b 
Oral CAB 30 mg + RPV (n=53) 
83% 
9%c 
a. 
Participants had HIV-1 RNA <50 c/mL at Week (-4) and received oral CAB 30 mg + 2 NRTIs as initial induction 
period therapy from Week (-20) to Day 1. 
b. 
Participants had HIV-1 RNA <50 c/mL at Week 20 and switched from oral CAB 30 mg + 2 NRTIs to Oral CAB 
30 mg + RPV at Week 24. 
c. 
Includes one participant (2%) that was a virologic success but was classified as failure due to background ART 
change that occurred during the induction period, which is not an applicable failure category for the CAB LA + 
RPV LA regimen. 
 
9.2.1.3. 
Assumption for Response Rate at Week 48 (Secondary Endpoint) 
Given the response rates shown in Table 9 and Table 11, a reasonable assumption for the 
true success response rate (HIV-1 RNA <50 c/mL) for both arms is 87%. 
9.2.2. 
Sample Size Sensitivity 
Figure 8 shows the sensitivity of the power curve for the primary comparison to different 
assumed ‘true’ virologic failure rates with 285 randomized per arm.  Even if the failure 
rates were 3% for CAB LA + RPV LA and 1% for the control arm, the study will have 
over 92% power to meet its primary objective.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
164 
 
Figure 8 
Sensitivity of Estimated Power for Snapshot Virologic Failure 
 
Table 12 shows power with 285 randomized per arm and the sample size required to 
guarantee 90% power, for a range of ‘true’ virologic failure rates.  For instance, even if 
the failure rates were 3% for CAB LA + RPV LA and 1% for the control arm, the study 
will still have over 92% power to meet its primary objective with the planned sample 
size.  However, if the failure rates were 4% for CAB LA + RPV LA and 2% for control, 
an additional ninety-six participants per arm would be required to obtain 90% power for 
the primary treatment comparison. 
Table 12 
Sensitivity of Estimated Power for Snapshot Virologic Failure 
Control Arm Virologic 
Failure Rate (%) 
CAB LA + RPV LA 
Arm Virologic 
Failure Rate (%) 
6% Non-inferiority Margin 
Power (%) 
with N=285 
per arm  
N Required 
 per arm for 
90% Power 
1% 
1% 
>99.9% 
73 
1% 
2% 
99.8 
124 
1% 
3% 
92.7 
257 
1% 
4% 
63.4 
564 
1.5% 
1.5% 
>99.9% 
98 
 1.5% 
3% 
95.2 
228 
2% 
2% 
>99.9% 
115 
2% 
2.5% 
99.3 
153 
2% 
3% 
96.8 
205 
2% 
3.5% 
90.8 
277 
2% 
4% 
80.0 
381 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
165 
 
Control Arm Virologic 
Failure Rate (%) 
CAB LA + RPV LA 
Arm Virologic 
Failure Rate (%) 
6% Non-inferiority Margin 
Power (%) 
with N=285 
per arm  
N Required 
 per arm for 
90% Power 
3% 
3% 
98.7 
170 
3% 
4% 
90.1 
284 
 
Table 13 shows the sensitivity of the estimated sample size and power for the secondary 
endpoint comparison of response rates (HIV-1 RNA <50 c/mL at Week 48) to different 
assumed ‘true’ response rates.  
Table 13 
Sensitivity of Estimated Power for Snapshot Virologic Success 
Control Arm 
Virologic Success 
Rate (%) 
CAB LA + RPV LA 
Arm Virologic 
Success Rate (%) 
-10% Non-inferiority Margin 
Power (%) 
With N=285 
N Required per arm 
for 
90% Power 
85% 
85% 
91.6 
268 
86% 
85% 
86.2 
322 
86% 
86% 
93.0 
254 
86% 
87% 
97.0 
203 
87% 
85% 
78.6 
396 
87% 
86% 
88.1 
303 
87% 
87% 
94.4 
238 
87% 
88% 
97.7 
190 
88% 
87% 
90.1 
284 
88% 
88% 
95.6 
222 
88% 
89% 
98.4 
177 
89% 
89% 
96.8 
206 
 
9.2.3. 
Sample Size Re-estimation or Adjustment 
No sample-size re-estimation based on response data is planned for this study. 
9.2.4. 
Sample Size Considerations for Week 124 Extension Switch 
Analysis 
For the Week 124 Extension Switch population analysis (Section 9.3.1.6), the primary 
efficacy endpoint of interest is the proportion of participants without oral lead-in who 
have HIV-1 RNA ≥50 c/mL at Week 124 (i.e., 24 weeks from initiation of CAB LA + 
RPV LA, ±6-week analysis window, using the FDA Snapshot algorithm).  The endpoint 
will be evaluated descriptively, with no formal statistical comparison to data generated in 
participants receiving oral lead-in by to initiation of CAB LA + RPV LA.  
Table 14 presents the precision in estimation according to sample size and observed 
proportion with HIV-1 RNA ≥ 50 c/mL.  For example, if the observed rate is 3% and 250 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
166 
 
Extension switch participants do not receive oral lead-in, then the upper bound of the 
95% CI would be 5.1%.    
 
Table 14 
Precision (Upper Limit of 95% CI) for Single Arm Proportion  
Sample Size  
without Oral Lead-In 
Observed Proportion 
HIV-1 RNA ≥ 50 c/mL 
Upper limit of 95% Confidence 
Interval† 
175 
2% 
4.1% 
200 
2% 
3.9% 
225 
2% 
3.8% 
250 
2% 
3.7% 
175 
3% 
5.5% 
200 
3% 
5.4% 
225 
3% 
5.2% 
250 
3% 
5.1% 
175 
4% 
6.9% 
200 
4% 
6.7% 
225 
4% 
6.6% 
250 
4% 
6.4% 
† Two-sided confidence Interval calculated using the Wald normal approximation method. 
9.3. 
Data Analysis Considerations 
9.3.1. 
Analysis Populations 
9.3.1.1. 
All Participants Enrolled 
The All Participants Enrolled population will consist of all enrolled participants who 
receive at least one dose of study drug in the Induction Phase.  The All Participants 
Enrolled population will be the secondary population for some analyses.  
9.3.1.2. 
Intent-to-Treat Exposed Population (ITT-E) 
The ITT-E population consists of all randomized participants who receive at least one 
dose of IP during the Maintenance Phase of the study (on or after Day 1 visit).  
Participants will be analyzed according to the randomized treatment regardless of what 
treatment was actually received.  Unless stated otherwise, the population used in the 
primary efficacy analysis will be the ITT-E population. 
9.3.1.3. 
Per-Protocol Exposed Population (PP) 
The Per-Protocol (PP) Population will consist of all participants in the ITT-E Population 
with the exception of major protocol violators.  The PP will be used for sensitivity 
analysis of the primary endpoint. 
9.3.1.4. 
Safety Population 
The Safety Population will consist of all randomized participants who receive at least one 
dose of IP during the Maintenance Phase of the study (on or after Day 1 visit).  
Participants will be assessed according to actual treatment received.  Unless otherwise 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
167 
 
stated, the Safety Population will be used for safety analyses. 
9.3.1.5. 
PK Population 
The PK Population will include all participants who receive CAB and / or RPV and 
undergo PK sampling during the study, and provide evaluable CAB and /or RPV plasma 
concentration data.  Participants in this population will be included in the PK analysis. 
9.3.1.6. 
Extension Switch Population (ES) 
The Extension Switch population will include all participants randomized to the 
Maintenance Phase ABC/DTC/3TC arm who switch to and receive at least one dose of 
CAB and/or RPV during the Extension Phase of the study.  The ES population will be 
used to evaluate safety and efficacy of switching to CAB LA + RPV LA, with and 
without oral lead-in. Participants will be assessed according to actual treatment received 
during the Extension Phase. 
9.3.2. 
Treatment Comparisons 
9.3.2.1. 
Primary Comparison of Interest 
The primary analysis will be based on the ITT-E population using the Snapshot dataset.  
The primary comparison of will be made at a one-sided 2.5% level of significance. 
Treatment with CAB LA + RPV LA will be declared non-inferior to current ART if the 
upper end of a two-sided 95% confidence interval for the difference between the two 
groups (CAB LA + RPV LA – current ART) in virologic failure rates at Week 48 lies 
below 6%. 
9.3.2.2. 
Other Comparisons of Interest 
The analysis described above will also be performed using the PP population and the 
results will be compared for consistency with the results from the ITT-E population.   
9.3.2.3. 
Secondary comparisons 
The following key secondary comparisons will be tested: 
• Treatment with CAB LA + RPV LA will be declared non-inferior to current ART if 
the lower end of a two-sided 95% confidence interval for the difference between the 
two groups in response rates at Week 48 lies above -10%. 
• Superiority of CAB LA + RPV LA compared to continuation of current ART with 
respect to change from baseline HIVTSQs total score at Week 44. 
• Changes in the PIN acceptance score within the CAB LA + RPV LA arm over time. 
9.3.3. 
Planned Analyses 
At least three analyses will be conducted to evaluate the objectives of the protocol: after 
all randomized participants have completed their visits at Week 48 and Week 96, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
168 
 
respectively, and after all Extension switch participants (Section 9.3.1.6) have completed 
the Week 124 visit.  Further data cuts and analyses may be conducted as necessary after 
Week 96 in order to support regulatory submissions and publications.  The Week 48 
analysis will be primary.  No adjustment for multiplicity caused by repeated evaluation of 
the primary endpoint will be made as the Week 96 analyses will be secondary.  
An IDMC will be instituted to ensure external objective medical and/or statistical review 
of efficacy and safety in order to protect the ethical interests and well-being of subjects 
and to protect the scientific validity of this study and study 201585.  An ad-hoc review of 
data by the IDMC will be triggered whenever the number of CVFs (Section 5.4.4) in the 
CAB LA + RPV LA arm exceeds thresholds pre-specified in the IDMC charter.  Further, 
an interim futility analysis will be performed for the IDMC to evaluate the efficacy and 
safety of CAB LA + RPV LA when approximately 50% of subjects have completed their 
visit at Week 24; the sponsor will remain blinded to this analysis.  Full details of the 
methods, timing, decision criteria and operating characteristics will be pre-specified in 
the IDMC Charter. 
Since the statistical stopping guidelines will not result in early stopping for positive 
efficacy findings, these planned analyses will not inflate the type I error rate for the 
primary treatment comparison at Week 48. 
9.4. 
Key Elements of Analysis Plan 
The study design is open-label.  However, the central team responsible for the conduct 
and analysis of the study will not review any summaries of data grouped by treatment 
prior to database freeze for the primary Week 48 analysis. 
201584 is conducted in parallel with study 201585 with the aim to pool data generated 
from the current study with study 201585, in order to evaluate key program objectives. 
9.4.1. 
Primary Analyses 
For the primary efficacy analysis, each participant’s response (e.g., virologic failure) will 
be calculated according to the FDA’s Snapshot algorithm.  The primary analysis at 
Week 48 will take place after the last participant has had their Week 48 viral load 
assessed, including a retest if required.  This algorithm treats all participants without 
HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of study 
drug prior to visit window) as non-responders, as well as subjects who switch their 
concomitant ART prior to the visit of interest since no switches are allowed in this 
protocol after randomization into the Maintenance Phase.  Otherwise, virologic success 
or failure will be determined by the last available HIV-1 RNA assessment while the 
participant is on-treatment within the window of the visit of interest.  Full details on the 
Snapshot algorithm will be contained in the RAP. 
The primary analysis will be based on the ITT-E population using the Snapshot dataset. 
The primary comparison will be made at a one-sided 2.5% level of significance. 
Treatment with CAB LA + RPV LA will be declared non-inferior to continued 
ABC/DTG/3TC if the upper end of a two-sided 95% confidence interval for the 
difference between the two groups (CAB LA + RPV LA – ABC/DTG/3TC) in virologic 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
169 
 
failure rates at Week 48 lies below 6%. 
For the primary comparison, adjusted estimates of the difference in the rate of failures 
between the two arms will be presented along with CIs based on a stratified analysis 
using CMH weights.  All CIs will be two-sided and the analysis will be stratified 
according to the Baseline HIV-1 RNA (<100,000, ≥100,000 c/mL) and gender at birth.  If 
the adjusted treatment difference is not estimable due to overly sparse stratification 
and/or low number of subjects with virologic failure, then the primary comparison will be 
adjusted for Baseline HIV-1 RNA only; if this also encounters numerical issues then the 
primary comparison will be based on the unadjusted analysis. 
The CMH estimate of the common difference in rates across strata will be calculated as 
the weighted average of the strata-specific estimates of the difference in response rates 
between the two arms as follows: 
• 
If nk is the number of CAB LA + RPV LA treated participants, mk is the number 
of ABC/DTG/3TC control arm treated participants, and Nk = nk + mk is the total 
number of participants in the kth stratum, then the CMH estimate is given by 
 
where 
 
are CMH weights and 
 are estimates of the differences in response rates 
between the two treatment arms, fla-fc, for the kth stratum using the variance 
estimator 
, given by [Sato, 1989], which is consistent in both sparse 
data and large strata.  The full equation for this variance estimate will be provided 
in the RAP. 
The weighted least squares chi-squared statistic [Fleiss, 1981] will be used to test for one-
way homogeneity across the levels of each categorical variable, with each categorical 
variable considered separately.  Following Lui and Kelly [Lui, 2000], ½ will be added to 
each cell in any strata for which the stratum-specific rate estimates of either fla or fc are 
zero or one, and tests will be one-sided.  Any heterogeneity found to be statistically 
significant will be explored and if necessary results will be reported for each level of the 
categorical variable.  Investigation of heterogeneity will be confined to the primary 
endpoint using the Week 48 Snapshot analysis.  Tests of homogeneity will be assessed at 
the one-sided 10% level of significance.  Full details will be contained in the RAP. 
On-treatment data collected from extra visits within a window will be included in the 
derivation of the Snapshot response/failure but summary tables using observed case (OC) 
∑
∑
=
k
k
k
cmh
W
d
W
d
ˆ
ˆ
 
 
k
dˆ
 
)
ˆ
r(
aˆ
v
cmh
d


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
170 
 
datasets will only use the data captured closest to the target visit date.  Detailed 
explanations of the derivation of visit windows will be included in the RAP.  Any 
changes to the original analysis plan in the protocol will be described in the RAP and/or 
clinical study report (CSR). 
The analysis described above will also be performed using the PP population and the 
results will be compared for consistency with the results from the ITT-E population.   
9.4.2. 
Secondary Analyses 
A key secondary analysis will evaluate the proportion of responders (HIV-1 RNA 
<50 c/mL per Snapshot) at Week 48 using a Cochran-Mantel Haenszel test stratified by 
randomization stratification factors.  A non-inferiority margin of -10% will be used for 
this secondary comparison, where if the lower limit of the 95% confidence interval (CI) 
of the difference in responder rate between the two study arms is greater than -10%, non-
inferiority will be demonstrated. 
Proportion of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL, and HIV-1 
RNA ≥200 c/mL and ≥50 c/mL, respectively, over time will be summarized using the 
Snapshot algorithm.   
Proportion of participants with confirmed virologic failure will also be summarized over 
time.  
Secondary analyses of efficacy data will include a repeat of the primary snapshot analysis 
of virologic failure and virologic success, as detailed above, at Week 96.  
Absolute values and change from Baseline in plasma HIV-1 RNA and CD4+ cell count 
will be summarized over time. 
The incidence of HIV-1 disease progression (AIDS and death) will be presented. 
The observed case dataset will be the primary dataset used for analysis of safety 
endpoints. 
The proportion of participants reporting AEs will be tabulated for each treatment group. 
The following summaries of AEs will be provided: 
• Incidence and severity of all AEs 
• Incidence and severity of treatment related AEs 
• Incidence and severity of AEs leading to withdrawal 
• Incidence of SAEs 
Changes from Baseline in laboratory (including fasting lipids) and vital signs data will be 
summarized.  Vital signs at Day 1 will be summarized.  In addition, the number and 
percentage of participants with graded laboratory toxicities (based on DAIDS categories) 
will be summarized by treatment group. 
Change from Baseline in renal and bone biomarkers will be summarized by treatment and 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
171 
 
visit.  
9.4.2.1. 
Week 124 Extension Switch Analysis 
For the Week 124 Extension Switch population analysis (Section 9.3.1.6), antiviral 
response will be assessed according to the proportion of participants with and without 
oral lead-in, respectively, who have HIV-1 RNA ≥50 c/mL at Week 124 (i.e., 24 weeks 
from initiation of CAB LA + RPV LA, ±6 week analysis window, using the FDA 
Snapshot algorithm), with corresponding 95% confidence interval.  The primary efficacy 
endpoint of interest for this analysis is the proportion of participants without oral lead-in 
who have HIV-1 RNA ≥50 c/mL at Week 124. No formal statistical comparison with 
respect to safety and efficacy outcomes will be performed. 
Proportion of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL and 
confirmed virologic failure, respectively, over time will be summarized. 
Absolute values and change from Extension Baseline CD4+ cell count will be 
summarized over time. 
The proportion of participants reporting AEs will be tabulated for each treatment group. 
The following summaries of AEs will be provided: 
• Incidence and severity of all AEs 
• Incidence and severity of treatment related AEs 
• Incidence and severity of AEs leading to withdrawal 
• Incidence of SAEs 
Changes from Extension Baseline in laboratory (including fasting lipids) and vital signs 
data will be summarized.  In addition, the number and percentage of participants with 
Extension emergent graded laboratory toxicities (based on DAIDS categories) will be 
summarized by treatment group. 
Further details for secondary efficacy, safety and exploratory analyses will be included in 
the RAP.   
9.4.3. 
Pharmacokinetic Analyses 
The GSK Division of Clinical Pharmacology Modelling and Simulation (CPMS) will be 
responsible for the PK analysis of CAB.  The Divisions of Clinical Pharmacology and 
Model-Based Drug Development at Janssen Research and Development will be 
responsible for conduct or oversight of the PK analysis for RPV.  
Actual sampling and dosing times as recorded in the eCRF will be used for analysis.   
Plasma CAB and RPV concentration data will be listed and summarized by week, day, 
and planned sampling time in both tabular and graphical forms.  A composite predose 
(C0) concentration may be estimated for purposes of PK/PD analysis.  Post hoc estimates 
of PK parameters will be determined by population PK modeling separately (see 
Population PK Analysis below). 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
172 
 
Population PK Analysis: 
CAB and RPV population PK models will be constructed separately and individual 
Bayesian PK parameter estimates may be obtained, if the quality of the data permits.  
Data from this study may be merged with previous data to support the model building 
process.  Sources of variability in pharmacokinetic parameters will be investigated during 
population modeling.  Demographic parameters including, but not limited to age, gender, 
ethnic origin, body size (weight, height, body surface area, body mass index), and 
relevant laboratory parameters, will be evaluated as potential predictors of inter- and 
intra-participant variability for pharmacokinetic parameters.  Population pharmacokinetic 
modeling will be performed using the non-linear mixed effects software NONMEM 
(ICON; Hanover, MD).  Further details of population pharmacokinetic analyses will be 
described in a separate RAP.  Population PK analyses will be done under separate 
Population-PK Reporting and Analysis Plans, and post hoc PK parameters may be 
determined. 
9.4.4. 
Pharmacokinetic/Pharmacodynamic Analyses 
• Relationships between various plasma CAB and / or RPV PK parameters and 
pharmacodynamic measures (e.g., HIV-1 RNA, or safety measures) may be explored 
using simple correlation analyses or population-based PK/PD approach.  Additional 
factors that may be considered include, e.g. age, weight, BMI, gender, race, Baseline 
HIV-1 RNA, HIV risk factors, CDC classification, and CD4+ cell count.   
Exploratory analyses will be performed to examine the relationship(s) between plasma 
concentrations of CAB and RPV and pharmacodynamic endpoints.  A population 
pharmacokinetic/pharmacodynamic modeling approach may be further applied to model 
the data using the nonlinear mixed effect modeling software, NONMEM (ICON LLC, 
Hanover, MD).  Details of the PK/PD analyses plans for CAB and / or RPV will be 
provided in separate RAPs. 
9.4.5. 
Viral Genotyping/Phenotyping Analyses 
• The incidence of treatment emergent genotypic and phenotypic resistance will be 
summarized by treatment arm for subjects meeting confirmed virologic failure criteria 
(Section 5.4.4).  Details of the analyses to be performed will be specified in the 
reporting and analysis plan (RAP). 
9.4.6. 
Health Outcomes Analyses 
Statistical analysis of the key secondary comparisons (Section 7.9.1) for the change from 
baseline in HIVTSQs total score at Week 44 (between treatment group comparison) and 
within treatment group change in PIN acceptance score for subjects randomized to CAB 
LA + RPV LA will be performed using appropriate methods for missing data.  
Further details of the analyses to be performed will be specified in the reporting and 
analysis plan (RAP).  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
173 
 
9.4.7. 
Other Analyses 
The proportion of participants with virologic failure (FDA Snapshot algorithm) and HIV-
1 RNA <50 c/mL (FDA snapshot algorithm), respectively, over time including Week 48 
and Week 96 will be analysed by important demographic and baseline characteristic 
subgroups factors (e.g. age, gender, BMI, race, HIV-1 subtype, and Baseline CD4+ cell 
counts).  Changes from baseline in CD4+ lymphocyte count at Week 48 and Week 96 
will also be summarized by subgroups.  Additional details on subgroup analyses will be 
provided in the RAP.   
Longer term antiviral and immunological effect, safety and tolerability of CAB LA + 
RPV LA will be assessed through Week 96 for the CAB LA + RPV LA arm in the 
Maintenance Phase.  Antiviral and immunological effect, safety and tolerability of CAB 
LA + RPV LA will also be evaluated for participants switching to CAB LA + RPV LA in 
the Extension Phase. 
Further details of exploratory analyses will be presented in the RAP. 
10. 
STUDY GOVERNANCE CONSIDERATIONS 
10.1. 
Posting of Information on Publicly Available Clinical Trial 
Registers 
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of participants begins. 
10.2. 
Regulatory and Ethical Considerations, Including the 
Informed Consent Process 
Prior to initiation of a site, ViiV Healthcare/GSK will obtain favourable opinion/approval 
from the appropriate regulatory agency to conduct the study in accordance with ICH 
Good Clinical Practice (GCP) and applicable country-specific regulatory requirements. 
The study will be conducted in accordance with all applicable regulatory requirements, 
and with GSK policy. 
The study will also be conducted in accordance with ICH Good Clinical Practice (GCP), 
all applicable participant privacy requirements, and the guiding principles of the current 
version of the Declaration of Helsinki.  This includes, but is not limited to, the following: 
• 
The IEC/IRB, and where applicable the regulatory authority, approve the clinical 
protocol and all optional assessments, including genetic research.   
• 
Optional assessments (including those in a separate protocol and/or any under a 
separate informed consent) and the clinical protocol should be concurrently 
submitted for approval unless regulation requires separate submission.   
• 
Approval of the optional assessments may occur after approval is granted for the 
clinical protocol where required by regulatory authorities.  In this situation, 
written approval of the clinical protocol should state that approval of optional 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
174 
 
assessments is being deferred and the study, with the exception of the optional 
assessments, can be initiated. 
• 
Signed informed consent must be obtained for each participant prior to 
participation in the study 
• 
Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IRB/IEC) 
• 
ViiV Healthcare/GSK will provide full details of the above procedures, either 
verbally, in writing, or both. 
• 
If follow-up information from a treating physician or other licensed medical 
practitioner is required for a medical device incident with an AE/SAE involving 
an associated person(s), the Associated Person Safety Reporting Information and 
Authorization Letter must be signed by the associated person to obtain consent.  
10.3. 
Quality Control (Study Monitoring) 
• 
In accordance with applicable regulations including GCP, and GSK procedures, 
GSK monitors will contact the site prior to the start of the study to review with the 
site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK requirements.   
• 
When reviewing data collection procedures, the discussion will also include 
identification, agreement and documentation of data items for which the eCRF 
will serve as the source document. 
GSK will monitor the study and site activity to verify that the: 
• 
Data are authentic, accurate, and complete. 
• 
Safety and rights of participants are being protected. 
• 
Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents 
10.4. 
Quality Assurance 
• 
To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and 
the regulatory agencies may conduct a regulatory inspection at any time during or 
after completion of the study.  
• 
In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss 
the conduct of the study, any findings/relevant issues and to implement any 
corrective and/or preventative actions to address any findings/issues identified. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
175 
 
10.5. 
Study and Site Closure 
• 
Upon completion or premature discontinuation of the study, the GSK monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSK Standard 
Operating Procedures. 
• 
GSK reserves the right to temporarily suspend or prematurely discontinue this 
study at any time for reasons including, but not limited to, safety or ethical issues 
or severe non-compliance. For multicenter studies, this can occur at one or more 
or at all sites.   
• 
If GSK determines such action is needed, GSK will discuss the reasons for taking 
such action with the investigator or the head of the medical institution (where 
applicable).  When feasible, GSK will provide advance notification to the 
investigator or the head of the medical institution, where applicable, of the 
impending action. 
• 
If the study is suspended or prematurely discontinued for safety reasons, GSK will 
promptly inform all investigators, heads of the medical institutions (where 
applicable) and/or institution(s) conducting the study. GSK will also promptly 
inform the relevant regulatory authorities of the suspension or premature 
discontinuation of the study and the reason(s) for the action.   
• 
If required by applicable regulations, the investigator or the head of the medical 
institution (where applicable) must inform the IRB/IEC promptly and provide the 
reason for the suspension or premature discontinuation. 
10.6. 
Records Retention 
• 
Following closure of the study, the investigator or the head of the medical 
institution (where applicable) must maintain all site study records (except for 
those required by local regulations to be maintained elsewhere), in a safe and 
secure location.   
• 
The records must be maintained to allow easy and timely retrieval, when needed 
(e.g., for a GSK audit or regulatory inspection) and must be available for review 
in conjunction with assessment of the facility, supporting systems, and relevant 
site staff.   
• 
Where permitted by local laws/regulations or institutional policy, some or all of 
these records can be maintained in a format other than hard copy (e.g., microfiche, 
scanned, electronic); however, caution needs to be exercised before such action is 
taken.   
• 
The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, 
including re-generating a hard copy, if required.  Furthermore, the investigator 
must ensure there is an acceptable back-up of these reproductions and that an 
acceptable quality control process exists for making these reproductions. 
• 
GSK will inform the investigator of the time period for retaining these records to 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
176 
 
comply with all applicable regulatory requirements.  The minimum retention time 
will meet the strictest standard applicable to that site for the study, as dictated by 
any institutional requirements or local laws or regulations, GSK 
standards/procedures, and/or institutional requirements.   
• 
The investigator must notify GSK of any changes in the archival arrangements, 
including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated with 
the site. 
10.7. 
Provision of Study Results to Investigators, Posting of 
Information on Publically Available Clinical Trials Registers 
and Publication 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location. 
GSK will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study participants, as 
appropriate. 
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy. 
10.8. 
Review Committee 
10.8.1. 
Independent Data Monitoring Committee 
An IDMC will be utilized in this study to ensure external objective medical and/or 
statistical review of safety and/or efficacy issues in order to protect the ethical and safety 
interests of participants and to protect the scientific validity of the study.  The schedule of 
any planned interim analysis and the analysis plan for IDMC review is described in 
Section 4.2.8 and the IDMC charter, which is available upon request. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
177 
 
11. 
REFERENCES 
Andrade RJ, Robles M, Lucena MI.  Rechallenge in drug-induced liver injury: the 
attractive hazard.  Expert Opin Drug Saf 2009;8(6):709-714. 
Arribas J, Clumeck N, Nelson M, et al. The MONET trial: week 144 analysis of the 
efficacy of darunavir/ritonavir (DRV/r) monotherapy versus DRV/r plus two nucleoside 
reverse transcriptase inhibitors, for patients with viral load <50 copies/ml at baseline. HIV 
MED, 2012: Aug;13(7):398-405. 
Arribas J, Girard PM, Landman R,et al.  Dual treatment with lopinavir-ritonavir plus 
lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or 
emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor.  Lancet Infect 
Dis., 2015: 15:785-792. 
Arribas JR, Pialoux G, Gathe J, et al. Simplification to coformulated elvitegravir, 
cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease 
inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV 
(STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority 
trial. Lancet Infect Dis. 2014;14:581-589. 
Bierman WF, van Aqtamael MA, Nijhuis M, et al. HIV monotherapy with ritonavir-
boosted protease inhibitors: a systematic review. AIDS, 2009; 23(3):279-291. 
Centers for Disease Control and Prevention (CDC). Revised Surveillance Case Definition 
for HIV Infection – United States, 2014. MMWR 2014; 63 (RR-03);1-10. 
Chevat C, Viala-Danten M, Dias-Barbosa C, et al. Development and psychometric 
validation of a self-administered questionnaire assessing the acceptance of influenza 
vaccination: the Vaccinees' Perception of Injection (VAPI©) questionnaire.  Health Qual 
Life Outcomes. 2009;7:21. 
Department of Health and Human Services (DHHS). Panel on Antiretroviral Guidelines 
for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-
infected adults and adolescents. Updated April 08, 2015. Available at: 
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0 
Department of Health and Human Services, Food and Drug Administration, Center for 
Drug Evaluation and Research (US). Guidance for Industry.  Human Immunodeficiency 
Virus-1 Infection: Developing Antiretroviral Drugs for Treatment, Revision 1, 
November 2015.  Available at:  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/defaul
t.htm 
Dube MP, Stein JH, Aberg JA, et al. Guidelines for the evaluation and management of 
dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving 
antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious 
Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis 
2003; 37(5):613-627. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
178 
 
Edurant Prescribing Information, February 2018. 
Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in 
Children and Adolescents. Pediatrics 2011;128;S213; originally published online 
November 14, 2011; DOI: 10.1542/peds.2009-2107C. 
Fleiss JL. Statistical Methods for Rates and Proportions. 2nd ed. New York:John Wiley; 
1981. 
GlaxoSmithKline Document Number 2011N112455_03: LAI115428: A Randomized, 
Open Label Study to Investigate the Safety, Tolerability and Pharmacokinetics of Repeat 
Dose Administration of Long-Acting GSK1265744 and Long-Acting TMC278 
Intramuscular and Subcutaneous Injections in Healthy Adult.  Effective Date:  
04Feb2013.   
GlaxoSmithKline Document Number 2011N130484_00:  LAI116181: A Phase 1, Open-
Label, Crossover Study to Evaluate the Pharmacokinetics and Safety of GSK1265744 
and Rilpivirine and Dolutegravir and Rilpivirine in Healthy Adult Subjects.  Effective 
Date:  18Jul2012. 
GlaxoSmithKline Document Number 2014N216014_00: LAI116482:  A Phase IIb, Dose 
Ranging Study of Oral GSK1265744 in Combination with Nucleoside Reverse 
Transcriptase Inhibitors for Induction of HIV-1 Virologic Suppression Followed by an 
Evaluation of Maintenance of Virologic Suppression when Oral GSK1265744 is 
Combined with Oral Rilpivirine in HIV-1 Infected, Antiretroviral Therapy Naive Adult 
Subjects - Week 96 Results.  Effective Date 02Sept2015. 
GlaxoSmithKline Document Number 2016N269422_00: 201120: A Phase IIa Study to 
Evaluate the Safety, Tolerability and Acceptability of Long Acting Injections of the HIV 
Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ÉCLAIR) –Week 81 Results. 
Effective Date: 25Oct2016. 
GlaxoSmithKline Document Number RH2009/00003/07: GSK1265744 (Cabotegravir) 
Clinical Investigator's Brochure, Version 07, December 2017. 
GlaxoSmithKline Document Number RM2007/00683/11: GSK1349572 Clinical 
Investigator's Brochure, Version 11, 13 October 2017; Supplement 01, 11 Dec 2017; 
Supplement 02, Jun 2018. 
Hatcher RA, Trussell J, Nelson AL, et al, Contraceptive Technology. 20th edition. 
Atlanta, Georgia: Ardent Media, Inc., 2011: 50.Table 3-2. 
Holmes WC, Shea JA. A new HIV/AIDS-targeted quality of life (HAT-QoL) instrument: 
development, reliability, and validity. Med Care. 1998 Feb;36(2):138-154. 
Hunt CM.  Mitochrondrial and Immunoallergic Injury Increase Risk of Positive Drug 
Rechallenge After Drug-Induced Liver Injury:  A Systematic Review.  Hepatol 
2010;52:2216-2222.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
179 
 
International Antiviral Society ( IAS)–USA ART Treatment of Adult HIV Infection: 
2015 Recommendations of the International Antiviral Society-USA Panel. Wensing AM 
et al. 2015 update of the drug resistance mutations in HIV-1. Topics in Antiviral 
Medicine October/November 2015: 23(4). Available at: 
http://www.iasusa.org/sites/default/files/tam/23-4-132.pdf. date accessed 22Mar2016.] 
International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use.  ICH Harmonised Tripartite Guideline; Clinical 
Safety Data Management:  Definitions and Standards for Expedited Reporting E2A.  
27Oct1994.  Available at:  
https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2A
/Step4/E2A_Guideline.pdf 
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of acetaminophen-protein 
adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab 
Dispos 2009;37(8):1779-1784.  
Levey AS, Stevens LA, Schmid CH, et.al. A new equation to estimate glomerular 
filtration rate.  Ann Int Med. 2009; 150: 604-612. 
Lui KJ, Kelly C. A revisit on tests for the homogeneity of the risk difference. Biometrics. 
2000; 56: 309-315. 
Marant C, Longin J, Gauchoux R, et al. Long-term treatment acceptance: what is it, and 
how can it be assessed? Patient. 2012;5(4):239-249. 
Martinez E, Larrousse M, Llibre JM, et al. Substitution of raltegravir for ritonavir-
boosted protease inhibitors in HIV-infected patients: the SPIRAL study. 
AIDS 2010;24:1697-1707. 
McGowan I, Siegel A, Engstrom J et al.  Persistence of Rilpivirine Following Single 
Dose of Long-Acting Injection.  21st International AIDS Conference (AIDS 2016).  
Durban, South Africa.  Abstract TUAC0103. 
Palella F, Tebas P, Gazzard B, et.al. SPIRIT study: switching to 
emtricitabine/rilpivirine/tenofovir df (FTC/RPV/TDF) single-tablet regimen (STR) from 
a ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors 
(NRTIS) maintains HIV suppression and improves seru. 19th International AIDS 
Conference: Abstract no. TUAB0104. 2014. 
Papay JI, Clines D, Rafi R, et al.  Drug-induced liver injury following drug rechallenge.  
Regul Tox Pharm 2009;54:84-90.  
Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification 
Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the 
FDA’s pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 
2007;164:1035–1043. 
Pozniak A, Markowitz M, Mills A, et al. Switching to coformulated elvitegravir, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
180 
 
cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse 
transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults 
with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b 
non-inferiority trial. Lancet Infect Dis. 2014;14:590-599. 
Raffi F, Jaeger H, Quiros-Roldan E, et al. Once-daily dolutegravir versus twice-daily 
raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 
week results from a randomised, double-blind, non-inferiority trial.  Lancet Infect Dis. 
2013;13(11):927-935.  
Rilpivirine Clinical Investigator Brochure [RPV IB], Edition Number 10, April 2017. 
Sato T. On the variance estimator for the Mantel-Haenszel risk difference. 
Biometrics.1989;45:1323-1324. 
TIVICAY Prescribing Information, November 2017. 
TRIUMEQ Prescribing Information, May 2018. 
Walmsley S, Baumgarten A, Berenguer J, et al.  Dolutegravir Plus Abacavir/Lamivudine 
for the Treatment of HIV-1 Infection in Antiretroviral Therapy-Naive Patients: Week  96 
and Week 144 Results from the SINGLE Randomized Clinical Trial.  J Acquir Immune 
Defic Syndrome.  2015; 70(5): 515-519. 
Ware JE, Kosinski M, Keller SD. SF-12: How to Score the SF-12 Physical and Mental 
Health Summary Scales. Boston, MA: The Health Institute, New England Medical 
Center, Second Edition, 1995. 
Woodcock A, Bradley C . Validation of the HIV treatment satisfaction questionnaire 
(HIVTSQ). Qual Life Res. 2001;10(6):517-531. 
Woodcock A, Bradley C. Validation of the revised 10-item HIV Treatment Satisfaction 
Questionnaire status version (HIVTSQs) and new change version (HIVTSQc). Value in 
Health. 2006;9(5):320-333. 
World Health Organization (WHO) Growth Reference:  Available at 
http://www.who.int/growthref/who2007_bmi_for_age/en/.


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
181 
 
12. 
APPENDICES 
12.1. 
Appendix 1: Abbreviations and Trademarks 
Abbreviations 
ABC 
Abacavir, ZIAGEN 
ABC/3TC 
Abacavir/lamivudine, EPZICOM, KIVEXA 
ACCEPT 
Chronic Treatment Acceptance questionnaire 
ABC/DTG/3TC 
Abacavir/dolutegravir/lamivudine, TRIUMEQ 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AIDS 
Acquired immunodeficiency syndrome 
ALT 
Alanine aminotransferase 
Anti-HBc 
Hepatitis B core Antibody 
Anti-HBsAg 
Antibodies against Hepatitis B surface Antigen 
APAP 
Acetaminophen 
API 
Active pharmaceutical ingredient 
ARV 
Antiretroviral 
ART 
Antiretroviral therapy 
ATV 
Atazanavir 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AUC(0-τ) 
Area under the curve (Area under the plasma drug 
concentration-time curve from pre-dose to the end of the 
dosing interval at steady state) 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CAB 
Cabotegravir 
CAB LA 
Cabotegravir long-acting 
CABG 
Coronary artery bypass grafting 
c/mL 
Copies/milliliter 
CDC 
Centers for Disease Control and Prevention 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
Cmax 
Maximum concentration 
CMH 
Cochran-Mantel Haenszel 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicidality Severity Rating Scale 
CI 
Confidence interval 
CONSORT 
Consolidated Standards of Reporting Trials 
CPK 
Creatine phosphokinase 
CPMS 
Clinical Pharmacology Modelling and Simulation 
CSR 
Clinical Study Report 
CV 
Cardiovascular 
CVF 
Confirmed virologic failure 
CYP3A 
Cytochrome P450 3A 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
182 
 
DAIDS 
Division of Acquired Immunodeficiency Syndrome 
DDI 
Drug-drug interaction 
DILI 
Drug induced liver injury 
DHHS 
Department of Health and Human Services 
DNA 
Deoxyribonucleic acid 
DRE 
Disease-Related Events 
DRESS 
Drug Reaction with Eosinophilia and Systemic Symptoms 
DRV 
Darunavir 
DTG 
Dolutegravir, TIVICAY 
DTP 
Direct to Patient 
ECG 
Electrocardiogram 
eC-SSRS 
Columbia Suicide Severity Rating Scale 
eCRF 
Electronic case report form 
EFV 
Efavirenz 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
ETR 
Etravirine 
EU 
European Union 
EVG 
Elvitegravir 
FC 
Fold change 
FDA 
Food and Drug Administration 
FDC 
Fixed-dose combination 
FSH 
Follicle Stimulating Hormone 
FTC 
Emtricitabine 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 
HAART 
Highly active antiretroviral therapy 
HAT-QoL 
HIV/AIDS-targeted quality of life 
HBc 
Hepatitis B core antibody 
HbsAg 
Hepatitis B surface Antigen 
HBV 
Hepatitis B virus 
hCG 
Human chorionic gonadotrophin 
HCP 
Healthcare Provider 
HCV 
Hepatitis C virus 
HDL 
High density lipoprotein 
HDPE 
High density polyethylene 
HIV 
Human immunodeficiency virus 
HIVTSQ 
HIV treatment satisfaction questionnaire 
HIVTSQc 
HIV treatment satisfaction questionnaire (change version) 
HIVTSQs 
HIV treatment satisfaction questionnaire (status version) 
HLA 
Human leukocyte antigen 
HLA-B 
Major Histocompatibility Complex, Class I, B 
HR 
Heart Rate 
HRQL 
Health-related quality of life 
HSR 
Hypersensitivity reaction 
HRT 
Hormonal replacement therapy 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
183 
 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
IDMC 
Independent data monitoring committee 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
IN 
Integrase 
INI 
Integrase inhibitor 
INR 
International normalized ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ISR 
Injection Site Reactions 
ITT-E 
Intent-to-treat Exposed 
ITT-ME 
Intent-to-treat Maintenance Exposed 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
LA 
Long acting 
LDH 
Lactate Dehydrogenase 
LDL  
Low density lipoprotein 
LLOD 
Lower Limit Of Detection 
LPV 
Lopinavir 
LPV/r 
Lopinavir/ritonavir 
LTFU 
Long-Term Follow Up 
MAA 
Marketing Application Authorization 
MCV 
Mean corpuscular volume 
MedDRA 
Medical dictionary for regulatory activities 
mg 
Milligram 
mg/dL 
Milligram per deciliter 
MHRA 
Medicines and Healthcare products Regulatory Agency 
m-ITT 
modified Intent to Treat 
MSD=F 
Missing, switch, or discontinuation equals failure 
MSDS 
Master Safety Data Sheet 
ng/mL 
Nanogram per millileter 
NNRTI 
Non-nucleoside reverse transcriptase inhibitor 
NRS 
Numeric Rating Scale 
NRTI 
Nucleoside reverse transcriptase inhibitor 
OC 
Observed case 
OLE 
Study Name for: Dual treatment with lopinavir-ritonavir 
plus lamivudine versus triple treatment with lopinavir-
ritonavir plus lamivudine or emtricitabine and a second 
nucleos(t)ide reverse transcriptase inhibitor for 
maintenance of HIV-1 viral suppression 
PA IC90 
Protein adjusted 90% inhibitory concentration 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
184 
 
PBMC 
Peripheral Blood Mononuclear Cell 
PI 
Protease inhibitor 
PI 
Prediction interval 
PIN 
Perception of iNjection questionnaire 
PI/r 
Ritonavir-Boosted Protease Inhibitor 
PK 
Pharmacokinetic 
PP 
Per-protocol 
PrEP 
Pre-Exposure Prophylaxis 
PRO 
Protease 
PRTD 
Proximal renal tubule dysfunction 
PSRAE 
Possible suicidality-related adverse event 
PT 
Prothrombin Time 
PTCA 
Percutaneous transluminal coronary angioplasty 
PTI 
Partial Thromboplastin Time 
Q4W 
Every 4 weeks 
Q8W 
Every 8 weeks 
QTc 
Corrected QT interval  
RAL 
Raltegravir 
RAMOS NG 
Randomization and Medication Ordering System Next 
Generation 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cell 
RBP 
Retinol binding protein 
RNA 
Ribonucleic acid 
RPR 
Rapid plasma reagin 
RPV 
Rilpivirine, Edurant 
RPV LA 
Rilpivirine long-acting 
RT 
Reverse transcriptase 
RTV, r 
Ritonavir 
SAE 
Serious adverse event 
SF 
Short form survey 
SJS 
Stevens-Johnson syndrome 
SOC 
Standard of care 
SPM 
Study Procedures Manual 
STR 
Single tablet regimen 
SVF 
Suspected Virological Failure 
TAF 
Tenofovir alafenamide 
TB 
Tuberculosis 
TDF 
Tenofovir disoproxil fumarate 
TEN 
Toxic epidermal necrolysis 
Tmax 
Time to maximum concentration 
TMC278 
Tibotec Medicinal Compound 278 
TSQ 
Treatment Satisfaction Questionnaire 
ULN 
Upper limit of normal 
UGT 
Glucuronosyltransferase 
US 
United States 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
185 
 
USP 
United States pharmacopeia 
VAPI  
Vaccines' Perception of Injection 
VAS 
Visual Analog Scale 
VSLC 
ViiV Safety and Labeling Committee 
WBC 
White blood cell 
WOCBP 
Woman of Childbearing Potential 
EQ-5D-5L 
European Quality of Life-5 Dimensions 
3TC 
Lamivudine, EPIVIR 
201584 
FLAIR (First Long-Acting Injectable Regimen 
 
Trademark Information 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by the ViiV 
Healthcare 
EPIVIR 
 
Edurant 
EPZICOM/KIVEXA 
 
GenoSure 
TIVICAY 
 
Genvoya 
TRIUMEQ 
 
Monogram Biosciences 
TRIZIVIR 
 
PhenoSense 
ZIAGEN 
 
Stribild 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
186 
 
12.2. 
Appendix 2: Division Of AIDS Table For Grading The Severity 
Of Adult And Pediatric Averse Events Version 2.0, November 
2014 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (“DAIDS AE Grading Table”) is a descriptive terminology which can be utilised 
for Adverse Event (AE) reporting.  A grading (severity) scale is provided for each AE 
term. 
Estimating Severity Grade for Parameters Not Identified in the Grading Table 
The functional table below should be used to grade the severity of an AE that is not 
specifically identified in the grading table.  In addition, all deaths related to an AE are to 
be classified as grade 5. 
 
PARAMETERGRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Clinical 
adverse 
event  NOT 
identified 
elsewhere in 
the 
grading table 
Mild 
symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities with 
intervention 
not indicated 
Moderate 
symptoms 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities with 
intervention 
indicated 
Severe 
symptoms 
causing 
inability to 
perform 
usual social 
& functional 
activities 
with 
intervention 
or 
hospitalizatio
n indicated 
Potentially life-
threatening 
symptoms causing 
inability to perform 
basic self-care 
functions with 
intervention 
indicated to 
prevent permanent 
impairment, 
persistent 
disability, or death 
 
Major Clinical Conditions 
Cardiovascular 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Arrhythmia 
(by ECG or 
physical 
examination) 
Specify type, if 
applicable 
No 
symptoms 
AND No 
intervention 
indicated 
No symptoms 
AND Non-
urgent 
intervention 
indicated 
Non-life-
threatening 
symptoms  
AND Non-
urgent 
intervention 
indicated 
Life-threatening 
arrhythmia OR 
Urgent 
intervention 
indicated 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
187 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Blood Pressure 
Abnormalities 1 
Hypertension 
(with the 
lowest reading 
taken after 
repeat testing 
during a visit) 
≥ 18 years of 
age 
140 to < 160 
mmHg 
systolic 
OR 
90 to < 100 
mmHg 
diastolic 
≥ 160 to < 
180 
mmHg 
systolic 
OR 
≥ 100 to < 
110 
mmHg 
diastolic 
≥ 180 mmHg 
systolic 
OR 
≥ 110 mmHg 
diastolic 
Life-threatening 
consequences in a 
participant not 
previously 
diagnosed with 
hypertension (e.g., 
malignant 
hypertension) OR 
Hospitalization 
indicated 
< 18 years of 
age 
> 120/80 
mmHg 
≥ 95th to < 99th 
percentile + 5 
mmHg 
adjusted for 
age, height, 
and gender 
(systolic 
and/or 
diastolic) 
≥ 99th 
percentile + 5 
mmHg 
adjusted for 
age, height, 
and gender 
(systolic 
and/or 
diastolic) 
Life-threatening 
consequences in a 
participant not 
previously 
diagnosed with 
hypertension (e.g., 
malignant 
hypertension) OR 
Hospitalization 
indicated 
Hypotension 
No symptoms Symptoms 
corrected with 
oral fluid 
replacement 
Symptoms 
AND IV fluids
indicated 
Shock requiring 
use of 
vasopressors or 
mechanical 
assistance to 
maintain blood 
pressure 
Cardiac 
Ischemia or 
Infarction 
Report only one 
NA 
NA 
New 
symptoms 
with ischemia 
(stable 
angina) OR 
New testing 
consistent 
with ischemia 
Unstable 
angina OR 
Acute 
myocardial 
infarction 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
188 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Heart Failure 
No 
symptoms 
AND 
Laboratory 
or cardiac 
imaging 
abnormalitie
s 
Symptoms 
with mild to 
moderate 
activity or 
exertion 
Symptoms at 
rest or with 
minimal 
activity or 
exertion 
(e.g., 
hypoxemia) 
OR 
Intervention 
indicated 
(e.g., 
Life-threatening 
consequences OR 
Urgent intervention 
indicated (e.g., 
vasoactive 
medications, 
ventricular assist 
device, heart 
transplant) 
Hemorrhage 
(with significant 
acute 
blood loss) 
NA 
Symptoms 
AND  No 
transfusion 
indicated 
Symptoms 
AND 
Transfusio
n of ≤ 2 
units 
packed 
RBCs 
indicated 
Life-threatening 
hypotension OR 
Transfusion of > 2 
units packed RBCs 
(for children, 
packed RBCs > 10 
cc/kg) indicated 
Prolonged PR 
Interval or 
AV Block 
Report only one 
> 16 years  of 
age 
PR interval 
0.21 to < 
0.25 seconds 
PR interval ≥ 
0.25 
seconds OR 
Type I 
2nd degree AV 
block 
Type II 2nd 
degree AV 
block OR 
Ventricular 
pause ≥ 3.0 
seconds 
Complete AV block 
≤ 16 years of 
age 
1st degree AV 
block 
(PR interval 
> normal for 
age and rate) 
Type I 2nd 
degree AV 
block 
Type II 2nd 
degree AV 
block OR 
Ventricular 
pause ≥ 3.0 
seconds 
Complete AV block 
Prolonged QTc 
Interval 2 
0.45 to 0.47 
seconds 
> 0.47 to 
0.50 
seconds 
> 0.50 seconds
OR 
≥ 0.06 
seconds 
above 
baseline 
Life-threatening 
consequences (e.g., 
Torsade de pointes, 
other associated 
serious ventricular 
dysrhythmia) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
189 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Thrombosis or 
Embolism 
Report only one 
NA 
Symptoms 
AND No 
intervention 
indicated 
Symptoms 
AND 
Intervention 
indicated 
Life-threatening 
embolic event 
(e.g., pulmonary 
embolism, 
thrombus) 
1. Blood pressure norms for children < 18 years of age can be found in: Expert Panel on Integrated Guidelines for 
Cardiovascular Health and Risk Reduction in Children and Adolescents Pediatrics 2011;128;S213; originally 
published online November 14, 2011; DOI: 10.1542/peds.2009-2107C.  
2. As per Bazett’s formula. 
Dermatologic 
PARAMETER 
 
GRADE 1 
MILD 
 
GRADE 2 
MODERATE 
 
GRADE 3 
SEVERE 
 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Alopecia (scalp 
only) 
Detectable by 
study 
participant, 
caregiver, or 
physician 
AND Causing 
no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Obvious on 
visual 
inspection 
AND Causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
NA 
NA 
Bruising 
Localized to 
one area 
Localized 
to more 
than one 
area 
Generalized NA 
Cellulitis 
NA 
Non-
parenteral 
treatment 
indicated 
(e.g., oral 
antibiotics, 
antifungals, 
antivirals) 
IV 
treatment 
indicated 
(e.g., IV 
antibiotics, 
antifungals, 
antivirals) 
Life-
threatening 
consequences 
(e.g., sepsis, 
tissue 
necrosis) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
190 
 
PARAMETER 
 
GRADE 1 
MILD 
 
GRADE 2 
MODERATE 
 
GRADE 3 
SEVERE 
 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Hyperpigmentation Slight or 
localized 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Marked or 
generalized 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
NA 
NA 
Hypopigmentation Slight or 
localized 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Marked or 
generalized 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
NA 
NA 
Petechiae 
Localized to 
one area 
Localized 
to more 
than one 
area 
Generalized NA 
Pruritus 3 
(without skin 
lesions) 
Itching 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Itching 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Itching 
causing 
inability 
to 
perform 
usual 
social & 
functional 
activities 
NA 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
191 
 
PARAMETER 
 
GRADE 1 
MILD 
 
GRADE 2 
MODERATE 
 
GRADE 3 
SEVERE 
 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Rash 
Specify type, if 
applicable 
Localized rash 
Diffuse 
rash OR 
Target 
lesions 
Diffuse 
rash AND 
Vesicles or 
limited 
number of 
bullae or 
superficial 
ulcerations 
of mucous 
membrane 
limited to 
one site 
Extensive or 
generalized 
bullous lesions 
OR Ulceration 
of mucous 
membrane 
involving two or 
more distinct 
mucosal sites 
OR Stevens- 
Johnson 
syndrome OR 
Toxic epidermal 
necrolysis 
3. For pruritus associated with injections or infusions, see the Site Reactions to Injections and 
Infusions section.  
 
Endocrine and Metabolic 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Diabetes Mellitus Controlle
d without 
medicatio
n 
Controlled 
with 
medication 
OR 
Modificatio
n of current 
medication 
regimen 
Uncontrolled 
despite 
treatment 
modification 
OR 
Hospitalization 
for immediate 
glucose control 
indicated 
Life-threatening 
consequences 
(e.g., 
ketoacidosis, 
hyperosmolar 
non- ketotic 
coma, end 
organ failure) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
192 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Gynecomastia 
Detectable 
by study 
participant
, caregiver, 
or 
physician 
AND 
Causing 
no or 
minimal 
interferenc
e with 
usual social 
& 
functional 
activities 
Obvious on 
visual 
inspection 
AND Causing 
pain with 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Disfiguring 
changes AND 
Symptoms 
requiring 
intervention or 
causing inability 
to perform usual 
social 
& functional 
activities 
NA 
Hyperthyroidism No 
symptoms 
AND 
Abnormal 
laboratory 
value 
Symptoms 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities OR 
Thyroid 
suppression 
therapy 
indicated 
Symptoms 
causing 
inability to 
perform usual 
social & 
functional 
activities OR 
Uncontrolled 
despite 
treatment 
modification 
Life-
threatening 
consequence
s (e.g., 
thyroid 
storm) 
Hypothyroidism 
No 
symptoms 
AND 
Abnormal 
laboratory 
value 
Symptoms 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities OR  
Thyroid 
replacement 
therapy 
indicated 
Symptoms 
causing 
inability to 
perform usual 
social & 
functional 
activities OR 
Uncontrolled 
despite 
treatment 
modification 
Life-
threatening 
consequence
s (e.g., 
myxedema 
coma) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
193 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Lipoatrophy 4 
Detectable 
by study 
participant
, caregiver, 
or 
physician 
AND 
Causing 
no or 
minimal 
interferenc
e with 
usual social 
& 
functional 
activities 
Obvious on 
visual 
inspection 
AND Causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Disfiguring 
changes 
NA 
Lipohypertrophy 5 Detectable 
by study 
participant
, caregiver, 
or 
physician 
AND 
Causing 
no or 
minimal 
interferenc
e with 
usual social 
& 
functional 
activities 
Obvious on 
visual 
inspection 
AND Causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Disfiguring 
changes 
NA 
4. Definition: A disorder characterized by fat loss in the face, extremities, and buttocks. 
5. Definition: A disorder characterized by abnormal fat accumulation on the back of the neck, 
breasts, and abdomen. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
194 
 
Gastrointestinal 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Anorexia 
Loss of 
appetite 
without 
decrease
d oral 
intake 
Loss of appetite 
associated with 
decreased oral 
intake without 
significant 
weight loss 
Loss of appetite 
associated with 
significant 
weight loss 
Life-threatening 
consequences OR 
Aggressive 
intervention 
indicated (e.g., 
tube feeding, 
total parenteral 
nutrition) 
Ascites 
No 
symptoms 
Symptoms AND 
Intervention 
indicated (e.g., 
diuretics, 
therapeutic 
paracentesis) 
Symptoms 
recur or 
persist 
despite 
intervention 
Life-
threatening 
consequenc
es 
Bloating or 
Distension 
Report only one 
Symptoms 
causing no 
or minimal 
interferenc
e with 
usual 
social & 
functional 
activities 
Symptoms 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
causing 
inability to 
perform usual 
social & 
functional 
activities 
NA 
Cholecystitis 
NA 
Symptoms 
AND Medical 
intervention 
indicated 
Radiologic, 
endoscopic, or 
operative 
intervention 
indicated 
Life-
threatening 
consequences 
(e.g., sepsis, 
perforation) 
Constipation 
NA 
Persistent 
constipation 
requiring regular 
use of dietary 
modifications, 
laxatives, or 
enemas 
Obstipation 
with manual 
evacuation 
indicated 
Life-
threatening 
consequences 
(e.g., 
obstruction) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
195 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Diarrhea 
≥ 1 year of 
age 
Transient 
or 
intermittent 
episodes of 
unformed 
stools OR 
Increase of 
≤ 3 stools 
over 
baseline 
per 24-hour 
period 
Persistent 
episodes of 
unformed to 
watery stools 
OR Increase of 
4 to  6 stools 
over baseline 
per 24-hour 
period 
Increase of ≥ 7 
stools 
per 24-hour 
period 
OR IV fluid 
replacement 
indicated 
Life-
threatening 
consequences 
(e.g., 
hypotensive 
shock) 
< 1 year of 
age 
Liquid 
stools 
(more 
unformed 
than 
usual) but 
usual 
number of 
stools 
Liquid stools 
with increased 
number of 
stools OR Mild 
dehydration 
Liquid stools 
with moderate 
dehydration 
Life-threatening 
consequences 
(e.g., liquid stools 
resulting in 
severe 
dehydration, 
hypotensive 
shock) 
Dysphagia or 
Odynophagia 
Report 
only one 
and specify 
location 
Symptom
s but able 
to eat 
usual diet 
Symptoms 
causing altered 
dietary intake 
with no 
intervention 
indicated 
Symptoms 
causing 
severely altered 
dietary intake 
with 
intervention 
indicated 
Life-threatening 
reduction in oral 
intake 
Gastrointestinal 
Bleeding 
Not 
requiring 
intervent
ion other 
than iron 
supplem
ent 
Endoscopic 
intervention 
indicated 
Transfusion 
indicated 
Life-
threatening 
consequences 
(e.g., 
hypotensive 
shock) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
196 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Mucositis or 
Stomatitis 
Report only 
one and specify 
location 
Mucosal 
erythema 
Patchy 
pseudomembran
es or ulcerations 
Confluent 
pseudomembran
es or ulcerations 
OR Mucosal 
bleeding with 
minor trauma 
Life-
threatening 
consequences 
(e.g., 
aspiration, 
choking) OR 
Tissue 
necrosis OR 
Diffuse 
spontaneous 
mucosal 
bleeding 
Nausea 
Transient 
(< 24 
hours) or 
intermitt
ent AND 
No or 
minimal 
interfere
nce with 
oral 
intake 
Persistent nausea 
resulting in 
decreased oral 
intake for 24 to 
48 hours 
Persistent nausea 
resulting in 
minimal oral 
intake for > 48 
hours OR 
Rehydration 
indicated (e.g., 
IV fluids) 
Life-
threatening 
consequences 
(e.g., 
hypotensive 
shock) 
Pancreatitis 
NA 
Symptoms with 
hospitalization 
not indicated 
Symptoms with 
hospitalization 
indicated 
Life-
threatening 
consequences 
(e.g., 
circulatory 
failure, 
hemorrhage, 
sepsis) 
Perforation 
(colon or 
rectum) 
NA 
NA 
Intervention 
indicated 
Life-
threatening 
consequences 
Proctitis 
Rectal 
discomfo
rt with 
no 
intervent
ion 
indicated 
Symptoms 
causing greater 
than minimal 
interference with 
usual social & 
functional 
activities OR 
Medical 
intervention 
indicated 
Symptoms 
causing inability 
to perform usual 
social & 
functional 
activities OR 
Operative 
intervention 
indicated 
Life-
threatening 
consequences 
(e.g., 
perforation) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
197 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Rectal 
Discharge 
Visible 
discharg
e 
Discharge 
requiring the use 
of pads 
NA 
NA 
Vomiting 
Transient 
or 
intermitt
ent AND 
No or 
minimal 
interfere
nce with 
oral 
intake 
Frequent 
episodes with no 
or mild 
dehydration 
Persistent 
vomiting 
resulting in 
orthostatic 
hypotension OR 
Aggressive 
rehydration 
indicated (e.g., 
IV fluids) 
Life-
threatening 
consequences 
(e.g., 
hypotensive 
shock) 
 
Musculoskeletal 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Arthralgia 
Joint pain 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Joint pain 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
Joint pain 
causing 
inability to 
perform 
usual 
social & 
functional 
activities 
Disabling joint 
pain causing 
inability to 
perform basic 
self-care 
functions 
Arthritis 
Stiffness or 
joint swelling 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Stiffness or 
joint swelling 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
Stiffness 
or joint 
swelling 
causing 
inability to 
perform 
usual 
social & 
functional 
activities 
Disabling joint 
stiffness or 
swelling causing 
inability to 
perform basic self-
care functions 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
198 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Myalgia 
(generalized) 
Muscle pain 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Muscle pain 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
Muscle 
pain 
causing 
inability to 
perform 
usual social 
& 
functional 
activities 
Disabling muscle 
pain causing 
inability to 
perform basic 
self-care 
functions 
Osteonecrosis 
NA 
No symptoms 
but with 
radiographic 
findings AND 
No operative 
intervention 
indicated 
Bone pain 
with 
radiographic 
findings OR 
Operative 
intervention 
indicated 
Disabling bone 
pain with 
radiographic 
findings causing 
inability to 
perform basic self-
care functions 
Osteopenia 6 
≥ 30 years of 
age 
BMD t-score 
-2.5 to -1 
NA 
NA 
NA 
< 30 years of 
age 
BMD z-score 
-2 to -1 
NA 
NA 
NA 
Osteoporosis6 
≥ 30 years of 
age 
NA 
BMD t-score < -
2.5 
Pathologic 
fracture 
(e.g., 
compressio
n fracture 
causing 
loss of 
vertebral 
height) 
Pathologic 
fracture causing 
life-threatening 
consequences 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
199 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
< 30 years of 
age 
NA 
BMD z-score < -
2 
Pathologic 
fracture 
(e.g., 
compressio
n fracture 
causing 
loss of 
vertebral 
height) 
Pathologic 
fracture causing 
life-threatening 
consequences 
6. BMD t and z scores can be found in: Kanis JA on behalf of the World Health Organization 
Scientific Group (2007). Assessment of osteoporosis at the primary health-care level. 
Technical Report. World Health Organization Collaborating Centre for Metabolic Bone 
Diseases, University of Sheffield, UK. 2007: Printed by the University of Sheffield. 
 
Neurologic 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Acute CNS 
Ischemia 
NA 
NA 
Transient 
ischemic 
attack 
Cerebral vascular 
accident (e.g., 
stroke with 
neurological 
deficit) 
Altered 
Mental Status 
(for Dementia, 
see Cognitive, 
Behavioral, or 
Attentional 
Disturbance 
below) 
Changes 
causing no 
or minimal 
interferenc
e with 
usual social 
& 
functional 
activities 
Mild 
lethargy or 
somnolence 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Confusion, 
memory 
impairment, 
lethargy, or  
somnolence 
causing 
inability to 
perform usual 
social & 
functional 
activities 
Delirium OR 
Obtundation 
OR Coma 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
200 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Ataxia 
Symptoms 
causing no 
or minimal 
interferenc
e with 
usual social 
& 
functional 
activities 
OR No 
symptoms 
with ataxia 
detected on 
examinatio
n 
Symptoms 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
causing 
inability to 
perform usual 
social & 
functional 
activities 
Disabling 
symptoms causing 
inability to perform 
basic self-care 
functions 
Cognitive, 
Behavioral, 
or 
Attentional 
Disturbance 
(includes 
dementia and 
attention 
deficit 
disorder) 
Specify type, if 
applicable 
Disability 
causing no 
or minimal 
interferenc
e with 
usual 
social & 
functional 
activities 
OR 
Specialized 
resources 
not 
indicated 
Disability 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities OR 
Specialized 
resources on 
part- time 
basis 
indicated 
Disability 
causing 
inability to 
perform usual 
social & 
functional 
activities OR 
Specialized 
resources on a 
full- time 
basis 
indicated 
Disability 
causing inability 
to perform basic 
self-care 
functions OR 
Institutionalizati
on indicated 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
201 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Developmental 
Delay 
< 18 
years of 
age 
Specify type, if 
applicable 
Mild 
developme
ntal delay, 
either 
motor or 
cognitive, 
as 
determined 
by 
comparison 
with a 
developme
ntal 
screening 
tool 
appropriate 
for the 
setting 
Moderate 
development
al delay, 
either motor 
or cognitive, 
as 
determined 
by 
comparison 
with a 
development
al screening 
tool 
appropriate 
for the 
setting 
Severe 
developmental 
delay, either 
motor or 
cognitive, as 
determined by 
comparison 
with a 
developmental 
screening tool 
appropriate for 
the setting 
Developmental 
regression, either 
motor or cognitive, 
as determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting 
Headache 
Symptoms 
causing no 
or minimal 
interferenc
e with 
usual 
social & 
functional 
activities 
Symptoms 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
causing 
inability to 
perform usual 
social & 
functional 
activities 
Symptoms 
causing inability 
to perform basic 
self-care 
functions OR 
Hospitalization 
indicated  OR 
Headache with 
significant 
impairment of 
alertness or other 
neurologic 
function 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
202 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Neuromuscular 
Weakness 
(includes 
myopathy and 
neuropathy) 
Specify type, if 
applicable 
Minimal 
muscle 
weakness 
causing no 
or minimal 
interferenc
e with 
usual 
social & 
functional 
activities 
OR No 
symptoms 
with 
decreased 
strength on 
examinatio
n 
Muscle 
weakness 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Muscle 
weakness 
causing 
inability to 
perform usual 
social & 
functional 
activities 
Disabling 
muscle 
weakness 
causing inability 
to perform basic 
self-care 
functions OR  
Respiratory 
muscle 
weakness 
impairing 
ventilation 
Neurosensory 
Alteration 
(includes 
paresthesia and
painful 
neuropathy) 
Specify type, if 
applicable 
Minimal 
paresthesia 
causing no 
or minimal 
interferenc
e with 
usual 
social & 
functional 
activities 
OR No 
symptoms 
with 
sensory 
alteration 
on 
Sensory 
alteration or 
paresthesia 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Sensory 
alteration or 
paresthesia 
causing 
inability to 
perform usual 
social & 
functional 
activities 
Disabling 
sensory 
alteration or 
paresthesia 
causing inability 
to perform basic 
self-care 
functions 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
203 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Seizures 
New Onset 
Seizure 
≥ 18 years of 
age 
 
NA 
 
NA 
 
1 to  3 
seizures 
 
Prolonged and 
repetitive 
seizures (e.g., 
status 
epilepticus) OR 
Difficult to 
control (e.g., 
refractory 
epilepsy) 
< 18 years of 
age (includes 
new or pre- 
existing febrile 
seizures) 
Seizure 
lasting < 5 
minutes 
with < 24 
hours 
postictal 
state 
Seizure 
lasting 5 to < 
20 minutes 
with 
< 24 hours 
postictal 
state 
Seizure 
lasting ≥ 20 
minutes OR > 
24 hours 
postictal state 
Prolonged and 
repetitive 
seizures (e.g., 
status 
epilepticus) OR 
Difficult to 
control (e.g., 
refractory 
epilepsy) 
Pre-existing 
Seizure 
NA 
Increased 
frequency 
from 
previous 
level of 
control 
without 
change in 
seizure 
character 
Change in 
seizure 
character 
either in 
duration or 
quality (e.g., 
severity or 
focality) 
Prolonged and 
repetitive 
seizures (e.g., 
status 
epilepticus) OR 
Difficult to 
control (e.g., 
refractory 
epilepsy) 
Syncope 
Near 
syncope 
without 
loss of 
consciousn
ess (e.g., 
pre-
syncope) 
Loss of 
consciousne
ss with no 
intervention 
indicated 
Loss of 
consciousness 
AND 
Hospitalizatio
n or 
intervention 
required 
NA 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
204 
 
Pregnancy, Puerperium, and Perinatal 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Fetal Death or 
Stillbirth (report 
using mother’s 
participant ID) 
Report only one 
NA 
NA 
Fetal loss 
occurring at ≥ 
20 weeks 
gestation 
NA 
Preterm 
Delivery 7 
(report using 
mother’s 
participant ID) 
Delivery at 34 
to < 37 weeks 
gestational age 
Delivery at 28 
to < 34 weeks 
gestational age 
Delivery at 24 
to < 28 weeks 
gestational age 
Delivery at < 
24 weeks 
gestational age 
Spontaneous 
Abortion or 
Miscarriage 8 
(report using 
mother’s 
participant ID) 
Report only one 
Chemical 
pregnancy 
Uncomplicated 
spontaneous 
abortion or 
miscarriage 
Complicated 
spontaneous 
abortion or 
miscarriage 
NA 
7. Definition:  A delivery of a live-born neonate occurring at ≥ 20 to < 37 weeks gestational age. 
8. Definition:  A clinically recognized pregnancy occurring at < 20 weeks gestational age. 
Psychiatric 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Insomnia 
Mild 
difficulty 
falling 
asleep, 
staying 
asleep, or 
waking up 
early 
Moderate 
difficulty 
falling asleep, 
staying asleep, 
or waking up 
early 
Severe 
difficulty 
falling asleep, 
staying asleep, 
or waking up 
early 
NA 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
205 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Psychiatric 
Disorders 
(includes 
anxiety, 
depression, 
mania, and 
psychosis) 
Specify disorder 
Symptoms 
with 
intervention 
not indicated 
OR Behavior 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
with 
intervention 
indicated OR 
Behavior 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
with 
hospitalization 
indicated OR 
Behavior 
causing 
inability to 
perform usual 
social & 
functional 
activities 
Threatens harm 
to self or others 
OR Acute 
psychosis OR 
Behavior 
causing inability 
to perform basic 
self-care 
functions 
Suicidal Ideation 
or 
Attempt 
Report only one 
Preoccupied 
with thoughts 
of death AND 
No wish to 
kill oneself 
Preoccupied 
with thoughts 
of death AND 
Wish to kill 
oneself with 
no specific 
plan or intent 
Thoughts of 
killing oneself 
with partial or 
complete plans 
but no attempt 
to do so OR 
Hospitalization 
indicated 
Suicide 
attempted 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
206 
 
Respiratory 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Acute 
Bronchospasm 
Forced 
expiratory 
volume in 1 
second or 
peak flow 
reduced to ≥ 
70 to < 80% 
OR Mild 
symptoms 
with 
intervention 
not indicated 
Forced 
expiratory 
volume in 1 
second or peak 
flow 50 to < 
70% OR 
Symptoms 
with 
intervention 
indicated OR 
Symptoms 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
Forced 
expiratory 
volume in 1 
second or 
peak flow 25 
to < 50% 
OR 
Symptoms 
causing 
inability to 
perform 
usual social 
& functional 
activities 
Forced 
expiratory 
volume in 1 
second or peak 
flow < 25% 
OR Life-
threatening 
respiratory or 
hemodynamic 
compromise 
OR Intubation 
Dyspnea or 
Respiratory 
Distress 
Report only one 
Dyspnea on 
exertion with 
no or minimal 
interference 
with usual 
social & 
functional 
activities OR 
Wheezing OR 
Minimal 
increase in 
respiratory 
rate for age 
Dyspnea on 
exertion 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities OR 
Nasal flaring 
OR Intercostal 
retractions OR 
Pulse oximetry 
90 to < 95% 
Dyspnea at 
rest causing 
inability to 
perform usual 
social & 
functional 
activities OR 
Pulse 
oximetry < 
90% 
Respiratory 
failure with 
ventilator 
support 
indicated (e.g., 
CPAP, BPAP, 
intubation) 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
207 
 
Sensory 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING
Hearing Loss 
≥ 12 years of 
age 
NA
Hearing aid 
or 
intervention 
not 
indicated 
Hearing aid 
or 
intervention 
indicated 
Profound 
bilateral 
hearing loss (> 
80 dB at 2 kHz 
and above) OR 
Non-
serviceable 
hearing (i.e., 
>50 dB 
audiogram and 
<50% speech 
discrimination) 
< 12 years of 
age (based on 
a 1, 2, 3, 4, 6 
and 8 kHz 
audiogram) 
> 20 dB 
hearing loss at  
≤ 4 kHz 
> 20 dB 
hearing loss at 
> 4 kHz 
> 20 dB 
hearing loss at  
≥ 3 kHz in 
one ear with 
additional 
speech 
language 
related 
services 
indicated 
(where 
available) OR 
Hearing loss 
sufficient to 
indicate 
therapeutic 
intervention, 
including 
hearing aids 
Audiologic 
indication for 
cochlear implant 
and additional 
speech- 
language related 
services 
indicated (where 
available) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
208 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING
Tinnitus 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities with 
intervention 
not indicated 
Symptoms 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities with 
intervention 
indicated 
Symptoms 
causing 
inability to 
perform 
usual social 
& functional 
activities 
NA 
Uveitis 
No symptoms 
AND 
Detectable on 
examination 
Anterior uveitis 
with symptoms 
OR Medical 
intervention 
indicated 
Posterior or 
pan- uveitis 
OR Operative 
intervention 
indicated 
Disabling 
visual loss in 
affected eye(s) 
Vertigo 
Vertigo 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Vertigo 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
Vertigo 
causing 
inability to 
perform 
usual social 
& functional 
activities 
Disabling 
vertigo 
causing 
inability to 
perform basic 
self-care 
functions 
Visual Changes 
(assessed from 
baseline) 
Visual 
changes 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Visual changes 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
Visual 
changes 
causing 
inability to 
perform 
usual social 
& functional 
activities 
Disabling 
visual loss in 
affected eye(s) 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
209 
 
Systemic 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Acute Allergic 
Reaction 
Localized 
urticaria 
(wheals) with 
no medical 
intervention 
indicated 
Localized 
urticaria with 
intervention 
indicated OR 
Mild 
angioedema 
with no 
intervention 
indicated 
Generalized 
urticaria OR 
Angioedema 
with 
intervention 
indicated OR 
Symptoms of 
mild 
bronchospas
m 
Acute 
anaphylaxis 
OR Life-
threatening 
bronchospasm 
OR Laryngeal 
edema 
Chills 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
causing 
inability to 
perform 
usual social 
& 
functional 
activities 
NA 
Cytokine 
Release 
Syndrome9 
Mild signs and 
symptoms 
AND Therapy 
(i.e., antibody 
infusion) 
interruption not 
indicated 
Therapy (i.e., 
antibody 
infusion) 
interruption 
indicated 
AND 
Responds 
promptly to 
symptomatic 
treatment OR 
Prophylactic 
medications 
indicated for ≤ 
24 hours 
Prolonged 
severe signs 
and 
symptoms OR 
Recurrence of 
symptoms 
following 
initial 
improvement 
Life-
threatening 
consequence
s (e.g., 
requiring 
pressor or 
ventilator 
support) 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
210 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Fatigue or 
Malaise 
Report only one 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms 
causing 
inability to 
perform 
usual social 
& 
functional 
activities 
Incapacitating 
symptoms of 
fatigue or 
malaise causing 
inability to 
perform basic 
self-care 
functions 
Fever (non-
axillary 
temperature
s only) 
38.0 to < 38.6°C 
or 100.4 to < 
101.5°F 
≥ 38.6  to < 
39.3°C or ≥ 
101.5 to < 
102.7°F 
≥ 39.3 to < 
40.0°C or ≥ 
102.7 to < 
104.0°F 
≥ 40.0°C or ≥ 
104.0°F 
Pain10 (not 
associated 
with study 
agent 
injections and 
not specified 
elsewhere) 
Specify location 
Pain causing 
no or minimal 
interference 
with usual 
social & 
functional 
activities 
Pain causing 
greater than 
minimal 
interference 
with usual 
social & 
functional 
activities 
Pain causing 
inability to 
perform usual 
social & 
functional 
activities 
Disabling pain 
causing inability 
to perform basic 
self-care 
functions OR 
Hospitalization 
indicated 
Serum 
Sickness 11 
Mild 
signs and 
symptom
s 
Moderate 
signs and 
symptoms 
AND 
Intervention 
indicated (e.g., 
antihistamines
) 
Severe signs 
and 
symptoms 
AND Higher 
level 
intervention 
indicated 
(e.g., steroids 
or IV fluids) 
Life-
threatening 
consequence
s (e.g., 
requiring 
pressor or 
ventilator 
support) 
Underweight12 
> 5 to 19 
years of 
age 
NA 
WHO BMI z-
score < -2 to ≤ -
3 
WHO BMI z-
score 
< -3 
WHO BMI z-score 
< -3 with life-
threatening 
consequences 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
211 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
2 to 5 years of 
age 
NA 
WHO 
Weight-for- 
height z-score 
< -2 to ≤ -3 
WHO 
Weight-
for- height 
z-score < -
3 
WHO Weight-
for-height z-score 
< -3 with life- 
threatening 
consequences 
< 2 years of 
age 
NA 
WHO 
Weight-for- 
length z-score 
< -2 to ≤ -3 
WHO 
Weight-
for- length 
z-score < -
3 
WHO Weight-
for-length z-score 
< -3 with life- 
threatening 
consequences 
Weight Loss 
(excludes 
postpartum 
weight 
loss) 
NA 
5 to < 9% 
loss in body 
weight from 
baseline 
≥ 9 to < 
20% loss in 
body 
weight from 
baseline 
≥ 20% loss in 
body weight from 
baseline OR 
Aggressive 
intervention 
indicated (e.g., 
tube feeding, total 
parenteral 
nutrition) 
9. Definition: A disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of 
breath. 
10. For pain associated with injections or infusions, see the Site Reactions to Injections and Infusions section. 
11. Definition: A disorder characterized by fever, arthralgia, myalgia, skin eruptions, lymphadenopathy, marked 
discomfort, and/or dyspnea. 
12. WHO, 2007 reference tables may be accessed by clicking the desired age range or by accessing the following 
URLs: http://www.who.int/growthref/who2007_bmi_for_age/en / for participants > 5 to 19 years of age and 
http://www.who.int/childgrowth/standards/chart_catalogue/en/ for those ≤ 5 years of age. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
212 
 
Urinary 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Urinary Tract 
Obstruction 
NA 
Signs or 
symptoms of 
urinary tract 
obstruction 
without 
hydronephrosis 
or renal 
dysfunction 
Signs or 
symptoms of 
urinary tract 
obstruction 
with 
hydronephrosis 
or renal 
dysfunction 
Obstruction 
causing life- 
threatening 
consequences 
 
Site Reactions to Injections and Infusions 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Injection Site 
Pain or 
Tenderness 
Report only one 
Pain or 
tenderness 
causing no 
or minimal 
limitation of 
use of limb 
Pain or 
tenderness 
causing greater 
than minimal 
limitation of use 
of limb 
Pain or 
tenderness 
causing 
inability to 
perform usual 
social & 
functional 
activities 
Pain or 
tenderness 
causing inability 
to perform basic 
self-care 
function OR 
Hospitalization 
indicated 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
213 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Injection Site 
Erythema or  
Redness 13 
Report only one 
> 15 years of 
age 
2.5 to < 5 cm 
in diameter 
OR 6.25 to < 
25 cm2 
surface area 
AND 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
≥ 5 to < 10 cm 
in diameter OR 
≥ 25 to < 100 
cm2 surface 
area OR  
Symptoms 
causing greater 
than minimal 
interference 
with usual 
social & 
functional 
activities 
≥ 10 cm in 
diameter OR ≥ 
100 cm2 surface 
area OR 
Ulceration OR 
Secondary 
infection OR 
Phlebitis OR 
Sterile abscess 
OR Drainage 
OR Symptoms 
causing inability 
to perform usual 
social & 
functional 
activities 
Potentially 
life- 
threatening 
consequence
s (e.g., 
abscess, 
exfoliative 
dermatitis, 
necrosis 
involving 
dermis or 
deeper 
tissue) 
≤ 15 years of 
age 
≤ 2.5 cm in 
diameter 
> 2.5 cm in 
diameter with < 
50% surface 
area of the 
extremity 
segment 
involved (e.g., 
upper arm or 
thigh) 
≥ 50% surface 
area of the 
extremity 
segment 
involved (e.g., 
upper arm or 
thigh) OR 
Ulceration OR 
Secondary 
infection OR 
Phlebitis OR 
Sterile abscess 
OR Drainage 
Potentially 
life- 
threatening 
consequence
s (e.g., 
abscess, 
exfoliative 
dermatitis, 
necrosis 
involving 
dermis or 
deeper 
tissue) 
Injection Site 
Induration or 
Swelling 
Report only one 
> 15 
years of 
age 
Same as for 
Injection Site 
Erythema or 
Redness, > 15 
years of age 
Same as for 
Injection Site 
Erythema or 
Redness, > 15 
years of age 
Same as for 
Injection Site 
Erythema or 
Redness, > 15 
years of age 
Same as for 
Injection Site 
Erythema or 
Redness, > 15 
years of age 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
214 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
≤ 15 years of 
age 
Same as for 
Injection Site 
Erythema or 
Redness, ≤ 15 
years of age 
Same as for 
Injection Site 
Erythema or 
Redness, ≤ 15 
years of age 
Same as for 
Injection Site 
Erythema or 
Redness, ≤ 15 
years of age 
Same as for 
Injection Site 
Erythema or 
Redness, ≤ 15 
years of age 
Injection Site 
Pruritus 
Itching 
localized to 
the injection 
site that is 
relieved 
spontaneously 
or in < 48 
hours of 
treatment 
Itching beyond 
the injection 
site that is not 
generalized OR 
Itching 
localized to the 
injection site 
requiring ≥ 48 
hours treatment 
Generalized 
itching causing 
inability to 
perform usual 
social & 
functional 
activities 
NA 
13. Injection Site Erythema or Redness should be evaluated and graded using the greatest single 
diameter or measured surface area. 
 
Laboratory Values 
Chemistries 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Acidosis 
NA 
pH ≥ 7.3 to < 
LLN 
pH < 7.3 
without life- 
threatening 
consequences 
pH < 7.3 with 
life- 
threatening 
consequences 
Albumin, 
Low 
(g/dL; 
g/L) 
3.0 to < LLN 
30  to < LLN 
≥ 2.0 to < 3.0 
≥ 20  to < 30 
< 2.0 
< 20 
NA 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
215 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Alkaline 
Phosphatase, 
High 
1.25  to 
< 2.5 x 
ULN 
2.5  to < 5.0 x 
ULN 
5.0 to < 10.0 x 
ULN 
≥ 10.0 x ULN 
Alkalosis 
NA 
pH > ULN to ≤ 
7.5 
pH > 7.5 
without life- 
threatening 
consequences 
pH > 7.5 with 
life- 
threatening 
consequences 
ALT or SGPT, 
High 
Report only one 
1.25  to 
< 2.5 x 
ULN 
2.5 to < 5.0 x 
ULN 
5.0  to < 10.0 x 
ULN 
≥ 10.0 x ULN 
Amylase 
(Pancreatic) or 
Amylase (Total), 
High 
Report only one 
1.1  to < 1.5 x 
ULN 
1.5  to < 3.0 x 
ULN 
3.0  to < 5.0 x 
ULN 
≥ 5.0 x ULN 
AST or SGOT, 
High 
Report only one 
1.25  to 
< 2.5 x 
ULN 
2.5  to < 5.0 x 
ULN 
5.0  to < 10.0 x 
ULN 
≥ 10.0 x ULN 
Bicarbonate, Low
(mEq/L; 
mmol/L) 
16.0 to <  LLN 
16.0 to <  LLN 
11.0  to < 16.0 
11.0  to < 16.0 
8.0  to < 11.0 
8.0  to < 11.0 
< 8.0 
< 8.0 
Bilirubin 
Direct  
Bilirubin14, 
High 
> 28 days of 
age 
NA 
NA 
> ULN 
> ULN with 
life- 
threatening 
consequences (e.g., 
signs 
and symptoms of 
liver failure) 
≤ 28 days of 
age 
ULN to ≤ 1 
mg/dL 
> 1 to ≤ 1.5 
mg/dL 
> 1.5 to ≤ 2 
mg/dL 
> 2 mg/dL 
Total 
Bilirubin, 
High 
> 28 days 
of age 
1.1 to < 1.6 x 
ULN 
1.6 to < 2.6 x 
ULN 
2.6 to < 5.0 x 
ULN 
≥  5.0 x ULN 
≤ 28 days of 
age 
NA 
NA 
NA 
NA 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
216 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Calcium, High 
(mg/dL; 
mmol/L) 
≥ 7 days of age 
10.6   to < 11.5 
2.65  to < 2.88 
11.5  to < 12.5 
2.88  to < 3.13 
12.5   to < 13.5 
3.13  to < 3.38 
≥  13.5 
≥  3.38 
< 7 days of age 11.5  to < 12.4 
2.88  to < 3.10 
12.4  to < 12.9 
3.10  to < 3.23 
12.9  to < 13.5 
3.23  to < 3.38 
≥  13.5 
≥  3.38 
Calcium 
(Ionized), High 
(mg/dL; 
mmol/L) 
> ULN to < 6.0 
> ULN  to < 
1.5 
6.0 to < 6.4 
1.5 to < 1.6 
6.4 to < 7.2 
1.6 to < 1.8 
≥ 7.2 
≥ 1.8 
Calcium, Low 
(mg/dL; 
mmol/L) 
 
≥ 7 days of age 
 
 
7.8  to < 8.4 
1.95  to < 2.10 
 
 
7.0   to < 7.8 
1.75  to < 1.95 
 
 
6.1  to < 7.0 
1.53  to < 1.75 
 
 
< 6.1 
< 1.53 
< 7 days of age 
6.5  to < 7.5 
1.63  to < 1.88 
6.0 to < 6.5 
1.50  to < 1.63 
5.50  to < 6.0 
1.38  to < 1.50 
< 5.50 
< 1.38 
Calcium 
(Ionized),  Low 
(mg/dL; mmol/L)
< LLN  to 4.0 
< LLN to 1.0 
3.6 to < 4.0 
0.9 to < 1.0 
3.2 to < 3.6 
0.8 to < 0.9 
< 3.2 
< 0.8 
Cardiac 
Troponin I, High 
NA 
NA 
NA 
Levels consistent 
with myocardial 
infarction or 
unstable angina as 
defined by the local 
laboratory 
Creatine Kinase, 
High 
3 to < 6 x ULN 6 to < 10 x 
ULN 
10 to < 20 x 
ULN 
≥ 20 x ULN 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
217 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Creatinine, High 1.1 to 1.3 x 
ULN 
> 1.3 to 1.8 x 
ULN OR 
Increase of > 
0.3 mg/dL 
above baseline 
> 1.8  to < 3.5 
x ULN OR 
Increase of 1.5 
to < 2.0 x 
above baseline 
≥ 3.5 x ULN OR 
Increase of ≥ 2.0 x 
above baseline 
Creatinine 
Clearance 15 
or eGFR, Low 
Report only one 
NA 
< 90 to 60 
ml/min or 
ml/min/1.73 m2 
OR 10 to < 
30% decrease 
from baseline 
< 60 to 30 
ml/min or 
ml/min/1.73 
m2 OR 
≥ 30 to < 50% 
decrease from 
baseline 
< 30 ml/min or 
ml/min/1.73 m2 
OR 
≥ 50% decrease 
from baseline or 
dialysis needed 
Glucose 
(mg/dL; 
mmol/L) 
 
Fasting, High 
 
 
110 to 125 
6.11 to < 6.95 
 
 
> 125 to 250 
6.95 to < 13.89 
 
 
> 250 to 500 
13.89 to < 
27.75 
 
 
> 500 
≥ 27.75 
Nonfasting, 
High 
116 to 160 
6.44 to < 8.89 
> 160 to 250 
8.89 to < 13.89 
> 250 to 500 
13.89  to < 
27.75 
> 500 
≥ 27.75 
Glucose, Low 
(mg/dL; 
mmol/L) 
 
≥ 1 month of age 
 
 
55  to 64 
3.05  to 3.55 
 
 
40  to < 55 
2.22  to < 3.05 
 
 
30  to < 40 
1.67 to < 2.22 
 
 
< 30 
< 1.67 
< 1 month of 
age 
50 to 54 
2.78  to 3.00 
40 to < 50 
2.22 to < 2.78 
30 to < 40 
1.67 to < 2.22 
< 30 
< 1.67 
Lactate, High 
ULN to  < 2.0 
x ULN without 
acidosis 
≥ 2.0 x ULN 
without 
acidosis 
Increased 
lactate with pH
< 7.3 without 
life- 
threatening 
consequences 
Increased lactate 
with pH < 7.3 with 
life- threatening 
consequences 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
218 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Lipase, High 
1.1  to < 1.5 x 
ULN 
1.5  to < 3.0 x 
ULN 
3.0  to < 5.0 x 
ULN 
≥ 5.0 x ULN 
Lipid Disorders 
(mg/dL; 
mmol/L) 
 
Cholesterol, 
Fasting, High 
≥ 18 years of 
age 
 
 
 
 
 
200  to < 240 
5.18  to < 6.19 
 
 
 
 
 
240  to < 300 
6.19  to < 7.77 
 
 
 
 
 
≥  300 
≥  7.77 
 
 
 
 
 
NA 
< 18 years of 
age 
170  to < 200 
4.40  to < 5.15 
200  to < 300 
5.15  to < 7.77 
≥  300 
≥  7.77 
NA 
LDL, Fasting, 
High 
≥ 18 years of 
age 
 
130  to < 160 
3.37  to < 4.12 
 
160 to < 190 
4.12  to < 4.90 
 
≥ 190 
≥ 4.90 
 
NA 
> 2 to < 18 
years of age 
110  to < 130 
2.85  to < 3.34 
130 to < 190 
3.34  to < 4.90 
≥ 190 
≥ 4.90 
NA 
Triglycerides, 
Fasting, High 
150 to 300 
1.71 to 3.42 
>300  to 500 
>3.42 to 5.7 
>500 to < 
1,000 
>5.7 to 11.4 
> 1,000 
> 11.4 
Magnesium16, 
Low 
(mEq/L; 
mmol/L) 
1.2   to < 1.4 
0.60  to < 0.70 
0.9  to < 1.2 
0.45  to < 0.60 
0.6  to < 0.9 
0.30  to < 0.45 
< 0.6 
< 0.30 
Phosphate, Low 
(mg/dL; 
mmol/L) 
 
> 14 years of 
age 
 
 
2.0 to < LLN 
0.81 to < LLN 
 
 
1.4 to < 2.0 
0.65 to < 0.81 
 
 
1.0 to < 1.4 
0.32 to < 0.65 
 
 
< 1.0 
< 0.32 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
219 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
1 to 14 years of 
age 
3.0  to < 3.5 
0.97  to < 1.13 
2.5  to < 3.0 
0.81  to < 0.97 
1.5  to < 2.5 
0.48  to < 0.81 
< 1.5 
< 0.48 
< 1 year of age 
3.5  to < 4.5 
1.13  to < 1.45 
2.5  to < 3.5 
0.81  to < 1.13 
1.5  to < 2.5 
0.48  to < 0.81 
< 1.5 
< 0.48 
Potassium, High 
(mEq/L; 
mmol/L) 
5.6  to < 6.0 
5.6  to < 6.0 
6.0  to < 6.5 
6.0  to < 6.5 
6.5  to < 7.0 
6.5  to < 7.0 
≥ 7.0 
≥ 7.0 
Potassium, Low 
(mEq/L; 
mmol/L) 
3.0  to < 3.4 
3.0  to < 3.4 
2.5  to < 3.0 
2.5  to < 3.0 
2.0  to < 2.5 
2.0  to < 2.5 
< 2.0 
< 2.0 
Sodium, High 
(mEq/L; 
mmol/L) 
146  to < 150 
146  to < 150 
150  to < 154 
150  to < 154 
154  to < 160 
154  to < 160 
≥ 160 
≥ 160 
Sodium, Low 
(mEq/L; 
mmol/L) 
130  to < 135 
130  to < 135 
125  to < 130 
125  to < 135 
121  to < 125 
121  to < 125 
≤ 120 
≤ 120 
Uric Acid, High 
(mg/dL; 
mmol/L) 
7.5  to < 10.0 
0.45  to < 0.59 
10.0  to < 12.0 
0.59  to < 0.71 
12.0  to < 15.0 
0.71  to < 0.89 
≥ 15.0 
≥ 0.89 
14. Direct bilirubin > 1.5 mg/dL in a participant < 28 days of age should be graded as grade 2, if < 
10% of the total bilirubin. 
15. Use the applicable formula (i.e., Cockroft-Gault in mL/min or CKD-EPI and Schwatrz in 
mL/min/1.73m2). 
16. To convert a magnesium value from mg/dL to mmol/L, laboratories should multiply by 0.4114. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
220 
 
Hematology 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Absolute CD4+ 
Count, Low 
(cell/mm3; cells/L) 
> 5 years of age 
(not HIV infected)
300 to < 400 
300 to < 400 
200 to <  300 
200 to < 300 
100 to < 200 
100  to < 200 
< 100 
< 100 
Absolute 
Lymphocyte 
Count, Low 
(cell/mm
3; 
cells/L) 
> 5 years 
of age 
(not HIV 
infected) 
600  to < 650 
0.600 x 109 to 
< 0.650 x 109 
500  to < 600 
0.500 x 109 to 
< 0.600 x 109 
350 to < 500 
0.350 x 109 to 
< 0.500 x 109 
< 350 
 
< 0.350 x 109 
Absolute 
Neutrophil 
Count 
(ANC), Low 
(cells/mm3; 
cells/L) 
> 7 days 
of age 
800 to 1,000 
0.800 x 109 
to 1.000 x 
109 
600 to 799 
0.600 x 109 to 
0.799 x 
109 
400 to 599 
0.400 x 109 to 
0.599 x 
109 
< 400 
< 0.400 x 109 
2 to 7 days of 
age 
1,250 to 1,500 
1.250 x 109 
to 1.500 x 
109 
1,000 to 1,249 
1.000 x 109 to 
1.249 x 
109 
750 to 999 
0.750 x 109 to 
0.999 x 
109 
< 750 
< 0.750 x 109 
≤ 1 day of age 
4,000 to 5,000 
4.000 x 109 to 
5.000 x 109 
3,000 to 3,999 
3.000 x 109 to 
3.999 x 
109 
1,500 to 2,999 
1.500 x 109 to 
2.999 x 
109 
< 1,500 
< 1.500 x 109 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
221 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Fibrinogen, 
Decreased 
(mg/dL; g/L) 
100  to < 200 
1.00 to < 2.00 
OR 
0.75 to 
< 1.00 x 
LLN 
75  to < 100 
0.75  to < 1.00 
OR 
≥ 0.50 to < 
0.75 
x LLN 
50  to < 75 
0.50  to < 0.75 
OR 
0.25 to 
< 0.50 x 
LLN 
< 50 
< 0.50 
OR 
< 0.25 x LLN 
OR 
Associated 
with gross 
bleeding 
Hemoglobin17, 
Low 
(g/dL;  
mmol/L)18 
≥ 13 years of age 
(male only) 
10.0 to 10.9 
6.19 to 6.76 
9.0 to < 10.0 
5.57 to < 6.19 
7.0 to < 9.0 
4.34 to < 5.57 
< 7.0 
< 4.34 
≥ 13 years of age 
(female only) 
9.5 to 10.4 
5.88 to 6.48 
8.5 to < 9.5 
5.25 to < 5.88 
6.5 to < 8.5 
4.03 to < 5.25 
< 6.5 
< 4.03 
57 days of age to 
< 13 years of age 
(male and female)
9.5 to 10.4 
5.88 to 6.48 
8.5 to < 9.5 
5.25 to < 5.88 
6.5 to < 8.5 
4.03 to < 5.25 
< 6.5 
< 4.03 
36 to 56 days of 
age 
(male and female)
8.5 to 9.6 
5.26 to 5.99 
7.0 to < 8.5 
4.32 to < 5.26 
6.0 to < 7.0 
3.72 to < 4.32 
< 6.0 
< 3.72 
22 to 35 days of 
age 
(male and female)
9.5 to 11.0 
5.88 to 6.86 
8.0 to < 9.5 
4.94 to < 5.88 
6.7 to < 8.0 
4.15 to < 4.94 
< 6.7 
< 4.15 
8 to ≤ 21 days of 
age 
(male and female)
11.0 to 13.0 
6.81 to 8.10 
9.0 to < 11.0 
5.57 to < 6.81 
8.0 to < 9.0 
4.96 to < 5.57 
< 8.0 
< 4.96 
≤ 7 days of age 
(male and female)
13.0 to 14.0 
8.05 to 8.72 
10.0 to < 13.0 
6.19 to < 8.05 
9.0 to < 10.0 
5.59 to < 6.19 
< 9.0 
< 5.59 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
222 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
INR, High 
(not on 
anticoagulation 
therapy) 
1.1  to < 1.5 x 
ULN 
1.5  to < 2.0 x 
ULN 
2.0  to < 3.0 x 
ULN 
≥  3.0 x ULN 
Methemoglobin 
(% hemoglobin) 
5.0  to < 
10.0% 
10.0  to < 
15.0% 
15.0  to < 
20.0% 
≥  20.0% 
PTT, High 
(not on 
anticoagulation 
therapy) 
1.1  to < 1.66 
x ULN 
1.66 to < 2.33 
x ULN 
2.33 to < 3.00 
x ULN 
≥  3.00 x ULN 
Platelets, 
Decreased 
(cells/mm3; 
cells/L) 
100,000  to 
< 124,999 
100.000 x 109  
to 
< 124.999 x 
109 
50,000  to 
< 100,000 
50.000 x 109  
to 
< 100.000 x 
109 
25,000  to 
< 50,000 
25.000 x 109  
to 
< 50.000 x 109 
< 25,000 
< 25.000 x 109 
PT, High 
(not on 
anticoagulation 
therapy) 
1.1  to < 1.25 
x ULN 
1.25  to < 1.50 
x ULN 
1.50  to < 3.00 
x ULN 
≥  3.00 x ULN 
WBC, Decreased 
(cells/mm3; cells/L) 
 
> 7 days of age 
 
 
2,000 to 2,499 
2.000 x 109 to 
2.499 x 109 
 
 
1,500 to 1,999 
1.500 x 109 to 
1.999 x 
109 
 
 
1,000 to 1,499 
1.000 x 109 to 
1.499 x 
109 
 
 
< 1,000 
< 1.000 x 109 
≤ 7 days of age 
5,500 to 6,999 
5.500 x 109 to 
6.999 x 109 
4,000 to 5,499 
4.000 x 109 to 
5.499 x 109 
2,500 to 3,999 
2.500 x 109 to 
3.999 x 
109 
< 2,500 
< 2.500 x 109 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
223 
 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
17. Male and female sex are defined as sex at birth. 
18. The conversion factor used to convert g/dL to mmol/L is 0.6206 and is the most commonly 
used conversion factor.  For grading hemoglobin results obtained by an analytic method with a 
conversion factor other than 0.6206, the result must be converted to g/dL using the 
appropriate conversion factor for the particular laboratory. 
Urinalysis 
PARAMETER 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Glycosuria 
(random 
collection 
tested by 
dipstick) 
Trace to 1+ or 
≤ 250 mg 
2+ or ˃ 250 to 
≤ 500 mg 
> 2+ or > 500 
mg 
NA 
Hematuria (not 
to be reported 
based on 
dipstick findings 
or on blood 
believed to be of 
menstrual origin) 
6  to < 10 
RBCs per 
high power 
field 
≥ 10 RBCs per 
high 
power field 
Gross, with 
or without 
clots OR 
With RBC 
casts OR 
Intervention 
indicated 
Life-
threatening 
consequences 
Proteinuria 
(random 
collection 
tested by 
dipstick) 
1+ 
2+ 
3+  or higher 
NA 
12.2.1. 
Reference 
U.S. Department of Health and Human Services, National Institutes of Health, National 
Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 
2.0. [November 2014]. Available from: 
http://rsc.tech-
res.com/Document/safetyandpharmacovigilance/DAIDS_AE_GRADING_TABLE_v2_
NOV2014.pdf  (accessed 10 September 2015).   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
224 
 
12.3. 
Appendix 3:  Liver Safety – Required Actions, Follow Up 
Assessments and Study Treatment Restart Guidelines  
VSLC GUIDELINES FOR DRUG RESTART  AFTER STOP FOR LIVER 
CRITERIA 
Drug Restart refers to resuming study treatment following liver events meeting stopping 
criteria in which there is a clear underlying cause (other than DILI) of the liver event 
(e.g. biliary obstruction, pancreatic events, hypotension, acute viral hepatitis). 
Furthermore, there should be no evidence of alcoholic hepatitis or hypersensitivity, and 
the drug should not be associated with HLA markers of liver injury. 
Restarts should be limited to cases in which there is clear evidence that the 
underlying cause of the liver event is not related to study drug. 
DRUG RESTART 
“Drug restart” can be approved by the VSLC for transient, defined non-drug-induced 
liver injury if no evidence of: 
• 
immunoallergic injury /HLA association with injury 
• 
alcoholic hepatitis 
Study drug must be held while labs and evaluation are completed to assess diagnosis. 
VSLC DECISION PROCESS FOR DRUG RESTART APPROVAL OR 
DISAPPROVAL  
• Principal Investigator (PI) requests consideration of drug re-initiation for a 
subject stable or improving on IP, who exhibits liver chemistry elevation 
meeting subject stopping criteria, which is transient, non-drug-related, and 
liver chemistries have improved to normal or are within 1.5x baseline and 
ALT< 5xULN.  
• GSK Medical Monitor and GCSP Physician to review the subject’s diagnosis 
restart risk factors (Hepatotoxicity Panel consultation is available) and complete 
checklist (Table 15). 
– must present source data defining the patient’s current resistance profile 
with documented evidence of extensive drug resistance and previous drug 
history. 
• The local operating company (LOC) medical director should be informed that 
study drug restart is under consideration and of the final decision, whether or 
not to proceed. 
• Relevant physicians (listed below) must review and agree on action to be taken 
regarding request for drug restart:   
• Safety Review Team Leader, Safety Development Leader, or Senior Safety 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
225 
 
Physician 
• MDL and PPL 
• 
Request is taken to VSLC for final decision. 
 
Table 15 
Checklist for Phase III drug restart after well-explained liver injury 
(e.g. biliary, pancreatic, hypotensive events, congestive heart failure 
(CHF), acute viral hepatitis), and improvement of liver chemistry to 
normal or ≤ 1.5x baseline & ALT<5xULN. 
 
Yes 
No 
Is subject stable or improving on IP? 
 
 
Do not restart if the following risk factors at initial liver injury: 
 
 
fever, rash, eosinophilia, or hypersensitivity  
 
 
drug-induced liver injury  
 
 
alcoholic hepatitis (AST>ALT, typically <10xULN) 
 
 
IP has an HLA genetic marker associated with liver injury (e.g. 
lapatinib, abacavir, amoxicillin/clavulanate) 
 
 
Source data defining the patients current resistance profile 
 
 
Previous drug history 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
226 
 
Figure 9 
VSLC process for drug restart approval or disapproval 
 
Subject exhibits transient, non-drug related liver injury while 
disease condition stable or improving 
 
 
 
 
 
 
 
 
Medical Monitor and Safety Physician(s) to discuss etiology of 
liver injury and 
Have liver injuries decreased to normal or to <1.5x Baseline and ALT 
<5xULN 
Any fever, rash, eosinophilia in this patient or HLA genetic marker 
associated with liver injury [Andrade, 2009]? 
Any evidence of alcoholic hepatitis or DILI in this patient? 
Any prior sever/fatal outcomes reported on drug restart [Papay, 
2009; Hunt, 2010] with this drug? 
Any Evidence of nonclinical hepatic liability/injury with this drug? 
LOC Medical Director to be informed of restart consideration and 
final decision 
 
 
 
 
 
 
 
 
Relevant physicians (from Safety and Clinical functions) review and 
agree on restart request 
 
 
 
 
 
 
 
 
Request is 
submitted to 
VSLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VSLC Approves Re-initiation of IP 
 
 
 
VSLC Does NOT Approve Re-
initiation of IP 
 
 
 
 
 
 
 
 
 
 
 
PI promptly informed of decision and 
dosing regimen 
Ethics Committee or IRB review, if 
needed 
Benefits/Risks discussed with subject 
and consent recorded in chart  
Liver chemistries obtained once weekly 
for a minimum of one month and 
thereafter for as long as clinically 
indicated 
Safety Review Teams record rechallenge 
outcome 
VSLC notified of rechallenge outcome 
 
 
 
PI promptly informed of decision 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
227 
 
MEDICAL MONITOR, GCSP PHYSICIAN AND PI ACTIONS FOR RESTART 
FOLLOWING VSLC DECISION 
Medical Monitor and GCSP Physician Actions: 
• Medical Monitor must notify PI of VSLC’s restart decision and recommended 
dosing regimen in writing and Medical Monitor must record note in study files. 
• The Safety Review Team must record restart outcomes and the GCSP Physician 
must send these to the VSLC (see template below). 
• All severe reactions (SAEs or fatalities which occur following a drug restart must 
be immediately reported to Line Management including, VSLC Chair, VP Global 
Medical Strategy and EU Qualified Person for Pharmacovigilance.  
PI Actions: 
• The PI must obtain Ethics Committee or Institutional Review Board approval of 
drug restart, as required.  
• If VSLC approves drug restart, the patient must sign a new informed consent 
containing a clear description of possible benefits and risks of drug administration 
including recurrent, more severe liver injury or possible death. 
– Targeted drug restart consent form must be used. 
• The patient’s informed consent must be recorded in the study chart, and the drug 
administered at agreed dose, as communicated by Medical Monitor. 
• Liver chemistries must be followed once weekly for ‘restart’ cases for a 
minimum of one month and thereafter for as long as clinically indicated following 
drug re-initiation.  If subject exhibits protocol-defined liver chemistry elevations, 
IP should be discontinued as protocol specified. 
• Medical Monitor and the Ethics Committee or Institutional Review Board must be 
informed of the patient’s outcome following drug restart. 
Drug Restart Outcomes Table Template 
To be completed/updated and provided to VSLC with each event 
recorded across studies and indications 
Drug Restart Outcomes Table – Update with each event 
Protocol# 
Subject# 
Safety outcome* 
Drug benefit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
228 
 
Restart safety outcomes: 
• 
0 = no liver chemistry elevation 
• 
1 = recurrent liver chemistry elevation not meeting subject stopping criteria 
• 
2 = recurrent liver chemistry elevation meeting subject stopping criteria 
• 
3 = serious adverse event 
• 
4 = fatality 
12.4. 
Appendix 4: CDC Classification System for HIV-1 Infections 
(2014) 
Note that the CD4+ T-lymphocyte count takes precedence over the CD4+ T-lymphocyte 
percentage in HIV infection stages 1, 2, and 3.  The CD4+ T-lymphocyte should only be 
considered if the count is missing. 
HIV infection, stage 0 
Indicates early HIV infection, inferred from a negative or indeterminate HIV test result 
within 180 days of a positive result.  The criteria for stage 0 supersede and are 
independent of criteria used for other stages. 
HIV infection, stage 1 
• 
Laboratory confirmation of HIV infection with no AIDS-defining condition, and 
o CD4+ T-lymphocyte count of ≥500 cells/µL, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of ≥26%. 
HIV infection, stage 2 
• 
Laboratory confirmation of HIV infection with no AIDS-defining condition, and 
o CD4+ T-lymphocyte count of 200 to 499 cells/µL, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of 14% to 25%. 
HIV infection, stage 3 (AIDS) 
• 
Laboratory confirmation of HIV infection, and 
o CD4+ T-lymphocyte count of <200 cells/µL, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of <14%, or 
o Documentation of an AIDS-defining condition (see below). 
Documentation of an AIDS-defining condition supersedes a CD4+ T-lymphocyte count 
of >200 cells/µL and a CD4+ T-lymphocyte percentage of total lymphocytes of >14%.  
HIV infection, stage unknown 
• 
Laboratory confirmation of HIV infection, and 
o No information on CD4+ T-lymphocyte count or percentage, and 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
229 
 
o No information on presence of AIDS-defining conditions. 
Stage-3-defining opportunistic illnesses in HIV infection 
• 
Candidiasis of bronchi, trachea, or lungs  
• 
Candidiasis of oesophagus  
• 
Cervical cancer, invasive 
• 
Coccidioidomycosis, disseminated or extrapulmonary  
• 
Cryptococcosis, extrapulmonary  
• 
Cryptosporidiosis, chronic intestinal (>1 month's duration) 
• 
Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month 
• 
Cytomegalovirus retinitis (with loss of vision) 
• 
Encephalopathy, HIV-related  
• 
Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or 
oesophagitis (onset at age >1 month) 
• 
Histoplasmosis, disseminated or extrapulmonary  
• 
Isosporiasis, chronic intestinal (>1 month's duration)  
• 
Kaposi's sarcoma  
• 
Lymphoma, Burkitt's (or equivalent term)  
• 
Lymphoma, immunoblastic (or equivalent term)  
• 
Lymphoma, primary, of brain  
• 
Mycobacterium avium complex or Mycobacterium kansasii, disseminated or 
extrapulmonary  
• 
Mycobacterium tuberculosis of any site, pulmonary, disseminated or extrapulmonary  
• 
Mycobacterium, other species or unidentified species, disseminated or 
extrapulmonary 
• 
Pneumocystis jirovecii pneumonia  
• 
Pneumonia, recurrent 
• 
Progressive multifocal leukoencephalopathy  
• 
Salmonella septicaemia, recurrent  
• 
Toxoplasmosis of brain, onset at age >1 month  
• 
Wasting syndrome attributed to HIV. 
12.4.1. 
Reference 
CDC.  Revised Surveillance Case Definition for HIV Infection – United States, 2014. 
MMWR 2014; 63 (RR-03);1-10. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
230 
 
12.5. 
Appendix 5: Genetic Research 
Genetic Research Objectives and Analyses 
The objectives of the genetic research are to investigate the relationship between genetic 
variants and:  
• 
Response to medicine, including CAB + RPV, ABC/DTG/3TC, or any 
concomitant medicines; 
• 
HIV-1 infection susceptibility, severity, and progression and related conditions  
Genetic data may be generated while the study is underway or following completion of 
the study.  Genetic evaluations may include focused candidate gene approaches and/or 
examination of a large number of genetic variants throughout the genome (whole genome 
analyses). Genetic analyses will utilize data collected in the study and will be limited to 
understanding the objectives highlighted above.  Analyses may be performed using data 
from multiple clinical studies to investigate these research objectives. 
Appropriate descriptive and/or statistical analysis methods will be used. A detailed 
description of any planned analyses will be documented in a Reporting and Analysis Plan 
(RAP) prior to initiation of the analysis. Planned analyses and results of genetic 
investigations will be reported either as part of the clinical RAP and study report, or in a 
separate genetics RAP and report, as appropriate. 
Study Population 
Any subject who is enrolled in the study can participate in genetic research.  Any subject 
who has received an allogeneic bone marrow transplant must be excluded from the 
genetic research. 
Study Assessments and Procedures 
A key component of successful genetic research is the collection of samples during 
clinical studies. Collection of samples, even when no a priori hypothesis has been 
identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.   
• 
A 6 mL blood sample will be taken for Deoxyribonucleic acid (DNA) extraction. 
A blood sample is collected at the baseline visit, after the subject has been 
enrolled and provided informed consent for genetic research. Instructions for 
collection and shipping of the genetic sample are described in the laboratory 
manual.  The DNA from the blood sample may undergo quality control analyses 
to confirm the integrity of the sample.  If there are concerns regarding the quality 
of the sample, then the sample may be destroyed.  The blood sample is taken on a 
single occasion unless a duplicate sample is required due to an inability to utilize 
the original sample.   
The genetic sample is labelled (or “coded”) with the same study specific number used to 
label other samples and data in the study.   This number can be traced or linked back to 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
231 
 
the subject by the investigator or site staff. Coded samples do not carry personal 
identifiers (such as name or social security number).  
Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study, or GSK may destroy the samples sooner.  GSK or those working 
with GSK (for example, other researchers) will only use samples collected from the study 
for the purpose stated in this protocol and in the informed consent form.  Samples may be 
used as part of the development of a companion diagnostic to support the GSK medicinal 
product. 
Participants can request their sample to be destroyed at any time. 
Informed Consent 
Participants who do not wish to participate in the genetic research may still participate in 
the study.  Genetic informed consent must be obtained prior to any blood being taken. 
Subject Withdrawal from Study 
If a subject who has consented to participate in genetic research withdraws from the 
clinical study for any reason other than being lost to follow-up, the subject will be given a 
choice of one of the following options concerning the genetic sample, if already 
collected: 
• 
Continue to participate in the genetic research in which case the genetic DNA 
sample is retained 
• 
Discontinue participation in the genetic research and destroy the genetic DNA 
sample  
In the event a participant withdraws from the study and requests destruction of their 
samples then the site staff must document this in the site study records, complete form F-
GRD-001 and must inform ViiV/GSK via the CRA within 5 days of notification by the 
participant to trigger sample destruction requests. 
Genotype data may be generated during the study or after completion of the study and 
may be analyzed during the study or stored for future analysis.  
• 
If a subject withdraws consent for genetic research and genotype data has not been 
analyzed, it will not be analyzed or used for future research.   
• 
Genetic data that has been analyzed at the time of withdrawn consent will 
continue to be stored and used, as appropriate.  
Screen and Baseline Failures 
If a sample for genetic research has been collected and it is determined that the subject 
does not meet the entry criteria for participation in the study, then the investigator should 
instruct the subject that their genetic sample will be destroyed. No forms are required to 
complete this process as it will be completed as part of the consent and sample 
reconciliation process.  In this instance a sample destruction form will not be available to 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
232 
 
include in the site files. 
Provision of Study Results and Confidentiality of Subject’s Genetic Data 
GSK may summarize the genetic research results in the clinical study report, or 
separately and may publish the results in scientific journals.  
GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the subject, 
family members, insurers, or employers of individual genotyping results that are not 
known to be relevant to the subject’s medical care at the time of the study, unless 
required by law. This is due to the fact that the information generated from genetic 
studies is generally preliminary in nature, and therefore the significance and scientific 
validity of the results are undetermined.  Further, data generated in a research laboratory 
may not meet regulatory requirements for inclusion in clinical care. 
12.6. 
Appendix 6: Definition of and Procedures for Recording, 
Evaluating, Follow-Up and Reporting of Adverse Events 
12.6.1. 
Definition of Adverse Events 
Adverse Event Definition: 
• 
An AE is any untoward medical occurrence in a patient or clinical investigation 
subject, temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
 
Events meeting AE definition include: 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECGs, radiological scans, vital signs 
measurements), including those that worsen from baseline, and felt to be clinically 
significant in the medical and scientific judgement of the investigator. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication (overdose per se will not be reported as an 
AE/SAE unless this is an intentional overdose taken with possible suicidal/self-


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
233 
 
Events meeting AE definition include: 
harming intent.  This should be reported regardless of sequelae). 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE.  However, the signs and symptoms and/or clinical 
sequelae resulting from lack of efficacy will be reported if they fulfil the definition 
of an AE or SAE. 
 
Events NOT meeting definition of an AE include: 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the subject’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
subject’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE. 
• 
Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
12.6.2. 
Definition of Serious Adverse Events 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease, etc). 
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose: 
a. Results in death 
b. Is life-threatening 
NOTE: 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
234 
 
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose: 
c. 
Requires hospitalization or prolongation of existing hospitalization 
NOTE: 
• 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or out-patient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious.  When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in disability/incapacity 
NOTE: 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g. sprained ankle) which may interfere or 
prevent everyday life functions but do not constitute a substantial disruption 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition.  These should also 
be considered serious. 
• 
Examples of such events are invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse 
g. Is associated with liver injury and impaired liver function defined as: 
• 
ALT ≥ 3xULN and total bilirubin* ≥ 2xULN (>35% direct), or 
• 
ALT ≥ 3xULN and INR** > 1.5. 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick.  If fractionation is unavailable and 
ALT ≥ 3xULN and total bilirubin ≥ 2xULN, then the event is still to be reported as an 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
235 
 
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose: 
SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants.  If INR measurement is obtained, the value is to 
be recorded on the SAE form. 
• 
Refer to Appendix 3 for the required liver chemistry follow-up instructions 
 
12.6.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• 
Revascularization 
12.6.4. 
Recording of AEs and SAEs 
AEs and SAE Recording: 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
relative to the event. 
• 
The investigator will then record all relevant information regarding an AE/SAE in 
the eCRF 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK, AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all participant identifiers, with the exception 
of the participant number, will be blinded on the copies of the medical records 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
236 
 
AEs and SAE Recording: 
prior to submission of to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis will be 
documented as the AE/SAE and not the individual signs/symptoms. 
• 
Participant-completed Value Evidence and Outcomes questionnaires and the 
collection of AE data are independent components of the study. 
• 
Responses to each question in the Value Evidence and Outcomes questionnaire 
will be treated in accordance with standard scoring and statistical procedures 
detailed by the scale’s developer. 
• 
The use of a single question from a multidimensional health survey to designate a 
cause-effect relationship to an AE is inappropriate. 
12.6.5. 
Evaluating AEs and SAEs 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and will assign it to one of the following categories: 
• 
Mild:  An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• 
Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities. 
• 
Severe:  An event that prevents normal everyday activities. - an AE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe. 
• 
An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study treatment 
and the occurrence of each AE/SAE. 
• 
A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the study 
treatment will be considered and investigated. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
237 
 
Assessment of Causality 
• 
The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in the determination of his/her assessment. 
• 
For each AE/SAE the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations when an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK.  However, it is very 
important that the investigator always make an assessment of causality for 
every event prior to the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AEs and SAEs 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to 
elucidate as fully as possible the nature and/or causality of the AE or SAE. 
• 
The investigator is obligated to assist.  This may include additional laboratory tests 
or investigations, histopathological examinations or consultation with other health 
care professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings, including histopathology. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The investigator will submit any updated SAE data to GSK within the designated 
reporting time frames. 
 
12.6.6. 
Reporting of SAEs to ViiV Healthcare / GSK 
SAE reporting to ViiV Healthcare / GSK via electronic data collection tool 
• 
Primary mechanism for reporting SAEs to ViiV Healthcare / GSK will be the 
electronic data collection tool 
• 
If the electronic system is unavailable for greater than 24 hours, the site will use 
the paper SAE data collection tool and fax it to the Medical Monitor. 
• 
Site will enter the serious adverse event data into the electronic system as soon as 
it becomes available. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
238 
 
SAE reporting to ViiV Healthcare / GSK via electronic data collection tool 
• 
The investigator will be required to confirm review of the SAE causality by 
ticking the ‘reviewed’ box at the bottom of the eCRF page within 72 hours of 
submission of the SAE. 
• 
After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) will be taken off-line to prevent the entry of new data or changes 
to existing data 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, the site can report this information on a paper SAE form 
or to the Medical Monitor by telephone. 
• 
Contacts for SAE receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page. 
 
12.7. 
Appendix 7:  Contraceptive Guidance and Collection of 
Pregnancy Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
a. Premenarchal 
b. Premenopausal female with ONE of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s: review of participant’s 
medical records, medical examination, or medical history interview. 
c. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
239 
 
use one of the non-hormonal highly effective contraception methods if they wish 
to continue their HRT during the study. Otherwise, they must discontinue HRT 
to allow confirmation of postmenopausal status before study enrollment. 
12.7.1. 
Contraception Guidance 
Female participants of childbearing potential are eligible to participate if they agree to 
use a highly effective method of contraception consistently and correctly as described in 
Table 16. 
Table 16 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• oral 
• intravaginal  
• transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation  
• injectable  
Highly Effective Methods That Are User Independent  
• Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.)  
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.)  
NOTES:  
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants in clinical 
studies.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
240 
 
Pregnancy Testing 
o WOCBP should only be included after a confirmed menstrual period and a 
negative highly sensitive serum pregnancy test. 
o Additional pregnancy testing should be performed as per the study Time and 
Events Table. 
o Pregnancy testing will be performed whenever a menstrual cycle is missed or 
when pregnancy is otherwise suspected. 
o Pregnancy testing will be performed and assayed in the central laboratory OR 
using the test kit provided by the central laboratory / provided by the sponsor 
/approved by the sponsor and in accordance with instructions provided in its 
package insert. 
o If pregnancy is confirmed, please see Appendix 10 for details regarding allowing 
pregnant participants to remain in the study. Not applicable in Russia. 
 
12.7.2. 
Collection of Pregnancy Information 
• 
The Investigator will collect pregnancy information on any participant who becomes 
pregnant while participating in this study. See Appendix 10 for information to be 
collected for participants who become pregnant while participating in this study. 
• 
Participants who become pregnant while in the study may remain in study and 
continue scheduled dosing with CAB + RPV LA, once a pregnancy specific ICF 
addendum is signed by the participant. See Appendix 10 for additional data and 
information regarding the management of participants who remain in the study while 
pregnant. Not applicable in Russia. 
• 
Participants in Russia who become pregnant while in study may not elect to remain 
in the study. They must discontinue LA study treatment and continue to be followed 
up in the LTFU Phase.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a participant's pregnancy. 
• 
Participant will be followed to determine the outcome of the pregnancy.  The 
investigator will collect follow up information on mother and infant, which will be 
forwarded to GSK.  Generally, follow-up will not be required for longer than 6 to 
8 weeks beyond the estimated delivery date.  
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE. 
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
241 
 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in Appendix 6. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting. 
 
12.8. 
Appendix 8: Country Specific Requirements 
12.8.1. 
United Kingdom (UK) 
This requirement has been included based on requests from the Medicines and Healthcare 
products Regulatory Agency (MHRA) to include information on the specific duration of 
the Extension or Continuation Phase/Study Treatment for similar Phase 3 trials. 
Study Duration 
In this study, the Extension Phase is intended to provide access to CAB LA + RPV LA 
until CAB LA + RPV LA receives local (by country) Regulatory approval, and becomes 
commercially available.  Therefore, the duration of the Extension Phase will vary from 
country to country and is dependent on the recruitment time for the study and the time 
taken to achieve local approval for marketing.  For participants in the UK, estimating a 6 
month recruitment period, Marketing Application Authorisation (MAA) submission in 
1-2Q2019, and 14 to 15 months approval time for the MAA, the Extension Phase is 
anticipated to conclude by approximately 2-3Q2020.  During this time, participants will 
be monitored every 4 weeks to ensure they continue to derive clinical benefit from CAB 
LA + RPV LA. 
12.8.2. 
Japan 
Pharmacokinetics 
For Japanese participants in the study, blood samples for CAB will be taken at the visit 
shown in the following table in addition to the visits scheduled in Table 5 of Section 7.1 
(Time and Event Table) in the protocol. 
Table 17 
Additional PK Visit and Sample Times for Japanese Participants 
Day 
Time (Related to Dosing of Study agent) 
Oral Cabotegravir 
Day 1 (following first oral dose 
during lead-in phase) 
Pre-dose, 1, 2, 3, 4, 8, and 24 hours post-dose 
 
The total, maximum, amount of blood drawn for PK during this entire study is 
approximately 146 mL for Japanese participants. 
Plasma concentration-time data on Day 1 and Week 4b in Japanese participants will be 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
242 
 
analyzed by non-compartmental methods with WinNonlin.  Calculations will be based on 
the actual sampling times recorded during the study.  From the plasma concentration-time 
data, pharmacokinetic parameters (e.g. Cmax, AUC, tmax, etc) will be determined, as 
data permit.  Pharmacokinetic data will be presented in graphical and/or tabular form and 
will be summarized descriptively as appropriate.  Plasma concentration levels of the drug 
from this study will be also evaluated using a population pharmacokinetics model. 
Full details of all summaries and analyses will be included in the RAP. 
12.8.3. 
Russia 
In accordance with part 6th of article 43rd of the Russian Federal Law dated by 
12.04.2010 (# 61-FZ "On the Circulation of Medicines"), it is prohibited to conduct a 
clinical trial of investigational medical product (IMP) of pregnant women, including 
women during breastfeeding, except for cases when a clinical trial with IMP is being 
specifically carried out for this population of patients. Therefore study participants in 
Russia who become pregnant while receiving IMP (CAB+RPV LA) must stop IMP, 
begin an approved oral ART and enter the LTFU phase. 
12.9. 
Appendix 9:  COVID-19 Pandemic and Clinical Trial 
Continuity 
Background 
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participants ability to attend clinic visits.  In some places, medical 
visits are occurring, and in others, research clinics are operating with only emergency 
staff. 
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in HIV-1 
treatment for participants enrolled in this clinical study, through continuous access to 
antiretroviral therapy. 
In order to maintain the scientific integrity of the study, and adhere to updated guidance 
from regulators, procedures have also been put into place to ensure that the actions taken 
to mitigate against any impact of COVID-19 are well documented in the trial database. 
A “Memo to Investigators” was issued on March 18th, 2020 and served as a record of 
approved emergency actions being taken within this clinical trial to manage issues related 
to COVID-19.  That memo continues to serve as record of approved actions which can be 
fully implemented by Investigators, in advance of this protocol guidance.  This appendix 
will remain consistent with the guidance provided within the “Memo to Investigators” 
and will also serve to provide additional protocol documentation requirements and 
procedures. 
This appendix outlines the measures which are approved for implementation within this 
clinical trial, to protect patient safety and to ensure the integrity of the clinical trial, as a 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
243 
 
result of COVID-19 only. These measures may be implemented in accordance with any 
requirements and expectations set out by local Independent Review Boards/Independent 
Ethics Committees and National Competent Authorities, as necessary. 
This appendix does not apply to participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19.  
12.9.1. 
Changes to Study Visits and Study Procedures 
• Where site staff resource is constrained due to COVID-19, IM dosing visits may 
proceed with limited or no other protocol-defined assessments (e.g. lab tests, 
questionnaires, etc.). If lab tests will be missed for more than one consecutive 
visit, the Medical Monitor must be contacted, to provide guidance for safety 
monitoring.  
• For WOCBP, point of care pregnancy testing should be performed, prior to IM 
dosing. 
• If central laboratory testing cannot be performed at a particular visit, and 
monitoring for safety is required, tests may be performed at an appropriately 
authorised/accredited local laboratory (or other relevant clinical facility), if this 
can be done within local restrictions on physical distancing. The site should 
proactively inform the Sponsor about such instances. Local laboratory results may 
be used to inform safety decisions. Results should be retained in source records. 
• When on-site visits are reduced, it is important that the investigator continue 
collecting relevant clinical information, including adverse events, from the 
participant through alternative means, e.g. by telephone contact. 
• There may be cases where the current principal investigator (PI) of a site is 
indisposed for a period and may need to delegate parts of his/her duties 
temporarily, e.g. to a sub-investigator. Any such changes should be documented 
in the site’s source records. Any permanent changes in PI should be 
communicated to the Sponsor. 
• There may also be circumstances where immediate actions are required by the 
Sponsor and/or investigator, outside of what is contemplated in the protocol, in 
order to protect a study participant from immediate hazard. Any such measures 
will be carefully documented and conducted in accordance with the National 
Competent Authority (NCA)/IRB/IEC regulations. 
 
12.9.2. 
Changes to Informed Consent 
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
244 
 
Any updated informed consent form or other subject-facing materials should be provided 
to participants by e-mail, mail or courier before re-consent is obtained. Any consent 
obtained this way should be documented in source records and confirmed by way of 
normal consent procedure at the earliest opportunity when participants attend their next 
on-site study visit. 
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval. 
 
12.9.3. 
Permissible Use of Antiretroviral Therapy 
In order to minimize the risk of gaps in HIV-1 antiretroviral therapy (ART) for 
participants impacted by COVID-19 in the clinical trial, the following options can be 
considered with regards to ART dosing, in order of preference: 
1. Where possible, and safe to do, please continue to prioritize IM dosing visits in 
order to keep the participants on the protocol-defined regimen. 
 
a. Qualified healthcare professionals (HCPs) trained on study procedures can 
administer IM injections outside of the study clinic setting (e.g. home, 
nursing facility, hospital), assuming this can be done safely, without 
compromising investigational product 
preparation/handling/storage/accountability requirements and done in 
accordance with local requirements. Please seek approval by the study 
team on a case-by-case basis. 
 
 
2. If a participant is not able to attend an IM injection visit due to COVID-19 related 
restrictions, the gap in IM dosing should be covered with oral ART, until IM 
dosing can resume. Participants should be reminded of the importance of adhering 
with daily oral dosing. Two options can be approved for oral bridging therapy in 
consultation with the Medical Monitor, listed in order of preference: 
 
a. Oral CAB + RPV  
i. Investigator should request availability of oral CAB + RPV supplies, 
prior to pursuing option b. 
b. Oral standard of care (SOC) commercial ART (prescribed locally); Note:  
For participants who are HLA-B*5701 negative, if the site has 
investigational product, ABC/DTG/3TC, remaining in study stock that is 
within expiry, this can also be used as the SOC bridging therapy. 
 
Oral bridging with CAB + RPV 
The protocol permits oral bridging to cover planned missed injections with oral CAB + 
RPV, only until IM dosing can be resumed. The start date of oral bridging should be 
within the dosing window for the missed IM dosing visit. This recommendation can be 
used to accommodate requests for oral dosing due to COVID-19. Oral bridging 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
245 
 
recommendations should be followed as per protocol Section 6.8.1. The process and 
required information for requesting oral bridging can be found in your Study 
Reference/Procedure Manual.  Please continue to reach out to your study Medical 
Monitor for approval of oral bridging, in order to document use and to ensure expeditious 
shipment of oral CAB + RPV to your site.  
Participants who use oral CAB + RPV as short-term oral bridging are permitted to return 
to IM dosing, on protocol, once the COVID-19 conditions permit resumption of site 
activities.  
The investigator should reach out to the Medical Monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with CAB/RPV is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the Medical Monitor to 
continue with oral bridging therapy. Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging. 
Oral bridging with Standard of Care Antiretroviral Therapy (SOC ART) 
For participants impacted by COVID-19, where the participant is unable to receive IM 
injections, and oral CAB + RPV is not available for use, oral bridging with any 
commercially available, guideline-recommended, SOC ART regimen is permitted. The 
start date of oral bridging should be within the dosing window for the missed IM dosing 
visit.  Please reach out to your study Medical Monitor for approval of SOC ART as oral 
bridging, in order to document the use of commercially available SOC ART within the 
study. 
Participants who use oral SOC ART as short-term oral bridging as a result of COVID-19 
will not be considered formally withdrawn insofar as they wish to continue on the study.  
Individuals who bridge with SOC ART will be permitted to return to IM dosing, on 
study, once the COVID-19 conditions permit resumption of site activities.   
The investigator should reach out to the Medical Monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with SOC ART is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the medical monitor to 
continue with oral bridging therapy.  Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging. 
12.9.4. 
Direct-To-Patient (DTP) Shipment of Oral Study IP 
If a participant is unable to travel to the clinic, either to receive IM injections or to be 
dispensed oral bridging, sites are encouraged to consider DTP shipments of drug, from 
the site, to the participant, to ensure access to medicines.  
• If the study site is considering DTP shipment of oral CAB + RPV investigational 
product (IP), the site must first verify if DTP IP dispensing by 
investigators/hospital pharmacies is locally permitted and whether it requires 
regulatory and/or local ethics pre-approval, or post-hoc notification. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
246 
 
• The study participant should express his/her agreement for DTP shipment and the 
sharing of their personal information with any third-party couriers (as applicable), 
in accordance with local requirements.  This agreement should be documented in 
source records. 
• Oral CAB + RPV IP can be shipped at ambient temperatures via ground transport 
without a temperature monitoring device, with low risk of temperature excursions. 
Sites are encouraged to use discretion in determining the need for in-transit 
temperature monitoring based on the labelled storage requirements and the 
planned mode of transport and apply this as appropriate.  Shipment of oral CAB + 
RPV via air courier continues to require appropriate temperature monitoring.  For 
shipment conditions of oral medications other than oral CAB + RPV, please 
consult the product labelling. 
• In all cases IP accountability must be maintained, and all DTP dispensing 
documentation should be reflected in source records and dispensing logs per GCP. 
• Please refer to your CRA or local study manager for support with the DTP 
process, ensuring reference to current sponsor guidance and arrangement of a 
courier that can support shipment of IMP directly to participants. 
 
12.9.5. 
COVID-19 Experimental Agents 
If any treatments for COVID-19 are planned for a study participant, please consult with 
the study Medical Monitor to ensure that relevant drug interactions are considered and to 
ensure that continued study participation remains appropriate. 
12.9.6. 
COVID-19 Specific Data Capture 
12.9.6.1. 
Capturing COVID-19 Specific Protocol Deviations 
In order to summarise the impact of COVID-19 in a systematic way and in line with 
regulatory authorities’ recommendations, any study-level impact around COVID-19 will 
be documented as a protocol deviation. This will include the permissible actions 
summarized in this Appendix, which are taken to protect patient safety, including the use 
of CAB + RPV or SOC ART as oral bridging as well as missed visits and assessments as 
a result of logistical challenges resulting from COVID-19. 
Although the conduct of remote visits and the continuity of antiretroviral therapy, via oral 
bridging, are being utilized to protect patient safety, these events fall outside of the intent 
of the original protocol design, may have an impact on data interpretation, and thus will 
be characterized as protocol deviations for the purposes of data summary and analysis. 
 
Any protocol deviations resulting from COVID-19 will be clearly identified as such 
within the protocol deviation description and summarised separately. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
247 
 
12.9.6.2. 
Capturing COVID-19 Specific AEs and SAEs 
It is important for the study team to describe COVID-19 related adverse events/serious 
adverse and their impact on study data and outcomes. Standardization of case definitions 
will facilitate future data analysis.  
Please use the following guidance:  
1. 
AEs should continue to be evaluated as to whether they meet SAE criteria as 
defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. SAEs and AEs should be submitted following usual 
study procedures and timelines.  
 
2. 
When an in-person clinic visit is not possible, please conduct a remote 
telehealth visit to assess for, and document any AEs/SAEs. 
3. 
Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released March 20, 2020, represents a time point for 
standardized collection. We recognize definitions are likely to continue to 
evolve. When reporting both serious and non- serious adverse events (related 
to COVID-19 infection, investigators should use the following Verbatim 
terms:  
a) Suspected COVID-19 infection; or  
b) Probable COVID-19 infection; or  
c) Confirmed COVID-19 infection  
 
4. 
Sites should contact the study Medical Monitor for questions related to 
definitions and reporting, and decisions around impact to study drug 
continuation.  
 
5. 
A new COVID-19 infection Case Report Form will be added to the eCRF to 
collect additional details about the reported COVID-19 AE or SAE data. It is 
important to collect the correct information from each participant reporting a 
COVID-19 AE or SAE.  Therefore, please use the CRF templates to help you 
collect this information, once available. 
 
WHO Case Definition - March 20, 2020 Version (https://www.who.int/publications-
detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov)):  
Suspected case:  
A. A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or 
residence in a location reporting community transmission of COVID-19 disease 
during the 14 days prior to symptom onset;  
OR  
B. A patient with any acute respiratory illness AND in contact (see definition of 
“contact” below) with a confirmed or probable COVID-19 case (see definition of 
contact) in the last 14 days prior to symptom onset;  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
248 
 
OR  
C. A patient with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation.  
 
Probable case:  
A. A suspect case for whom testing for the COVID-19 virus is inconclusive 
(Inconclusive being the result of the test reported by the laboratory).  
OR  
B. A suspect case for whom testing could not be performed for any reason.  
 
Confirmed case:  
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms.  
Covid-19 Contact: 
A contact is a person who experienced any one of the following exposures during the 2 
days before and the 14 days after the onset of symptoms of a probable or confirmed case:  
1. 
Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes;  
2. 
Direct physical contact with a probable or confirmed case;  
3. 
Direct care for a patient with probable or confirmed COVID-19 disease 
without using proper personal protective equipment; OR  
4. 
Other situations as indicated by local risk assessments.  
 
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken which led to 
confirmation. 
12.10. 
Appendix 10: Information and Guidance for Managing 
Pregnant Participants 
Not applicable to participants in Russia. In Russia, women who become pregnant or who 
desire to become pregnant while in the study will have study treatment discontinued and 
will be withdrawn from the study. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
249 
 
12.10.1. 
Collection of Pregnancy Information 
The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a participant's pregnancy. 
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on mother and infant, which will be 
forwarded to GSK.  Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date. 
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in the protocol in Section 12.7.2., Appendix 7.  While the investigator is 
not obligated to actively seek this information in former study participants, he or she 
may learn of an SAE through spontaneous reporting. 
• 
Females who become pregnant while in the study may remain in study, and continue 
scheduled dosing with CAB + RPV LA, once a pregnancy ICF addendum is signed 
by the participant. 
12.10.2. 
Introduction 
Pregnancy increases the risk of HIV progression, while HIV increases the risk for 
maternal complications from pregnancy and poses the risk of perinatal HIV transmission 
to the unborn fetus.  Mother to child transmission (MTCT) of HIV can occur during 
pregnancy, labor, delivery or postpartum through breastfeeding.  In the absence of any 
interventions, vertical HIV transmission rates approximate 35%, but fall below 5% with 
effective interventions [WHO, 2010].  In the United States and other developed countries, 
the risk of perinatal infection has decreased from 25% without intervention to less than 
2% with intervention [WHO, 2012].  The HIV-infected mother who breastfeeds her 
infant while taking ARVs herself or giving ARVs to her infant reduces the risk of 
transmission to about 2% after 6 months of breastfeeding, or 4% over 12 months 
[UNAIDS, 2011]. 
The 2013 WHO Guidelines thus recommend (strong recommendation, moderate-quality 
evidence) all pregnant and breastfeeding women with HIV should initiate triple ARVs 
(ART), which should be maintained at least for the duration of mother-to-child 
transmission risk. Women meeting treatment eligibility criteria should continue lifelong 
ART [WHO, 2013]. The global benefits anticipated from ART in pregnant women who 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
250 
 
are eligible for treatment include treatment of the mother’s underlying HIV disease, 
eliminating pediatric transmission/infection and reducing sexual transmission of HIV. 
Recent recommendation updates to treatment guidelines have included objectives to 
increase HIV screening of patients, including pregnant women (noting the importance of 
adopting HIV screening to be a part of prenatal care). 
The ART recommendation for pregnant females prioritizes the health of women over 
potential risks and increased cost.  For females who are on ARV therapy at the time that 
they become pregnant, the World Health Organization recommends that they continue 
such therapy if they are responding to the ARV. 
In line with this recommendation, this study will allow those females participating in 
201584 who are receiving CAB + RPV LA but become pregnant on study, to continue in 
the study in order to maintain their effective regimen with minimal disruption.  The PK of 
CAB + RPV LA, characterization of the safety of CAB + RPV LA administered during 
pregnancy, and characterization of maternal, birth and infant outcomes following 
treatment with CAB + RPV LA will be examined.  
12.10.3. 
Benefit/Risk Assessment 
Discuss with pregnant participant the benefit-risk of continuing in the study and 
continuing to receive CAB + RPV LA injections, or being withdrawn from study, as a 
result of her pregnancy. All participants who chose to stay in the study during pregnancy, 
and who choose to continue to receive CAB + RPV LA injections will need to sign a 
pregnancy specific ICF addendum. 
There is a pregnancy exposure registry that monitors pregnancy outcomes in women 
exposed to CAB + RPV LA (CABENUVA) during pregnancy. Healthcare providers are 
encouraged to register all pregnant study participants, whether or not they choose to 
remain in the study, by calling the Antiretroviral Pregnancy Registry [Antiretroviral 
Pregnancy Registry (APR) Steering Committee, 2013] at 1-800-258-4263. 
12.10.3.1. Cabotegravir 
Cabotegravir use in pregnant women has not been evaluated and there are insufficient 
human data on the use of during pregnancy to adequately assess a drug-associated risk of 
birth defects and miscarriage.  
The rate of miscarriage is not reported in the APR. The background risk for major birth 
defects and miscarriage for the indicated population is unknown. The background rate for 
major birth defects in a U.S. reference population of the Metropolitan Atlanta Congenital 
Defects Program (MACDP) is 2.7%. The estimated background rate of miscarriage in 
clinically recognized pregnancies in the U.S. general population is 15% to 20%. The APR 
uses the MACDP as the U.S. reference population for birth defects in the general 
population. The MACDP evaluates women and infants from a limited geographic area 
and does not include outcomes for births that occurred at less than 20 weeks’ gestation. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
251 
 
Animal Data (pre-clinical)  
Cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day 
from 15 days before cohabitation, during cohabitation, and from Gestation Days 0 to 17. 
There were no effects on fetal viability when fetuses were delivered by caesarean 
although a minor decrease in fetal body weight was observed at 1,000 mg/kg/day (greater 
than 30 times the exposure in humans at the RHD). No drug-related fetal toxicities were 
observed at 5 mg/kg/day (approximately 13 times the exposure in humans at the RHD) 
and no drug-related fetal malformations were observed at any dose. 
Cabotegravir was administered orally to pregnant rabbits at 0, 30, 500, or 2,000 
mg/kg/day from Gestation Days 7 to 19. No drug-related fetal toxicities were observed at 
2,000 mg/kg/day (approximately 0.7 times the exposure in humans at the RHD). 
In a rat pre- and postnatal development study, cabotegravir was administered orally to 
pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from Gestation Day 6 to Lactation Day 21. 
A delay in the onset of parturition and increases in the number of stillbirths and neonatal 
deaths by Lactation Day 4 were observed at 1,000 mg/kg/day (greater than 30 times the 
exposure in humans at the RHD); there were no alterations to growth and development of 
surviving offspring. In a cross-fostering study, similar incidences of stillbirths and early 
postnatal deaths were observed when rat pups born to cabotegravir-treated mothers were 
nursed from birth by control mothers. There was no effect on neonatal survival of control 
pups nursed from birth by cabotegravir-treated mothers. A lower dose of 5 mg/kg/day (13 
times the exposure at the RHD) was not associated with delayed parturition or neonatal 
mortality in rats. Studies in pregnant rats showed that cabotegravir crosses the placenta 
and can be detected in fetal tissue. 
During the pre-clinical development of CAB, there were no positive genotox findings. 
Embryo-fetal studies also showed no adverse findings including neural tube defects.  In a 
pre and postnatal study, there were some test article-related decreases in F1 pup survival 
(87.4% vs 98.9% in control) in the highest dose (1000mg/kg/day) during postnatal days 
1-4.  No findings in the 0, 0.5 and 5 mg/kg/day doses).  
The clinical significance of these finding in humans is unknown. 
Human Data  
Cabotegravir use in pregnant females has not been evaluated and there are insufficient 
human data on the use of CAB + RPV LA during pregnancy to adequately assess a drug-
associated risk of birth defects and miscarriage.  
While there are insufficient human data to assess the risk of neural tube defects (NTDs) 
with exposure to CAB + RPV LA during pregnancy, preliminary findings from an 
unscheduled analysis of a birth outcomes surveillance study conducted in Botswana 
(Tsepamo Study) and presented in May 2018 showed a higher than expected number of 
neural tube defects (NTDs) among newborns whose mothers were exposed to DTG based 
ART at conception.  DTG is a different molecule in the same integrase class of 
medications as CAB. As of May 2018 four cases of neural tube defects were identified in 
426 infants born to mothers who were exposed to DTG-containing regimens from the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
252 
 
time of conception. In the same study, no infant born to a woman who started DTG 
during pregnancy had a neural tube defect, out of 2,824 women. Updated analysis of 
interim data from the Tsepamo study became available in 2019 and more recently in 
2020. Subsequently, the study team presented an updated analysis, including data through 
to 30 April 2020, at the 23rd International AIDS Society (IAS) Meeting [Zash, 2020].  
The latest data from the Tsepamo study included additional data accrued between 1 April 
2019 (the cut-off for the last formal analysis) and 30 April 2020. Over this 13-month 
period, 39,200 additional births were recorded, including 1908 additional exposures to 
DTG at conception. Two additional NTDs were detected in 1908 (0.10%) deliveries to 
mothers taking DTG at conception, compared with six NTDs in 4569 (0.13%) deliveries 
in mothers taking non-DTG regimens at conception, of which five NTDs in 2999 (0.17%) 
deliveries were to mothers taking efavirenz at conception. The incidence in HIV negative 
mothers over the 13-month period was 17/30,258 (0.06%).  
As of the Tsepamo April 2020 analysis, seven cases of neural tube defects were reported 
in 3,591 deliveries (0.19%) to mothers taking dolutegravir -containing regimens at the 
time of conception, compared with 21 cases in 19,361 deliveries (0.11%) to mothers 
taking non- dolutegravir containing regimens at the time of conception (Prevalence 
Difference 0.09%; 95% CI -0.03, 0.30).  Since the first analysis the estimated prevalence 
of neural tube defects with DTG exposure at conception has decreased in magnitude from 
0.94% to 0.19%. In the same study, no increased risk of neural tube defects was reported 
in women who started dolutegravir during pregnancy. Two out of 4,448 deliveries 
(0.04%) to mothers who started dolutegravir during pregnancy had a neural tube defect, 
compared with five out of 6,748 deliveries (0.07%) to mothers who started non-
dolutegravir -containing regimens during pregnancy. 
A causal relationship of these events to the use of DTG has not been established.  
The incidence of neural tube defects in the general population ranges from 0.5-1 case per 
1,000 live births. There are insufficient human data on the use of CAB + RPV LA during 
pregnancy to adequately assess a drug-associated risk of miscarriage or birth defects, 
including NTDs. 
12.10.3.2. Rilpivirine 
Animal Data  
Rilpivirine was administered orally to pregnant rats (40, 120, or 400 mg/kg/day) and 
rabbits (5, 10, or 20 mg/kg/day) through organogenesis (on Gestation Days 6 through 17, 
and 6 through 19, respectively). No significant toxicological effects were observed in 
embryo-fetal toxicity studies performed with rilpivirine in rats and rabbits at exposures 
15 (rats) and 70 (rabbits) times the exposure in humans at the RHD. In a pre- and 
postnatal development study, rilpivirine was administered orally up to 400 mg/kg/day 
through lactation. No adverse effects were noted in the offspring at maternal exposures 
up to 63 times the exposure in humans at the RHD 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
253 
 
Human Data  
Based on prospective reports to the APR of over 390 exposures to oral rilpivirine-
containing regimens during the first trimester of pregnancy and over 170 during 
second/third trimester of pregnancy, the prevalence of birth defects in live births was 
1.3% (95% CI: 0.4% to 3.0%) and 1.1% (95% CI: 0.1% to 4.0%) following first and 
second/third trimester exposures. 
Available data from the APR show no difference in the overall risk of birth defects for 
rilpivirine compared with the background rate for major birth defects of 2.7% in a U.S. 
reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) 
In a clinical trial, total oral rilpivirine exposures were generally lower during pregnancy 
compared with the postpartum period. Refer to Edurant for additional information on 
rilpivirine. 
12.10.4. 
Clinical Considerations 
12.10.4.1. Exposure 
Lower exposures with oral rilpivirine were observed during pregnancy. Cabotegravir and 
rilpivirine are detected in systemic circulation for up to 12 months or longer after 
discontinuing injections of CAB + RPV LA; therefore, consideration should be given to 
the potential for fetal exposure during pregnancy. 
With the change in volume of distribution associated with pregnancy, drug concentrations 
of CAB and RPV during pregnancy will be assessed in pregnant participants who 
contiune to receive LA therapy while on study. For these participants, PK samples will be 
collected at every study visit throughout the duration of the pregnancy and at the first 
postpartum LA injection visit. Additionally, all other scheduled assessments will continue 
as reflected in as described in the protocol in the Time and Events Table (see Section 
7.1.). 


T M F -1 6 4 4 1 7 6 7  
C O N FI D E N TI A L  
2 0 1 5 8 4  
 
 
Pr ot o c ol A m e n d m e nt 0 9  
 
2 5 4  
 
Fi g ur e 1 0  
L T F U P K i n F e m al e a n d Pr e g n a nt P arti ci p a nt s  
( L A T T E-2, A T L A S)  
W e e k s P o st Fi n al I nj e cti o n
0
1 2
2 4
3 6
4 8
6 0
Pl a s m a C A B ( g/ m L)
0. 0 1
0. 1
1
1 0
L 2 5 1 2
A 5 9 1 1
L 2 5 9 2
A 5 4 8 7 ( + H C G)
A 5 4 8 5 (- H C G)
A 7 2 2 4 (- H C G)
A 6 5 9 5 (- H C G)


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
255 
 
12.10.4.2. Use of Supplements with CAB + RPV LA 
During pregnancy, additional supplements including vitamins, minerals and other 
mediations including OTC meds may be prescribed to the pregnant woman. It is 
important for all female participants who remain in the study to be aware of any potential 
DDIs that may occur with study medications and other agents used during pregnancy. 
Oral Cabotegravir Only 
Antacid products containing divalent cations (e.g., aluminium, calcium and 
magnesium) must be taken at least 2 hours before or at least 4 hours after CAB. 
Concurrent administration of multivitamins is acceptable. 
12.10.4.3. Overall Benefit:Risk Conclusion  
All medications have AE profiles that must be assessed prior to use, allowing for an 
appropriate risk/benefit assessment.  Additional considerations when using CAB + RPV 
LA can be found in the protocol in Section 4.6. 
There is limited data regarding the use of CAB + RPV LA in pregnant females. Based on 
animal data, the use of CAB + RPV LA is not anticipated to increase the risk of adverse 
developmental or reproductive outcomes in humans.  Available data from the APR show 
no difference in the overall risk of birth defects for rilpivirine compared with the 
background rate for major birth defects of 2.7% in a U.S. reference population of the 
Metropolitan Atlanta Congenital Defects Program (MACDP). 
Refer to Section 12.10.4.1. for additional data. 
The use of CAB + RPV LA during pregnancy may offer unique benefits. It is well 
documented that treatment adherence challenges to oral therapy exists both in the peri-
partum and post-partum periods with LA dosing offering an opportunity to overcome 
such adherence challenges. LA therapy may also help with nausea (50 % mild to 
moderate) or hyperemesis (2%). Female participants on LA dosing who become pregnant 
will have exposures throughout pregnancy due to the long half-life and PK tail of 
CAB/RPV. Pregnant participants who are withdrawn from study and are initiated on an 
alternative oral ART regimen consisting of either 2 or 3 antiretrovirals to protect the life 
of the mother and for the prevention of MTCT, potentially expose the fetus to additional 
ARVs during gestation (in some cases upwards of 5 antiretrovirals). 
In summary, taking into account the measures taken to minimize risk to participants 
participating in this study, the potential risks identified in association with CAB + RPV 
LA are justified by the anticipated benefits that may be afforded to pregnant participants 
with HIV infection. 
Given the risk/benefit ratio for CAB + RPV LA dosing in WCBP, coupled with concerns 
of increasing fetal exposure to several additional antiretrovirals upon participant 
withdrawal, pregnant participants will be allowed to remain in the study and continue to 
receive CAB + RPV LA injections, once the new pregnancy ICF addendum is signed by 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
256 
 
the participant.  
 
12.10.5. 
Study Assessments and Procedures: specific assessments for 
pregnant participants 
Participants who become pregnant while in the study, and who sign the informed consent 
pregnancy addendum may remain in the study and continue to receive CAB + RPV LA.  
Please note: The HIV provider is responsible for HIV care and will collaborate and share 
information with the subject’s obstetric care provider, discuss the subject’s participation 
in this study, the necessary procedures at delivery, to share HIV information, and to 
collect birth and infant outcomes from the subject’s obstetric care provider and/or the 
pediatric health provider for the infant. 
Because obstetric and/or pediatric care will not be specifically provided via this study, the 
subject must also establish appropriate obstetric and pediatric care (including prenatal 
care) per local standard of care (SoC) in parallel.  It will be necessary for the subject to 
provide a release of medical information to facilitate collection of pregnancy and 
pregnancy outcomes by the investigator 
All assessments will be conducted in accordance with the protocol, Section 7, and as 
described in the Time and Events Table (see Section 7.1.). 
12.10.5.1. Safety Assessments 
Pregnancy related complications and diagnoses, and outcomes will be captured as AEs 
and SAEs as outlined in the protocol in Section 7.4.3. 
Pregnancy complications (e.g., preeclampsia or eclampsia, prolonged hospitalization after 
delivery, for wound infections etc, seizures) and elective terminations for medical reasons 
must be reported as an AE or SAE.  Spontaneous abortions must be reported as an SAE. 
In the event of a pregnancy loss, after the loss is confirmed the subject may continue to 
receive CAB + RPV LA unless they meet the criteria for confirmed virologic withdrawal.  
They may continue to CAB + RPV LA until study medications are locally approved and 
commercially available or until they no longer receive benefit.  In this case the subject 
must agree to use contraception to avoid a ‘new’ pregnancy (See Appendix 7 of the 
protocol). 
Any SAE occurring in association with the pregnancy brought to the investigator’s 
attention after the subject has completed the study and considered by the investigator as 
possibly related to the study treatment, must be promptly reported to GSK 
12.10.5.2. Pharmacokinetics 
Refer to Section 7.5. in the protocol. 
All pregnant participants who elect to remain in the study will have the following PK 
samples obtained at each LA injection visit throughout the pregnancy and at the first 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
257 
 
postpartum LA injection visit: 
• Blood samples for evaluation of total CAB (2mL each) and total RPV (2mL each) 
plasma PK concentrations.  
• Blood sample for evaluation of unbound CAB (9mL each) plasma PK 
concentration. 
All PK samples will be trough levels and will be collected prior to the scheduled LA 
injection. The pre-dose trough PK sample is to be collected within 15 minutes prior to the 
LA dose, on the day of the study visit.  
For participants pregnant during the Long Term Follow Up Phase, plasma concentrations 
of cabotegravir and rilpivirine will be collected as per 7.1 Time and Events table. 
Please refer to the SPM for PK sample collection, processing, and shipping instructions. 
The actual date and time of each PK sample collection will be recorded in the eCRF. 
12.10.6. 
References 
Antiretroviral Pregnancy Registry (APR) Steering Committee. Antiretroviral Pregnancy 
Registry International Interim Report for 1 January 1989 through 31 January 2013. 
Wilmington, NC: Registry Coordinating Center; 2013. Available from URL: 
www.APRegistry.com. 
Edurant Prescribing Information, February 2018 
UNAIDS (2011) Reference Group on Estimates, Modelling and Projections. Working 
Paper on Mother-to-Child HIV Transmission Rates for use in Spectrum, 6 June 2011. 
Available online at http://www.epidem.org/Publications/MTCTratesworkingpaper.pdf. 
World Health Organization (WHO) (2010). Antiretroviral drugs for treating pregnant 
women and preventing HIV infection in infants: Recommendations for a public health 
approach.  Available online at: 
http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf, accessed 6 Feb 
2013. 
World Health Organization (WHO) (2012). Antiretroviral Treatment as Prevention 
(TasP) of HIV and TB:  2012 Update.  June 2012, Available online at: 
http://www.who.int/hiv/pub/mtct/programmatic_update_tasp/en/index.html 
World Health Organization (WHO) (2013). Consolidated Guidelines on the Use of 
Antiretroviral Drugs for Treating and Preventing HIV Infection. 30 June 2013.  Available 
online at: http://www.who.int/hiv/pub/guidelines/arv2013/download/en/index.html 
Zash R, Holmes L, Diseko M, Jacobson D, Mayondi G. Update on neural tube defects 
with antiretroviral exposure in the Tsepamo study, Botswana. JAIDS 2020, 23:183 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
258 
 
12.11. 
Appendix 11: Device Deficiencies: Definition and 
Procedures for Recording, Evaluating, Follow-up, and 
Reporting in Medical Device Studies 
The definitions and procedures detailed in this appendix are in accordance with ISO 
14155, European Medical Device Regulation (MDR) 2017/745 for clinical device 
research, and the US Food and Drug Administration (FDA) combination product 
reporting rule, 21 CFR 4, Subpart B. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements for medical devices. 
The detection and documentation procedures described in this protocol apply to all 
medical devices used in the study (see Section 6.14 for the list of medical devices). 
12.11.1. 
Definition of Device Deficiency 
Device Deficiency Definition 
• 
A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors, and information supplied by the manufacturer. 
12.11.2. 
Recording and Follow-Up of Device Deficiencies 
Device Deficiency Recording 
• 
When a device deficiency occurs, with or without an associated AE/SAE, it is the 
investigator’s responsibility to review all applicable documentation (e.g., hospital 
progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The investigator will then record all relevant device deficiency information on the 
appropriate form. If applicable, any associated AE or SAE will be documented in 
the participant’s medical records, in accordance with the investigator’s standard 
clinical practice. 
• 
There may be instances when copies of medical records for certain cases are 
requested by the sponsor. In this case, all participant identifiers, with the exception 
of the participant number, will be redacted on the copies of the medical records 
before submission to the sponsor. 
• 
The investigator will attempt to fully describe the device deficiency and provide 
details on any treatment provided.  
• 
For device deficiencies, it is very important that the investigator describe any 
corrective or remedial actions taken to prevent the deficiency’s recurrence. 
o A remedial action is any action other than routine maintenance or servicing of 
a medical device where such action is necessary to prevent the recurrence of a 
device deficiency. This includes any amendment to the device design to 
prevent recurrence. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
259 
 
Assessment of Intensity of associated AE/SAEs 
• If an AE or SAE is associated with a device deficiency, the investigator will make 
an assessment of intensity for each AE or SAE as outlined in Section 12.6.5. 
Follow-up of device deficiency 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature of the device deficiency and any associated AE or 
SAE as fully as possible 
• New or updated information regarding the device deficiency will be recorded in the 
originally completed medical device deficiency report form. 
• If there is an associated SAE with the device deficiency, the investigator will 
submit any updated SAE data to GSK within 24 hours of receipt of the information. 
12.11.3. 
Reporting of Medical Device Deficiencies for Participants 
• 
Reporting to GSK  
• 
NOTE: There are additional reporting obligations for medical device deficiencies 
that are potentially related to SAEs that must fulfil the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies.  
• Medical device deficiencies that are not related to an AE or SAE should be 
reported via email to gsk-rd.complaints@gsk.com, using the medical device 
deficiency report form.  
 
• If the medical device deficiency is related to a non-serious AE and not linked to an 
SAE, please send the medical device deficiency report form via email to gsk-
rd.complaints@gsk.com only. The eCRF for the subject should also be updated 
with AE information, as outlined in Section 7.4.3 
 
• If the device incident is linked to an SAE, please email the medical device 
deficiency report form, within 24 hours, to both uk.gsk-rd-gcsp-ctsm-
admin@gsk.com (or fax +44(0)20 8754 7822) and gsk-rd.complaints@gsk.com. 
The SAE form should also be reported, as outlined in Section 7.4.3. The eCRF for 
the subject should also be updated with the SAE information. 
 
• GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported 
to the regulatory authorities and IRBs/IECs as required by national regulations. 
• Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
260 
 
12.11.4. 
Reporting of Medical Device Deficiencies for Associated Person 
• 
Reporting to GSK  
If an Associated Person (i.e. a healthcare professional) experiences a device 
deficiency, the medical device deficiency information and any associate AE/SAE 
information will be reported to GSK. The associated person will be provided with 
the safety reporting information and authorization to contact physician letter.  
If follow up information is required, authorization to contact physician (or other 
licensed medial practitioner) must be signed to obtain consent.  
• Medical device deficiencies that are not related to an AE or SAE should be 
reported via email to gsk-rd.complaints@gsk.com, using the medical device 
deficiency report form.  
 
• If the medical device deficiency is related to a non-serious AE and not linked to an 
SAE, please send the medical device deficiency report form with details of the 
associated AE via email to gsk-rd.complaints@gsk.com only. 
 
• If the device incident is linked to an SAE, please email the medical device 
deficiency report form, within 24 hours, to both uk.gsk-rd-gcsp-ctsm-
admin@gsk.com (or fax +44(0)20 8754 7822) and gsk-rd.complaints@gsk.com. 
The associated SAE form should also be reported to uk.gsk-rd-gcsp-ctsm-
admin@gsk.com (or fax +44(0)20 8754 7822). 
 
• GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported 
to the regulatory authorities and IRBs/IECs as required by national regulations. 
 
• Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 
 
 
12.12. 
Appendix 12: Sub-Cutaneous Administration PK Sub-Study 
Amendment 
TITLE PAGE  
Parent Study Protocol Title: A Phase III, Randomized, Multicenter, Parallel-group, Open 
Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-Acting 
Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression 
Following Switch from an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected 
Antiretroviral Therapy Naive Adult Participants. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
261 
 
Sub-study Protocol Amendment Title: An Amendment to the FLAIR Study to Evaluate 
the Pharmacokinetics, Safety, Tolerability, Maintenance of Virological Suppression and 
Patient Reported Outcomes for Participants Receiving Cabotegravir (CAB 200 mg/mL) 
and Rilpivirine (300 mg/mL) Long-Acting Injections Following Sub-cutaneous (SC) 
Administration in the Anterior Abdominal Wall SC Tissue  Compared with Intramuscular 
(IM) Administration in the Gluteus Medius Muscle in Adult Participants Living with HIV-
1 infection in the FLAIR Study. 
 
12.12.1. 
Sub-Study Amendment Background 
Cabotegravir/rilpivirine (CAB/RPV) long acting (LA) intramuscular (IM) injection has 
been approved as a two-drug regimen for the treatment of HIV-1 infection in treatment 
experienced adults and adolescents, virologically suppressed on an orally administered 
regimen, who switch to long-acting therapy. CAB/RPV LA is currently administered in the 
clinic as monthly or every two months dosing for intramuscular gluteal injections  by a 
health care provider.   
 
As more HIV-infected individuals opt for LA therapy to control their HIV infection, there 
has been interest in research and development of potential options to allow for at-home-
based therapy administered by the patient via an auto-injector or pre-filled syringe. In 
assessing options for home based self-administration, data needs to be generated evaluating 
pharmacokinetics, safety and tolerability, virologic response and patient report outcomes 
of cabotegravir and rilpivirine LA following sub-cutaneous (SC) administration. Assessing 
the utility of SC injections in an existing study like FLAIR is an efficient pathway to 
evaluate and compare these parameters among study participants with ongoing experience 
receiving CAB and RPV LA via IM administration. To allow for self-administration, the 
sub-cutaneous tissue of the anterior abdomen   is an easily accessible location  and will be 
the subcutaneous site  utilized in the FLAIR SC amendment (sub-study).   
 
While the ultimate aim of self-administration would be via an auto-injector or pre-filled 
syringe (under development), the FLAIR SC amendment (sub-study) will require HCP 
administered injections via a SC approach in the subcutaneous tissue of the anterior 
abdomen)  compared with HCP administered IM gluteal injections in the gluteus medius. 
 
The currently approved IM formulations for CAB (200 mg/mL) and RPV (300 mg/mL), as 
also used in the FLAIR parent study, will be utilized to assess both IM and SC routes of 
administration.  
 
12.12.1.1. Data Utilizing CAB 200/mL Subcutaneously (SC) 
Two phase I studies have reported the tolerability, safety, and pharmacokinetics of 
cabotegravir long-acting injection administered intramuscularly or via a sub-cutaneous 
route [Spreen et al; J Acquir Immune Defic Syndr 2014;67:481–486)]. In a randomized, 
placebo-controlled, double-blinded, single-dose study, 58 HIV-uninfected adults received 
cabotegravir as a gluteal intramuscular injection of 100 mg, 200 mg, 400 mg or 800 mg 
(administered as two equally divided split injections) or as a subcutaneous abdominal 
injection of 100 mg, 200 mg or 400 mg (administered as two equally divided split 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
262 
 
injections) or as a placebo injection vehicle. Following single intramuscular or 
subcutaneous injection, plasma drug concentrations increased rapidly over the first week, 
with sustained mean plasma concentrations above the PA–IC90 for approximately 24 weeks 
or longer for doses of at least 200 mg, as shown in Figure 11 
Figure 11 
Mean plasma levels of GSK1265744 over time following single-dose 
administration of long-acting formulation. 
 
Figure 11. GSK1265744 (200 mg/ml) was administered as a single IM (gluteal) or SC (abdominal) 
injection or equally divided IM or SC injection. Each cohort comprised eight healthy adult patients (six 
active/two placebo). The dashed line represents the plasma PA-IC90 value for GSK1265744 against wild-
type HIV-1 of 0.166 mg/ml. 
CAB was detected in plasma for up to 48 weeks. Following LA injections, mean 
absorption-limited apparent terminal-phase half-life ranged from 21 to 50 days as 
compared to approximately 40 h following single-dose oral administration. This longer 
apparent half-life following injection is a result of low solubility of the drug particle, 
prompting a slow absorption rate of drug from the injectable formulation with no change 
in the plasma elimination half-life of the dissolved active drug.  
When the injectable formulation was administered as two equally divided, split dose 
injections (Cohort 4, 400 mg x 2 intramuscular and Cohort 7, 200 mg x 2 subcutaneous), 
total drug release was increased so that the maximum observed plasma concentration 
(Cmax) was greater than dose proportional and there was a more pronounced decay in drug 
concentrations over time. However, overall extent of exposure [area under the curve (AUC) 
from time zero to infinity] was dose proportional and did not change (Table 18).  
Additionally, using a power model, PK parameters seemed to increase proportionally to 
dose after unsplit SC administration (100 and 200 mg).  Administration of the dose as 2 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
263 
 
separate injections (dose splitting)— 400 mg (200 mg x 2) IM and SC as well as 800 mg 
(400 mg x 2) IM—achieved geometric mean Cw4 above the protein-adjusted IC90.  
Table 18 
Plasma CAB PK Parameter Summary 
 
Although no formal statistical analysis of cabotegravir PK parameters by gender was 
performed, there was a general trend of higher plasma exposures in female subjects after 
SC administration of cabotegravir and of higher exposures in males after split IM 
injections. Gender differences in absorption rate after IM injections may reflect greater 
skin-to-muscle depth in females, which would result in an increased likelihood of 
delivering cabotegravir into the SC space. 
Safety and Tolerability 
Thirty-eight (79%) of 48 subjects receiving an IM injection and 22 (92%) of 24 subjects 
receiving a SC injection reported at least 1 AE. A higher percentage of AEs identified as 
ISRs occurred in subjects receiving CAB than placebo. In subjects receiving IM injections, 
33 (83%) of 40 subjects receiving CAB reported an AE compared with 5 (63%) of 8 
subjects receiving placebo, whereas in subjects receiving SC injections, 17 (94%) of 18 
subjects receiving CAB reported an AE compared with 5 (83%) of 6 subjects receiving 
placebo. Most frequent (>2 subjects in any dose cohort) AEs that occurred while on therapy 
by treatment are shown in Table 19. 
The most common adverse events were self-limited injection site reactions (ISR). ISRs 
were generally mild, with pain and erythema at the injection site reported as the most 
common findings for both IM and SC administration. Erythema, however, was more 
commonly reported after SC administration compared with IM. While nodule formation 
was also seen after both IM and SC administrations, it too was more commonly reported 
after SC vs IM dosing. While ISR of pain did not increase in incidence with increasing 
volume after IM administration (from 0.5 to 2.0 mL), pain was more commonly reported 
with increasing volume after SC administration (0.5 to 1.0 mL). There were no systemic 
serious or grade 3 to 4 adverse events (see Table 19). 
Specific to SC-related ISRs, pain was described in 50%, 100%, and 83% of subjects 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
264 
 
receiving CAB SC 100 mg, 200 mg, or 400 mg split injections, respectively, relative to 
33% of placebo subjects describing pain. The mean duration of pain ranged from 7 to 12 
days. Erythema was described in 33%, 83%, and 67% of subjects receiving CAB SC 
100 mg, 200 mg, or 400 mg split injections, respectively, relative to 17% of subjects 
receiving SC placebo injection. The mean duration of erythema ranged from 2 to 10.7 days.  
Overall, cabotegravir was generally safe and well tolerated when administered as a single 
or separate IM injection from 100 to 800 mg and as a single SC injection from 100 to 400 
mg. ISRs were reported by most subjects; however, they were all mild (grade 1) in severity. 
In addition, ISRs were self-limited, no subjects required symptomatic treatment, and there 
were no withdrawals due to ISRs. The incidence of ISRs seemed to be related to active 
drug as a higher percentage of AEs occurred in subjects who received cabotegravir than 
placebo. There were no substantial differences in reporting of non-ISR AEs between 
cabotegravir and placebo [Spreen et al, 2014]. 
Table 19 
Summary of Most Frequent (≥ 2 subjects in Any Arm) AEs on 
Therapy by treatment (Safety Population) 
 
In a second phase I study, HIV-negative adults received a 14-day lead-in of oral 
cabotegravir 30 mg per day to assess safety and tolerability before administration of the 
long-acting injection [Spreen et al, 2014].  
Patients were randomized into one of four cohorts: all received cabotegravir 800 mg 
intramuscular (as 400 mg x 2) as a loading dose followed by three monthly doses of 200 mg 
subcutaneous (Cohort 1); 200 mg intramuscular (Cohort 2); 400 mg intramuscular (Cohort 
3); or after 3 months, a single further injection of 800 mg intramuscular (Cohort 4). Cohorts 
2 and 3 also received gluteal intramuscular doses of rilpivirine LA at months 3 (1200 mg) 
and 4 (900 or 600 mg, respectively). Forty-seven patients enrolled, with 40 patients 
receiving at least one long-acting injection; 38 completed all planned injections. Seven 
patients discontinued the oral lead-in phase, six for non-drug-related reasons and one for 
an adverse event (dizziness following first 30 mg dose).  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
265 
 
Mean plasma CAB concentration–time profiles are shown in Figure 12. All regimens 
achieved therapeutically relevant plasma concentrations within 3 days after injection as 
defined by attaining mean plasma concentrations greater than 4-fold the protein binding–
adjusted IC90 for wild-type HIV (0.66 mg/mL) and persisted until the end of the dosing 
interval. Accumulation over 4 monthly doses was observed for the 800 mg/400 mg IM 
dose regimen while the other regimens seemed to be at or near steady state by the third 
month of dosing.  
Figure 12 
Mean plasma concentration-time profiles of 744 following monthly or 
quarterly injections. 
 
Figure 12: Solid arrows indicate 744 LA as injection administer quarterly (every 84 
days); open arrows indicate 744 LA as injection administered monthly (every 28 days). 
PK parameters following the last dose of 744 (CAB) LA and RPV LA in each cohort are 
shown in Table 20. Geometric mean PK parameters for 744 LA were similar between 
groups receiving IM and SC doses of 200 mg. Cmax and AUC0–t were generally linear 
between the 200 mg and 400 mg 744 LA IM doses. Moreover, for cohort 4, geometric 
mean plasma GSK1265744 Ctau was 1.1 µg/mL, 6.7-fold above the PA-IC90.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
266 
 
Table 20 
PK Parameters of 744 LA (both IM and SC) and RPV LA (IM data 
only) After the Last Injection 
 
 
CAB LA was generally well tolerated when administered alone or with RPV LA. The 
majority of AEs were mild or moderate in severity.  ISRs were the most commonly 
observed AEs and reported in the majority of subjects. Table 21 describes the incidence of 
ISRs by subject cohort and Table 22 provides data by ISR event and treatment.  
Cabotegravir SC administration was associated with a greater number of ISR events per 
patient than observed after IM administration with either cabotegravir or rilpivirine LA. 
There was no grade 3 or 4 ISRs. Pain was the most common ISR; the majority of ISRs 
were reported to be mild in severity (Table 22). The median duration of pain was less than 
7 days and similar between CAB LA and RPV LA dosing. Erythema, nodules, induration, 
and warmth at the injection site were also reported. The incidence of nodules was higher 
in those receiving SC CAB LA than in subjects with IM injections of either CAB LA or 
RPV LA. 
Table 21 
Most Common ISRs (> Subjects) by Cohort 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
267 
 
Table 22 
Summary of Incidence, Severity, and Duration of ISRs Across 
Treatments by Event 
 
12.12.1.2. Data Utilizing RPV LA Subcutaneously (SC) 
A phase 1 study of rilpivirine LA with a previous 100 mg/ml nanosuspension evaluated the 
pharmacokinetics and safety of single gluteal intramuscular or abdominal subcutaneous 
injections in 51 HIV-negative adult participants at doses of 200, 400 and 600 mg, vehicle 
(placebo) or saline [Verloes R, 2008]. An additional nine patients received a single 400 mg 
IM injection or saline into the deltoid muscle. Consistent with the preclinical experience, 
rilpivirine was slowly released from the injection site into plasma, with drug concentrations 
of more than 10 ng/ml for 12–26 weeks. Dose proportionality and similar plasma 
concentration–time profiles were observed for both subcutaneous and gluteal 
intramuscular injections (see Figure 13 and Table 23). ISRs consisted of redness, bruising, 
pain and to a lesser extent, induration, and were more frequent with active drug injections 
versus placebo. There was a greater frequency of ISRs with subcutaneous as compared to 
intramuscular administration. Among intramuscular injections, gluteal injections were 
better tolerated than deltoid injections. There were no serious adverse events or grade 3 or 
4 adverse events. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
268 
 
Figure 13 
Single-dose TMC278 LA provided sustained plasma levels for up to 
12 weeks in humans. 
 
Table 23 
Plasma levels and PK profiles following single-dose TMC278 LA 
injections 
 
Preliminary short-term data of an ongoing Phase 1 study in healthy adult participants with 
the 
current 
commercial 
RPV 
LA 
300 mg/mL 
formulation 
(https://clinicaltrials.gov/ct2/show/NCT05112939) 
suggest 
that 
RPV 
plasma 
concentrations in the first month after SC administration of RPV LA may be somewhat 
lower compared to historical data for IM administration. Modelling and simulation was 
used to estimate what the impact could be for HIV-infected patients on monthly CAB+RPV 
at steady-state switching from IM to SC administration, as planned in this sub-study. A 
conservative estimate of 50% lower bioavailability for SC administration compared to IM 
administration was used. Even with an estimated 50% lower bioavailability, it is predicted 
that after 3 RPV LA 600 mg SC injections, administrated a month apart each time, the RPV 
plasma concentrations would still remain above those observed for the every 2 months IM 
dosing regimen, which has been shown to be efficacious. As a cautionary measure for this 
exploratory sub-study, however, the visit window for the SC administrations will be 
reduced to only allow injections to be administered up to one week earlier (as opposed to 
allowing injections one week earlier through one week later) and will not allow injections 
to be administered up to one week later. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
269 
 
Figure 14 
Modelling and Simulation Data for RPV to Support SC FLAIR Sub-
study 
 
RPV plasma concentrations over time after monthly RPV LA 600 mg (current 
formulation) IM injections (through Week 128), followed by 3 SC injections of RPV LA 
600 mg every month (Week 128, 132, 136) with a conservative assumption of  50% 
lower bioavailability (relF/2), followed by returning to monthly RPV LA 600 mg IM 
injections (as of Week 140). 
12.12.2. 
Sub-Study Amendment Rationale 
Data from several Phase 1, healthy volunteer studies assessing various doses of CAB 
200 mg/mL and RPV 100 mg/mL administered subcutaneously demonstrated similar 
plasma PK parameters to intramuscular dosing with achieved concentrations above the PA-
IC90 for both drugs. For CAB, the geomean Ctau after 200 mg administered SC was 
1.61 µg/mL and was 1.66 µg/mL after 200 mg administered IM suggesting that switching 
400 mg IM with SC dosing will likely result in similar CAB plasma concentrations and 
above those shown to be efficacious for the every 2 months IM dosing regimen.  For the 
300 mg/mL formulation of RPV, prior data suggest that concentrations after SC 
administration could either be similar or somewhat lower compared to IM administration. 
Modelling and simulation showed that even when using a conservative estimation of 50% 
lower bioavailability for SC administration compared to IM administration, it is predicted 
that after 3 monthly RPV LA 600 mg SC injections, the RPV plasma concentrations would 
still remain above those observed for the every 2 months IM dosing regimen, which has 
been shown to be efficacious. 
Co-administration of both CAB and RPV was generally safe and well tolerated, with the 
most reported AEs classified as grade 1. SC administration was overall less well tolerated 
than IM injections with higher frequency of ISRs being reported after SC administration 
compared with IM administration although there were no SAEs or grade 3 or 4 AEs 
reported with SC administration. These data provided an initial assessment of SC 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
270 
 
administration of LA CAB and RPV in healthy volunteers and allows for further evaluation 
of SC dosing of LA CAB and RPV in HIV-infected individuals.  
 
The FLAIR study is a large, on-going, Phase 3 clinical study that assessed monthly LA IM 
dosing of CAB and RPV compared with an orally administered standard of care regimen 
in treatment naïve subjects, all of whom received 20 weeks of oral induction therapy with 
abacavir/dolutegravir/lamivudine prior to being randomized to either continue with 
abacavir/dolutegravir/lamivudine therapy or to switch to long-acting CAB/RPV. For those 
randomized at baseline to LA therapy, a 4-week oral lead in with CAB (30 mg) and RPV 
(25 mg) was required to assess tolerability prior to proceeding with LA therapy [Orkin, 
NEJM, 2020]. Since participants in the FLAIR study were randomized either at baseline to 
LA therapy or were given the opportunity to transition to LA therapy in the extension phase 
of FLAIR at week 100 (either with or without an OLI), participants enrolling into the 
FLAIR sub-study would have been exposed to LA therapy for a minimum of at least 12 
months (for those starting LA in the extension phase of FLAIR, with LSLV for the Week 
124 endpoint having occurred on 21-FEB-2020) to over three years (those originally 
randomized at the start of FLAIR to the LA arm).  
 
In addition to PK and safety parameters, other important outcome measures to be assessed 
in the FLAIR sub-study include the ability to maintain virologic suppression for 
participants who transition from IM to SC injections as well as several important patient-
reported outcomes including a preference questionnaire that aims to assess participants’ 
preference for SC vs IM injections and reasons for such a preference.  
 
The use of SC injections in the on-going FLAIR study allows an efficient pathway for 
evaluation of the two routes of administration of CAB and RPV LA as alternative 
approaches to injectable HIV treatment. This approach will generate important data to 
inform future development of a patient self-administered option of CAB and RPV LA. 
Therefore, the FLAIR study has been amended to allow an assessment of IM versus SC 
injections for participants who are currently in the extension phase of FLAIR and are 
receiving maintenance dosing of CAB with the 200 mg/mL formulation (2 mL=400 mg) 
along with RPV 300 mg/mL formulation (2 mL=600 mg).    
 
The window period around the administration of SC dosing will be up to 7 days earlier but 
will not allow injections to be given up to one week later.  This is different from what is 
allowed in the FLAIR parent study (-7 to +7 days) and is due to data emerging from an on-
going healthy volunteer study of RPV 300 mg that suggests RPV plasma concentrations in 
the first month after SC administration of RPV LA may be somewhat lower compared to 
historical data for IM administration but still above those observed for the every 2 months 
IM dosing regimen, which has been shown to be efficacious. 
Overall outcomes being measured include PK parameters Ctau, concentrations 1-week post 
dose (~Cmax), and area under the curve [AUC (0-tau)]); safety, tolerability, virologic 
response and various patient reported outcomes including Numerical Rating Scale (NRS); 
HIV Treatment Satisfaction Questionnaire c and s (HIVTSQc and HIVTSQs ); Perception 
of Injection (PIN), a preference questionnaire and various exploratory objectives including  
reasons to switch from IM to SC in HIV-1 infected participants receiving CAB and RPV 
LA administered via SC versus IM injections. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
271 
 
12.12.2.1. Data on CAB/RPV Subcutaneous Injection Site Reactions 
The FLAIR SC sub-study will be the first study in HIV-infected individuals and will 
assess the safety, tolerability and various PK parameters after SC administration of 
CAB/RPV for subjects currently enrolled in FLAIR who opt to enroll (after screening in) 
into this sub-study. Several prior Phase 1, healthy volunteer studies have individually 
assessed SC administration of CAB and RPV and have demonstrated overall tolerability 
after SC dosing with the most commonly reported ISRs being pain, erythema and nodular 
formation. These ISRs tended to be self-limited, have been mostly grade 1 and grade 2.  
Specifically, two Phase 1 studies investigated CAB200 mg/mL administered 
subcutaneously, with single and multiple dose studies ranging from 200-400 mL [Spreen 
et al., 2014; Spreen et al., 2014]. A Phase 1 FTIH healthy volunteer study (212482) 
assessed various doses and routes of administration of a 400mg formulation of 
cabotegravir with IM injections administered into the gluteal and thigh muscles and SC 
injections administrated into the anterior abdominal muscle, with up to 1.5 mL of volume 
administered subcutaneously (600mg total dose of CAB 400mg/mL formulation). 
Specific to the SC arm of study 212482, no SAEs were reported with 1/9 participants 
reporting a grade 3 ISR of rednes/erythema leading to withdrawal. Maximum grade ISRs 
for all other SC participants were grade 1 (2/9) and grade 2 (6/9).   
Finally, an ongoing study supported by Janssen (TMC278LAHTX1003) is assessing 3mL 
of the standard RPV formulation (G001 at 300mg/mL) dosed SC. While the study is still 
ongoing, the initial assessment of the ISR data received to date have shown that almost 
all subjects experienced an ISR, although most were grade 1 or 2 with no grade 3 or 
higher ISRs being reported. The majority of these ISRs were classified as erythema, 
induration, pain, swelling or nodules. Given the results from these healthy volunteer 
studies, the sub-study team does not anticipate an ISR profile to be any different in a 
HIV-infected population than what was seen in the healthy volunteer studies detailed 
above. However, since the FLAIR SC sub-study will be the first study to assess SC 
dosing of CAB and RPV in HIV-infected individuals, the study team has developed ISR 
monitoring/pausing criteria (detailed in Section 12.12.4.7) that will be applied in the 
FLAIR sub-study.  
12.12.2.2. ISR Monitoring Criteria Process 
Most ISRs observed in the healthy volunteer studies were either due to erythema, pain, 
induration or nodules.  Therefore, these typical and anticipated ISRs will not be 
considered as part of the criteria that leads to an ISR monitoring/pausing criteria. 
However, the ISR monitoring/pausing criteria will be applied when considering the 
incidence of ISRs of interest following SC dosing of CAB+RPV, detailed in Section 
12.12.4.7.  
After 50% of participants (equating to 25 out of the expected 50) have experienced their 
first SC injection and after the Week 1 follow-up visit an in-stream safety data cut will be 
performed for ISR data including site reports of details of ISRs of interest. The posterior 
probability that the rate of ISRs of interest is > 0.05 will be calculated based on ISRs of 
interest collected through Week 1 for each participant. A target rate of 0.05 was chosen 
as it would be the equivalent of >1 participant out of 25 having an ISR of interest. If the 
Bayesian posterior probability that the true rate of ISRs of interest is >0.05 is low (< 5%), 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
272 
 
then individual ISRs will undergo standard safety review. However, if the Bayesian 
posterior probability that the true rate of ISRs of interest is >0.05 is high (>5%), then a 
formal review of all ISR safety data will take place by the ViiV Safety and Labeling 
Committee (the VSLC) with the potential consideration to pause SC injections. If 1 or 2 
participants experience an ISR of interest, these individual cases will be assessed and 
discussed with the FLAIR Medical Monitor and the Clinical Development Lead for the 
CAB Treatment Program to determine whether to continue SC dosing for such 
participants. However, if 3 or more participants experience an ISR of interest, this would 
produce a study likelihood rate of 0.12, leading to posterior probability of >5%. Thus, as 
enrollment is staggered by country, if 3 participants experience an ISR of interest prior to 
25 participants reaching the Week 1 visit, VSLC review will automatically be triggered, 
no matter when the ISR of interest occurs. Otherwise, VSLC will only be triggered based 
on the interim posterior probability. An evidence threshold of 5% gives us 95% 
confidence that the true rate of ISRs of interest is not >0.05 should our interim posterior 
probability not trigger a decision to bring forth formal VSLC review.   
Table 24 and Figure 15 below show predictions of our potential to make a decision to 
formally monitor with 95% confidence based on 1000 simulations with 50 participants. 
Likelihood data was simulated based on the binomial distribution with a potential 
response of failure vs non-failure given the various levels of true rate of ISRs of interest. 
A conjugate beta prior with parameters of a=0.001 (# of failures) and b=79 (# of 
successes) was selected based on participant level data from the previous studies 
mentioned and, as no previous ISRs of interest have been noted, a failure count of 0.001 
is being used conservatively for modeling purposes. As seen in Table 24, if the true rate 
of ISRs of interest is 0.05, then we have a 23.3% chance of formal VSLC review while if 
the true rate is 0.08 or higher, we have a >50% chance of formal VSLC review.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
273 
 
Figure 15 
Probability of Formal VSLC Review Given the True Rate of ISRs of 
Interest 
 
Note: The vertical reference line indicates the target acceptable rate of ISRs of interest at 
0.05. The horizontal reference line indicates the posterior probability evidence threshold 
of formal VSLC review at 5%.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
274 
 
Table 24 
Probability that True Rate of ISRs > 0.05 
 
12.12.3. 
Sub-Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary Endpoint 
Pharmacokinetic  
To evaluate PK of monthly dosing of 
CAB LA (200 mg/mL) with RPV LA 
(300 mg/mL) following SC  
administration in the anterior abdominal 
wall SC tissue  compared with 
intramuscular administration in the 
gluteus medius muscle in HIV-1 infected 
participants currently enrolled in the 
FLAIR Phase 3 study 
Plasma PK parameters for CAB LA 
200 mg/mL and RPV LA 300 mg/mL 
(Ctau, concentrations 1-week post dose 
[~Cmax], and area under the curve [AUC 
(0-tau)]) for SC injections during the SC 
injection phase compared with similar PK 
parameters for gluteal IM injections 
  
Probability that True Rate of ISRs > 0.05 
True Rate of ISRs of 
Interest 
Probability (Rate of ISRs > 0.05) < 5% 
(No VSLC Review) 
Probability (Rate of ISRs > 0.05) > 
5% (VSLC Review) 
0 
100 
0 
0.01 
99.8 
0.2 
0.02 
98.6 
1.4 
0.03 
94.6 
5.4 
0.04 
86.4 
13.6 
0.05 
76.7 
23.3 
0.06 
65.2 
34.8 
0.07 
53.2 
46.8 
0.08 
41.6 
58.4 
0.09 
32.3 
67.7 
0.1 
23 
77 
0.11 
18.7 
81.3 
0.12 
14.2 
85.8 
0.13 
8.1 
91.9 
0.14 
7.1 
92.9 
0.15 
4.4 
95.6 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
275 
 
Objectives 
Endpoints 
Secondary Endpoints 
Safety and tolerability 
 
To assess safety and tolerability of monthly 
dosing 
of 
CAB 
LA 
(200 mg/mL) 
administered with RPV (300 mg/mL) LA 
following SC administration in the anterior 
abdominal wall SC tissue  compared with 
intramuscular injections in the gluteus 
medius 
muscle 
in 
HIV-1 
infected 
participants currently enrolled in the 
FLAIR Phase 3 study 
 
 
 
To 
assess 
additional 
safety 
events 
including other AEs, SAEs, and safety labs 
of monthly dosing of CAB LA and RPV 
LA following SC injections in the 
abdominal wall SC tissue  in HIV-1 
infected participants currently enrolled in 
the FLAIR sub-study 
Incidence and severity of ISRs and AEs of 
special interest during the SC injection 
phase.  
  
Proportion of participants who discontinue 
treatment due to ISRs and AEs of special 
interest during the SC injection phase. 
 
 
 
Incidence of other AEs not of special 
interest, SAEs and change in laboratory 
parameters from the last IM gluteal 
injection (prior to the SC abdominal 
Injection Phase) to the end of the SC 
injection phase (week 12). 
Virologic Response  
 
To assess the ability to maintain virologic 
suppression (HIV-RNA <50 copies) in 
participants who transition from IM to SC 
administrations of CAB LA (200 mg/mL) 
plus RPV LA (300 mg/mL) in the FLAIR 
sub-study. 
 
 
 
To assess virologic non-response (HIV-
RNA ≥50 c/mL and ≥200 c/mL) in 
participants who transition from IM to SC 
administrations of CAB LA (200 mg/mL) 
Proportion of participants with plasma 
HIV-1 RNA <50 copies at week 12 during 
the SC abdominal injection phase using the 
FDA Snapshot algorithm. 
  
 
 
 
Proportion of participants with plasma 
HIV-RNA ≥50 c/mL as per Food and Drug 
Administration (FDA) Snapshot algorithm 
at week 12 during the SC abdominal 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
276 
 
Objectives 
Endpoints 
plus RPV LA (300 mg/mL) in the FLAIR 
sub-study. 
 
 
 
injection phase. 
 
  
Proportion of participants with protocol-
defined confirmed virologic failure (CVF) 
of ≥200 c/mL at week 12 during the SC 
injection phase. 
 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure. 
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV 
during the SC injection phase. 
 
 
Health Outcomes 
 
To assess patient reported outcomes during 
the SC injection phase by administering the 
following health outcome measurements: 
NRS, HIVTSQ (both s and c versions), and 
PIN. 
Numerical Rating Scale (NRS): To assess 
the tolerability of injections during both the 
SC abdominal and IM Gluteal Injection 
Phases, separate for CAB LA and RPV LA.  
 
HIVTSQ (both s and c versions): To 
measure levels of satisfaction and detect 
change in satisfaction when switching 
from IM gluteal to SC abdominal 
injections in total “treatment satisfaction” 
score, and individual item scores of the 
HIV Treatment Satisfaction Questionnaire 
(HIVTSQ) during the SC Injection Phase 
as well as change from SC during the 
Return to IM Gluteal Phase. 
 
Perception of injection questionnaire 
(PIN): To assess the acceptance of pain 
and injection site reactions following SC 
abdominal and IM gluteal injections 
separate for CAB LA and RPV LA. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
277 
 
Objectives 
Endpoints 
 
To assess participant’s preference of SC 
injections during the SC abdominal 
injection phase compared to IM gluteal 
injections. 
Preference Questionnaire: To assess 
patient’s preference, and reasons for 
preference, for injections received during 
the SC Injection Phase compared with 
prior IM gluteal injections as well as for 
injections received during the Return to 
Gluteal phase compared with prior SC 
injections. 
Exploratory 
 
To assess reasons for switch to SC from IM 
injection and interest in a potential option 
for self-administration of SC injections 
Reasons for switch and interest for home 
administration options questions: To assess 
the reasons participants agreed to switch to 
a SC abdominal injection from a IM gluteal 
injection and their interest in a potential 
option for self-administration of SC 
injections. 
 
12.12.4. 
Sub-Study FLAIR Amendment Design 
The FLAIR amendment (sub-study) will consist of three phases including a Screening/IM 
Gluteal injection Phase (T-4 weeks with 1 gluteal injection interval of 4 weeks), a Sub-
Cutaneous Abdominal Injection Phase (12 weeks with 3 injection intervals of 4 weeks 
each) and a Return to Intramuscular Gluteal Injection Phase (8 weeks with 2 injection 
intervals of 4 weeks each). 80 participants will be targeted for enrollment in order to reach 
the 30-50 necessary to assess the primary PK endpoint as well as to achieve a more robust 
safety conclusion. At the conclusion of the sub-study, participants will have the option to 
continue on the FLAIR parent study or if commercial access is available, the participant 
can transition off the sub-study, complete their participation in the FLAIR study and 
proceed directly to commercially sourced CAB/RPV LA treatment.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
278 
 
Figure 16 
Sub-Cutaneous Sub-Study Amendment Design (included as part of 
the Parent FLAIR Study) 
 
NOTE: All injection visits during the sub-study should be kept to the same projected visit 
schedule as in the parent study. 
12.12.4.1. Sub-Study Amendment: Inclusion and Exclusion Criteria  
Sub-Study Inclusion Criteria 
7. Capable of giving signed informed consent (Sub-study specific informed consent), 
which includes compliance with the requirements and restrictions listed in the 
consent form and in this protocol.  Eligible participants or their legal guardians (and 
next of kin when locally required), must sign a written Informed Consent Form 
before any protocol-specified assessments are conducted. Enrolment of participants 
who are unable to provide direct informed consent is optional and will be based on 
local legal/regulatory requirements and site feasibility to conduct protocol 
procedures. 
8. Eligible participants must have been on CAB LA + RPV LA regimen for a 
minimum of 12 months while on the FLAIR study. Any disruptions in dosing 
during FLAIR must be discussed with the Medical Monitor for a final 
determination of eligibility into the sub-study.   
9. Plasma HIV-1 RNA <50 c/mL at Sub-Study Screening. 
 
10. History of SARS-COV-2 vaccination (or booster dosing) is allowed prior to sub-
study screening and will be allowed during the conduct of the sub-study as long as 
the vaccine (or boosters) are not administered within 14 days of VL assessments   
 
Sub-Study Exclusion Criteria (at Screening) 
31. More than 1 plasma HIV-1 RNA measurement ≥50 c/mL to <200 c/mL (virologic 
blip) within 24 weeks prior to sub-study Screening visit that was investigated and 
found NOT to be associated with alternative causes including recent vaccinations 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
279 
 
received within 4 weeks of the viral blip or NOT associated with intercurrent illness 
that developed within 2-4 weeks of the viral blip. 
a. All viral blips that occurred within 24 weeks prior to screening should be 
discussed with the Medical Monitor to assess whether such a participant can 
enrol into the sub-study  
32. Any Suspected Virologic Failure (HIV-RNA ≥200 c/mL) as defined in Section 
5.4.4 during FLAIR study. 
33. Subjects planning to require oral bridging during participation in the FLAIR sub-
study. 
34. The participant has a tattoo or any dermatological condition overlying the 
abdominal or gluteal regions which may interfere with interpretation of injection 
site reactions. 
35. Any condition which, in the opinion of the Investigator, may interfere with the 
absorption, distribution, metabolism or excretion of the study drugs or render the 
participant unable to receive study medication. 
36. Any woman of childbearing potential who is pregnant at screening will be 
excluded from entering the sub-study. 
Additional Exclusion Criteria While on the FLAIR Sub-Study 
37. Any women of childbearing potential who gets pregnant while on the sub-study 
will have to be withdrawn from the sub-study but will be allowed to transition 
back to the parent FLAIR study if a pregnancy specific ICF is signed, and 
commercial access is not available at the time of pregnancy. For more 
information, please refer to Section 12.12.4.10.Additionally, the following entry 
criteria for the FLAIR parent study will also apply to the sub-study:  
The inclusion and exclusion criteria are the same as in the FLAIR parent study but are 
repeated here for data capture considerations. 
 
FLAIR Parent Study – Inclusion Criteria 
AGE 
1. HIV-1 infected, ART-naive men or women aged 18 years or greater at the time of 
signing the informed consent. 
TYPE OF PARTICIPANT AND DIAGNOSIS INCLUDING DISEASE SEVERITY  
2. HIV-1 infection as documented by Screening plasma HIV-1 RNA ≥1000 c/mL; 
3. Antiretroviral-naïve (≤ 10 days of prior therapy with any antiretroviral agent 
following a diagnosis of HIV-1 infection).  Any previous exposure to an HIV 
integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be 
exclusionary. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
280 
 
FLAIR Parent Study – Inclusion Criteria 
SEX 
4. Female Participants: 
A female participant is eligible to participate if she is not pregnant at Screening and 
first day of Induction Phase (as confirmed by a negative serum human chorionic 
gonadotrophin [hCG] test), not lactating, and at least one of the following conditions 
applies: 
 
a. 
Non-reproductive potential defined as: 
• Pre-menopausal females with one of the following: 
• Documented tubal ligation 
• Documented hysteroscopic tubal occlusion procedure with follow-up 
confirmation of bilateral tubal occlusion  
• Hysterectomy 
• Documented Bilateral Oophorectomy 
• Postmenopausal defined as 12 months of spontaneous amenorrhea [in 
questionable cases a blood sample with simultaneous follicle stimulating 
hormone (FSH) and estradiol levels consistent with menopause (refer to 
laboratory reference ranges for confirmatory levels)].  Females on hormone 
replacement therapy (HRT) and whose menopausal status is in doubt will be 
required to use one of the highly effective contraception methods if they wish 
to continue their HRT during the study.  Otherwise, they must discontinue HRT 
to allow confirmation of post-menopausal status prior to study enrolment. 
b. Reproductive potential and agrees to follow one of the options listed in the 
Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of 
Reproductive Potential (FRP) (see Appendix 7.) from 30 days prior to the first dose 
of study medication, throughout the study, and for at least 30 days after 
discontinuation of all oral study medications and for at least 52 weeks after 
discontinuation of CAB LA and RPV LA. 
The investigator is responsible for ensuring that participants understand how to 
properly use these methods of contraception. 
ALL participants in the study should be counselled on safer sexual practices 
including the use and benefit/risk of effective barrier methods (e.g., male condom) and 
on the risk of HIV transmission to an uninfected partner. 
5. INFORMED CONSENT 
5. Capable of giving signed informed consent as described in Section 6.2 which 
includes compliance with the requirements and restrictions listed in the consent form 
and in this protocol. 
6. OTHER 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
281 
 
FLAIR Parent Study – Inclusion Criteria 
6. French participants: In France, a participant will be eligible for inclusion in this 
study only if either affiliated to or a beneficiary of a social security category. 
 
 
FLAIR Parent Study – Exclusion Criteria 
Exclusionary Medical Conditions  
1. Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed 
during the study. 
2. Any evidence at Screening of an active Centers for Disease and Prevention Control 
(CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not 
requiring systemic therapy or historic or current CD4+ cell count <200 cells/mm3 
are not exclusionary (local guidelines dictate). 
3. Participants with known moderate to severe hepatic impairment. 
4. Any pre-existing physical or mental condition (including substance abuse disorder) 
which, in the opinion of the Investigator, may interfere with the participant’s ability 
to comply with the dosing schedule and/or protocol evaluations or which may 
compromise the safety of the participant. 
5. Participants determined by the Investigator to have a high risk of seizures, 
including participants with an unstable or poorly controlled seizure disorder.  A 
participant with a prior history of seizure may be considered for enrolment if the 
Investigator believes the risk of seizure recurrence is low.  All cases of prior 
seizure history should be discussed with the Medical Monitor prior to enrolment.  
6. Participant who, in the investigator's judgment, poses a significant suicide risk.  
Participant’s recent history of suicidal behavior and/or suicidal ideation should be 
considered when evaluating for suicide risk. 
7. The participant has a tattoo or other dermatological condition overlying the gluteus 
region which may interfere with interpretation of injection site reactions. 
8. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at 
Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody 
(anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV DNA as follows: 
• Participants positive for HBsAg are excluded; 
• Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg 
status) and positive for HBV DNA are excluded.   
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for 
anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. 
9. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not 
be excluded, however Investigators must carefully assess if therapy specific for 
HCV infection is required; participants who are anticipated to require HCV 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
282 
 
FLAIR Parent Study – Exclusion Criteria 
treatment prior to Week 48 of the Maintenance Phase must be excluded.  HCV 
treatment on study may be permitted post Week 48, following consultation with the 
Medical Monitor.   
Participants with HCV co-infection will be allowed entry into Phase 3 studies if: 
• Liver enzymes meet entry criteria. 
• HCV Disease has undergone appropriate work-up, HCV is not advanced, and 
will not require treatment prior to the Week 48 visit.  Additional information 
(where available) on participants with HCV co-infection at screening should 
include results from any liver biopsy, fibroscan, ultrasound, or other fibrosis 
evaluation, history of cirrhosis or other decompensated liver disease, prior 
treatment, and timing/plan for HCV treatment.   
• In the event that recent biopsy or imaging data is not available or is 
inconclusive, the Fib-4 score will be used to verify eligibility.   
• 
A Fib-4 score > 3.25 is exclusionary  
• 
Fib-4 scores 1.45 – 3.25 requires Medical Monitor consultation. 
Fibrosis 4 Score Formula:  
(Age x AST) / (Platelets x (√ALT)) 
10. Unstable liver disease (as defined by any of the following:  presence of ascites, 
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or 
persistent jaundice), known biliary abnormalities (with the exception of Gilbert's 
syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per 
investigator assessment).   
11. History of liver cirrhosis with or without hepatitis viral co-infection. 
12. Ongoing or clinically relevant pancreatitis. 
13. All participants will be screened for syphilis (rapid plasma reagin 
[RPR]).  Participants with untreated syphilis infection, defined as a positive RPR 
without clear documentation of treatment, are excluded.  Participants with a 
positive RPR test who have not been treated may be rescreened at least 30 days 
after completion of antibiotic treatment for syphilis. 
14. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, 
or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or 
penile intraepithelial neoplasia; other localized malignancies require agreement 
between the investigator and the study Medical Monitor for inclusion of the 
participant prior to enrolment. 
15. Any condition which, in the opinion of the Investigator, may interfere with the 
absorption, distribution, metabolism or excretion of the drug or render the 
participant unable to receive study medication. 
16. History or presence of allergy or intolerance to the study drugs or their components 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
283 
 
FLAIR Parent Study – Exclusion Criteria 
or drugs of their class.  In addition, if heparin is used during PK sampling, 
participants with a history of sensitivity to heparin or heparin-induced 
thrombocytopenia must not be enrolled. 
17. Current or anticipated need for chronic anti-coagulation. 
18. Alanine aminotransferase (ALT) ≥3 times ULN.   
19. Clinically significant cardiovascular disease, as defined by history/evidence of 
congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery 
bypass grafting (CABG) surgery or percutaneous transluminal coronary 
angioplasty (PTCA) or any clinically significant cardiac disease. 
FLAIR Parent Study – Concomitant Medications  
20. Exposure to an experimental drug and/or experimental vaccine within 28 days or 
5 half-lives of the test agent, or twice the duration of the biological effect of the test 
agent, whichever is longer, prior to the first dose of IP. 
21. Treatment with any of the following agents within 28 days of Screening: 
• radiation therapy 
• cytotoxic chemotherapeutic agents 
• tuberculosis (TB) therapy, with the exception of treatment of latent TB with 
isoniazid 
• Immunomodulators that alter immune responses (such as chronic systemic 
corticosteroids, interleukins, or interferons).  Note: Participants using short-
term (e.g. ≤21 day) systemic corticosteroid treatment; topical, inhaled or 
intranasal corticosteroids are eligible for enrolment. 
22. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening. 
23. Treatment with any agent, except recognized ART as allowed above, with 
documented activity against HIV-1 within 28 days of the first dose of IP. 
24. Use of medications which are associated with Torsades de Pointes (See SPM for a 
list of relevant medications). 
FLAIR Parent Study – Diagnostic Assessments and Other Criteria 
25. Any evidence of primary resistance to NNRTIs (except for K103N which is 
allowed), or any known resistance to INIs from historical resistance test results 
(International AIDS Society [ IAS]-USA, 2015).  Note:  re-tests of Screening 
genotypes are allowed only at the discretion of the study virologist. 
26. Participants who are HLA-B*5701 positive and are unable to use an NRTI 
backbone that does not contain abacavir (participants who are HLA-B*5701 
positive may be enrolled if they use a NRTI backbone that does not contain 
abacavir; HLA-B*5701 positive participants may be excluded from the study if 
local provision of an alternate NRTI backbone is not possible). 
27. Any verified Grade 4 laboratory abnormality.  A single repeat test is allowed 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
284 
 
FLAIR Parent Study – Exclusion Criteria 
during the Screening Phase to verify a result. 
28. Any acute laboratory abnormality at Screening, which, in the opinion of the 
Investigator, would preclude the participant’s participation in the study of an 
investigational compound. 
29. Participant has estimated creatinine clearance <50 mL/min/1.73m2 via the Chronic 
Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey, 2009). 
30. Participation in other interventional studies is generally not permitted, however for 
eligible subjects in South Africa, co-enrolment in the AIDS Clinical Trial Group 
(ACTG) interventional study (A5392) could be exceptionally permitted after 
review and approval by the Medical Monitor. 
 
12.12.4.2. Screening Phase (Gluteal IM) 
During the screening phase for the sub-study, participants will receive an  IM injection 
while being screened for the sub-study. Eligibility criteria must be assessed at the 
Screening Visit and confirmed prior to the first SC injection. Participants who are enrolled 
in the sub-study and subsequently withdraw from the parent FLAIR study for any reason 
may not be re-screened. Screening procedures should occur within 35 days prior to Day 1 
of the first dose in the SC Abdominal Injection Phase.  
After the Screening Visit/Gluteal Injection Visit, participants will need to return to the 
clinic 1 week later to obtain PK sampling as outlined in the Sub-Study Time and Events 
Table in Section 12.12.5. 
12.12.4.3. Sub-Cutaneous Abdominal Injection Phase (12 Weeks) 
After confirming eligibility into the sub-study, participants will enter into the Sub-
Cutaneous Abdominal Injection Phase and receive a sub-cutaneous injection of CAB LA 
(2 mL; 400 mg) and RPV LA (2 mL; 600 mg) at the following visits: 
• Day 1 
• Week 4 
• Week 8 
The window period around the administration of SC dosing will be up to one week earlier 
and will not allow injections to be given up to one week later (-7 days only without the 
allowance of a +7 day dosing window)  
Participants will need to return to the clinic 1 week after each  injection for PK sampling 
as outlined in the Sub-Study Time and Events Table in Section 12.12.5. 
12.12.4.4. Return to Intramuscular Gluteal Injection Phase 
Following 12 weeks of SC injections, participants will return to the clinic to receive an IM 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
285 
 
gluteal injection of CAB LA (2 mL; 400 mg) and RPV LA (2 mL; 600 mg) at the following 
visits: 
• Week 12 (-7 days) 
• Week 16 (+/-7 days) 
Participants will complete 8 weeks (2 injections cycles) of CAB/RPV LA therapy. After 
the Week 20 pre-dose assessments are obtained (AEs, SAEs and concomitant medications)  
the participant’s participation in the sub-study will have concluded.  
12.12.4.5. Sub-Study Completion 
Participants are considered to have completed the sub-study once the final Week 20 pre-
dose assessments (AEs, SAEs and concomitant medications) are obtained. The IM 
injection and all other assessments will be considered part of the parent study and 
assessments should be completed as per the parent study time and events table in Section 
7.1. 
Depending on the local availability of the marketed product in each country, after the sub-
study is completed, and based on the particular country the participant is enrolled from, 
such participants in:  
• Countries where CAB LA+RPV LA marketed product is not yet locally 
available: Continue in the Extension Phase of the parent study and complete 
study visits as per the Time and Events table in Section 7.1. 
• Countries where CAB LA+RPV LA marketed product is locally available: 
Transition to CAB LA + RPV LA marketed product or an alternative ART as 
indicated below: 
o After the pre-injection assessments are completed at Week 20, the 
participant will receive the last IM gluteal injection as part of the parent  
study. 
o Participant will complete the Safety Follow Up Visit 2-4 weeks after the 
last injections (please refer to Section 5.5 of the protocol) before 
transitioning to a marketed ART.  
Note: If the participant has to withdraw from the study due to safety related reasons once 
CAB LA + RPV LA marketed product is locally available (see Section 5.4) the subjects 
would need to complete a withdrawal visit and enter the Long Term Follow Up Phase (see 
Section 4.2.6.). 
12.12.4.6. Sub-Study Amendment Withdrawal/Stopping Criteria 
Participants meeting Withdrawal/Stopping criteria as per Section 5.4. will discontinue the 
study treatment and be withdrawn from both FLAIR and the sub-study, and will complete 
all assessments per the Time & Events table in Section 7.1. and enter in the Long Term 
Follow-Up Phase. 
Participants who decide to discontinue their participation in the sub-study for non-safety 
reasons (refer to Section 5.5.), including participants who require Oral Bridging during 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
286 
 
the sub-study or participants who decide to discontinue their participation in the sub-study 
due to injection-site (abdominal) related tolerability reasons:  
• In countries were the marketed products of CAB and RPV LA are not yet locally 
available, such patients will be allowed to transition back to the parent study and 
continue with IM gluteal injections per the randomized dosing schedule. 
• In countries were the marketed products of CAB and RPV LA are locally available: 
patients will be invited to return to gluteal injections in the parent  study and receive 
1 more gluteal injections (additional injections might be required if requested by 
the Medical Monitor) before transitioning to marketed product as described in 
Section 5.5. 
12.12.4.7. Sub-Study Injection Site Reactions 
For IM administrations, injection site reactions (ISRs) should be assessed as per the 
parent study instructions in Section 7.4.1. and Section 7.4.10.10. 
For SC administrations, any participant who experiences an ISR meeting the below 
criteria must be discussed with both the Medical Monitor and the Clinical Development 
Lead for CAB Treatment. These are ISRs of interest and will be included when 
considering the ISR monitoring/pausing criteria, as mentioned in Section 12.12.2.2.: 
• 
A Grade 4 injection site reaction. 
• 
An ISR of at least Grade 3 in severity where the ISR AE includes any of the 
following: 
o Ulceration 
o Secondary infection 
o Phlebitis 
o Sterile abscess 
o Drainage 
 
ISRs that are Grade 3 based upon the size of erythema or induration alone or based upon 
pain or symptoms causing inability to perform usual social & functional activities will be 
not be included for the purpose of the ISR monitoring/pausing criteria but will be 
reviewed and considered when reviewing the ISR data. 
For SC administration, injection site erythema, redness, induration and swelling will be 
assessed by calculating both the length and width of the affected area.  
Any ISR associated with SC administration of CAB/RPV should be followed to 
resolution. 
Digital photographs may be documented, where possible, on all participants who have an 
injection site reaction, with observable findings, that is either serious or Grade 3 or 
higher, or that persist beyond 2 weeks.  Dermatology will be consulted on all participants 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
287 
 
who have an injection site reaction considered serious, Grade 3 or above, or if clinically 
significant and persistent beyond 30 days and others if the Investigator or Medical 
Monitor feels it is medically necessary. 
 
12.12.4.8. Sub-Study Amendment Specific Virological Failure Guidance 
Refer to Section 5.4.3., Section 5.4.4., and Section 5.4.5. 
12.12.4.9. Sub-Study Amendment HIV-1 RNA Blips Guidance 
Guidance on SVF management can be found in Section 5.4.5.1.  
The Medical Monitor should discuss all cases of viral blips (defined as HIV-1 RNA 
≥50 c/mL and <200 c/mL) with the site PI to assess whether any recent vaccinations were 
administered (within 4 weeks of blip) or any intercurrent illnesses developed (within 2-4 
weeks of the viral blip) that can spuriously elevate viral load. If there are possible 
alternative causes for the viral blip, further guidance will be provided by the Medical 
Monitor in these instances.  
Participants who have an HIV-1 RNA ≥50 c/mL and <200 c/mL during the SC Injection 
Phase of the sub-study, with no alternative cause for the viral blip identified, will need to 
have a repeat viral load assessment 2-4 weeks after the initial viral blip for confirmation.  
If the repeat HIV-1 RNA is confirmed (≥50 c/mL and <200 c/mL) in participants with no 
recent history of vaccinations or intercurrent illnesses, the participant will have to withdraw 
from the SC sub-study and return to IM dosing in the parent study, or, if access is available, 
continue IM dosing via a commercial source.  
If the repeat VL is not confirmed (i.e, HIV-RNA is < 50 c/mL), the participant can continue 
the sub-study.  
If the repeat VL is ≥ 200 c/mL, the participant has achieved a Suspected Virologic Failure 
and see Section 5.4.5.1 for further details 
Participants who have a viral blip (HIV-1 RNA ≥50 c/mL and <200 c/mL) during the IM 
Injection Phase of the sub-study including during the Return to Gluteal Injection Phase, 
see Section 5.4.5.1 of the parent study for further details on the management of HIV-1 
RNA blips.  
12.12.4.10. Sub-Study Amendment Specific Withdrawal Criteria – Pregnancy 
If a subject becomes pregnant during the sub-study, the subject will need to withdraw 
from the sub-study and will have the option to continue with gluteal injections in the 
parent FLAIR study after signing a pregnancy-specific ICF addendum or be withdrawn 
from FLAIR. Please refer to Appendix 10 for additional information.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
288 
 
12.12.4.11. Sub-Study Pharmacokinetics Sample Collection 
Table 25 
Sub-study CAB and RPV Plasma Pharmacokinetic Sample Schedule 
Group 
Analytes 
Sample Times Relative to Dose 
Participants 
receiving CAB 
200 mg/mL LA + 
RPV 300 mg/mL 
LA Q4W 
injections 
CAB and RPV 
Pre-Dose: Screening (Week -4), Day 1, Week 
4, Week 8 (SC abdominal injections), Week 
12, Week 16 (IM gluteal injection) 
1 Week Post dose: Week -3, Week 1, Week 5, 
Week 9 (SC abdominal injections), Week 13 
and Week 17 (IM gluteal injections) 
PK window collection: All scheduled PK samples should be collected on the Day of the 
corresponding visit. Pre-dose samples will be taken prior to performing dosing within the 
clinic.   
Additional details concerning handling of PK samples, labelling and shipping directions 
will be supplied in the central laboratory manual. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
289 
 
12.12.5. 
Sub-Study Time and Events Table 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d  
Screening, 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20 n 
IM Gluteal 
Administration 
X 
 
 
 
 
 
 
 
X k 
 
X  
 
 
SC Abdominal 
Administration k 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Written 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Verification  
 
Inclusion / 
Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom 
directed 
physical exam 
and medical 
assessment a 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Height, Weight 
and BMI 
 
 
X 
 
 
 
 
 
X 
 
 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
290 
 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d  
Screening, 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20 n 
Vital Signs, BP, 
HR, temp b 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12 EKG c 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
HIV associated 
conditions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
AEs, SAEs, 
concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ISR 
assessments 
for IM injections 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
 
ISR 
assessments 
for SC 
injections 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Clinical 
Chemistry and 
Hematology 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Pregnancy 
testing, serum e 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
291 
 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d  
Screening, 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20 n 
HIV-1 RNA and 
sample for 
storage (S) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
CD4+ cell count 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
CD8+ cell count 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Urinalysis f 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
Fasting lab 
assessments: 
glucose, 
cholesterol 
(total, HDL and 
LDL) and 
triglycerides g 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
PK Sample Collection j 
Pre dose PK 
samples for 
CAB and RPV  
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Post dose PK 
sampling 
(~Cmax) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
292 
 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d  
Screening, 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20 n 
PROs m 
HIVTSQC 
 
 
 
 
 
 
 
X 
 
 
 
 
 
HIVTSQS l 
 
X m 
 
 
 
 
 
X 
 
 
 
X 
 
NRS h 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
PIN i 
 
X 
 
X 
 
 
 
X 
 
X 
 
 
 
Preference SC 
Abdominal 
injection vs IM 
Gluteal injection 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Reason for 
switch 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Interest for 
home 
administration 
 
 
 
 
 
 
 
X 
 
 
 
 
 
a. Physical exams should be conducted as part of normal routine clinical care. 
b. Measure vital signs about 5 minutes of rest in a semi-supine position. 
c. A 12-lead ECG will be performed after resting in a semi-supine position for at least 5 minutes. ECGs will be performed pre-dose. 
d. All injection visits during the sub-study should be kept to the same projected visit schedule as in the parent study. 
e. Women of childbearing potential only. SR = serum, UR = urine. Urine pregnancy test can be performed at study visits where other 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
293 
 
blood draws are not required in order to limit needle sticks.  
f. A morning specimen is preferred. 
g. An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
h. Should be collected 30 to 60 minutes post injection. To be assessed separately for CAB LA and RPV LA 
i. To be assessed separately for CAB LA and RPV LA. 
j. PK window allowed for sample collection: For 1-week post dose sample (3 to 10 days post dose). 
k. During the SC phase (and for the first IM injection in the return to IM injection phase), the dosing window can be -7 days, however, it 
cannot be +7 days from the projected visit date. Once SC injections begin, the next SC administration can be 3-4 weeks later, however, 
SC administration may not take place 5 weeks later. See details in Section 12.12.1.2. and Section 12.12.4.3. 
l.  All Patient Reported Outcome Questionnaires/Surveys will be administered via paper instrument (in exception circumstances, the 
questionnaires could be completed via telephonic interview, please refer to the COVID19 appendix for additional details) at the 
beginning of the visit before any other assessments are conducted, with the exception of the NRS. 
m. For HIVTSQS, we want to measure satisfaction with IM gluteal injection prior to switch to sub-cutaneous. This will be assessed at week 
-3 (questionnaire can be administered at any time during the visit). 
n. AEs, SAEs and concomitant medications to be assessed pre-dose. IM administration itself and all other assessments will be 
considered part of the parent study, and should be completed as per the parent study time and events table in Section 7.1. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
294 
 
12.12.6. 
Sub-Study Health Outcomes Questionnaires 
12.12.6.1. Sub-Study: Value Evidence and Outcomes 
Health outcomes assessments will be conducted according to the Time and Events Table 
(Section 12.12.5.). Assessments are recommended to be administered with a paper 
instrument at the beginning of the visit (except for NRS which is performed after the 
injections) prior to collection of blood for analysis and other scheduled assessments. There 
will be five health outcome measurements that will be administered during the sub-study 
including Numerical Rating Scale (NRS), HIVTSQc, HIVTSQs, PIN, and a Preference 
questionnaire. 
12.12.6.2. Numerical Rating Scale (NRS) 
A numeric rating scale was used to assess the level of pain experienced following SC vs 
IM injections with CAB + RPV. The scale contains one item, and the response scale is 
ranging from 0= “no pain” to 10= “extreme pain”. The NRS was used to assess 
maximum level of pain on the day of the injection as well as maximum level of pain one 
week following injection. NRS questionnaires should be collected 30 to 60 minutes post 
injection. 
12.12.6.3. HIV Treatment Satisfaction Questionnaire (HIVTSQ) 
HIVTSQ is a self-completion measure specifically designed to measure treatment 
satisfaction in PLHIV. It explores multiple aspects of treatment satisfaction including side 
effects, treatment demands, convenience, flexibility and understanding of HIV.  
There are two versions of this questionnaire: HIVTSQs and HIVTSQc.  
HIVTSQs (status version) is needed to measure absolute level of satisfaction while the 
HIVTSQ change version (HIVTSQc) was developed to overcome ceiling effects associated 
with HIVTSQs and enhance sensitivity to change by allowing those who were optimally 
(or close to optimally) satisfied at baseline to express even greater satisfaction at follow 
up. The HIVTSQc (change version) is assessing the change in patients’ satisfaction 
between their previous and their current treatment within the same group.  
Total score for HIVTSQs ranges from 0-66. Higher scores indicate a greater satisfaction 
and a lower score indicate dissatisfaction. Individual scores range from 0-6.  
HIVTSQc total score ranges from -33 to 33. A higher score indicate improvement in 
satisfaction with treatment; lower scores indicate a greater deterioration in satisfaction with 
treatment; a score of 0 represents no change. Individual items scores range from -3 to 3 (-
3= much less satisfied now, 3= much more satisfied now). 
12.12.6.4. Perception of Injection (PIN) 
The Perception of Injection (PIN) questionnaire explores the bother of pain at the injection 
site and ISR, anxiety before and after injection (SC vs IM), willingness to receive an HIV 
injectable treatment the following visit and satisfaction with the mode of treatment 
administration of individuals receiving injection and perceptions of individuals associated 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
295 
 
with receiving injections. The PIN questionnaire was derived from the Vaccines' 
Perception of Injection (VAPI) questionnaire (Chevat, 2009), and adapted for HIV-infected 
patients who will receive the CAB LA and RPV LA regimen. This measure contains 21 
items that measure pain at injection site, local site reactions, impact on functioning and 
willingness to pursue injectable treatment outside of a clinical trial. Scores range from 1 to 
5, and questions are phrased in such a way as to ensure that 1 always equated with the most 
favourable perception of vaccination, and 5 the most unfavourable. 
12.12.6.5. Preference Questionnaire 
A preference question was used to assess patients’ preference, and reasons for preference, 
for the SC abdominal injections compared with IM gluteal injections. The “Preference” 
questionnaire will include a single item question evaluating preference of HIV treatment 
and the attributes supporting this preference. 
12.12.6.6. Reason for switch questionnaire. 
A single item question will be used to assess reasons participants agreed to switch to a SC 
injection from their current IM injection at screening.  
12.12.6.7. Interest in potential self-administration option 
A single item question will be used to assess participants interest in potential upcoming 
option for self-administering the SC injection. Response options will be evaluated using a 
likert scale ranging from: “Not at all interested” to “Extremely interested”. 
12.12.7. 
Sub-Study Treatment 
12.12.7.1. Sub-Study Amendment: Investigational product and Other Study 
Treatment 
Please refer to Section 6.1.3. Cabotegravir Injectable Suspension (CAB LA) and Section 
6.1.4. Rilpivirine Injectable Suspension (RPV LA) included in the main FLAIR protocol. 
12.12.7.2. Sub-Study Dosage and Administration 
NOTE: All injection visits during the sub-study should be kept to the same projected visit 
schedule as in the parent study. 
Participants who enter into the SC Abdominal Injection Phase will receive a SC injection 
of CAB LA (2 mL; 400 mg) and RPV LA (2 mL; 600 mg) on Day 1. Subsequent SC 
injections with CAB LA 400 mg (2 mL) and RPV LA 600 mg (2 mL) will occur every 4 
weeks (-7 days).  Participants who receive SC injections for a total of 12 weeks during the 
SC Abdominal Injection Phase will return to the clinic 4 weeks later (-7 days) to receive 
their first IM gluteal injections (at Week 12) of CAB LA (2 mL; 400 mg) and RPV LA 
(2 mL; 600 mg) during the Return to Gluteal Injection Phase. The subsequent gluteal 
injection with CAB LA 400 mg (2 mL) and RPV LA 600 mg (2 mL) will occur 4 weeks 
later (±-7 days) at Week 16. Gluteal injections and all assessments administered at the 
Week 20 visit will be considered part of the parent study.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
296 
 
The interval between injection visits will be limited to a maximum of 4 weeks during the 
SC Abdominal Injection Phase, and 5 weeks during the Return to Gluteal Injection Phase. 
The Medical Monitor must be contacted to discuss individual participant case management 
if the length of time between injections exceeds or is projected to exceed these intervals.  
During both the SC Abdominal Injection Phase and the Return to Gluteal Injection Phase, 
CAB injections should be given on the left side of the body and RPV injections should be 
given on the right side of the body.  
12.12.7.3. Oral Bridging During the Sub-Study 
Oral bridging will not be allowed during the sub-study as it will interfere with data 
interpretation in the SC injection phase. If oral bridging is needed for any reason, the 
participant must be withdrawn from the sub-study and either continue onto the parent 
FLAIR study or transition to commercial drug supply if locally available. 
12.12.8. 
Sub-Study Data Management 
Please refer to Section 8. 
12.12.9. 
Sub-Study Statistical Considerations and Data Analyses 
12.12.9.1. Statistical Hypotheses 
The primary objective of this sub-study is to evaluate the pharmacokinetics of cabotegravir 
LA (200 mg/mL) and rilpivirine (RPV) LA (300 mg/mL) for monthly dosing as a SC 
injection in the anterior abdominal muscle versus an IM injection into the gluteal muscle 
in HIV-1 infected participants currently enrolled in the FLAIR study. 
An estimation approach will be taken and point estimates and confidence intervals will be 
constructed for the ratio of the geometric mean of SC abdominal injection PK parameters 
to the geometric mean of the IM gluteal injection PK parameters. 
12.12.9.2. Sample Size Considerations 
The sample size of 30-50 subjects is deemed sufficient to evaluate the geometric mean ratio 
(SC abdominal injection vs IM gluteal injection) of PK parameters and to assess the safety, 
tolerability, virologic responses and patient reported outcomes during 12 weeks of the SC 
abdominal injection phase.  
Although a larger sample size is not needed solely to assess the various PK parameters, 
the larger sample size of 30-50 will allow a more robust analysis regarding the safety of 
CAB/RPV when administered subcutaneously. Additionally, the larger sample size will 
provide more insight into subgroup analyses for safety, allowing for a higher likelihood 
of having more than a few participants in a certain age or BMI category.   
Sample size calculations assume the treatment ratio is 1 with confidence intervals within 
0.8-1.25 and a steady state concentration coefficient of variation of 0.4. Assuming 40 
participants, a CV of 0.4, and power of at least 80%, and a true ratio of 1 we would expect 
a 90% confidence interval of approximately (0.831, 1.203) on the original scale. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
297 
 
Power 
Total N  
Alpha 
0.70668 
30 
0.05 
0.81565 
40 
0.05 
0.82340 
30 
0.1 
0.89981 
40 
0.1 
12.12.9.3. Sub-Study Analysis Populations 
The Enrolled Population will consist of all participants who sign informed consent into the 
sub-study, excluding screen failures.  
The Safety Population will consist of all enrolled participants who receive at least one SC 
injection. This population will be used to summarize safety, virologic response , and health 
outcomes endpoints. 
The Pharmacokinetic Concentration (PC) Population will consist of all participants who 
received at least one CAB and/or RPV SC injection and provide at least one non-missing 
CAB and/or RPV plasma concentration value during the sub-study.  
The Pharmacokinetic Parameter (PP) Population will consist of all participants who 
received at least one CAB and/or RPV SC injection and have at least one evaluable PK 
parameter estimated. PK samples that may be affected by protocol deviations will be 
reviewed by the study team to determine whether or not the sample will be excluded.  
12.12.9.4. Primary Analysis 
The primary analysis is to compare the abdominal SC injection with  gluteal IM injection 
using the ratio of the geometric mean of SC injection to the geometric mean of IM injection 
for a PK parameter within each analyte (CAB, RPV). The primary PK parameters of 
interest include concentrations at the end of the dosing interval [Ctau], concentrations 1-
week post dose [~Cmax], and area under the curve for the dosing interval [AUC (0-tau)] 
(Table 25).  CAB and RPV concentrations and parameters will be summarized 
descriptively.  No formal bioequivalence testing will be performed.  
 
Following log-transformation, Cmax, Ctau and AUC(0-tau) will be separately analyzed by 
analyte using a mixed effects model with fixed effect term for type of injection (SC, gluteal) 
and and BMI (≥30 Kg/m2, <30 Kg/m2) in addition to a random effect term for subject. As 
it is suspected that varying participant BMI may impact the PK concentration distribution, 
BMI is being included in the model as a covariate to control for any potential impact 
beyond the effect of injection type. In each model, only participants with PK parameter 
estimates from corresponding both SC and gluteal injections are included. For example, in 
the model for comparing Cmax between the first CAB SC injection vs gluteal CAB 
injection, only participants with Cmax estimates from both first CAB SC injection and CAB 
gluteal injection are included.  
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
298 
 
Point estimates and their associated 90% confidence intervals will be constructed for the 
differences between the SC injection and the gluteal injection. The point estimates and their 
associated 90% confidence intervals from the log-transformed analysis will then be back-
transformed to provide point estimates and 90% confidence intervals for the ratios between 
the SC injection and the gluteal injection on the original scale. This analysis will be 
performed using the PK Parameter (PP) population.  
Slope of the Ctau  following the last IM through 3rd SC injection will also be determined 
in an attempt to assess changes in steady state conditions established previously.   
Table 26 
Parameters and dosing 
Parameters (CAB 
200mg/mL + 
RPV 300mg/mL) 
Q Monthly Dosing  
Cmax (1-week 
post injection), 
Ctau (end of 
dosing interval) 
AUC(0-tau) 
SC Injection 1: 
gluteal injection 
SC Injection 2: 
gluteal injection 
 
SC Injection 3: 
gluteal injection 
 
12.12.9.5. Secondary and Exploratory Analyses 
The proportion of participants with HIV-1 RNA ≥50 c/mL and HIV-1 RNA <50 c/mL at 
Week 12 of the SC injection phase will be summarized using FDA Snapshot algorithm for 
the Safety population in the sub-study. Proportion of participants with protocol-defined 
confirmed virologic failures at Week 12 will also be summarized. 
 
The proportion of participants reporting AEs will be tabulated for each injection type. 
The following summaries of AEs will be provided: 
• Incidence and severity of ISRs and AEs of special interest during the SC injection phase 
• Proportion of participants who discontinue treatment due to ISRs and proportion of AEs 
of special interest during the SC injection phase 
• Incidence and severity of AEs not of special interest 
• Incidence of SAEs 
• Change from baseline (latest non-missing value prior to the first SC injection) 
in laboratory parameters will be summarized by visit through the end of the SC phase. 
• The incidence of observed genotypic and phenotypic resistance to NRTIs and INIs, PIs, 
and NNRTIs will be summarized for subjects meeting confirmed virologic failure criteria. 
 
The health outcomes analyses include analyses of data collected from the following 
questionnaires, HIVTSQ (both s and c versions), NRS, PIN, and Preference between SC 
and gluteal injections. The reasons for switch to SC from IM injections will be assessed, 
as well as the interest in a potential option for self-administration of SC injections. Further 
details will be provided in the RAP. Health Outcomes assessments will be summarized, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
299 
 
where applicable, by study drug (CAB and RPV), domain, and item.  
 
12.12.9.6. Sub-Study Interim Analysis 1: ISR Monitoring/Pausing Criteria 
As mentioned in Section 12.12.2.2. an early interim analysis (Interim Analysis 1) will 
take place to assess the rate of ISRs of interest after 50% of participants (equating to 25 
out of the expected 50) have experienced their first SC injection with a follow-up Week 
1. An in-stream safety data cut will be performed for ISR data including site reports of 
details of ISRs of interest. The posterior probability that the rate of ISRs of interest being 
>0.05 will be calculated based on ISRs of interest collected through Week 1 for each 
participant. A target rate of 0.05 was chosen as it would be the equivalent of >1 
participant out of 25 having an ISR of interest. If the Bayesian posterior probability that 
the true rate of ISRs of interest is >0.05 is low (< 5%), then individual ISRs will undergo 
standard safety review. However, if the Bayesian posterior probability that the true rate of 
ISRs of interest is >0.05 is high ( >5%), then a formal review of all ISR safety data will 
take place by the VSLC with the potential consideration to pause SC injections. As 
enrollment will be staggered by country, if 3 participants experience an ISR of interest 
prior to 25 participants reaching the Week 1 visit, VSLC review will automatically be 
triggered as 3 out of 25, or a sub-study rate of 0.12, would lead to the posterior 
probability of the rate of ISRs of interest >0.05 being >5%. Otherwise, VSLC will only 
be triggered based on the interim posterior probability. An evidence threshold of 5% 
gives us 95% confidence that the true rate of ISRs of interest is not >0.05 should our 
interim posterior probability not trigger a decision to bring forth formal VSLC review.  If 
1 or 2 participants experience an ISR of interest, these individual cases will be assessed 
and discussed with the FLAIR Medical Monitor and the Clinical Development Lead for 
the CAB Treatment Program to determine whether to continue SC dosing for such 
participants.  
 
12.12.9.7. Sub-Study Interim Analysis 2: Week 9 Safety and PRO Review 
A second interim analysis (Interim Analysis 2) will focus on safety, tolerability and 
selected PROs and will not include PK related analyses. The interim analysis will allow 
for an early assessment of the main safety parameters (ISR type and rate; AEs/SAEs, 
safety related labs including eGFR, ALT, AST, total bilirubin, haematology, and basic 
chemistry) and PROs (preference and NRS) being assessed in the sub-study. 
Interim Analysis 2 will take place when 50% of enrolled participants have completed 
their sub-study Week 9 visit. The analysis will consist of an internal review of key 
safety/tolerability and preference endpoints in order to assist in compound development. 
No formal stopping decisions will be made. No formal data cleaning activities will occur. 
Data will be processed instream with what is available at the time of the data cut. Queries 
will be issued as needed. 
12.12.10. Sub-Study Pharmacokinetics 
Pharmacokinetic analysis will be the responsibility of the Clinical Pharmacology 
Modeling & Simulation Department (CPMS), GSK. Individual Plasma CAB and RPV 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
300 
 
concentration-time data will be analyzed by non-compartmental methods with WinNonlin 
5.2 or higher. Calculations will be based on the actual sampling times recorded during the 
study.  The following pharmacokinetic parameters will be determined for each interval, as 
data permit: maximum concentration (Cmax), time to Cmax (tmax), area under the plasma 
concentration-time curve through the end of the dosing interval (AUC(0-tau), and 
concentration at the end of the dosing interval (Ct).  
 
Plasma concentration data will be summarized descriptively by analyte and injection type 
and presented in graphical and/or tabular form.  Parameters will be summarized by analyte 
and injection type, Cmax, AUC (0-tau) and Ct treatment comparisons (seeTable 25); tmax 
will not be compared statistically.  All pharmacokinetic data (both CAB and RPV) will be 
stored in the Archives, GSK Pharmaceuticals, R&D.  Additional analyses including 
modelling, simulation and external validation may be performed to assist in the clinical 
interpretation of these data and will be reported separately. 
12.12.11. References 
Chevat C, Viala-Danten M, Dias-Barbosa C, Nguyen VH. Development and 
psychometric validation of a self-administered questionnaire assessing the acceptance of 
influenza vaccination: the Vaccinees' Perception of Injection (VAPI©) questionnaire. 
Health Qual Life Outcomes. 2009;7:21. 
ClinicalTrials.gov Identifier: NCT05112939 (Study CR109089). A Phase 1, Single-blind, 
Randomized, Parallel-group Study in Healthy Participants to Investigate the Single-dose 
Pharmacokinetics, Safety and Tolerability of Rilpivirine After Subcutaneous 
Administration of a Rilpivirine Extended-Release Suspension Alone, and of Rilpivirine 
and Cabotegravir After Co-administration With Cabotegravir Extended-Release 
Suspension. Available at: https://clinicaltrials.gov/ct2/show/NCT05112939. 
Orkin C, Arasteh K, Górgolas Hernández-Mora M, Pokrovsky V, Overton ET, Girard 
PM, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 
infection. N Engl J Med. 2020;382(12):1124-35. 
Spreen W, PharmD; Ford Susan L, PharmD; Chen Shuguang, PhD; Wilfret DMD; 
Margolis D, MD; Gould E, BS; and Piscitelli Stephen, PharmD. GSK1265744 
Pharmacokinetics in Plasma and Tissue After Single-Dose Long-Acting Injectable 
Administration in Healthy Subjects. J Acquir Immune Defic Syndr 2014;67:481–486 
Spreen W, PharmD; Williams Peter, PhD; Margolis D, MD; Ford Susan L, PharmD; 
Crauwels Herta, PhD; Lou Yu, MS; Gould Elizabeth, BS; Stevens Marita, MD; and 
Piscitelli Stephen, PharmD. Pharmacokinetics, Safety, and Tolerability with Repeat 
Doses of GSK1265744 and Rilpivirine (TMC278) Long-Acting Nanosuspensions in 
Healthy Adults. J Acquir Immune Defic Syndr _ Volume 67, Number 5, December 15, 
2014; 67:487-492 
Verloes, R vanÔt Klooster G; Baert L; van Velsen F; Bouche M-P; Spittaels K; 
Leempoels J;Williams P; Kraus G; Wigerinck, P. TMC278 long acting - a parenteral 
nanosuspension formulation that provides sustained clinically relevant plasma 
concentrations in HIV-negative volunteers. XVII International AIDS Conference, Mexico 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
301 
 
City, Mexico, 3-8 August 2008 
12.13. 
Appendix 13: Mitigation for Geopolitical Situation in 
Russia/Ukraine 
Background 
Due the geopolitical situation between Russia and Ukraine there is potential for there to 
be significant logistical challenges for many clinical sites within Russia with risk of 
restrictions being placed on site resources, operations, and on an individual participants 
ability to attend clinic visits.  
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in HIV-1 
treatment for participants enrolled in this clinical study, through continuous access to 
antiretroviral therapy. 
This appendix outlines the measures which are approved for implementation within this 
clinical trial, to protect patient safety and to ensure the integrity of the clinical trial, as a 
result of the geopolitical crisis. These measures may be implemented in accordance with 
requirements and expectations set out by local Independent Review Boards/Independent 
Ethics Committees (IRB/IEC) and National Competent Authorities (NCA), as necessary. 
12.13.1. Changes to Study Visits and Study Procedures  
• Where site staff resources is constrained due to the geopolitical situation, IM 
dosing visits may proceed with limited or no other protocol defined assessments 
(e.g lab tests, questionnaires, etc.). If lab tests will be missed for more than one 
consecutive visit, the medical monitor must be contacted, to provide guidance for 
safety monitoring.  
• For WOCBP, point of care pregnancy testing should be performed, prior to IM 
dosing. 
• If central laboratory testing cannot be performed at a particular visit, and 
monitoring for safety is required, tests may be performed at an appropriately 
authorised/accredited local laboratory (or other relevant clinical facility). The site 
should proactively inform the sponsor about such instances. Local laboratory 
results may be used to inform safety decisions. Results should be retained in 
source records. Please refer to the Q2 MEMO sent 03 Mar 2022 for additional 
guidance 
• When on-site visits are reduced, it is important that the investigator continue 
collecting relevant clinical information, including adverse events, from the 
participant through alternative means, e.g. by telephone contact. 
• There may also be circumstances where immediate actions are required by the 
sponsor and/or investigator, outside of what is contemplated in the protocol, in 
order to protect a study participant from immediate hazard. Any such measures 
will be carefully documented and conducted in accordance with the National 
Competent Authority (NCA)/IRB/IEC regulations. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
302 
 
12.13.2. Changes to Informed Consent  
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   
Any updated informed consent form or other subject-facing materials should be provided 
to participants by e-mail, mail or courier before re-consent is obtained. Any consent 
obtained this way should be documented in source records and confirmed by way of 
normal consent procedure at the earliest opportunity when participants attend their next 
on-site study visit. 
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval. 
 
12.13.3. 
Permissible Use of Antiretroviral Therapy  
In order to minimize the risk of gaps in HIV-1 antiretroviral therapy (ART) for 
participants impacted by the geopolitical situation in the clinical trial, the following 
options can be considered with regards to ART dosing:  
If a participant is not able to attend an IM injection visit due to geopolitical related 
restrictions, the gap in IM dosing should be covered with oral ART, until IM dosing can 
resume. Participants should be reminded of the importance of adhering with daily oral 
dosing. Two options can be approved for oral bridging therapy in consultation with the 
Medical Monitor.  
 
1. Oral CAB + RPV  
a. Investigator should request availability of oral CAB + RPV supplies OR ,  
2. Oral standard of care (SOC) commercial ART (prescribed locally) 
 
Oral bridging with CAB + RPV 
The protocol permits oral bridging to cover planned missed injections with oral CAB + 
RPV, only until IM dosing can be resumed.  The start date of oral bridging should be 
within the dosing window for the missed IM dosing visit. This recommendation can be 
used to accommodate requests for oral dosing due to the geopolitical situation. Oral 
bridging recommendations should be followed as per protocol Section 6.8.1. The process 
and required information for requesting oral bridging can be found in your Study 
Reference Manual.  Please continue to reach out to your study medical monitor for 
approval of oral bridging, in order to document use and to ensure expeditious shipment of 
oral CAB + RPV to your site.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
303 
 
Participants who use oral CAB + RPV as short-term oral bridging are permitted to return 
to IM dosing, on protocol, once the geopolitical situation permits resumption of site 
activities.  
The investigator should reach out to the medical monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with CAB/RPV is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the medical monitor to 
continue with oral bridging therapy. Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging. 
Oral bridging with Standard of Care Antiretroviral Therapy (SOC ART) 
For participants impacted by the  logistic issues, where the participant is unable to receive 
IM injections,  oral  bridging with either oral CAB/RPV or SOC ART guideline-
recommended, SOC ART regimen is permitted. The start date of oral bridging should be 
within the dosing window for the missed IM dosing visit.  Please reach out to your study 
medical monitor for approval of SOC ART as oral bridging, in order to document the use 
of commercially available SOC ART within the study.  In order to assure that participants 
have access to SOC ART during short-term oral bridging, GSK may allow for 
reimbursement of SOC ART or copayments as needed. 
Participants who use oral SOC ART as short-term oral bridging as a result of the 
geopolitical situation will not be considered formally withdrawn insofar as they wish to 
continue on the study.  Individuals who bridge with SOC ART will be permitted to return 
to IM dosing, on study, once the geopolitical situation permits resumption of site 
activities.   
The investigator should reach out to the medical monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with SOC ART is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the medical monitor to 
continue with oral bridging therapy.  Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging. 
12.13.4. 
Direct To Patient (DTP) Shipments of Oral Study IP  
If a participant is unable to travel to the clinic, either to receive IM injections or to be 
dispensed oral bridging, sites are encouraged to consider DTP shipments of drug, from 
the site, to the participant, to ensure access to medicines.  
• If the study site is considering DTP shipment of oral CAB + RPV investigational 
product (IP), the site must first verify if DTP IP dispensing by 
investigators/hospital pharmacies is locally permitted and whether it requires 
regulatory and/or local ethics pre-approval, or post-hoc notification. 
• The study participant should express his/her agreement for DTP shipment and the 
sharing of their personal information with any third-party couriers (as applicable), 
in accordance with local requirements.  This agreement should be documented in 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
304 
 
source records. 
• Oral CAB + RPV IP can be shipped at ambient temperatures via ground transport 
without a temperature monitoring device, with low risk of temperature excursions. 
Sites are encouraged to use discretion in determining the need for in-transit 
temperature monitoring based on the labelled storage requirements and the 
planned mode of transport and apply this as appropriate.  Shipment of oral CAB + 
RPV via air courier continues to require appropriate temperature monitoring.  For 
shipment conditions of oral medications other than oral CAB + RPV, please 
consult the product labelling. 
• In all cases IP accountability must be maintained, and all DTP dispensing 
documentation should be reflected in source records and dispensing logs per GCP. 
Please refer to your CRA or local study manager for support with the DTP process, 
ensuring reference to current sponsor guidance and arrangement of a courier that can 
support shipment of IMP directly to participants. 
12.14. 
Appendix 14:  Protocol Amendments 
12.14.1. 
Amendment 01 (All Countries) 
12.14.1.1. Protocol Amendment Rationale 
 
The rationale for this amendment includes changes to the following:  added new primary 
Medical Monitor contact information; added lipid objective and endpoint back in to the 
table within the Synopsis section; added clarification of text for patient reported outcome 
endpoints; added additional clarification regarding provision of CAB LA and RPV LA 
until available through public/government health sectors; new text added to allow use of 
local labs to determine eligibility in exceptional circumstances; updated Time and Events 
Table to provide more clarity around assessments conducted during the Extension Phase, 
added ‘X’ to include collection of cardiovascular risk information at Screening, added 
temperature to Vital Signs row, added row for randomization, and clarified timings for 
completion of patient reported questionnaires relative to other clinical assessments in the 
table footnotes; clarified timing of dosing for abacavir/dolutegravir/lamivudine 
(ABC/DTG/3TC, Triumeq) for the Day 1 visit; added additional clarification that 
participants of child bearing potential must continue contraception for at least 52 weeks 
after the last injection; revised text to say that Investigators may provide ‘bridging’ 
supply after consultation with Medical Monitor (vs Medical Monitor authorizing bridging 
supply); provided clarification that cabotegravir and rilpivirine exposure may persist for 
more than one year in some participants after intramuscular administration (with added 
references); minor edits to prohibited medication information; added statement that drugs 
that cause Torsade de Pointes should be used with caution when taking rilpivirine; 
additional clarification that background NRTI therapy is not considered Investigational 
Product and accountability will not be done for NRTI background; changed film coat 
color for Tivicay (dolutegravir) from white (clinical trial material supply) to yellow 
(commercial supply) and removed statement to “protect from light” (for both Triumeq 
and Tivicay); sentence added for collection of additional details for the injection device 
used for IM administration; additional information included regarding randomization 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
305 
 
schedule; added text stating the investigator must discuss long-term commitment for the 
study with potential participants; added statement regarding serofast RPR results; allowed 
serum pregnancy testing where required locally (e.g. when urine testing is not available);  
removed duplicate text regarding monitoring for suicidal related events; added option for 
patient reported outcomes to be collected on paper instrument if needed; removed 
information in Appendix requiring collection of pregnancy information for female 
partners of male study participants; definition of ACCEPT, HIVTSQc, and HIVTSQs 
added to abbreviations table, duplication of ICH abbreviation removed; other minor 
corrections (e.g., updated references, adding cross reference to sections, correction of 
hyperlink to one table). 
New text is bolded below (Table headings and bolded text within the existing document 
may also appear in bold font).  Deleted text has strikethrough in original text field, or is 
noted as ‘deleted text’. 
12.14.1.2. Protocol Changes/Clarifications 
Medical Monitor/Sponsor Information Page 
Rationale:  Updated Medical Monitor information page to include contact information 
for new Medical Monitor: 
Original Text: 
Primary Medical Monitor/SAE Contact Information:  
, MD, MPH 
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail:  
 
Secondary Medical Monitor: 
, MD 
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail:  
 
Sponsor Serious Adverse Events (SAE) Contact Information:  
, MD, MPH 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
306 
 
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail: 
 
Revised Text: 
Primary Medical Monitor/SAE Contact Information:  
, DO, MSc 
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail:  
 
Secondary Medical Monitor: 
, MD, MPH 
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail:  
 
Sponsor Serious Adverse Events (SAE) Contact Information:  
, DO, MSc  
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail: 
 
Section 1 Protocol Synopsis; Objective/Endpoints: 
Rationale:  Secondary lipid endpoint and objective inadvertently left out of synopsis 
table (included in Section 3.  Objective and Endpoints) 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
307 
 
Added Text: 
Objectives 
Endpoints 
To evaluate the effects of CAB LA + RPV 
LA every 4 weeks on fasting lipids over 
time compared to continuation of 
ABC/DTG/3TC over time. 
• Change from Baseline in fasting 
lipids over time including Week 48 
and Week 96. 
 
Section 1 Protocol Synopsis; Objective/Endpoints AND Section 3 Objectives and 
Endpoints: 
Rationale:  Clarification provided for Health Outcomes Endpoints 
Original Text: 
Objectives 
Endpoints 
To assess the acceptance of pain and 
injection site reactions following injections. 
• Dimension scores (e.g., “Bother of 
ISRs”, “Leg movement”, “Sleep”, and 
“Acceptance) and individual item scores 
assessing pain during injection, anxiety 
before and after injection, willingness to 
be injected in the future and overall 
satisfaction with mode of administration 
over time using the Perception of 
iNjection questionnaire (PIN).  
• Proportion of participants considering 
pain and local reactions following 
injection to be extremely or very 
acceptable based on the acceptability 
score over time using the Perception of 
iNjection questionnaire (PIN). 
To assess treatment satisfaction of CAB LA 
+ RPV LA compared to continuation of 
ABC/DTG/3TC. 
 
• Change from baseline in total “treatment 
satisfaction” score, and “pain discomfort” 
and “ease of administration” sub-scores 
of the HIVTSQs over time. 
• Change in treatment satisfaction over 
time (using the HIVTSQc) at Week 48 
(or Withdrawal). 
To assess degree of health-related quality of 
life (HR QoL) using the HIV/AIDS-targeted 
quality of life (HAT-QoL) questionnaire short 
form. 
• Summary statistics and between and 
within treatment group comparisons of 
change in HR QoL from Day 1 and 
Week 24, Week 48, Week 96 (or 
Withdrawal). 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
308 
 
Objectives 
Endpoints 
To assess the health status using the 12-
item Short Form Survey (SF-12). 
• Summary statistics and between and 
within treatment group comparisons of 
change in health status from Day 1 and 
Week 24, Week 48, and Week 96 (or 
Withdrawal). 
To assess treatment acceptance using the 
“General acceptance” dimension of the 
Chronic Treatment Acceptance (ACCEPT) 
questionnaire which consists of 3 items 
grouped into one single score of overall 
acceptance. 
• Summary statistics and between and 
within treatment group comparisons of 
change in treatment acceptance (using 
the ACCEPT) from Day 1 and Week 8, 
Week 24, Week 48, Week 96 (or 
Withdrawal). 
To assess tolerability of injections using the 
Numeric Rating Scale (NRS) for participants 
randomized to the CAB + RPV LA arm. 
• Summary statistics and within treatment 
group comparisons and change in 
tolerability of injection from Week 4b, 
Week 5, Week 40, Week 41, and 
Week 96. 
 
Revised Text: 
Objectives 
Endpoints 
To assess the acceptance of pain and 
injection site reactions following injections. 
• Change from Week 5 in Dimension 
scores (e.g., “Bother of ISRs”, “Leg 
movement”, “Sleep”, and “Injection 
Acceptance”) and individual item scores 
assessing pain during injection, anxiety 
before and after injection, willingness to 
be injected in the future and overall 
satisfaction with mode of administration 
over time using the Perception of 
iNjection questionnaire (PIN).  
• Proportion of participants considering 
pain and local reactions following 
injection to be extremely or very 
acceptable based on the acceptability 
score over time using the Perception of 
iNjection questionnaire (PIN). 
To assess treatment satisfaction of CAB LA 
+ RPV LA compared to continuation of 
ABC/DTG/3TC. 
 
• Change from baseline in total “treatment 
satisfaction” score, and individual item 
scores of the HIV Treatment 
Satisfaction Questionnaire (status 
version) (HIVTSQs) at Week 4b, 
Week 24, Week 44, Week 96 (or 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
309 
 
Objectives 
Endpoints 
Withdrawal). 
• Change in treatment satisfaction over 
time (using the HIVTSQ change 
version [HIVTSQc]) at Week 48 (or 
Withdrawal). 
To assess degree of health-related quality of 
life (HR QoL). 
• Change from Baseline in HR QoL 
using the HIV/AIDS targeted quality of 
life questionnaire (HAT-QoL) short 
form at Week 24, Week 48, Week 96 
(or Withdrawal). 
To assess health status. 
• Change from Baseline in health status 
at Week 24, Week 48, and Week 96 (or 
Withdrawal) using the 12-item Short 
Form Survey (SF-12). 
To assess treatment acceptance. 
• Change from Baseline in treatment 
acceptance at Week 8, Week 24, 
Week 48, Week 96 (or Withdrawal) 
using the “General Acceptance” 
dimension of the Chronic Treatment 
Acceptance (ACCEPT) questionnaire. 
To assess tolerability of injections. 
• Change from Week 4b in tolerability of 
injections at Week 5, Week 40, 
Week 41, and Week 96 using the 
Numeric Rating Scale (NRS) within 
the CAB LA + RPV LA arm. 
 
Section 1 Protocol Synopsis: Overall Design;  
Section 1 Treatment Arms and Duration (both Induction and Maintenance Phase 
Sections);  
Section 4.1 Overall Design;  
Section 4.2.2 Induction Phase;  
Section 4.2.3, Maintenance Phase (Day 1 to Week 100); and  
Section 6.3 Dose and Administration: 
Rationale:  New text added providing clarification of timing of Day 1 dose relative to 
randomization. 
New Text Added: 
ABC/DTG/3TC dosing on Day 1 should occur after randomization to avoid overlap 
of regimens (in the event that the participant is assigned to the CAB LA + RPV LA 
treatment arm).  However, if the participant takes ABC/DTG/3TC prior to coming 
into the clinic, randomization and initiation of oral CAB and RPV should continue 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
310 
 
as planned for Day 1. 
Section 1 Protocol Synopsis, Long-Term Follow-Up Phase – IM Regimen Only and 
Section 4.2.6.  Long-Term Follow-Up Phase – IM Regimen Only 
Rationale:  Clarification added that adequate contraception must be used for at least 52 
weeks (rather than stating throughout the entire year of follow-up): 
Original Text: 
Female participants of child bearing potential must continue to use adequate 
contraception methods for the entire year of follow-up. 
Revised Text: 
Female participants of child bearing potential must continue to use adequate 
contraception methods for at least 52 weeks after the last injection. 
Section 1 Protocol Synopsis, Protocol Permitted Substitutions, and 
Section 6.8.1 Oral Bridging 
Rationale:  Text revised to state Investigators may provide bridging supply following 
consultation with the Medical Monitor (vs Medical Monitor authorizing bridging supply) 
Original Text: 
Following the Induction Phase, in exceptional circumstances, the Medical Monitor may 
authorize the use of oral CAB and/or RPV as a short-term “bridging” strategy for 
participants who have begun CAB LA + RPV LA.  Should a participant need “oral 
bridging”, sites must contact the Medical Monitor for authorization and guidance for 
treatment strategies prior to a missed CAB LA + RPV LA dose.  Should a participant not 
notify the site in advance, the Medical Monitor must be contacted for further treatment 
guidance. 
Revised Text: 
Following the Induction Phase, in exceptional circumstances, and in consultation with 
the Medical Monitor, Investigators may provide oral CAB and RPV as a short-term 
“bridging” strategy for participants who have begun CAB LA + RPV LA and who will 
miss a subsequent scheduled LA injection.  Should a participant need “oral bridging”, 
sites must contact the Medical Monitor for guidance on treatment strategies prior to a 
missed CAB LA + RPV LA dose.  Should a participant not notify the site in advance, the 
Medical Monitor must be contacted for further treatment guidance. 
Section 4.2.1. Screening Phase 
Rationale:  New text added to allow use of local labs to determine eligibility in 
exceptional circumstances. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
311 
 
New Text Added:   
In exceptional circumstances only, if a repeat lab is required because a central lab 
result cannot be generated, local labs can be reviewed and approved by the Medical 
Monitor, for consideration of participant eligibility.  A repeat central lab will be 
submitted concurrently or at the next planned visit.  Similarly, if a central 
laboratory result cannot be generated for genotype/phenotype, a local result can be 
considered following review and approval by the study virologist. 
 
Section 4.2.3.  Eligibility for the Maintenance Phase – Text Slightly Revised and 
Moved to Section 4.2.4.  Maintenance Phase (Day 1 to Week 100) 
Rationale:  Text is referring to potential safety issues while a participant is taking oral 
CAB and RPV, which will not be administered until Day 1 of the Maintenance Phase. 
Original Text: 
In addition to the viral load criteria above, if in the opinion of the Investigator, a 
participant experiences a significant safety event while taking either CAB or RPV, 
Maintenance eligibility will be determined ONLY in consultation with the Medical 
Monitor.  Any rash that is possibly related to study drug, and is present between Day 1 
and Week 4b, must be discussed with the Medical Monitor prior to initiation of CAB LA 
or RPV LA (See Section 7.4.5.13). 
Revised Text: 
If, in the opinion of the Investigator, a participant experiences a significant safety event 
while taking oral CAB or RPV, administration of the first injections will be determined 
ONLY in consultation with the Medical Monitor.  Any rash that is possibly related to 
study drug, and is present between Day 1 and Week 4b, must be discussed with the 
Medical Monitor prior to initiation of CAB LA or RPV LA (See Section 7.4.5.13). 
Section 4.2.5.1.  Participants Entering from the CAB LA + RPV LA Arm 
Rationale:  Added additional clarification regarding provision of CAB LA and RPV LA 
until available through public/government health sectors. 
Original Text: 
All participants who successfully complete 100 weeks of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase until CAB LA and RPV LA are either locally approved and 
commercially available, the participant no longer derives clinical benefit, the participant 
meets a protocol-defined reason for discontinuation or until development of either CAB 
LA or RPV LA is terminated.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
312 
 
Revised Text: 
All participants who successfully complete 100 weeks of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase until CAB LA and RPV LA are either locally approved and 
commercially available (including through local public/government health sectors), 
the participant no longer derives clinical benefit, the participant meets a protocol-defined 
reason for discontinuation or until development of either CAB LA or RPV LA is 
terminated.   
 
Section 4.2.5.2.  Participants Entering from the ABC/DTG/3TC Arm 
Rationale:  Clarification that labs must be reviewed before the Week 104b visit. 
Original Text: 
In addition, central lab results and safety parameters from the Week 104a visit must be 
available and reviewed.  
Revised Text: 
In addition, central lab results and safety parameters from the Week 104a visit must be 
available and reviewed before the Week 104b visit.  
Section 4.6.1.  Risk Assessment 
Rationale:  Clarification that CAB and RPV can have residual concentrations beyond 1 
year.  
Original CAB Text: 
Development of 
Resistance following 
discontinuation of CAB 
LA 
 
Residual concentrations of CAB would remain in the 
systemic circulation of participants for prolonged 
periods (up to 1 year) despite stopping treatment (e.g. 
for tolerability issues or treatment failure).  
Participants discontinuing CAB LA regimen may be at 
risk for developing HIV-1 resistance to CAB many 
weeks after discontinuing injectable therapy.  
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
313 
 
Revised CAB Text: 
Development of 
Resistance following 
discontinuation of 
CAB LA 
 
Residual concentrations of CAB would remain in the 
systemic circulation of participants for prolonged periods 
(more than 1 year in some participants; 
GlaxoSmithKline Document Number 2016N269422_00; 
Study 201120) despite stopping treatment (e.g. for 
tolerability issues or treatment failure).  
Participants discontinuing CAB LA regimen may be at risk 
for developing HIV-1 resistance to CAB many weeks after 
discontinuing injectable therapy.  
 
Original RPV Text: 
Development of 
Resistance 
 
Residual concentrations 
of RPV would remain in 
the systemic circulation 
of participants who 
stopped treatment (e.g. 
for tolerability issues or 
treatment failure) for 
prolonged periods 
(months).   
 
 
Participants discontinuing 
a LA regimen may be at 
risk for developing 
resistance to RPV many 
weeks after discontinuing 
injectable therapy. 
• Alternative oral 
HAART regimens will 
be prescribed within 
four weeks after 
participants stop RPV 
LA.  This would be 
anticipated to result in 
rapid resuppression of 
HIV-1 RNA thus 
minimizing of the risk 
of emergent resistance. 
• The Sponsor will 
continue to monitor 
participants in this 
study who discontinue 
a LA regimen for any 
reason for a minimum 
of 52 weeks from the 
time of the last LA 
administration. 
Revised RPV Text: 
Development of 
Resistance 
 
Residual concentrations 
of RPV can remain in the 
systemic circulation of 
participants who stopped 
treatment (e.g. for 
tolerability issues or 
treatment failure) for 
more than one year in 
• Alternative oral 
HAART regimens will 
be prescribed within 
four weeks after 
participants stop RPV 
LA.  This would be 
anticipated to result in 
rapid resuppression of 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
314 
 
some participants 
[McGowan, 2016].   
 
 
Participants discontinuing 
a LA regimen may be at 
risk for developing 
resistance to RPV many 
weeks after discontinuing 
injectable therapy. 
HIV-1 RNA thus 
minimizing of the risk 
of emergent resistance. 
• The Sponsor will 
continue to monitor 
participants in this 
study who discontinue 
a LA regimen for any 
reason for a minimum 
of 52 weeks from the 
time of the last LA 
administration. 
 
Section 4.6.1.  Risk Assessment, CAB Table 
Rationale:  allowance of short term glucocorticoids use changed from 14 days to 21 days 
within CAB table. 
Original Text: 
Drug-Drug 
Interactions 
(DDIs) 
Chronic use of oral glucocorticoids must be avoided; however, 
short treatment courses (for example, 14 days or less) and topical, 
inhaled or intranasal use of glucocorticoids will be allowed.  
 
Revised Text: 
Drug-Drug 
Interactions 
(DDIs) 
Chronic use of oral glucocorticoids must be avoided; however, 
short treatment courses (for example, 21 days or less) and topical, 
inhaled or intranasal use of glucocorticoids will be allowed.  
 
Section 5.1. Inclusion Criteria: 
Rationale:  New text added to allow use of local labs to determine eligibility in 
exceptional circumstances. 
New Text Added:   
In exceptional circumstances only, if a repeat lab is required because a central lab 
result cannot be generated, local labs can be reviewed and approved by the Medical 
Monitor, for consideration of participant eligibility.  A repeat central lab will be 
submitted concurrently or at the next planned visit.  Similarly, if a central 
laboratory result cannot be generated for genotype/phenotype, a local result can be 
considered following review and approval by the study virologist. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
315 
 
Section 5.2. Exclusion Criteria #21: 
Rationale:  Short term corticosteriod use modified to 21 days, further clarified this 
exemption is related to chronic (vs short term use). 
Original Text: 
Immunomodulators that alter immune responses (such as systemic corticosteroids, 
interleukins, or interferons).  Note: Participants using short-term (e.g. ≤14 day) systemic 
corticosteroid treatment, topical, inhaled or intranasal corticosteroids, are eligible for 
enrollment. 
Revised Text: 
Immunomodulators that alter immune responses (such as chronic systemic 
corticosteroids, interleukins, or interferons).  Note: Participants using short-term (e.g. ≤21 
day) systemic corticosteroid treatment; topical, inhaled or intranasal corticosteroids, are 
eligible for enrolment. 
Section 6.1.  Investigational Product and Other Study Treatment 
Rationale:  Provided clarification that dual NRTI to be taken with single entity DTG is 
not considered IP. 
Original Text: 
In this study, investigational product (IP) refers to oral ABC/DTG/3TC (or alternate DTG 
+ NRTI background therapy), oral CAB, and CAB LA, which will be supplied by 
GlaxoSmithKline and oral RPV and RPV LA which will be supplied by Janssen 
Pharmaceuticals.   
Revised Text: 
In this study, investigational product (IP) refers to oral ABC/DTG/3TC single tablet 
regimen (or alternately DTG), oral CAB, and CAB LA, which will be supplied by 
GlaxoSmithKline and oral RPV and RPV LA which will be supplied by Janssen 
Pharmaceuticals.  The dual NRTI background therapy that is administered with single 
entity DTG is not considered IP. 
Section 6.1.5.  ABC/DTG/3TC STR – Tablet 
Rationale:  Removed statement to ‘protect from light’ as this is not a storage requirement 
for ABC/DTG/3TC. 
Original Text: 
ABC/DTG/3TC tablets are to be stored at 25°C [77°F] (excursions permitted to 15°-30°C 
[59°-86°F]) and protected from light. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
316 
 
Revised Text: 
ABC/DTG/3TC tablets are to be stored at 25°C [77°F] (excursions permitted to 15°-30°C 
[59°-86°F]). 
Section 6.1.6.  Dolutegravir – Tablet 
Rationale:  Film coat color changed from white (clinical trial material [CTM] color) to 
yellow (commercial supply color), sentence removed that the film coat was the only 
difference between CTM and commercial supply, and statement removed to ‘protect from 
light’. 
Original Text: 
Dolutegravir is manufactured by GlaxoSmithKline and will be provided to participants 
who are HLA-B*5701 positive (to be used in combination with 2 NRTIs).  DTG 50 mg 
tablets are white, round, biconvex, film-coated tablets.  The tablets contain 52.62 mg 
dolutegravir sodium salt, which is equivalent to 50 mg dolutegravir free acid.  Each tablet 
is debossed with “SV 572” on one side and “50” on the other side.  The tablets are the 
same formulation as the commercial material with the exception of the film coat 
color.  The tablets are packaged into high density polyethylene (HDPE) bottles with 
induction seals and child-resistant closures.  Each bottle contains 30 tablets and a 
desiccant.  DTG tablets are to be stored at 25°C [77°F] (excursions permitted to 15°-30°C 
[59°-86°F]) and protected from light. 
Revised Text: 
Dolutegravir is manufactured by GlaxoSmithKline and will be provided to participants 
who are HLA-B*5701 positive (to be used in combination with 2 NRTIs).  DTG 50 mg 
tablets are yellow, round, biconvex, film-coated tablets.  The tablets contain 52.62 mg 
dolutegravir sodium salt, which is equivalent to 50 mg dolutegravir free acid.  Each tablet 
is debossed with “SV 572” on one side and “50” on the other side.   The tablets are 
packaged into high density polyethylene (HDPE) bottles with induction seals and child-
resistant closures.  Each bottle contains 30 tablets and a desiccant.  DTG tablets are to be 
stored at 25°C [77°F] (excursions permitted to 15°-30°C [59°-86°F]). 
Section 6.2. Treatment Assignment: 
Rationale:  Text added to describe the randomization schedule and the benefit of central 
randomization to eliminate selection bias. 
New Text: 
The randomization schedule is comprised of a series of blocks, with equal treatment 
allocation within each block, which are shared across centres via central 
randomization.  Given the open-label study design, central randomization was used 
to eliminate selection bias due to foreknowledge of randomized treatment.  With 
central randomization, knowledge at a site of the randomized treatment group for 
previous subjects does not predict which treatment group will be assigned to the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
317 
 
next randomized subject. 
Section 6.3.  Dose and Administration (in addition to text noted above regarding 
changes to Day 1 ABC/DTG/3TC dosing) 
Rationale:  Clarification to dosing table regarding timing of Day 1 ABC/DTG/3TC 
dosing and that Induction Phase is Week [-20] to (vs through) Day 1. 
Original Text: 
Induction Phase (Week [-20] through Day 1) – All Subjects 
Week (-20) to Day 1 
(1 tablet once daily) 
Take 1 tablet ABC 600 mg / DTG 50 mg / 3TC 300 mg once 
daily with or without food 
 
And 
ABC/DTG/3TC Once Daily Arm* 
Day 1 to Week 100 
(1 tablet once daily) 
Take 1 tablet ABC 600 mg / DTG 50 mg / 3TC 300 mg once 
daily with or without food 
 
 
Revised Text: 
Induction Phase (Week [-20] to Day 1) – All Subjects 
Week (-20) to Day 1 
(1 tablet once daily) 
Take 1 tablet ABC 600 mg / DTG 50 mg / 3TC 300 mg once daily 
with or without food 
*Take Day 1 dose after randomization. 
 
And  
ABC/DTG/3TC Once Daily Arm* 
Day 1 to Week 100 
(1 tablet once daily) 
Take 1 tablet ABC 600 mg / DTG 50 mg / 3TC 300 mg once daily 
with or without food 
*Take Day 1 dose after randomization. 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
318 
 
Section 6.3. Dose and Administration 
Rationale:  deleted text regarding how often IP was taken (with a meal) on average, as 
this is not recorded in the eCRF. 
Deleted Text: 
The participant will be asked how often the IP was taken (with a meal) on average, 
since the last visit, and this information will be recorded in the eCRF. 
Section 6.6.  Preparation/Handling/Storage/Accountability 
Rationale:  clarification added that accountability will not be done for NRTI background 
therapy taken with single entity DTG. 
Original Text: 
IP accountability will be evaluated using pill counts of unused IP for participants 
receiving oral treatment (ABC/DTG/3TC [or alternate DTG + NRTIs], oral CAB, oral 
RPV).  This assessment will be conducted each time the participant receives a new/refill 
supply of IP, when the participant completes oral CAB and RPV (including oral bridging 
supply), and through the Withdrawal visit, study completion, or Week 104b of the 
Extension Phase.   
Revised Text: 
IP accountability will be evaluated using pill counts of unused IP for participants 
receiving oral treatment (ABC/DTG/3TC [or alternate DTG], oral CAB, oral RPV).  Pill 
counts will not be done for the dual NRTIs taken with DTG, as these will not be 
provided centrally.  IP accountability will be conducted each time the participant 
receives a new/refill supply of IP, when the participant completes oral CAB and RPV 
(including oral bridging supply), and through the Withdrawal visit, study completion, or 
Week 104b of the Extension Phase.   
Section 6.6.1.  Dosing Considerations for CAB LA + RPV LA 
Rationale:  Added statement to allow collection of more information on injection 
device.. 
New Text:  Additional details of the injection device used by sites for IM 
administration, including, but not limited to functional performance, may also be 
collected within the eCRF. 
Section 6.7.  Compliance with Study Treatment Administration 
Rationale:  Provided clarification that pill counts will not be done for NRTIs taken 
with single entity DTG, that start and stop dates will be recorded in the eCRF, and 
that Investigators should discuss the long-term commitment for the study with the 
participants and have counselling plans in place for both treatment arms. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
319 
 
Original Text: 
IP accountability will be evaluated using pill counts of unused IP (CAB and RPV tablets 
at the end of oral dosing [including bridging supply], and ABC/DTG/3TC [or alternate 
DTG + NRTIs]).  This assessment will be conducted each time the participant receives a 
supply of oral study medication.  These data will be recorded in the participant’s eCRF. 
When participants are dosed with CAB LA and RPV LA at the site, they will receive IM 
injections directly from the investigator or designee, under medical supervision.  The date 
and time of each injection of CAB LA and RPV LA administered in the clinic will be 
recorded in the source documents.  These data will be recorded in the participant’s eCRF.  
The dose of study treatment and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study treatment.   
IP accountability will not be assessed during the Long-Term Follow-Up Phase. 
Due to the long acting nature of the CAB LA and RPV LA, it will be imperative that the 
participant is compliant with dosing visits.   
Investigators must have plans in place for adherence counselling.   
Revised Text: 
IP accountability will be evaluated using pill counts of unused IP (CAB and RPV tablets 
at the end of oral dosing [including bridging supply], and ABC/DTG/3TC [or alternate 
DTG]).  This assessment will be conducted each time the participant receives a supply of 
oral study medication.  These data will be recorded in the participant’s eCRF.  
Treatment start and stop dates will also be recorded in the eCRF. 
When participants are dosed with CAB LA and RPV LA at the site, they will receive IM 
injections directly from the investigator or designee, under medical supervision.  The date 
and time of each injection of CAB LA and RPV LA administered in the clinic will be 
recorded in the source documents.  These data will be recorded in the participant’s eCRF.  
The dose of study treatment and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study treatment.   
IP accountability (e.g. pill counts) will not be assessed for alternate NRTIs taken with 
single entity DTG, or during the Long-Term Follow-Up Phase. 
Due to the long acting nature of the CAB LA and RPV LA, it will be imperative that the 
participant is compliant with dosing visits.  As part of the screening and participant 
selection process, Investigators must discuss with potential participants the long-
term commitments for the study, and the importance of adhering to treatment 
regimens. 
Investigators must have plans in place for adherence counselling for both treatment 
arms.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
320 
 
Section 6.9.1.  IM Dosing 
Rationale:  clarification that both LA drugs may have measurable plasma concentrations 
beyond 1 year, and reiterated the need for HAART as concentrations decline over time. 
 
Original Text: 
Participants receiving CAB LA and/or RPV LA are anticipated to be at high risk for 
development of virologic resistance if ART is interrupted.  The time period during which 
participants are at risk for development of virologic resistance may be determined by the 
period between when drug levels fall below therapeutic values and when they fall below 
levels which exert selective pressure on HIV.  This time period will vary by ART agent 
and is dependent upon effective concentration, inhibitory concentration and half-life. 
Plasma concentrations of both drugs may be measurable for approximately 52 weeks 
following IM injections. 
Revised Text: 
Participants receiving CAB LA and RPV LA are anticipated to be at high risk for 
development of virologic resistance if ART is interrupted.  The time period during which 
participants are at risk for development of virologic resistance may be determined by the 
period between when drug levels fall below therapeutic values and when they fall below 
levels which exert selective pressure on HIV.  This time period will vary by ART agent 
and is dependent upon effective concentration, inhibitory concentration and half-life. 
Plasma concentrations of both LA drugs may be measurable for more than one year in 
some participants following IM injections.  Any interruption in IM dosing should be 
discussed with the Medical Monitor.  Investigators should ensure that the 
participant initiates alternative highly active ART (e.g. in the Long-Term Follow-Up 
Phase) to minimize the risk of developing resistance as concentrations of CAB and 
RPV decline over time. 
Section 6.13.  Concomitant Medications and Non-Drug Therapies;  Oral RPV 
administration Only 
Rationale:  Added drugs that may cause TdP should be used with caution during the 
study when taking rilpivirine. 
New Text: 
Drugs that cause Torsade de Pointes (TdP) should be used with caution when taking 
rilpivirine (see SPM for list of drugs associated with TdP). 
Section 6.13.1.  Prohibited Medications and Non-Drug Therapies 
Rationale:  Removed restricted duration for topical imiquimod as minimal systemic 
exposure is expected (other than maintaining [‘short term use’], changed duration for 
glucorticoid use to 21 days to allow, e.g., for treatment of pneumocystis pneumonia, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
321 
 
clarified HCV treatment is also prohibited during Induction.  Corrected typo in 
glucocorticoids. 
Original Text:   
• 
Systemically administered immunomodulators (such as interleukin and interferon 
agents) are prohibited (a list of examples is provided in the SPM).  This includes 
topical agents with substantial systemic exposure and systemic effects.  Short term 
use (30 days or less) of topical imiquimod is permitted.    
• 
Acetaminophen (paracetamol) cannot be used in participants with acute viral 
hepatitis (James, 2009). 
• 
Chronic use of systemic (oral or parenteral) glucocortioids must be avoided due to 
immunosuppressive effect and potential decreases in RPV plasma concentrations; 
however, short treatment courses (e.g., ≤14 days) of oral prednisone/ 
prednisolone/methylprednisolone are allowed.  A single dose of systemic 
dexamethasone is permitted (more than a single dose may cause significant 
decrease in RPV plasma concentration and is prohibited) and topical, inhaled or 
intranasal use of glucocortioids will be allowed.   
• 
Hepatitis C infection therapy is prohibited during the Maintenance Phase before 
the Week 48 primary endpoint, and interferon-based HCV therapy is prohibited 
throughout the entire study.  Options for treatment of hepatitis C should be 
discussed with the Medical Monitor prior to initiation of therapy. 
Revised Text: 
• 
Systemically administered immunomodulators (such as interleukin and interferon 
agents) are prohibited (a list of examples is provided in the SPM).  This includes 
topical agents with substantial systemic exposure and systemic effects.  Use of 
topical imiquimod is permitted.    
• 
Acetaminophen (paracetamol) cannot be used in participants with acute viral 
hepatitis (James, 2009). 
• 
Chronic use of systemic (oral or parenteral) glucocorticoids must be avoided due 
to the immunosuppressive effect and potential decreases in RPV plasma 
concentrations; however, short treatment courses with oral prednisone/ 
prednisolone/methylprednisolone (e.g. adjunctive treatment of pneumocystis 
pneumonia with 21 days of tapering prednisone) are allowed.  A single dose of 
systemic dexamethasone is permitted, but more than a single dose in a treatment 
course may cause a significant decrease in RPV plasma concentration and is 
prohibited.  Topical, inhaled or intranasal use of glucocorticoids will be allowed.   
• 
Hepatitis C infection therapy is prohibited during the Induction and Maintenance 
Phase before the Week 48 primary endpoint, and interferon-based HCV therapy is 
prohibited throughout the entire study.  Options for treatment of hepatitis C 
should be discussed with the Medical Monitor prior to initiation of therapy. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
322 
 
Section 6.13.1.  Prohibited Medications and Non-Drug Therapies:  Concurrent with 
RPV 
Rationale:  Clarification added that local prescribing information for oral RPV should be 
reviewed for drugs that ‘are prohibited’ with RPV as the list within the protocol may not 
be as current as local prescribing information. 
Original Text: 
Please refer to the local prescribing information for other drugs that should be used with 
caution, require dose adjustment, or increased clinical monitoring if taken with oral RPV. 
Revised Text: 
Please refer to the local prescribing information for other drugs that are prohibited, 
should be used with caution, require dose adjustment, or increased clinical monitoring if 
taken with oral RPV. 
Section 7.1.  Time and Events Table 
Rationale:  New text added before table to explain visits and assessments during the 
Extension Phase. 
New Text Added Before Table: 
Beginning at Week 112, the schedule of assessments for participants continuing in 
the Extension Phase from the CAB LA + RPV LA arm will be modified to collect 
clinical chemistries, HIV-1 RNA, and CD4+ cell count every 12 weeks.  
Participants originally randomized to ABC/DTG/3TC at Day 1, who choose to 
continue into the Extension Phase and transition to CAB LA + RPV LA, will have 
all assessments noted in the Time and Events table below performed Q4W from 
Week 108 through Week 124.  Beginning at Week 124, the schedule of assessments 
for these participants transitioning from ABC/DTG/3TC into the Extension Phase 
will be modified to collect clinical chemistries, HIV-1 RNA, and CD4+ cell count 
every 12 weeks as noted in the Time and Events schedule below. 
From Week 124 forward, all participants (from both originally randomized 
treatment arms), will have the same schedule of events (same visits, same 
assessments, same time frame). 
Changes to Time and Events Table (see Section 7.1 for example): 
• 
Row added for randomization at Day 1 
• 
Cardiovascular Risk Assessment:  “X” noted at Screening 
• 
Temperature added to Vital Signs row 
• 
PK row – Clarified S = Storage sample 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
323 
 
• 
Study treatment accountability – Corrected footnote in column for Week 104b to 
reflect footnote ‘u’ instead of footnote ‘v’. 
• 
Column added for assessments performed Q4W after Week 108 (LA Arm) or after 
Week 124 (Switch Arm) 
• 
Column for Q12W assessments in Extension renamed to clarify assessments begin at 
W112 (LA Arm) and W124 (Switch Arm) 
• 
Footnote ‘i’ regarding eCSSR completion clarifies that this assessment should be the 
last patient reported outcome assessment completed (still completed at the beginning 
of the visit). 
• 
Footnote ‘j’ changed to allow serum pregnancy testing if required locally:  “Serum 
pregnancy test can substitute for urine pregnancy test if locally required, but 
must be appropriately timed to confirm pregnancy status prior to e.g 
randomization and first IM administration.” 
• 
Footnote ‘s’ symbol removed from Week 104b column and “- LA Arm Only” added 
to column 
• 
Footnote ‘z’ deleted reference to “PIN” questionnaire, added that patient reported 
assessments should be completed prior to eCSSRs assessments, and changed to 
include completion of health outcomes questionnaires at withdrawal if prior to 
Week 96 (vs Week 48).   
• 
Footnote aa:  “NRS” questionnaire added to first sentence, e.g. The PIN, Preference, 
and NRS questionnaires are to be administered only to participants receiving CAB 
LA + RPV LA injections. The NRS should be collected 30 to 60 minutes post-
injection (and at Week 5 and Week 41, one week post-injections) 
Section 7.2.1. Screening 
Rationale:  New text added to allow use of local labs to determine eligibility in 
exceptional circumstances.  Additionally, text deleted regarding Screening labs available 
prior to ‘randomization’ (earlier statement in preceeding paragraph explains that all 
Screening labs must be available prior to ‘enrollment’[e.g., Week -20]). 
Original Text: 
Laboratory results from the central laboratory services provided by this trial will be used 
to assess study eligibility.  A single repeat of a procedure / lab parameter is allowed to 
determine eligibility (unless otherwise specified).  All Screening labs must be available 
prior to randomization. 
Each participant screened will be assigned a participant number.  Participants not meeting 
all inclusion and exclusion criteria at initial screen may be re-screened one time with a 
new participant number.  Participants who are enrolled into the trial and subsequently 
withdrawn from the study for any reason may not be rescreened. 
At Screening, samples for HIV-1 genotypic and phenotypic resistance testing and plasma 
HIV-1 RNA measurement will be obtained. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
324 
 
Revised Text:   
Laboratory results from the central laboratory services provided by this trial will be used 
to assess study eligibility.  A single repeat of a procedure / lab parameter is allowed to 
determine eligibility (unless otherwise specified).  In exceptional circumstances only, if 
a repeat lab is required because a central lab result cannot be generated, local labs 
can be reviewed and approved by the Medical Monitor, for consideration of 
participant eligibility.  A repeat central lab will be submitted concurrently or at the 
next planned visit.   
Each participant screened will be assigned a participant number.  Participants not meeting 
all inclusion and exclusion criteria at initial screen may be re-screened one time with a 
new participant number.  Participants who are enrolled into the trial and subsequently 
withdrawn from the study for any reason may not be rescreened. 
At Screening, samples for HIV-1 genotypic and phenotypic resistance testing and plasma 
HIV-1 RNA measurement will be obtained.  If a central laboratory result cannot be 
generated for Screening genotype/phenotype, a local result can be considered 
following review and approval by the study virologist. 
Section 7.2.1. Screening 
Rationale:  Clarification added that HBV DNA will only be performed for participants 
with positive anti-HBc and negative HBsAg and negative anti-HBs. 
Original Text: 
HBV DNA will only be performed for participants with both anti-HBc and negative 
HBsAg and negative anti-HBs (past and/or current evidence). 
Revised Text: 
HBV DNA will only be performed for participants with positive anti-HBc and negative 
HBsAg and negative anti-HBs (past and/or current evidence). 
Section 7.2.1.  Screening 
Rationale:  Additional information included regarding participants with a serofast RPR 
result. 
New Text: 
Participants with a serofast RPR result despite history of adequate therapy and no 
evidence of re-exposure may enrol after consultation with the Medical Monitor. 
Section 7.4.1. Clinical Evaluations 
Rationale:  Clarification of temperature collection. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
325 
 
New Text:  
Temperature will also be collected. 
Section 7.4.1. Clinical Evaluations 
Rationale:  Added allowance for serum pregnancy testing to replace urine testing if 
locally required. 
New Text:  
If serum testing is required locally, the results should be available prior to the visit 
where urine testing is indicated per the Time and Events Schedule (Section 7.1). 
Section 7.4.2.  Laboratory Assessments 
Rationale:  Footnote ‘g’ added to Table to address when HBV DNA will be performed 
(previously stated in Section 7.2.1. Screening).  Footnote letters within the table updated 
to include this addition. 
New Text: 
g. 
HBV DNA will only be performed for participants with a positive anti-HBc, 
negative HBsAg, and negative anti-HBs (past and / or current evidence). 
Section 7.4.3.4.   
Rationale:  Link provided to sections for reporting cardiovascular and death events. 
New Text: 
Additional information for reporting cardiovascular and death events is included in 
Section 7.4.3.7. and Section 7.4.3.8., respectively. 
Section 7.4.6. Suicidal Risk Monitoring 
Rationale:  Duplicate Text Removed 
Original Text: 
Therefore, it is appropriate to monitor participants prospectively for suicidal ideation and 
/ or behavior before and during treatment.  It is recommended that the Investigator 
consider mental health consultation or referral for participants who experience signs of 
suicidal ideation or behavior. 
Participants should be monitored appropriately and observed closely for suicidal ideation 
and behavior or any other unusual changes in behavior.  It is recommended that the 
investigator consider mental health consultation or referral for participants who 
experience signs of suicidal ideation or behavior.  Participants presenting with new 
onset/treatment emergent depression should be advised to contact the investigator 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
326 
 
immediately if symptoms of severe acute depression (including suicidal 
ideation/attempts) develop, because medical intervention and discontinuation of the study 
medication may be required. 
Revised Text: 
Therefore, it is appropriate to monitor and closely observe participants prospectively,  
before and during treatment, for suicidal ideation and / or behavior, or any other 
unusual changes in behavior.  It is recommended that the Investigator consider mental 
health consultation or referral for participants who experience signs of suicidal ideation 
or behavior. 
Participants presenting with new onset/treatment emergent depression should be advised 
to contact the investigator immediately if symptoms of severe acute depression (including 
suicidal ideation/attempts) develop, because medical intervention and discontinuation of 
the study medication may be required. 
Section 7.4.6.  Suicidal Risk Monitoring 
Rationale:  Added text to ensure sites have a plan for managing risk of and possible 
suicide related events. 
New Text: 
All sites should have a plan in place for managing risk of and possible suicide 
related events. 
Section 7.5.1. PK Sample Collection 
Rationale:  Added clarification regarding visits windows and sample collection 
windows, and added 20 to 28 hour window for pre-dose samples at Week 4b and 
Week 104b. 
Original Text: 
d. PK window for sample collection: Pre-dose visits: ±3 days (1st injection), minus 7 
days (2nd and 3rd injection), and± 7days (4th and all subsequent injections), 2 hours 
post dose: ±one hour; one week post dose visits: 3 to 10 days post injection. 
 
Revised Text: 
e. PK visit window and sample collection: Pre-dose visits (from projected visit date): 
±3 days (1st injection), minus 7 days (2nd and 3rd injection), and± 7 days (4th and all 
subsequent injections);  Sample Collection:  Pre-dose at Week 4b (and Week 104b 
for participants transitioning from ABC/DTG/3TC Arm):  20 to 28 hours after 
the last oral dose of CAB and RPV was taken; 2 hours post dose: ±one hour; one 
week post dose visits: 3 to 10 days post injection. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
327 
 
Section 7.9 Value Evidence and Outcomes 
Rationale:  Added option of paper instrument collection if needed, and clarified timing 
of NRS assessment: 
Original Text: 
Health outcomes assessments will be conducted according to the Time and Events Table 
(Table 5).  Assessments are recommended to be administered at the beginning of the visit 
prior to collection of blood for analysis and other scheduled assessments. 
Revised Text: 
Health outcomes assessments will be conducted according to the Time and Events Table 
(Table 5).  Assessments are recommended to be administered with an electronic site pad 
or paper instrument at the beginning of the visit prior to collection of blood for analysis 
and other scheduled assessments with the exception of the NRS (administered post 
injection).   
Section 7.9.1.  Value Evidence and Outcomes Endpoints (Secondary) 
Rationale:  Additional clarification provided for patient reported outcome analyses. 
Original Text: 
• 
Dimension scores (e.g., “Bother of ISRs”, “Leg movement”, “Sleep”, and 
“Acceptance) and individual item scores assessing pain during injection, anxiety 
before and after injection, willingness to be injected in the future and overall 
satisfaction with mode of administration over time using the Perception of iNjection 
questionnaire (PIN).  
• 
Proportion of participants considering pain and local reactions following injection to 
be extremely or very acceptable based on the acceptability score over time using the 
Perception of iNjection questionnaire (PIN). 
• 
Change from baseline in total “treatment satisfaction” score, and “pain discomfort” 
and “ease of administration” sub-scores of the HIVTSQs over time. 
• 
Change in treatment satisfaction over time (using the HIVTSQc) at Week 48 (or 
Withdrawal). 
• 
Summary statistics and between and within treatment group comparisons will be 
assessed on change in treatment acceptance from Day 1 (using the ACCEPT) and 
Weeks 8, 24, 48, 96 (or Withdrawal from the study). 
• 
Summary statistics and between and within treatment group comparisons will be 
assessed in the broader impact on health status (using the SF-12) from Day 1, and 
Weeks 24, 48, 96 (or Withdrawal from the study). 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
328 
 
• 
Summary statistics and between and within treatment group comparisons will be 
asses on change in HR QoL (using the HAT-QoL short form) from Day 1, Weeks 24, 
48, 96 (or Withdrawal from the study). 
• 
Summary statistics and within treatment group comparisons will be assessed on the 
tolerability of injections (using the NRS) at Weeks 4b, 5, 40, 41, 96 on participants 
randomized to the “CAB LA and RPV LA” arm.  Change in tolerability of injection 
will be assessed from Week 4b and Week 48 (primary analysis), and from Week 4b 
and Week 96 (secondary analysis). 
Revised Text: 
• 
Change from Week 5 in Dimension scores (e.g., “Bother of ISRs”, “Leg 
movement”, “Sleep”, and “Injection Acceptance”) and individual item scores 
assessing pain during injection, anxiety before and after injection, willingness to be 
injected in the future and overall satisfaction with mode of administration over time 
using the Perception of iNjection questionnaire (PIN).  
• 
Proportion of participants considering pain and local reactions following injection to 
be extremely or very acceptable based on the acceptability score over time using the 
Perception of iNjection questionnaire (PIN). 
• 
Change from baseline in total “treatment satisfaction” score, and individual item 
scores of the HIVTSQs at Week 4b, Week 24, Week 44, Week 96 (or 
Withdrawal). 
• 
Change in treatment satisfaction over time (using the HIVTSQc) at Week 48 (or 
Withdrawal). 
• 
Change from Baseline in treatment acceptance at Weeks 8, 24, 48, 96 (or 
Withdrawal from the study) using the “General acceptance” dimension of the 
Chronic Treatment Acceptance (ACCEPT) questionnaire. 
• 
Change from Baseline in health status at Weeks 24, 48, 96 (or Withdrawal) 
using the 12-item Short Form Survey (SF-12). 
• 
Change from Baseline in HR QoL (using the HAT-QoL short form) at Weeks 24, 
48, 96 (or Withdrawal from the study). 
• 
Change from Week 4b in the tolerability of injections (using the NRS) at Weeks 5, 
40, 41, 96. 
Section 12.7.2.  Collection of Pregnancy Information 
Rationale:  Bullets regarding collecting information for female partner (of male study 
participants) who become pregnant while participating in the study were deleted.  CAB is 
characterized as low risk for teratogenicity or genotoxicity on the basis of available non-
clinical data, and therefore, in the 201584 study, there are not plans to monitor 
pregnancies outcomes in female partners of male subjects, consistent with GSK standard 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
329 
 
operating procedures.  There is also a statement within inclusion criteria number two that 
'ALL subjects participating in the study must be counseled on safer sexual practices to 
minimize risk of HIV transmission.'  While there is an expectation that men taking part in 
the study will practice safe sex, it is not being monitored as part of the study.  
Removed ‘female’ in statement describing follow-up for participants who become 
pregnant while on LA treatment. 
Original Text: 
Any female participant who becomes pregnant while participating will discontinue 
study medication and be withdrawn from the study.  If the female participant is 
receiving CAB LA + RPV LA, they will be followed for 52 weeks in the Long-Term 
Follow-Up Phase. 
• 
Investigator will attempt to collect pregnancy information on any female partner of a 
male study participant who becomes pregnant while participating in this study.  This 
applies only to participants who are randomized to receive study medication.  
• 
After obtaining the necessary signed informed consent from the female partner 
directly, the investigator will record pregnancy information on the appropriate form 
and submit it to GSK within 2 weeks of learning of the partner’s pregnancy 
• 
Partner will also be followed to determine the outcome of the pregnancy.  
Information on the status of the mother and child will be forwarded to GSK.  
• 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date.  Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure. 
Revised Text: 
Any participant who becomes pregnant while participating will discontinue study 
medication and be withdrawn from the study.  If the participant is receiving CAB 
LA + RPV LA, they will be followed for 52 weeks in the Long-Term Follow-Up 
Phase. 
 
Administrative Corrections (e.g. Typographical Errors, New References) 
Throughout document: 
Rationale:  Corrected typo in “enrolment” (vs “enrollment”) 
Section 4.2.8.  Independent Data Monitoring Committee 
Rationale:  clarification that IDMC will review 201584 and 201585, and corrected typo 
with “of of”. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
330 
 
Original Text: 
An Independent Data Monitoring Committee (IDMC) will be instituted to ensure external 
objective medical and/or statistical review of efficacy and safety in order to protect the 
ethical interests and well-being of subjects and to protect the scientific validity of this 
study and study 201584. 
An IDMC will evaluate accumulating efficacy, tolerability / safety, and PK of of 
CAB LA + RPV LA at predetermined times during the study.   
Revised Text: 
An Independent Data Monitoring Committee (IDMC) will be instituted to ensure external 
objective medical and/or statistical review of efficacy and safety in order to protect the 
ethical interests and well-being of subjects and to protect the scientific validity of this 
study (201584) and study 201585. 
An IDMC will evaluate accumulating efficacy, tolerability / safety, and PK of CAB LA + 
RPV LA at predetermined times during the study.   
Section 5.4.1.2.  Liver Event Adjudication Committee 
Rationale:  Added “be” to the following statement: 
A liver safety panel will be used to evaluate all subjects who meet liver stopping criteria. 
Uniform sets of data and standards for adjudication will be applied across cases to inform 
outcomes. 
Section 5.4.5.1.  HIV-1 RNA Blips 
Rationale:  Corrected typo in “scheduled” 
Original Text: 
Following discussion with the Medical Monitor, additional viral load testing may be 
performed between visits to determine the appropriate participant disposition for the next 
secheduled visit (e.g. if additional injections should be administered). 
Revised Text: 
Following discussion with the Medical Monitor, additional viral load testing may be 
performed between visits to determine the appropriate participant disposition for the next 
scheduled visit (e.g. if additional injections should be administered). 
Section 7.4.2.  Laboratory Assessments – typo corrected for labelled (vs labeled). 
Section 9.2.1. Sample Size Assumptions – hyperlink corrected in second paragraph 
from Table 10 to Table 13, e.g.,  This sample size of 285 participants per arm will also 
provide at least 90% power to show non-inferiority in the proportion of participants with 
plasma HIV-1 RNA <50 c/mL (per FDA’s Snapshot algorithm) at Week 48 over a range 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
331 
 
of true response rates, on the basis of a -10% non-inferiority margin and 2.5% one-sided 
significance level (see Table 13).   
Section 11.  References 
Rationale:  Added references for CAB and RPV exposures beyond 1 year in some 
participants. 
New Text: 
GlaxoSmithKline Document Number 2016N269422_00: 201120: A Phase IIa Study 
to Evaluate the Safety, Tolerability and Acceptability of Long Acting Injections of 
the HIV Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ÉCLAIR) –
Week 81 Results. Effective Date: 25Oct2016. 
McGowan I, Siegel A, Engstrom J et al.  Persistence of Rilpivirine Following Single 
Dose of Long-Acting Injection.  21st International AIDS Conference (AIDS 2016).  
Durban, South Africa.  Abstract TUAC0103. 
Section 11.  References 
Rationale:  Updated Reference for Hunt CM 2010 and added ICH E2 Reference. 
Revised (bolded) / New Text: 
Hunt CM.  Mitochrondrial and Immunoallergic Injury Increase Risk of Positive 
Drug Rechallenge After Drug-Induced Liver Injury:  A Systematic Review.  Hepatol 
2010;52:2216-2222.  
International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use.  ICH Harmonised Tripartite Guideline; Clinical 
Safety Data Management:  Definitions and Standards for Expedited Reporting E2A.  
27Oct1994.  Available at:  
https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2A
/Step4/E2A_Guideline.pdf 
Section 12.1  Appendix 1: Abbreviations and Trademarks 
The following abbreviations were added to the table: 
ACCEPT 
Chronic Treatment Acceptance questionnaire 
HIVTSQc 
HIV treatment satisfaction questionnaire (change version) 
HIVTSQs 
HIV treatment satisfaction questionnaire (status version) 
 
The following row was deleted the from the table (2 rows with ICH abbreviation): 
ICH 
International Conference on Harmonisation 
Harmonisation Harmonisation of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
332 
 
Section 12.2 Appendix 2:  Division of AIDS Table – the following typo was 
corrected: (Medical intervention vs Medicamylasal intervention) 
Uveitis 
No 
symptoms 
AND 
Detectable 
on 
examination 
Anterior 
uveitis with 
symptoms OR 
Medicamylasal 
intervention 
indicated 
Posterior or 
pan- uveitis 
OR Operative 
intervention 
indicated 
Disabling 
visual loss in 
affected eye(s) 
 
Section 12.3  Appendix 3 Liver Safety – Study Treatment Restart or Rechallenge 
“Table” was entered twice in the following sentence (first instance of “Table” has 
been deleted: 
– Drug Rechallenge refers to resuming study treatment following drug induced 
liver injury (DILI). Because of the risks associated with rechallenge after DILI 
(see Drug Rechallenge Background below) this should only be considered for 
a subject for whom there is compelling evidence of benefit from a critical or 
life-saving medicine, there is no alternative approved medicine available, and 
a benefit:risk assessment of rechallenge is considered to be favorable (Table 
Table 14, Figure 9). 
12.14.2. 
Amendment 02 (All Countries) 
Protocol changes for Amendment 02 (19-JUL-2017), from amendment 01 (13-DEC-
2016) 
12.14.2.1. Protocol Amendment Rationale 
The rationale for this amendment includes:  update of contact information for secondary 
Medical Monitor; modify text to allow dose reduction for participants who have a decline 
in creatinine clearance to <50 mL/min; clarify that for participants not eligible to 
continue into the Maintenance Phase, only samples with HIV-1 RNA > 400 c/mL will be 
sent for resistance testing; add mitigation for ECG pad removal; clarify ± 3 day window 
is for all oral dosing (both Induction and Maintenance Phase); add "LA Arm" back to 
columns for Week 68, 76, 84, 92 on Time and Events Schedule (hidden when column 
was narrowed); clarify Week 104b visit is specific to those participants transitioning from 
oral IP to CAB LA + RPV LA; clarification added to footnote ‘p’ that genetics sample 
can be collected at any visit after signing informed consent, but the Week [-20] visit is 
preferred; correct footnote on Week 5 visit to reflect footnote 't'; add footnote 'y' back to 
Time and Events column for Withdrawal Visit (for Induction Phase); add clarification to 
Time and Events column that ISR assessments are only conducted for subjects receiving 
injections.  Administrative typographical errors corrected (e.g. clarification provided 
regarding genetics sample taken after participants are enrolled into the study [vs when 
participants are randomized]), and investigator brochure references updated, references 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
333 
 
added. 
12.14.2.2. Protocol Changes/Clarifications  
Medical Monitor/Sponsor Information Page 
Rationale:  Updated phone contact information for secondary Medical Monitor: 
Original Text: 
Secondary Medical Monitor: 
, MD, MPH 
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail:  
 
New Text: 
Secondary Medical Monitor: 
, MD, MPH 
ViiV Healthcare 
Research Triangle Park 
Five Moore Drive, Research Triangle Park, NC 27709 (USA) 
Mobile: 
 
Office Telephone: 
 
Fax: 
 
e-mail:  
 
Section 1:  PROTOCOL SYNOPSIS, Protocol Permitted Substitutions 
Rationale:  Clarification provided that dose reduction for lamivudine is allowed for 
participant’s with creatinine clearance <50 mL/min (consistent with prescribing 
information). 
Original Text: 
…..  Local prescribing information should be consulted for information regarding use of 
these medications. 
Following the Induction Phase, in exceptional circumstances, and in consultation with the 
Medical Monitor, Investigators may provide oral CAB and RPV as a short-term 
“bridging” strategy for participants who have begun CAB LA + RPV LA and who will 
miss a subsequent scheduled LA injection.  Should a participant need “oral bridging”, 
sites must contact the Medical Monitor for guidance on treatment strategies prior to a 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
334 
 
missed CAB LA + RPV LA dose.  Should a participant not notify the site in advance, the 
Medical Monitor must be contacted for further treatment guidance. 
No other dose reductions, modifications, or changes in the frequency of any components 
of any regimen will be allowed during the Maintenance and Extension Phases of the 
study.   
Revised Text: 
…..  Local prescribing information should be consulted for information regarding use of 
these medications.   
For consistency with prescribing information, dose reductions of lamivudine (or 
emtricitabine if used as alternate NRTI) are permitted as needed for creatinine 
clearance <50 mL/min throughout the study.  No other dose reductions, modifications, 
or changes in the frequency of any components of any regimen will be allowed during the 
Maintenance and Extension Phases of the study.   
Following the Induction Phase, in exceptional circumstances, and in consultation with the 
Medical Monitor, Investigators may provide oral CAB and RPV as a short-term 
“bridging” strategy for participants who have begun CAB LA + RPV LA and who will 
miss a subsequent scheduled LA injection.  Should a participant need “oral bridging”, 
sites must contact the Medical Monitor for guidance on treatment strategies prior to a 
missed CAB LA + RPV LA dose.  Should a participant not notify the site in advance, the 
Medical Monitor must be contacted for further treatment guidance. 
Section 4.2.3.  Eligibility for the Maintenance Phase 
Rationale:  Clarification provided that only samples with HIV-1 RNA >400 c/mL at 
Week -4 will be resent for resistance testing. 
Original Text: 
If the participant is ineligible for the Maintenance Phase, samples will be sent to a central 
laboratory for resistance testing and results provided to the Investigator once available. 
Revised Text: 
If the participant is ineligible for the Maintenance Phase, samples with a HIV-1 RNA 
>400 c/mL will be sent to a central laboratory for resistance testing and results provided 
to the Investigator once available. 
Section 4.2.7.  Dose Modifications / Permitted Treatment Substitutions 
Rationale:  Clarification provided that dose reduction for lamivudine is allowed for 
participant’s with creatinine clearance <50 mL/min (consistent with prescribing 
information). 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
335 
 
Original Text:  
During the Induction Phase, prior to randomization into the Maintenance Phase at Day 1, 
one switch to an alternate approved background NRTI therapy is allowed for toxicity or 
tolerability management.  The date of a decision to switch the NRTI background therapy 
for toxicity or tolerability management must be documented in the eCRF.  Switches of a 
background NRTI for any other reason are not permitted in the study.  Local prescribing 
information should be consulted for information regarding use of these medications. 
A short term bridging supply for participants on the CAB LA + RPV LA arm may be 
permitted following discussion with the Medical Monitor (see Section 6.8.1.).  No other 
dose reductions, modifications, or changes in the frequency of any components of any 
regimen will be allowed during the Maintenance and Extension Phases of the study.   
Revised Text: 
During the Induction Phase, prior to randomization into the Maintenance Phase at Day 1, 
one switch to an alternate approved background NRTI therapy is allowed for toxicity or 
tolerability management.  The date of a decision to switch the NRTI background therapy 
for toxicity or tolerability management must be documented in the eCRF.  Switches of a 
background NRTI for any other reason are not permitted in the study.  Local prescribing 
information should be consulted for information regarding use of these medications. 
A short term bridging supply for participants on the CAB LA + RPV LA arm may be 
permitted following discussion with the Medical Monitor (see Section 6.8.1.). 
For consistency with prescribing information, dose reductions of lamivudine (or 
emtricitabine if used as alternate NRTI) are permitted in the context of renal 
insufficiency (throughout the study), e.g. as needed for creatinine clearance 
<50 mL/min.   
If a dose reduction of lamivudine, a component of TRIUMEQ, is required for 
participants with creatinine clearance less than 50 mL/min, the individual entities 
should be used (e.g. DTG tablets, ABC tablets, 3TC tablets as separate medications, 
with dosing consistent with prescribing information).  DTG can be provided 
centrally through the study.  Single entity products will need to be sourced locally 
and can be reimbursed by the Sponsor as needed.  Lamivudine (3TC) dose 
reduction will be allowed throughout the study, and is not considered to be a 
“switch to an alternative approved background NRTI therapy”, but rather an 
alignment with prescribing information to maintain consistent 3TC plasma 
exposure for participants with renal insufficiency. 
No other dose reductions, modifications, or changes in the frequency of any components 
of any regimen will be allowed during the Maintenance and Extension Phases of the 
study. 
Section 4.6.1. Risk Assessment; Table, Study Procedures 
Rationale:  Added mitigation for ECG pad removal. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
336 
 
Original Text: 
Risks of 
ECG pad 
removal 
Participants will be required to 
have ECG tracings recorded 
periodically throughout the 
study. 
 
• Some discomfort and 
rash may occur where 
the ECG pads are 
removed. 
 
Revised Text: 
Risks of 
ECG pad 
removal 
Participants will be required 
to have ECG tracings 
recorded periodically 
throughout the study. 
Some discomfort and rash 
may occur where the ECG 
pads are removed. 
• ECGs will be conducted by 
appropriately trained personnel and 
effort made to minimise contact time 
for application of the pads. 
 
Section 5.4.  Withdrawal/Stopping Criteria 
Rationale:  Clarification provided that dose reduction for lamivudine is allowed for 
participant’s with creatinine clearance <50 mL/min (consistent with prescribing 
information). 
Original Text: 
• 
Participant requires a second switch or a dose adjustment of any component of the 
ABC/DTG/3TC.  A substitution for NRTI backbone is allowed at Screening, e.g. 
ABC/3TC to TDF/FTC or TAF/FTC for participants who are HLA-B*5701 positive. 
During the Induction Phase, prior to randomization into the Maintenance Phase at 
Day 1, one switch to an alternate approved background NRTI therapy is allowed for 
toxicity or tolerability management.   
Revised Text: 
• 
Participant requires a second switch or a dose adjustment of any component of the 
ABC/DTG/3TC (with exception of dose reduction for renal insufficiency as 
noted in Section 4.2.7.).  A substitution for NRTI backbone is allowed at Screening, 
e.g. ABC/3TC to TDF/FTC or TAF/FTC for participants who are HLA-B*5701 
positive. During the Induction Phase, prior to randomization into the Maintenance 
Phase at Day 1, one switch to an alternate approved background NRTI therapy is 
allowed for toxicity or tolerability management.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
337 
 
Section 6.8.  Protocol Permitted Substitutions 
Rationale:  Clarification provided that dose reduction for lamivudine is allowed for 
participant’s with creatinine clearance <50 mL/min (consistent with prescribing 
information). 
New Text Added: 
For consistency with prescribing information, dose reductions of lamivudine (or 
emtricitabine if used as alternate NRTI) are permitted throughout the study in the 
context of renal insufficiency, e.g. as needed for creatinine clearance <50 mL/min 
(See Section 4.2.7. for additional information). 
Section 6.9.2. Oral Dosing 
Rationale:  Clarification that ± 3 day window applies to all oral dosing in Induction, 
Maintenance, and Extension Phases of the study. 
Original Text: 
There is a (+ or -) 3 day visit window, from the projected visit date.   
Revised Text: 
There is a (+ or -) 3 day visit window, from the projected visit date (for all oral dosing 
in the Induction, Maintenance, and Extension Phases of the study).   
Section 7.1.  Time and Events Table 
Rationale:  Columns and Footnotes updated that were accidently deleted with 
Amendment 1. 
Corrections made: 
•  ‘y’ footnote added back to WD column for Induction Phase.  Also added the word 
‘oral’ to clarify this is a follow-up visit for participants withdrawing from oral IP 
(participants withdrawing from CAB LA + RPV LA will go into Long-Term Follow-
Up). 
• clarification added to footnote ‘p’ that genetics sample can be collected at any visit 
after signing informed consent, but the Week [-20] visit is preferred; 
• Week 5 footnote corrected to letter ‘t’ (vs ‘s’). 
• ‘LA Arm’ added back to column for Weeks 68, 76, 84, 92 (hidden when column was 
narrowed). 
• Week 104b – clarification that this visit is only required for the participants switching 
from oral to LA. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
338 
 
12.14.2.3. Administrative Corrections (e.g. Typographical Errors, Updated 
References) 
Section 11.  References (Also updated in Section 4.6 and Section 5.0) 
Rationale:  Updated investigator brochure references to include most recent version 
numbers. 
Original Text: 
GlaxoSmithKline Document Number RH2009/00003/05: GSK1265744 (Cabotegravir) 
Clinical Investigator's Brochure, Version 05, January 2016. 
Revised Text: 
GlaxoSmithKline Document Number RH2009/00003/06: GSK1265744 (Cabotegravir) 
Clinical Investigator's Brochure, Version 06, December 2016. 
Original Text: 
Rilpivirine Clinical Investigator Brochure [RPV IB], April 2016. 
Revised Text: 
Rilpivirine Clinical Investigator Brochure [RPV IB], Edition Number 10, April 2017. 
Section 11.0.  References 
Rationale:  Added references identified in DAIDS table to Reference Section. 
New Text: 
Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk 
Reduction in Children and Adolescents. Pediatrics 2011;128;S213; originally 
published online November 14, 2011; DOI: 10.1542/peds.2009-2107C. 
New Text: 
World Health Organization (WHO) Growth Reference:  Available at 
http://www.who.int/growthref/who2007_bmi_for_age/en/. 
Section 12.5.  Appendix 5: Genetic Research, Study Assessments and Procedures 
Rationale:  Clarification that samples are collected after participant’s are ‘enrolled’ 
versus ‘randomized.’ 
Original Text: 
A blood sample is collected at the baseline visit, after the subject has been randomized 
and provided informed consent for genetic research.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
339 
 
Revised Text: 
A blood sample is collected at the baseline visit, after the subject has been enrolled and 
provided informed consent for genetic research.  
Section 12.9.1. Amendment 01 (All Countries) 
Rationale:  Correction made to rationale section to be consistent with protocol text 
regarding 52 weeks of contraception required (vs 52 years). 
Original Text: 
Section 1 Protocol Synopsis, Long-Term Follow-Up Phase – IM Regimen Only and 
Section 4.2.6.  Long-Term Follow-Up Phase – IM Regimen Only 
Rationale:  Clarification added that adequate contraception must be used for at least 52 
years (rather than stating throughout the entire year of follow-up): 
Revised Text: 
Section 1 Protocol Synopsis, Long-Term Follow-Up Phase – IM Regimen Only and 
Section 4.2.6.  Long-Term Follow-Up Phase – IM Regimen Only 
Rationale:  Clarification added that adequate contraception must be used for at least 52 
weeks (rather than stating throughout the entire year of follow-up): 
12.14.3. 
Amendment 03 (All Countries) 
Protocol changes for Amendment 03 (25-JUN-2018), from amendment 02 (19-JUL-
2017) 
12.14.3.1. Protocol Amendment Rationale 
Changes for Amendment 3 were made to the protocol to manage and mitigate risks 
following identification of a potential safety issue related to neural tube defect in infants 
born to women with exposure to dolutegravir (DTG) at the time of conception. 
• A Risk Assessment table was added to include language regarding risk and mitigation 
of neural tube defects seen with DTG. 
• The withdrawal criteria were updated to include a reminder that females of 
reproductive potential who change their minds and desire to be pregnant should also 
be withdrawn from the study. 
• The Time and Events table was updated to include a reminder for investigators to 
check at every visit that females of reproductive potential are avoiding pregnancy. 
 
Additionally, clarifications were provided for the following: 
• the DTG IB should be referenced for additional risks, safety information, drug 
interactions, etc.; 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
340 
 
• ‘suspected’ was added to the text prior to the bulleted definition of suspected 
virologic failure in Section 5.4.5.3.; 
• specific storage conditions were removed from the protocol for IP, and a statement 
added to store according to product label; 
• insulin was removed from the section regarding clinical assessments performed 
during the study; 
• timeframe for pregnancy reporting and follow-up were updated to 24 hours to align 
with current reporting process; 
• prescribing information and IB references were updated. 
 
12.14.3.2. Protocol Changes/Clarifications  
Section 4.6 Benefit:Risk Assessment 
Rationale:  DTG IB added as reference for benefit/risk profile (and typos corrected) 
Original Text: 
ABC/DTG/3TC is established regimen that has been in clinical use for several years and 
has well an established benefit/risk profile described in detail in the respective country 
product labels (TRIUMEQ Prescribing Information, 2015). 
Revised Text: 
ABC/DTG/3TC is an established regimen that has been in clinical use for several years 
and has an established benefit/risk profile described in detail in the DTG IB 
(GlaxoSmithKline Document Number RM2007/00683/11) and respective country 
product labels (TRIUMEQ Prescribing Information, 2018). 
Section 4.6 Benefit:Risk Assessment 
Rationale:  New text adding regarding risk of neural tube defects associated with DTG: 
New Text: 
A potential safety issue related to neural tube defect in infants born to women with 
exposure to dolutegravir (DTG) at the time of conception has been recently 
identified as noted below: 
Potential Risk 
of Clinical 
Significance 
Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (IP) [ABC/DTG/3TC, DTG] 
Refer to DTG IB and country product labels for additional information 
DTG: Neural 
tube defects 
In one ongoing birth outcome 
surveillance study in Botswana, early 
results from an unplanned interim 
analysis show that 4/426 (0.9%) of 
women who were taking DTG when they 
became pregnant had babies with neural 
1. A female subject is eligible to 
participate if she is not 
pregnant, not lactating, and, if 
she is a female of 
reproductive potential, agrees 
to follow one of the options 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
341 
 
tube defects compared to a background 
rate of 0.1%. 
listed in the Modified List of 
Highly Effective Methods for 
Avoiding Pregnancy in 
Females of Reproductive 
Potential (FRP) (see Section 
12.7) from 30 days prior to the 
first dose of study medication 
and for at least 30 days after 
discontinuation of all oral 
study medications, and for at 
least 52 weeks after 
discontinuation of CAB LA 
and RPV LA. 
2. Women who are breastfeeding 
or plan to become pregnant or 
breastfeed during the study are 
excluded; 
3. Women who become pregnant, 
or who desire to be pregnant 
while in the study will have 
study treatment discontinued 
and withdrawn from the study. 
4. Females of reproductive 
potential are reminded re: 
pregnancy avoidance and 
adherence to contraception 
requirements at every study 
visit. 
5. Pregnancy status is monitored 
at every study visit. 
 
Section 5 Selection of Study Population and Withdrawal Criteria 
Rationale:  DTG IB added as reference. 
Original Text: 
Information for ABC/DTG/3TC or DTG is provided in the US or country product label 
(TRIUMEQ Prescribing Information, 2015; TIVICAY Prescribing Information, 2015). 
Revised Text: 
Information for ABC/DTG/3TC or DTG is provided in the current DTG IB 
(GlaxoSmithKline Document Number: RM2007/00683/11) and US or country product 
label (TRIUMEQ Prescribing Information, 2018; TIVICAY Prescribing Information, 
2017). 
Section 5.4. Withdrawal/Stopping Criteria 
Rationale:  Reminder added to withdraw participants from the study if they desire to 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
342 
 
become pregnant or who are no longer willing to comply with contraceptive 
requirements. 
New Text: 
As a reminder, females of reproductive potential who changed their minds and desire 
to be pregnant, or who state they are no longer willing to comply with the approved 
pregnancy avoidance methods, should also be withdrawn from the study. 
Section 5.4.5.2. Suspected Virologic Failure 
Rationale:  “suspected” added to the paragraph directing investigators to obtain 
confirmation of virologic failure. 
Original Text: 
Upon notification that a participant’s HIV-1 RNA plasma level meets any of the 
definitions of virologic failure, the Investigator should confirm the definition is met by 
initiating a repeat of the HIV-1 RNA assessment.   
Revised Text: 
Upon notification that a participant’s HIV-1 RNA plasma level meets any of the 
definitions of suspected virologic failure, the Investigator should confirm the definition 
is met by initiating a repeat of the HIV-1 RNA assessment.   
Section 6.1.1. Cabotegravir (CAB) – Tablet 
Rationale:  Storage conditions removed from text and direction provided to refer to the 
product label. 
Original Text: 
CAB tablets are to be stored up to 30°C [86°F] and protected from moisture.  
Revised Text: 
CAB tablets are to be stored according to the product label. 
Section 6.1.2. Rilpivirine (RPV) – Tablet 
Rationale:  Storage conditions removed from text and direction provided to refer to the 
product label. 
Original Text: 
RPV tablets should be stored at 25°C (excursions permitted to 15°-30°C [59°-86°F]) and 
protected from light.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
343 
 
Revised Text: 
RPV tablets are to be stored according to the product label. 
Section 6.1.3. Cabotegravir – Injectable Suspension (CAB LA) 
Rationale:  Storage conditions removed from text and direction provided to refer to the 
product label. 
Original Text: 
CAB LA injectable suspension is to be stored at up to 30°C, do not freeze.  
Revised Text: 
CAB LA injectable suspension is to be stored according to the product label. 
Section 6.1.4. Rilpivirine – Injectable Suspension (RPV LA) 
Rationale:  Storage conditions removed from text and direction provided to refer to the 
product label. 
Original Text: 
RPV LA injectable suspension should be kept in the outer package and stored at 2-8°C 
(do not freeze).  RPV LA should also be protected from light.  
Revised Text: 
RPV LA injectable suspension should be stored according to the product label and 
should be protected from light. 
Section 6.1.5. ABC/DTG/3TC STR - Tablet 
Rationale:  Storage conditions removed from text and direction provided to refer to the 
product label. 
Original Text: 
ABC/DTG/3TC tablets are to be stored at 25°C [77°F] (excursions permitted to 15°-30°C 
[59°-86°F]). 
Revised Text: 
ABC/DTG/3TC tablets are to be stored according to the product label. 
Section 6.1.6. Dolutegravir (DTG) - Tablet 
Rationale:  Storage conditions removed from text and direction provided to refer to the 
product label. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
344 
 
Original Text: 
DTG tablets are to be stored at 25°C [77°F] (excursions permitted to 15°-30°C [59°-
86°F]). 
Revised Text: 
DTG tablets are to be stored according to the product label. 
Section 6.13. Concomitant Medications and Non-Drug Therapy 
Rationale:  Added use of investigator brochure to evaluate potential drug:drug 
interactions. 
Original Text: 
The investigator should evaluate any potential drug:drug interactions at every visit, 
including reviewing the most current version of the U.S and/or local prescribing 
information for RPV, and ABC/DTG/3TC (or DTG + NRTIs), especially if any new 
concomitant medications are reported by participants. 
Revised Text: 
The investigator should evaluate any potential drug:drug interactions at every visit, 
including reviewing the most current version of the investigator brochures, the U.S 
and/or local prescribing information for RPV, and ABC/DTG/3TC (or DTG + NRTIs), 
especially if any new concomitant medications are reported by participants. 
Section 6.13.1. Prohibited Medications and Non-Drug Therapies 
Rationale:  Added use of investigator brochure to evaluate potential drug:drug 
interactions. 
Original Text: 
For additional information on concurrent therapies and interactions suspected to be 
relevant to other antiretroviral therapy used during the study (e.g. ABC/DTG/3TC), 
please consult and local prescribing information. 
Revised Text: 
For additional information on concurrent therapies and interactions suspected to be 
relevant to other antiretroviral therapy used during the study (e.g. ABC/DTG/3TC), 
please consult the current DTG Investigator brochure and local prescribing 
information. 
Original Text (Concurrent with RPV): 
Please refer to local prescribing information for other drugs that are prohibited, should 
be used with caution, require dose adjustment, or increased clinical monitoring if taken 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
345 
 
with oral RPV. 
Revised Text: 
Please refer to the current RPV Investigator brochure and local prescribing information 
for other drugs that are prohibited, should be used with caution, require dose adjustment, 
or increased clinical monitoring if taken with oral RPV. 
Original Text (Concurrent with ABC/DTG/3TC): 
Please refer to the local prescribing information for other drugs that should be used with 
caution, require dose adjustment, or increased clinical monitoring if taken with 
ABC/DTG/3TC (or DTG with alternate NRTI background therapy). 
Revised Text: 
Please refer to the current DTG IB and local prescribing information for other drugs 
that should be used with caution, require dose adjustment, or increased clinical 
monitoring if taken with ABC/DTG/3TC (or DTG with alternate NRTI background 
therapy). 
Original Text (Concurrent with DTG + 2 NRTIs): 
In addition to the prohibited medications noted for DTG above (as a component of 
ABC/DTG/3TC), for participants who are HLA-B*5701 positive and who are receiving 
DTG + alternate NRTI background therapy, refer to local prescribing information for 
details regarding concurrent therapies. 
Revised Text: 
In addition to the prohibited medications noted for DTG above (as a component of 
ABC/DTG/3TC), for participants who are HLA-B*5701 positive and who are receiving 
DTG + alternate NRTI background therapy, refer to the current DTG IB and local 
prescribing information for details regarding concurrent therapies. 
Section 7.1. Time and Events Table 
Rationale:  Reminder added to footnote ‘j’ to avoid pregnancy while on study and to 
adhere to contraceptive requirements. 
Original Text: 
j. 
Conduct pregnancy tests for only women of childbearing potential at every visit throughout the study, including 
Q4W during the Extension Phase.  A negative urine pregnancy test is required prior to beginning the Induction 
Phase (Week [-20]), on Day 1 (preferably prior to randomization), and at Week 4b (or Week 104b for subjects 
transitioning from ABC/DTG/3TC) prior to the first injection. Serum pregnancy test can substitute for urine 
pregnancy test if locally required, but must be appropriately timed to confirm pregnancy status prior to e.g. 
randomization and first IM administration. S=Serum/U=Urine. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
346 
 
Revised Text:  
j. 
Conduct pregnancy tests for only women of childbearing potential at every visit throughout the study, including 
Q4W during the Extension Phase.  Remind females of reproductive potential of the need to avoid pregnancy 
while in study and adherence to the study’s contraception requirements.  A negative urine pregnancy test is 
required prior to beginning the Induction Phase (Week [-20]), on Day 1 (preferably prior to randomization), and at 
Week 4b (or Week 104b for subjects transitioning from ABC/DTG/3TC) prior to the first injection. Serum 
pregnancy test can substitute for urine pregnancy test if locally required, but must be appropriately timed to 
confirm pregnancy status prior to e.g. randomization and first IM administration. S=Serum/U=Urine. 
Section 7.4.1. Clinical Evaluations 
Rationale:  Removed insulin as a periodic assessment, as this was not collected for 
201584. 
Original Text: 
• 
Periodic assessment of glucose, insulin, and bone and renal markers. 
Revised Text: 
• 
Periodic assessment of glucose, and bone and renal markers. 
Section 7.4.3.4. Prompt Reporting of Serious Adverse Events and Other Event (Text 
and Table 7) – Pregnancy Reporting Row 
Rationale:  Updated timeframe for pregnancy reporting and follow-up. 
Original Text:  
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form.  To ensure participant safety, if a pregnancy is reported then the 
investigator should inform GSK within 2 weeks of learning of the pregnancy and should 
follow the procedures outlined in Appendix 7. 
Revised Text: 
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form.  The investigator should inform GSK within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 7. 
Original Table Row: 
Table 7 
Reporting of Serious Adverse Events and Other Events 
 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
Pregnancy 
2 weeks 
“Pregnancy 
Notification Form” 
2 weeks 
“Pregnancy Follow-
up Form” 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
347 
 
Revised Table Row: 
Table 7 
Reporting of Serious Adverse Events and Other Events 
 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
Pregnancy 
24 hours 
“Pregnancy 
Notification Form” 
Within 24 hours of 
investigator 
awareness of 
pregnancy outcome 
“Pregnancy 
Follow-up Form” 
 
Section 7.4.7.3. Action to be Taken if Pregnancy Occurs 
Rationale:  Updated timeframe for pregnancy reporting. 
Original Text: 
To ensure participant safety, if a pregnancy is reported then the investigator should 
inform GSK within 2 weeks of learning of the pregnancy and should follow the 
procedures outlined in Appendix 7. 
Revised Text: 
The investigator should inform GSK within 24 hours of learning of the pregnancy and 
should follow the procedures outlined in Appendix 7. 
Section 12.7.2.  Collection of Pregnancy Information 
Rationale:  Updated timing for collection of pregnancy information. 
Original Text: 
• 
Information will be recorded on the appropriate form and submitted to GSK within 
2 weeks of learning of a participant's pregnancy. 
Revised Text: 
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a participant's pregnancy. 
12.14.3.3. Administrative Corrections (e.g., Updated References) 
Section 11:  References 
Original Text: 
Edurant Prescribing Information, August 2015. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
348 
 
Revised Text: 
Edurant Prescribing Information, February 2018. 
Original Text: 
GlaxoSmithKline Document Number RH2009/00003/06: GSK1265744 (Cabotegravir) 
Clinical Investigator's Brochure, Version 06, December 2016. 
Revised Text: 
GlaxoSmithKline Document Number RH2009/00003/07: GSK1265744 (Cabotegravir) 
Clinical Investigator's Brochure, Version 07, December 2017. 
Original Text: 
GlaxoSmithKline Document Number RM2007/00683/09: GSK1349572 Clinical 
Investigator's Brochure, Version 09, 09 October 2015. 
Revised Text: 
GlaxoSmithKline Document Number RM2007/00683/11: GSK1349572 Clinical 
Investigator's Brochure, Version 11, 13 October 2017; Supplement 01, 11 Dec 2017; 
Supplement 02, Jun 2018. 
Original Text: 
TIVICAY Prescribing Information, August 2015. 
Revised Text: 
TIVICAY Prescribing Information, November 2017. 
Original Text: 
TRIUMEQ Prescribing Information, September 2015. 
Revised Text: 
TRIUMEQ Prescribing Information, May 2018. 
12.14.4. 
Amendment 04 (All Countries) 
Protocol changes for Amendment 04 (24-SEP-2018), from Amendment 03 (25-JUN-
2018).  Some of the modifications noted below are not inclusive of full text within a 
section, but rather the edited pieces of the section. 
12.14.4.1. Protocol Amendment Rationale 
The primary reason for protocol amendment 04 is to allow an optional (vs mandatory) 
oral lead-in for participants randomized to the ABC/DTG/3TC arm who choose to 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
349 
 
continue into the Extension Phase of the study and receive CAB LA + RPV LA.  The 
Appendix (Appendix 7) for contraceptive guidance and collection of pregnancy 
information was updated to be consistent with current protocol template text.  Other 
minor clarifications were made as needed, e.g., the eCSSRs timing in the footnote for the 
Time and Events Table, updated abbreviations, etc. 
12.14.4.2. Protocol Changes/Clarifications 
Section 1.0 Protocol Synopsis for 201584, Rationale: 
Rationale for change:  to highlight direct to injection as an option for participants 
transitioning from ABC/DTG/3TC to CAB LA + RPV LA in the Extension Phase.  
Original Text: 
Eligible participants (HIV-1 ribonucleic acid [RNA] <50 c/mL at Week 96) would 
transition to LA dosing, beginning with 4 weeks oral CAB + RPV therapy at Week 100, 
and receive the first IM CAB LA + RPV LA injections at Week 104b. 
Revised Text: 
Eligible participants (HIV-1 ribonucleic acid [RNA] <50 c/mL at Week 96) would 
transition to LA dosing, beginning with the first IM CAB LA + RPV LA injections at 
either Week 100 (direct to injection) or Week 104b (following optional oral lead-in 
with CAB 30 mg and RPV 25 mg). 
Section 1.0. Protocol Synopsis for 201584, Objectives/Endpoints AND Section 3.0.  
Objectives And Endpoints: 
Rationale for change: an objective that was Exploratory in previous versions of the 
protocol has been modified to a Secondary endpoint to provide data for participants 
transitioning from ABC/DTG/3TC to CAB LA + RPV LA in the Extension Phase, with 
or without CAB + RPV oral lead-in.  Secondary endpoint also added to support the 
importance of collecting PK data in participants who do not use an oral lead-in. 
Original Text: 
Exploratory 
To evaluate the antiviral and immunologic 
effects, safety and tolerability, and viral 
resistance of CAB LA + RPV LA for all 
participants in the Extension Phase. 
• Proportion of participants with plasma 
HIV-1 RNA <200 c/mL and HIV-1 RNA 
<50 c/mL over time. 
• Proportion of participants with confirmed 
virologic failure over time. 
• Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB and 
RPV in over time. 
• Absolute values and change from Baseline 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
350 
 
Exploratory 
in plasma HIV-1 RNA over time. 
• Absolute values and changes from 
Baseline in CD4+ cell counts over time. 
• Incidence of disease progression (HIV-
associated conditions, acquired 
immunodeficiency syndrome [AIDS] and 
death). 
• Incidence and severity of AEs and 
laboratory abnormalities over time. 
• Proportion of participants who discontinue 
treatment due to AEs over time. 
• Absolute values and changes in laboratory 
parameters over time. 
Revised Text: 
Secondary 
To evaluate the antiviral and immunologic 
effects, safety and tolerability, and 
development of viral resistance to CAB LA 
+ RPV LA at Week 124 and over time for 
participants switching from ABC/DTG/3TC 
in the Extension Phase, with and without 
optional oral lead-in. 
• Proportion of participants with HIV-1 
RNA ≥ 50 c/mL at Week 124, with and 
without oral lead-in (FDA Snapshot 
algorithm, Extension Switch 
population). 
• Proportion of participants with plasma 
HIV-1 RNA <50 c/mL and HIV-1 RNA 
<200 c/mL over time. 
• Proportion of participants with 
confirmed virologic failure over time. 
• Incidence of treatment emergent 
genotypic and phenotypic resistance to 
CAB and RPV over time. 
• Absolute values and change from 
Baseline in CD4+ cell counts over time. 
• Incidence and severity of AEs and 
laboratory abnormalities over time. 
• Proportion of participants who 
discontinue treatment due to AEs over 
time. 
• Absolute values and change in 
laboratory parameters over time. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
351 
 
To evaluate the pharmacokinetics of CAB 
and RPV in the setting of no oral lead-in for 
participants switching from ABC/DTG/3TC 
in the Extension Phase. 
• To evaluate plasma CAB and RPV 
concentrations over time (Week 100 
[direct to inject without oral lead-in] 
and Week 104 [both direct to inject and 
optional oral lead-in participants]) 
Section 1.0. Protocol Synopsis for 201584, Overall Design AND Section 4.1. Overall 
Design, Study Schematic: 
Rationale for change:  to highlight direct to injection as an option for participants 
transitioning from ABC/DTG/3TC to CAB LA + RPV LA in the Extension Phase.  Also 
corrected error in schematic entry viral load from >1000 c/mL to ≥1000 c/mL. 
Original Text: 
 
†Optional switch to CAB LA + RPV LA at Wk 100 for subjects randomized to ABC/DTG/3TC.
¥Subjects who withdraw from IM CAB LA + RPV LA treatment must enter the 52 week long term follow up phase. 
Wk 104a
ARV-naïve,  
HIV-1 
RNA>1000
Any CD4
n≈620
Screening 
Phase
Maintenance Phase
Extension Phase†
ABC/DTG/3TC
Oral CAB
+ RPV
CAB LA + RPV LA¥
Oral CAB
+ RPV
Extension¥
Phase
1o Endpoint
2o Endpoint
Day 1
Wk 96
Wk 24
Wk 48
Wk 4b
Wk 100
Wk 104b
ABC/DTG/3TC 
Single Tablet 
Regimen
Induction 
Phase
Wk -20
Wk -4
Randomization 
(1:1)
N=570
Confirm HIV-1 RNA <50 c/mL
Wk 108
Wk 4a
Wk 8
Q4 Weeks


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
352 
 
Revised Text: 
 
1.  
 
¥Subjects who withdraw from IM CAB LA + RPV LA must enter the 52 week Long Term Follow-Up 
Phase. 
Section 1.0. Protocol Synopsis for 201584, Treatment Arms and Duration AND 
Section 4.2.4. Maintenance Phase (Day 1 to Week 100): 
Rationale for change:  to highlight patients must remain virologically suppressed 
through Week 96 to continue into the Extension Phase.  
Original Text: 
• Continue on the oral ABC/DTG/3TC initiated during the Induction Phase for at 
least an additional 100 weeks.  Participants who successfully complete Week 100 
(without meeting study defined withdrawal criteria and who remain virologically 
suppressed:  HIV-1 RNA <50 c/mL) will be given the option to switch to the LA 
arm in the Extension Phase or be withdrawn from the study. 
Revised Text: 
• Continue on the oral ABC/DTG/3TC initiated during the Induction Phase for at 
least an additional 100 weeks.  Participants who successfully complete Week 100 
(without meeting study defined withdrawal criteria and who remain virologically 
suppressed through Week 96:  HIV-1 RNA <50 c/mL) will be given the option 
to switch to the LA arm in the Extension Phase or be withdrawn from the study. 
Section 1.0 Protocol Synopsis for 201584, Treatment Arms and Duration, Extension 
Phase: 
Rationale for change:  updated to reflect the two options for participants transitioning 
from ABC/DTG/3TC to CAB LA + RPV LA in the Extension Phase.  Also rearranged 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
353 
 
some text to improve flow of section. 
Original Text: 
Extension Phase 
Participants Entering from the CAB LA + RPV LA Arm 
All participants who successfully complete Week 100 of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase until CAB LA and RPV LA are either locally approved and 
commercially available, the participant no longer derives clinical benefit, the participant 
meets a protocol-defined reason for discontinuation or until development of either CAB 
LA or RPV LA is terminated.   
Visits will continue to occur every 4 weeks. 
Participants Entering from the ABC/DTG/3TC Arm 
Participants randomized to continue ABC/DTG/3TC will have the option to either 
continue study participation by switching to CAB LA + RPV LA in the Extension Phase, 
or to complete their study participation at Week 100. 
Participants who choose to continue on to the Extension Phase will need to be assessed 
for eligibility to begin the CAB LA + RPV LA regimen.  Participants will continue on 
ABC/DTG/3TC while eligibility is being confirmed.   
All participants with an undetectable HIV-1 RNA (<50 c/mL) result from the Week 96 
visit are eligible to enter the Extension Phase.  A single repeat of HIV-1 RNA for any 
participant with a HIV-1 RNA ≥50 c/mL and < 400 c/mL at Week 96 must be performed.  
The retest should be scheduled as soon as possible (but no later than 4 weeks from the 
Week 96 visit).  Participants with a HIV-1 RNA <50 c/mL upon retest are eligible to 
enter the Extension Phase.  Participants with HIV-1 RNA ≥400 c/mL at Week 96 are not 
eligible to enter the Extension Phase, will not be allowed a repeat to determine eligibility, 
and will therefore be withdrawn from the study. 
Participants with a Week 96 HIV-1 RNA <50 c/mL, will initiate a 4 week lead-in of oral 
CAB 30 mg + oral RPV 25 mg once daily at Week 100.  Clinical chemistries will also be 
assessed at Week 100.  At Week 104a, following the 4 week CAB + RPV oral lead-in, 
participants will have additional safety assessments including clinical chemistries.  In 
addition, central lab results and safety parameters from the Week 104a visit must be 
available and reviewed.  If a clinical chemistry retest is required based on Week 104a 
labs, the retest should be performed as soon as possible (and preferably no later than 
7 days following Week 104a).  Participants will remain on oral CAB 30 mg + RPV 
25 mg until the Week 104b injection visit, and until any required Visit 104a retest results 
are available for review. 
Participants will continue study treatment in the Extension Phase until CAB LA and RPV 
LA are either locally approved and commercially available, the participant no longer 
derives clinical benefit, the participant meets a protocol-defined reason for 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
354 
 
discontinuation or until development of either CAB LA or RPV LA is terminated.  Visits 
will continue to occur every 4 weeks. 
Participants not eligible to enter the Extension Phase will end their study participation 
(Week 100 will be the last study visit, no withdrawal visit needed).  Sites may be 
reimbursed for up to a one month supply of antiretroviral medication to facilitate 
transition to non-study ART for participants that do not qualify for the Extension Phase. 
Revised Text: 
Extension Phase 
All eligible participants who transition into the Extension Phase will continue study 
treatment until CAB LA and RPV LA are either locally approved and commercially 
available, the participant no longer derives clinical benefit, the participant meets a 
protocol-defined reason for discontinuation or until development of either CAB LA 
or RPV LA is terminated.  Visits will continue to occur every 4 weeks. 
Participants not eligible to enter the Extension Phase will end their study 
participation (Week 100 will be the last study visit, no withdrawal visit needed).  
Sites may be reimbursed for up to a one month supply of antiretroviral medication 
to facilitate transition to non-study ART for participants that do not qualify for the 
Extension Phase. 
Participants Entering from the CAB LA + RPV LA Arm 
All participants who successfully complete Week 100 of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase.   
Visits will continue to occur every 4 weeks. 
Participants Entering from the ABC/DTG/3TC Arm 
Participants randomized to continue ABC/DTG/3TC will have the option to either 
continue study participation by switching to CAB LA + RPV LA in the Extension Phase, 
or to complete their study participation at Week 100.   
The transition from ABC/DTG/3TC to CAB LA + RPV LA within the Extension 
Phase can be completed with or without an oral lead-in prior to commencement of 
injectable treatment.  The oral lead-in decision will be made by the participant in 
consultation with the investigator and must be appropriately documented.  As 
participants approach the Week 100 visit, sites must ensure sufficient CAB and 
RPV supply are available to support the participant’s decision for transition to LA. 
Participants who choose to continue on to the Extension Phase will need to be assessed 
for eligibility to begin the CAB LA + RPV LA regimen.  Participants will continue on 
ABC/DTG/3TC while eligibility is being confirmed.   
All participants with an undetectable HIV-1 RNA (<50 c/mL) result from the Week 96 
visit are eligible to enter the Extension Phase.  A single repeat of HIV-1 RNA for any 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
355 
 
participant with a HIV-1 RNA ≥50 c/mL and < 400 c/mL at Week 96 must be performed.  
The retest should be scheduled as soon as possible (but no later than 4 weeks from the 
Week 96 visit).  Participants with a HIV-1 RNA <50 c/mL upon retest are eligible to 
enter the Extension Phase.  Participants with HIV-1 RNA ≥400 c/mL at Week 96 are not 
eligible to enter the Extension Phase, will not be allowed a repeat to determine eligibility, 
and will therefore be withdrawn from the study. 
Participants Transitioning Direct to Injection in the Extension Phase 
Central lab results and safety parameters from the Week 96 visit must be available 
and reviewed for participants who choose to transition direct to injection.  
Participants with ongoing safety issues or laboratory abnormalities of clinical 
concern (e.g., Grade 3 or Grade 4 liver enzyme elevations), will require consultation 
and agreement with the Medical Monitor prior to proceeding directly to injections 
in the Extension Phase.  
If a clinical chemistry retest is required based on Week 96 labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following 
Week 96).  Participants will remain on oral ABC/DTG/3TC until the Week 100 
injection visit, and until any required Week 96 retest results are available for 
review. 
At Week 100, eligible participants will take the last dose of ABC/DTG/3TC (or DTG 
+ 2 NRTIs), and receive the first injections of CAB LA (600 mg) + RPV LA (900 mg) 
as initial loading doses.  Clinical chemistries will also be assessed at Week 100.  At 
Week 101, participants will return to the clinic for PK and safety assessments 
including clinical chemistries.  The second and third injections (CAB LA 400 mg + 
RPV LA 600 mg) will be administered at Week 104a and Week 108.  There will be a 
one week dosing window for the second and third IM injections such that the second 
injections occur within the window of Week 103 to Week 104a, but not later than 
Week 104a, and the third injections occur within the window of Week 107 to Week 
108, but no later than Week 108.  Subsequent injections (CAB LA 400 mg + RPV 
LA 600 mg) will occur every 4 weeks thereafter, from the projected visit date, with a 
(+ or -) 7 day dosing window being allowed (but not preferred).  Following the Week 
108 injection, the interval between injection visits should be limited to a maximum 
of 5 weeks.  The Medical Monitor must be contacted if the length of time between 
injections exceeds, or is projected to exceed, 5 weeks. 
Participants Receiving Optional Oral Lead-In in the Extension Phase 
At Week 100, eligible participants who after discussion with the investigator, choose 
to receive the optional oral lead-in will initiate a 4 week lead-in of oral CAB 30 mg + 
oral RPV 25 mg once daily.  It is not necessary to dose ABC/DTG/3TC on the day the 
participant begins the oral lead-in with CAB + RPV.  However, if the participant 
takes ABC/DTG/3TC prior to coming into the clinic, initiation of oral CAB and 
RPV should continue as planned.  Clinical chemistries will also be assessed at Week 
100.  At Week 104a, following the 4 week CAB + RPV oral lead-in, participants will 
have additional safety assessments including clinical chemistries.  In addition, central lab 
results and safety parameters from the Week 104a visit must be available and reviewed.  
If a clinical chemistry retest is required based on Week 104a labs, the retest should be 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
356 
 
performed as soon as possible (and preferably no later than 7 days following 
Week 104a).  Participants will remain on oral CAB 30 mg + RPV 25 mg until the 
Week 104b injection visit, and until any required Visit 104a retest results are available 
for review.  An HIV-1 RNA sample will not be collected at Week 104a for 
participants receiving the optional oral lead in, but will be obtained at the Week 
104b visit to serve as the injection baseline viral load. 
Section 1.0 Protocol Synopsis for 201584, Analysis: 
Rationale for change:  to describe new Week 124 analysis.  
New Text: 
In descriptive analyses, antiviral response will be assessed according to the 
proportion of participants with and without oral lead-in who have HIV-1 RNA 
≥50 c/mL at Week 124 (i.e., 24 weeks from initiation of CAB LA + RPV LA at 
Week 100, ±6 week analysis window, using the FDA Snapshot algorithm), with 
corresponding 95% confidence interval.  No formal statistical comparison with 
respect to safety and efficacy outcomes will be performed.   
 
Section 2.1. Study Rationale: 
Rationale for change:  to include information on the reason for assessing no oral lead-in.  
Original Text: 
Additionally, participants initially randomized to continue ABC/DTG/3TC will have an 
option to switch to CAB LA + RPV LA after completion of the Week 100 visit.  Eligible 
participants (HIV-1 RNA <50 c/mL at Week 96) would transition to LA dosing, 
beginning with 4 weeks oral CAB + RPV therapy at Week 100, and receiving the first IM 
CAB LA + RPV LA injections at Week 104b. 
Revised Text: 
Additionally, participants initially randomized to continue ABC/DTG/3TC will have an 
option to switch to CAB LA + RPV LA at, or after, completion of the Week 100 visit.  
Amendment 04 of the FLAIR study will provide an opportunity to access an 
optional (vs mandatory) oral lead-in for these participants who transition to LA 
treatment at Week 100.  Eligible participants (HIV-1 RNA <50 c/mL at Week 96) 
would transition to LA dosing, beginning at either Week 100 (direct to injection) or 
Week 104b (optional oral lead-in with CAB 30 mg and RPV 25 mg). 
Importantly, the oral lead-in during the early development program for CAB LA 
and RPV LA was instituted to minimize the risk of severe adverse drug reactions 
during LA dosing (e.g. acute hypersensitivity).  The 4 week oral lead-in allowed for 
an evaluation of any untoward adverse events and an assessment of safety labs prior 
to initiation of LA therapy.  To date, the principal safety risk identified with 
cabotegravir, following 3145 exposures to drug (oral and/or LA), is suspected DILI, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
357 
 
which has occurred in a few individuals, all of whom were receiving oral CAB.  The 
time to onset ranged between 4 weeks and one year and manifested as asymptomatic 
elevations of ALT, without compromise to hepatic function.  Each participant fully 
recovered, with removal of investigational product, without hospitalization or 
intervention.  During the Phase 3 ATLAS and FLAIR studies, no cases of DILI have 
been identified, during the oral lead-in period, or following initiation of LA dosing.  
There has been no evidence to date of a risk for clinically significant hepatotoxicity 
observed with cabotegravir.  Additionally, throughout the development program to 
date, no cases of severe drug hypersensitivity or severe drug allergy have been 
observed.  While the risk of idiosyncratic severe drug reactions cannot be fully 
excluded, the risk of occurrence is felt to be low, on the basis of safety data 
generated to date. 
Based on blinded, instream review of ongoing Phase 3 aggregate AE data (from 
FLAIR, and ATLAS) and of individual case reports (SAEs), no new, emerging, drug 
related safety issues have been identified within the four week oral lead-in dosing 
period (e.g., hypersensitivity, Drug Reaction with Eosinophilia and Systemic 
Symptoms [DRESS], severe drug induced liver injury [DILI]) that would have 
precluded participants from proceeding to CAB LA + RPV LA injections during the 
Maintenance Phase of the studies.  Additionally, review of accumulating data has 
not identified any new safety issues occurring on CAB LA + RPV LA that were 
otherwise predictable based on oral exposure experience. 
As a result of the accumulated safety data, which has been generated over the 
course of the Phase 1, 2 and 3 clinical studies, this amendment has been developed to 
generate safety, efficacy and PK data for the transition from oral ART to CAB LA + 
RPV LA without receiving an oral lead-in.  These data are intended to inform 
regulatory discussions around the safe and effective direct to inject dosing option 
with CAB LA + RPV LA.  The decision to dose with or without an oral-lead-in will 
be optional in this study, as elected by the study participant following informed 
consent discussions with the investigator. 
At Week 124, a descriptive analysis will be conducted to assess antiviral response 
(HIV-1 RNA ≥50 c/mL) for participants who choose no oral lead-in.  No formal 
statistical comparison will be performed with respect to safety and efficacy 
outcomes at Week 124. 
Data from this optional oral lead in will provide valuable knowledge/insight into the 
evolution of the ‘direct to injection’ concept. 
Section 4.1 Overall Design: 
Rationale for change:  to highlight direct to injection as an option for participants 
transitioning from ABC/DTG/3TC to CAB LA + RPV LA in the Extension Phase.  
Original Text: 
Participants randomized to ABC/DTG/3TC during the Maintenance Phase will continue 
ABC/DTG/3TC for at least an additional 100 weeks.  Participants who successfully 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
358 
 
complete Week 100 (without meeting study defined withdrawal criteria and who remain 
virologically suppressed:  HIV-1 RNA <50 c/mL) will be given the option to switch to 
the LA arm in the Extension Phase or be withdrawn from the study. 
Revised Text: 
Participants randomized to ABC/DTG/3TC during the Maintenance Phase will continue 
ABC/DTG/3TC for at least an additional 100 weeks.  Participants who successfully 
complete Week 100 (without meeting study defined withdrawal criteria and who remain 
virologically suppressed through Week 96:  HIV-1 RNA <50 c/mL) will be given the 
option to switch to the LA arm in the Extension Phase or be withdrawn from the study.  
The transition from ABC/DTG/3TC to CAB LA + RPV LA within the Extension 
Phase can be completed with or without an oral lead-in prior to commencement of 
injectable treatment.  The oral lead-in decision will be made by the participant in 
consultation with the investigator and must be appropriately documented. 
Section 4.2.5.  Extension Phase: 
Rationale for change:  Text moved from the end of Section 4.2.5.2 to under main 
Section 4.2.5. heading as applicable to all participants who go into the Extension Phase: 
Rearranged Text within section (deleted from the end of Section 4.2.5.2.): 
All eligible participants who transition into the Extension Phase will continue study 
treatment until CAB LA and RPV LA are either locally approved and commercially 
available, the participant no longer derives clinical benefit, the participant meets a 
protocol-defined reason for discontinuation or until development of either CAB LA 
or RPV LA is terminated.  Visits will continue to occur every 4 weeks. 
Participants not eligible to enter the Extension Phase will end their study 
participation (Week 100 will be the last study visit, no withdrawal visit needed).  
Sites may be reimbursed for up to a one month supply of antiretroviral medication to 
facilitate transition to non-study ART for participants that do not qualify for the 
Extension Phase. 
Section 4.2.5.1.  Participants Entering from the CAB LA + RPV LA Arm 
Rationale for change:  Simplified text as this information is duplicate text provided in 
multiple sections, including Section 4.2.5. 
Original Text: 
All participants who successfully complete 100 weeks of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase until CAB LA and RPV LA are either locally approved and 
commercially available (including through local public/government health sectors), the 
participant no longer derives clinical benefit, the participant meets a protocol-defined 
reason for discontinuation or until development of either CAB LA or RPV LA is 
terminated.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
359 
 
Visits will continue to occur every 4 weeks.  See the Time and Events Table (Section 7.1) 
for more information. 
Section 4.2.5.2.  Protocol Synopsis for 201584, Treatment Arms and Duration, 
Extension Phase (edited pieces included below – not inclusive of entire section): 
Rationale for change:  to highlight direct to injection as an option for participants 
transitioning from ABC/DTG/3TC to CAB LA + RPV LA in the Extension Phase.  
Original Text: 
Participants randomized to continue ABC/DTG/3TC will have the option to either 
continue study participation by switching to CAB LA + RPV LA in the Extension Phase, 
or to complete their study participation at Week 100 (no withdrawal visit needed). 
Participants receiving ABC/DTG/3TC with a Week 96 HIV-1 RNA <50 c/mL, will 
initiate a 4 week lead-in of oral CAB 30 mg + oral RPV 25 mg once daily at Week 100.  
Clinical chemistries will be assessed at Week 100.  At Week 104a, following the 4 week 
CAB + RPV oral lead-in, participants will have additional safety assessments including 
clinical chemistries as per the Time and Events Table (Section 7.1).  In addition, central 
lab results and safety parameters from the Week 104a visit must be available and 
reviewed before the Week 104b visit.  If a clinical chemistry retest is required based on 
Week 104a labs, the retest should be performed as soon as possible (and preferably no 
later than 7 days following Week 104a).  Participants will remain on oral CAB 30 mg + 
RPV 25 mg until the Week 104b injection visit, and until any required Visit 104a retest 
results are available for review. 
Revised Text: 
Participants randomized to continue ABC/DTG/3TC will have the option to either 
continue study participation by switching to CAB LA + RPV LA in the Extension Phase, 
or to complete their study participation at Week 100 (no withdrawal visit needed).  The 
transition from ABC/DTG/3TC to CAB LA + RPV LA within the Extension Phase 
can be completed with or without an oral lead-in prior to commencement of 
injectable treatment.  The participant’s decision will be taken in consultation with 
the investigator and must be appropriately documented.  As participants approach 
the Week 100 visit, sites must ensure sufficient CAB and RPV supply are available 
to support the participant’s decision for transition to LA. 
Participants Transitioning Direct to Injection in the Extension Phase:   
Central lab results and safety parameters from the Week 96 visit must be available 
and reviewed for participants who choose to transition directly to injections.  
Participants with ongoing safety issues or laboratory abnormalities of clinical 
concern (e.g. Grade 3 or Grade 4 liver chemistry elevations) will require 
consultation and agreement with the Medical Monitor prior to proceeding directly 
to injections in the Extension Phase. 
If a clinical chemistry retest is required based on Week 96 labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
360 
 
Week 96).  Participants will remain on oral ABC/DTG/3TC until the Week 100 
injection visit, and until any required Week 96 retest results are available for 
review. 
At Week 100, eligible participants will take the last dose of ABC/DTG/3TC (or DTG 
+ 2 NRTIs), and receive the first injections of CAB LA (600 mg) + RPV LA (900 mg) 
as initial loading doses.  Clinical chemistries will also be assessed at Week 100.  At 
Week 101, participants will return to the clinic for PK and safety assessments 
including clinical chemistries.  The second and third injections (CAB LA 400 mg + 
RPV LA 600 mg) will be administered at Week 104a and Week 108.  There will be a 
one week dosing window for the second and third IM injections such that the second 
injections occur within the window of Week 103 to Week 104a, but not later than 
Week 104a, and the third injections occur within the window of Week 107 to Week 
108, but no later than Week 108.  Subsequent injections (CAB LA 400 mg + RPV 
LA 600 mg) will occur every 4 weeks thereafter, from the projected visit date, with a 
(+ or -) 7 day dosing window being allowed (but not preferred).  Following the Week 
108 injection, the interval between injection visits should be limited to a maximum 
of 5 weeks.  The Medical Monitor must be contacted if the length of time between 
injections exceeds, or is projected to exceed, 5 weeks. 
Participants Receiving Optional Oral Lead-In in the Extension Phase: 
As participants approach the Week 100 visit, sites must ensure sufficient oral CAB 
and RPV are available for participants who choose to use the oral lead-in. 
At Week 100, eligible participants who after discussion with the investigator, choose 
to receive the optional oral lead-in will initiate a 4 week lead-in of oral CAB 30 mg + 
oral RPV 25 mg once daily.  It is not necessary to dose ABC/DTG/3TC on the day the 
participant begins the oral lead-in with CAB + RPV.  However, if the participant 
takes ABC/DTG/3TC prior to coming into the clinic, initiation of oral CAB and 
RPV should continue as planned. 
Section 4.5.1.  Dose Justification, Oral Lead-In Phase: 
Rationale for change:  to discuss ART coverage for participants who choose no oral 
CAB + RPV lead-in when transitioning from ABC/DTG/3TC to LA.  
New Text Added: 
The oral lead-in for participants randomized to the ABC/DTG/3TC arm who choose 
to receive CAB LA + RPV LA during the Extension Phase of the study is optional.  
Without oral lead-in dosing, CAB LA and RPV LA achieve concentrations following 
their initial injections similar to induction doses of their respective efficacious oral 
products.  Oral ABC/DTG/3TC administered up to and including the day of the 
initial CAB LA + RPV LA injections will provide additional exposure to active 
antiviral agents during the transition from oral to LA treatment (e.g., exposure that 
would replace oral CAB + RPV exposure). 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
361 
 
Section 4.6.1. Risk Assessment Oral CAB and CAB LA (GSK1265744/ GSK1265744 LA): 
Rationale for change:  to update information relating to no oral lead-in.  
Original Text: 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Drug Induced Liver 
Injury 
A small proportion of participants in the CAB 
program to date (total exposure approximately 1198 
to 01 April 2016) have developed transaminitis 
(elevated liver transaminases characterised by 
predominant ALT elevation).  In some of these 
participants’ transient transaminitis were explained 
by acute hepatitis C infection and whilst a small 
number of others did not have alternative 
explanations, suggesting a mild form of DILI 
without hepatic dysfunction which resolved upon 
withdrawal of treatment with CAB.  
Of the five participants with possible or probable 
cases of DILI identified in Phase 2 studies, four 
participants were receiving oral CAB and one 
participant developed probable DILI following CAB 
LA or Placebo LA administration.   
• Exclusion criteria as described in Section 5.2will 
prohibit participants with significant liver 
impairment based on screening liver chemistry 
including transaminases (ALT and AST) as well on 
prior medical history.  Participants with a history 
of chronic liver disease with ongoing inflammation 
and/or fibrosis will have additional confirmatory 
assessments to confirm suitability for entry into the 
study.  
• A 4-week oral lead-in period is being implemented 
in this study, where all participants will receive 
oral CAB prior to the administration of CAB LA to 
determine individual safety and tolerability 
• Liver transaminases (ALT and AST) will be 
closely monitored throughout this study (refer to 
Time & Events Table) and the liver chemistry 
stopping criteria will be adopted as described in 
Section 5.4.1 of this protocol. Participants will be 
withdrawn from CAB treatment where no 
compelling alternative cause is identified and DILI 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
362 
 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
is suspected 
• Participants who develop ALT ≥3 times ULN 
while on study must consult with Medical Monitor 
prior to initiation or continuation of CAB LA.   
• All instances of liver transaminase elevations of 
Grade 2 and above will be followed to resolution.  
Participants withdrawn from CAB treatment due to 
meeting liver chemistry stopping criteria will be 
regularly monitored and both clinically and using 
liver chemistries to determine progress towards 
resolution of the liver event. 
Injection Site 
Reactions (ISRs) 
 
Clinical, experience to date has demonstrated ISRs 
occur in the majority of exposed participants treated 
with CAB LA but are generally mild (Grade 1) or 
moderate (Grade 2) and include events of pain, 
tenderness, erythema, or nodule formation of several 
days duration (median duration for individual events 
<1 week).  ISRs may occur more than once in an 
individual participant receiving multiple injections. 
Although some Grade 3 ISRs were reported, overall 
ISRs have been well tolerated and have not to date 
been associated with an excess of participants’ 
withdrawal. 
None of the ISRs reported to date was serious and 
• Administration advice to minimize risk of poor 
administration technique giving rise to injection 
site reactions.  Advice on care, monitoring, natural 
course, and treatment of ISRs given in study 
documentation  
• Advice will be given to participants on care of 
injection site on day/days immediately post 
administration, use of analgesia, compresses where 
appropriate. 
• Participants will be closely monitored for ISRs 
particularly for signs of pain, tenderness, 
infections, erythema, swelling, induration, or 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
363 
 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
no clinically significant complications were 
reported. 
nodules (granulomas or cysts) throughout the 
study.   
• Complications of ISRs such as infections (abscess, 
cellulitis) and collections of fluid requiring 
drainage will be monitored. 
• Specialist dermatology consultation will be sought 
if warranted for individual participants. 
Hypersensitivity 
Reactions (HSR) 
 
Hypersensitivity reactions have been reported as 
uncommon occurrences with integrase inhibitors, 
including the closely related compound dolutegravir, 
and were characterized by rash, constitutional 
findings, and sometimes, organ dysfunction, 
including liver injury.  
While there have been no clinical cases of 
hypersensitivity to CAB, there is a theoretical risk of 
systemic or severe hypersensitivity reactions with or 
without hepatic symptoms associated with use of 
CAB LA.  The long exposures anticipated after 
CAB LA injection may complicate the management 
of a drug hypersensitivity reaction, were it to occur. 
 
• The risk of developing a hypersensitivity reaction 
post administration of CAB LA will be minimized 
by the use of a 4-week oral lead-in of CAB to 
determine individual safety and tolerability prior to 
the introduction of CAB LA.  
• Clinical assessments, laboratory tests (including 
liver transaminases) and vital signs will be 
performed throughout this study (refer to Time & 
Events Table).  Results from these assessments 
may aid early detection of HSR. 
• Oral CAB will be withdrawn immediately for cases 
with suspected HSR during the oral lead-in phase.  
During oral and CAB LA treatment, any HSR 
reactions that occur would be managed 
supportively 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
364 
 
Revised Text: 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Drug Induced Liver 
Injury 
A small proportion of participants in the CAB 
program to date (total exposure >3100 
participants) have developed transaminitis 
(elevated liver transaminases characterised by 
predominant ALT elevation).  In some of these 
participants’ transient transaminitis were explained 
by acute hepatitis C infection and whilst a small 
number of others did not have alternative 
explanations, suggesting a mild form of DILI 
without hepatic dysfunction which resolved upon 
withdrawal of treatment with CAB.  
Of the four participants with possible or probable 
cases of DILI identified in Phase 2 studies, all were 
receiving oral CAB.  
• Exclusion criteria as described in Section 5.2will 
prohibit participants with significant liver 
impairment based on screening liver chemistry 
including transaminases (ALT and AST) as well on 
prior medical history.  Participants with a history of 
chronic liver disease with ongoing inflammation 
and/or fibrosis will have additional confirmatory 
assessments to confirm suitability for entry into the 
study.  
• A 4-week oral lead-in period was implemented at 
the beginning of this study, where all participants 
will receive oral CAB prior to the administration of 
CAB LA to determine individual safety and 
tolerability.  During the Extension Phase of the 
study, following review of available oral lead-in 
and Maintenance Phase safety data, the protocol 
was amended to allow an optional oral lead-in 
for the participants transitioning from 
ABC/DTG/3TC to CAB LA+RPV LA. 
• Liver transaminases (ALT and AST) will be closely 
monitored throughout this study (refer to Time & 
Events Table) and the liver chemistry stopping 
criteria will be adopted as described in Section 
5.4.1 of this protocol. Participants will be 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
365 
 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
withdrawn from CAB treatment where no 
compelling alternative cause is identified and DILI 
is suspected. 
• Participants who develop ALT ≥3 times ULN while 
on study must consult with Medical Monitor prior 
to initiation or continuation of CAB LA.   
• All instances of liver transaminase elevations of 
Grade 2 and above will be followed to resolution.  
Participants withdrawn from CAB treatment due to 
meeting liver chemistry stopping criteria will be 
regularly monitored both clinically and using liver 
chemistries to determine progress towards 
resolution of the liver event. 
Injection Site 
Reactions (ISRs) 
 
Clinical, experience to date has demonstrated ISRs 
occur in the majority of exposed participants treated 
with CAB LA but are generally mild (Grade 1) or 
moderate (Grade 2) and include events of pain, 
tenderness, erythema, or nodule formation of 
several days duration (median duration for 
individual events <1 week).  ISRs may occur more 
than once in an individual participant receiving 
multiple injections. Although some Grade 3 ISRs 
were reported, the majority of ISRs have not, to 
date, been associated with an excess of participants’ 
• Administration advice to minimize risk of poor 
administration technique giving rise to injection 
site reactions.  Advice on care, monitoring, natural 
course, and treatment of ISRs given in study 
documentation  
• Advice will be given to participants on care of 
injection site on day/days immediately post 
administration, use of analgesia, compresses where 
appropriate. 
• Participants will be closely monitored for ISRs 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
366 
 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
withdrawal. 
None of the ISRs reported to date was serious and 
no clinically significant complications were 
reported. 
particularly for signs of pain, tenderness, infections, 
erythema, swelling, induration, or nodules 
(granulomas or cysts) throughout the study.   
• Complications of ISRs such as infections (abscess, 
cellulitis) and collections of fluid requiring 
drainage will be monitored. 
• Specialist dermatology consultation will be sought 
if warranted for individual participants. 
Hypersensitivity 
Reactions (HSR) 
 
Hypersensitivity reactions have been reported as 
uncommon occurrences with integrase inhibitors, 
including the closely related compound 
dolutegravir, and were characterized by rash, 
constitutional findings, and sometimes, organ 
dysfunction, including liver injury.  
While there have been no clinical cases of 
hypersensitivity to CAB, there is a theoretical risk 
of systemic or severe hypersensitivity reactions with 
or without hepatic symptoms associated with use of 
CAB LA.  The long exposures anticipated after 
CAB LA injection may complicate the management 
of a drug hypersensitivity reaction, were it to occur. 
 
• The risk of developing a hypersensitivity reaction 
post administration of CAB LA was minimized at 
the start of the study by the use of a mandatory 
4-week oral lead-in of CAB to determine individual 
safety and tolerability prior to the introduction of 
CAB LA.  During the Extension Phase of the 
study, following review of available oral lead-in 
and Maintenance Phase safety data, the protocol 
was amended to allow an optional oral lead-in 
for the participants transitioning from 
ABC/DTG/3TC to CAB LA+RPV LA. 
• Clinical assessments, laboratory tests (including 
liver transaminases) and vital signs will be 
performed throughout this study (refer to Time & 
Events Table).  Results from these assessments 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
367 
 
Potential Risk of 
Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
may aid early detection of HSR. 
• Oral CAB will be withdrawn immediately for cases 
with suspected HSR during the oral lead-in phase.  
During oral and CAB LA treatment, any HSR 
reactions that occur would be managed 
supportively 
 
Section 4.6.1. Risk Assessment Oral RPV and RPV LA: 
Rationale for change:  to update information relating to no oral lead-in.  
Original Text: 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Injection Site Reactions 
Clinical, experience to date has 
demonstrated ISRs occur in the majority of 
exposed participants treated with RPV LA 
but are generally mild (Grade 1) or 
moderate (Grade 2) and include events of 
pain, tenderness, erythema, or nodule 
formation of several days duration (median 
duration for individual events <1 week).  
ISRs may occur more than once in an 
individual participant receiving multiple 
injections. Although some Grade 3 ISRs 
were reported, overall ISRs have been well 
• Administration advice to minimize 
risk of poor administration 
technique giving rise to injection 
site reactions.  Advice on care, 
monitoring, natural course, and 
treatment of ISRs given in study 
documentation. 
• Advice to participants on care of 
injection site on day/days 
immediately post administration, 
use of analgesia, compresses where 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
368 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
tolerated and have not to date been 
associated with an excess of participants’ 
withdrawal due to ISRs. 
None of the ISRs was serious and no 
clinical significant complications were 
reported. 
 
appropriate. 
• Participants will be closely 
monitored for ISRs particularly for 
signs of pain, tenderness, infections, 
erythema, swelling, induration, or 
nodules (granulomas or cysts) 
throughout the study.   
• Complications of ISRs such as 
infections (abscess, cellulitis) and 
collections of fluid requiring 
drainage will be monitored. 
• Specialist dermatology consultation 
will be sought if warranted for 
individual participants. 
Rash 
 
Some observations of rash with oral RPV 
have been reported in clinical studies 
executed to date (the majority are Grade 1 
or Grade 2).  
Severe skin and hypersensitivity reactions 
have been reported during the 
postmarketing experience, including cases 
of Drug Reaction with Eosinophilia and 
Systemic Symptoms (DRESS), with oral 
RPV containing regimens.  While some 
skin reactions were accompanied by 
• In this study, RPV LA 
administration will be preceded by a 
four week oral RPV lead-in to 
evaluate safety and tolerability in 
individual participants. 
• Participants with a Grade 1 or 2 rash 
will be allowed to continue 
treatment or to be rechallenged, 
depending on the clinical judgment 
of the investigator. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
369 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
constitutional symptoms such as fever, 
other skin reactions were associated with 
organ dysfunctions, including elevations in 
hepatic serum biochemistries. 
 
• Participants experiencing a grade 3 
or 4 rash should discontinue their 
ART medication and will be 
withdrawn from the study. 
• All rash events should be assessed 
with special attention to systemic 
symptoms, laboratory 
abnormalities, or mucosal 
involvement.  Close clinical follow-
up, including follow-up of 
laboratory abnormalities, and 
appropriate medical intervention, 
including referral to dermatologist 
as appropriate, should be instituted 
for these events; daily follow-up is 
recommended for 5 days from the 
onset of the event to monitor for 
progression of the event. 
 
Revised Text: 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Injection Site Reactions 
Clinical, experience to date has 
demonstrated ISRs occur in the majority of 
exposed participants treated with RPV LA 
but are generally mild (Grade 1) or 
moderate (Grade 2) and include events of 
• Administration advice to minimize 
risk of poor administration 
technique giving rise to injection 
site reactions.  Advice on care, 
monitoring, natural course, and 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
370 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
pain, tenderness, erythema, or nodule 
formation of several days duration (median 
duration for individual events <1 week).  
ISRs may occur more than once in an 
individual participant receiving multiple 
injections. Although some Grade 3 ISRs 
were reported, the majority of ISRs have 
not, to date, been associated with an excess 
of participants’ withdrawal due to ISRs. 
 
 
treatment of ISRs given in study 
documentation. 
• Advice to participants on care of 
injection site on day/days 
immediately post administration, 
use of analgesia, compresses where 
appropriate. 
• Participants will be closely 
monitored for ISRs particularly for 
signs of pain, tenderness, infections, 
erythema, swelling, induration, or 
nodules (granulomas or cysts) 
throughout the study.   
• Complications of ISRs such as 
infections (abscess, cellulitis) and 
collections of fluid requiring 
drainage will be monitored. 
• Specialist dermatology consultation 
will be sought if warranted for 
individual participants. 
Rash 
 
Some observations of rash with oral RPV 
have been reported in clinical studies 
executed to date (the majority are Grade 1 
or Grade 2).  
• At the beginning of this study, 
RPV LA administration was 
preceded by a four week oral RPV 
lead-in to evaluate safety and 
tolerability in individual 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
371 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Severe skin and hypersensitivity reactions 
have been reported during the 
postmarketing experience, including cases 
of Drug Reaction with Eosinophilia and 
Systemic Symptoms (DRESS), with oral 
RPV containing regimens.  While some 
skin reactions were accompanied by 
constitutional symptoms such as fever, 
other skin reactions were associated with 
organ dysfunctions, including elevations in 
hepatic serum biochemistries. 
 
participants.  During the Extension 
Phase of the study, following 
review of available oral lead-in 
and Maintenance Phase safety 
data, the protocol was amended to 
allow an optional oral lead-in for 
the participants transitioning 
from ABC/DTG/3TC to CAB 
LA+RPV LA. 
• Participants with a Grade 1 or 2 rash 
will be allowed to continue 
treatment or to be rechallenged, 
depending on the clinical judgment 
of the investigator. 
• Participants experiencing a grade 3 
or 4 rash should discontinue their 
ART medication and will be 
withdrawn from the study. 
• All rash events should be assessed 
with special attention to systemic 
symptoms, laboratory abnormalities, 
or mucosal involvement.  Close 
clinical follow-up, including follow-
up of laboratory abnormalities, and 
appropriate medical intervention, 
including referral to dermatologist 
as appropriate, should be instituted 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
372 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
for these events; daily follow-up is 
recommended for 5 days from the 
onset of the event to monitor for 
progression of the event. 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 373 - 
 
Section 5.  Selection of Study Population and Withdrawal Criteria 
Rationale for change:  Similar text duplicated in Section 5.1. and Section 5.2.  
Text Deleted: 
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
participant safety.  Therefore, adherence to the criteria as specified in the protocol is 
essential. 
Section 6.3. Dose and Administration 
Rationale for change:  Table revised to explain direct to inject dosing option during the 
Extension Phase. 
Original Text: 
Extension Phase (Week 100 through End of Study)  
CAB LA + RPV LA Arm – continue IM dosing Every 4 Weeks+ 
ABC/DTG/3TC Arm (Transition to CAB LA + RPV LA)* 
Oral Lead-In 
Week 100 to Week 104a 
(2 tablets once daily) 
Take 1 tablet CAB 30 mg once daily. 
Take 1 tablet RPV 25 mg once daily. 
 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injection (Loading Dose) – Week104b^ 
Week 104b^ 
(two 3 mL injections once) 
Receive last dose of oral CAB + RPV 
 
Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
Receive RPV LA 900 mg given as 1 X 3 mL IM injection  
Maintenance Injections – Every 4 Weeks following Week 104b 
Week 108 forward 
(two 2 mL injections every 4 
weeks) 
Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
 
Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
 
Revised Text: 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 374 - 
 
Extension Phase (Week 100 through End of Study)  
CAB LA + RPV LA Arm – continue IM dosing Every 4 Weeks+ 
ABC/DTG/3TC Arm (Transition to CAB LA + RPV LA)* - Optional Oral Lead-In 
Dosing If Using Optional Oral Lead-In 
Week 100 to Week 104b 
(2 tablets once daily) 
Take 1 tablet CAB 30 mg once daily. 
Take 1 tablet RPV 25 mg once daily. 
 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injection (Loading Dose) – Week104b^ - Optional Oral Lead-In 
Week 104b^ 
(two 3 mL injections once) 
Receive last dose of oral CAB + RPV 
 
Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
Receive RPV LA 900 mg given as 1 X 3 mL IM injection  
Maintenance Injections – Every 4 Weeks following Week 104b – Optional Oral Lead-In 
Week 108 forward 
(two 2 mL injections every 4 
weeks) 
Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
 
Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
ABC/DTG/3TC Arm (Transition to CAB LA + RPV LA)* 
Direct to Inject Dosing - if Not Using Oral Lead-In 
First Injection (Loading Dose) – Week100^ - No Oral Lead-In 
Week 100^ 
(two 3 mL injections once) 
Receive last dose of oral ABC/DTG/3TC 
Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
Receive RPV LA 900 mg given as 1 X 3 mL IM injection 
Maintenance Injections – Every 4 Weeks following Week 100 – No Oral Lead-In 
Week 104a forward 
(two 2 mL injections every 
4 weeks) 
Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
 
Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 375 - 
 
Section 6.9.1. IM Dosing 
Rationale for change:  Text moved to before Extension Phase dosing transition for 
participants beginning LA dosing in the Extension Phase  
Rearranged text within Section 6.9.1. and addition of Week 101 to one week post dose 
visits: 
At one-week post dose visits (Week 5, Week 41, and Week 101), there is no defined 
visit window, rather visits should occur approximately one week from the last injection. 
• Dosing may occur without consultation from the Medical Monitor if performed 
within the (+ or -) 7 day window.   
• Any request for the visit/dosing to occur outside of the allowed window must be 
discussed and agreed with the Medical Monitor prior to dosing.  In the event of a 
late dose, a revised dosing schedule for subsequent dosing may be required and 
will be communicated to the site staff at the time of approval for continued 
dosing.  Temporary switch to oral dosing of CAB and/or RPV may be an option 
based on individual participant circumstance as described in Section 6.8.   
• See the SPM for scheduling guidance and further information and examples. 
Note: All decisions regarding dose interruption/ resumption must be discussed with 
the Medical Monitor in advance. 
Section 6.9.1. IM Dosing 
Rationale for change:  To explain dosing transition into the Extension Phase using 
optional oral lead-in. 
Original Text: 
Participants who were randomized to the ABC/DTG/3TC arm and are eligible to enter 
the Extension Phase will begin a 4 week lead-in of oral CAB 30 mg + oral RPV 25 mg 
once daily at Week 100.   
New Text Added: 
Transition from ABC/DTG/3TC to IM Dosing into the Extension Phase: 
Participants who were randomized to ABC/DTG/3TC and are eligible to enter the 
Extension Phase will transition to IM dosing at, or after, Week 100.  The transition 
from ABC/DTG/3TC to CAB LA + RPV LA can be completed with or without an 
oral lead-in prior to commencement of injectable treatment.  The participant 
decision will be taken in consultation with the investigator and appropriately 
documented.  In order to ensure no interruption in study treatment, the transition 
into Extension should be performed as follows: 
Participants Transitioning Directly to Injections in the Extension Phase:   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 376 - 
 
Central lab results and safety parameters from the Week 96 visit must be available 
and reviewed for participants who choose to transition direct to injection.  If a 
clinical chemistry retest is required based on Week 96 labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following 
Week 96).  Participants will remain on oral ABC/DTG/3TC until the Week 100 
injection visit, and until any required Week 96 retest results are available for 
review. 
At Week 100, eligible participants will take the last dose of ABC/DTG/3TC (or DTG 
+ 2 NRTIs), and receive the first injections of CAB LA (600 mg) + RPV LA (900 mg) 
as initial loading doses.  Clinical chemistries will also be assessed at Week 100.  At 
Week 101, participants will return to the clinic for PK and safety assessments 
including clinical chemistries.  The second and third injections (CAB LA 400 mg + 
RPV LA 600 mg) will be administered at Week 104a and Week 108.  There will be a 
one week dosing window for the second and third IM injections such that the second 
injections occur within the window of Week 103 to Week 104a, but not later than 
Week 104a, and the third injections occur within the window of Week 107 to Week 
108, but no later than Week 108.  Subsequent injections (CAB LA 400 mg + RPV 
LA 600 mg) will occur every 4 weeks thereafter, from the projected visit date, with a 
(+ or -) 7 day dosing window being allowed (but not preferred).  Following the Week 
108 injection, the interval between injection visits should be limited to a maximum 
of 5 weeks.  The Medical Monitor must be contacted if the length of time between 
injections exceeds, or is projected to exceed, 5 weeks. 
Participants Receiving Optional Oral Lead-In in the Extension Phase: 
At Week 100, eligible participants who after discussion with the investigator, choose 
to receive the optional oral lead-in will begin a 4 week lead-in of oral CAB 30 mg + 
oral RPV 25 mg once daily.  It is not necessary to dose ABC/DTG/3TC on the day 
the participant begins the oral lead-in with CAB + RPV.  However, if the 
participant takes ABC/DTG/3TC prior to coming into the clinic, initiation of oral 
CAB and RPV should continue as planned. 
Section 7.1. Time and Events Table: 
Rationale for change:  Updated to reflect changes for transition into the Extension Phase 
based on Oral Lead-In Design. 
Original Text: 
Participants originally randomized to ABC/DTG/3TC at Day 1, who choose to continue 
into the Extension Phase and transition to CAB LA + RPV LA, will have all assessments 
noted in the Time and Events table below performed Q4W from Week 108 through 
Week 124.   
Revised Text: 
Participants originally randomized to ABC/DTG/3TC at Day 1, who choose to continue 
into the Extension Phase and transition to CAB LA + RPV LA, will have all assessments 
noted in the Time and Events table below performed Q4W through Week 124.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 377 - 
 
Section 7.1. Time and Events Table: 
Rationale for change:  Updated to reflect changes for transition into the Extension Phase 
based on Oral Lead-In Design. 
Changes made to Table: New columns added to describe assessments for Direct to 
Inject Arm (changes to table noted in teal) 
 
 
 
Symptom Directed 
Physical Exam 
and Medical 
Assessment d
X
X
X
X
X
X
HIV Associated 
Conditions
X
X
X
X
X
X
AE and SAE 
Assessment, Con 
Meds
X
X
X
X
X
X
Clinical Chemistry
Pregnancy 
Testingj
UjS
S
S
U
S
HIV-1 RNA and 
sample for 
storagek 
Sk 
X
X
X
PK Sample
IM Study 
Treatment 
Administration – 
Q4W throughout 
Maintenance and 
Extension Phase
X
X
X
Xs
X
Procedures
Maintenance 
Phase by Week
Extension Phase
by Week
104b – Oral 
Lead-InSwitch 
Arm
108
100
101 – Direct to 
Inject Arm
104a – Direct to 
Inject Arm
104a LA and 
Oral Lead-In 
Arm
ISR Assessment 
(LA Arm Only)
X
X
X
X
X
X
X
X
X
X
Xv w
S
X
Xv
Xv


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 378 - 
 
Also clarified Oral Lead-In Dispensing and Accountability for participants using 
optional oral lead-in only. 
 
 
 
 
 
 
 
Table Footer and Footnotes Amended (only edited footnotes included below): 
Note: Footnote i clarifies differences in eCSSRs for participants receiving 
ABC/DTG/3TC after Week 48 (based on every 8 week visits compared to continued 
Q4W visits for participants on LA). 
 
i.  On Day 1, the eC-SSRS is to be administered prior to randomization.  During the 
Maintenance Phase, the eC-SSRS will be administered at each Q4W visit through the 
Week 48 primary endpoint, and then followed by Q12W assessments for CAB LA + 
RPV LA arm, thereafter through Week 96 (LA:  Week 60, 72, 84, 96).  The 
ABC/DTG/3TC arm will have assessments at Week 72 and Week 96.  Preferably 
completed at the beginning of the visit following administration of other patient reported 
questionnaires required prior to injections 
 
v.  Take PK samples pre-dose.  At Week 4b (and Week 104b for participants 
transitioning to LA from ABC/DTG/3TC using the optional oral lead-in), the pre-dose 
PK sample should be taken after review of the PK diary and prior to the final oral CAB + 
RPV dose.  A sample will be also be taken at Week 4b, Week 48, and Week 96 (and 
Week 100 [direct to inject] or Week 104b [using CAB + RPV oral lead-in]), 
approximately 2 hours post-injections.  The Week 5, Week 41, and Week 101 visit can 
be performed at any time from 3 to 10 days after the Week 4b, Week 40, and Week 100 
Procedures 
Week 100 
Week 104a 
Week 104b 
Oral CAB and 
Oral RPV 
Dispensation  
Xx 
OLI Only 
Xx 
OLI Only 
 
ABC/DTG/3TC 
Dispensation (or 
DTG alternate) 
 
 
 
Study Treatment 
Accountability  
(pill counts) 
X 
OLI Only 
X 
OLI Only 
Xu 
OLI Only 
Follow Up Visit:  Conduct ~4 weeks after the last dose of oral IP.  Required only if the participant has ongoing AEs / 
lab abnormalities at the last on-study visit.  This visit may be conducted by telephone. 
Direct to Inject:  Participants transitioning into the Extension Phase who do not use the optional CAB + RPV 
oral lead-in beginning at Week 100. 
Oral Lead-In:  Participants transitioning into the Extension Phase who do use the optional CAB + RPV oral 
lead-in beginning at Week 100. 
LA Arm:  Participants who were originally randomized to CAB LA + RPV LA at Day 1. 
Switch Arm:  All participants who transition into the Extension Phase from ABC/DTG/3TC (or DTG + 2 
NRTI’s) at Week 100 – e.g., both direct to inject and oral lead-in participants. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 379 - 
 
injection, respectively. PK samples at Week 5, Week 41, and Week 101 can be taken at 
any time during the visit. 
w.  Participants should take the last dose of oral CAB+RPV at Week 4b (and Week 104b 
for participants transitioning to LA from ABC/DTG/3TC if using the optional oral lead-
in) in the clinic after PK sampling.  Participants should take the last dose of 
ABC/DTG/3TC at Week 100 if transitioning directly to injections at Week 100.  
Injections should be administered within 2 hours of the last oral dose where possible. 
Section 7.4.3.1. Adverse Events and Serious Adverse Events (SAEs) 
Rationale for change:  Bullet removed as all AEs will be collected during Extension and 
Long-Term Follow-Up Phase (not just AEs leading to Withdrawal): 
Deleted Text: 
• 
During the Extension Phase and Long-Term Follow-Up Phase, AEs leading to 
Withdrawal and all SAEs will be recorded. 
Section 7.4.3.4. Prompt Reporting of Serious Adverse Events and Other Events 
Rationale for change:  clarification that ABC HSR will be collected for participants 
receiving ABC in the Long-Term Follow-Up Phase. 
Original Text: 
Suspected ABC HSR 
in participants 
randomized to the STR 
arm  
1 week 
ABC HSR eCRF 
1 week 
Updated ABC HSR 
eCRF 
 
Revised Text: 
Suspected ABC HSR 
in participants 
randomized to the STR 
arm or receiving an 
oral ABC-containing 
regimen during the 
Long-Term Follow-
Up Phasea 
1 week 
ABC HSR eCRF 
1 week 
Updated ABC HSR 
eCRF 
Section 7.4.7.1. Pregnancy Testing 
Rationale for change: Clarification added for negative pregnancy test at Week 100 if 
particpants choose no oral CAB + RPV lead-in.  
Original Text: 
Women of childbearing potential must have a negative pregnancy test at Screening, 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 380 - 
 
Baseline (Week [-20]), the first Induction Phase visit (Day 1), and Week 104b for women 
transitioning into the Extension Phase from the ABC/DTG/3TC arm (prior to 
administration of first CAB LA and / or RPV LA injections).   
Revised Text: 
Women of childbearing potential must have a negative pregnancy test at Screening, 
Baseline (Week [-20]), the first Induction Phase visit (Day 1), and Week 100 (if no oral 
lead-in is used) or Week 104b (if using CAB and RPV oral lead-in) for women 
transitioning into the Extension Phase from the ABC/DTG/3TC arm (prior to 
administration of first CAB LA and / or RPV LA injections).   
Section 7.5.1. PK Sample Collection 
Rationale for change:  Clarification of text for optional oral lead-in. 
Original Text: 
At Week 4b (and Week 104b for participants transitioning into the Extension Phase from 
the ABC/DTG/3TC arm), PK samples must be collected within the window of 20 to 28 
hours after the oral dose of CAB + RPV was taken the day prior to the clinic visit.   
Revised Text: 
At Week 4b (and Week 104b for participants using the oral CAB + RPV lead-in and 
transitioning into the Extension Phase from the ABC/DTG/3TC arm), PK samples must 
be collected within the window of 20 to 28 hours after the oral dose of CAB + RPV was 
taken the day prior to the clinic visit.   
Section 7.5.1. PK Sample Collection 
Rationale for change:  Updated sampling schedule based on optional oral CAB + 
RPV lead-in during the Extension Phase. 
Original Text (Table 8): 
ABC/DTG/3TC 
Arm Transitioning 
to CAB LA + RPV 
LA at Week 100 
CAB 
Pre-Dose:  Week 104b, Week 108, Withdrawal 
2 Hours Post Dose:  Week 104b 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
RPV 
Pre-Dose:  Week 104b, Week 108, Withdrawal 
2 Hours Post Dose:  Week 104b 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
1. 
PK visit window and sample collection: Pre-dose visits (from projected visit date): ±3 days (1st injection), 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 381 - 
 
minus 7 days (2nd and 3rd injection), and± 7 days (4th and all subsequent injections); Sample Collection:  Pre-
dose at Week 4b (and Week 104b for participants transitioning from ABC/DTG/3TC Arm):  20 to 28 hours after 
the last oral dose of CAB and RPV was taken; 2 hours post dose: ±one hour; one week post dose visits: 3 to 
10 days post injection. 
a. 
Each analyte in individual collection tube. 
b. 
Samples taken at Week 5, Week 41, may be collected from 3 to 10 days after Week 4b, Week 40, respectively.  
These samples may be collected at anytime during those visits.   
 
Revised Text: 
ABC/DTG/3TC Arm 
Transitioning to 
CAB LA + RPV LA 
at Week 100 
(participants 
using CAB + RPV 
oral lead-in) 
CAB 
Pre-Dose:  Week 104b, Week 108 (for storage), 
Withdrawal 
2 Hours Post Dose:  Week 104b 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
RPV 
Pre-Dose:  Week 104b, Week 108 (for storage), 
Withdrawal 
2 Hours Post Dose:  Week 104b 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
ABC/DTG/3TC 
Arm Transitioning 
to CAB LA + RPV 
LA at Week 100 
(Direct to Inject - 
participants not 
using CAB + RPV 
oral lead-in) 
CAB 
Pre-Dose:  Week 104a, Week 108 (for storage), 
Withdrawal 
2 Hours Post Dose:  Week 100 
1 Week Post Doseb:  Week 101 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
RPV 
Pre-Dose:  Week 104a, Week 108 (for storage), 
Withdrawal 
2 Hours Post Dose:  Week 100 
1 Week Post Doseb:  Week 101 
Long-term follow-up Period (off-drug; storage sample) 
Months 1, 3, 6, 9, and 12 
k. 
PK visit window and sample collection: Pre-dose visits (from projected visit date): ±3 days (1st injection), 
minus 7 days (2nd and 3rd injection), and± 7 days (4th and all subsequent injections); Sample Collection:  Pre-
dose at Week 4b (and Week 104b for participants transitioning from ABC/DTG/3TC Arm using oral lead-in):  
20 to 28 hours after the last oral dose of CAB and RPV was taken; 2 hours post dose: ±one hour; one week 
post dose visits: 3 to 10 days post injection. 
a. 
Each analyte in individual collection tube. 
b. 
Samples taken at Week 5, Week 41, and Week 101 may be collected from 3 to 10 days after Week 4b, 
Week 40, and Week 100, respectively.  These samples may be collected at anytime during those visits.   


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 382 - 
 
Section 9.2.4.  Sample Size Considerations for Week 124 Extension Switch Analysis 
– New Section 
Rationale for change:  Text added regarding sample size for endpoint for Extension 
Phase endpoint.  
New Text Added: 
For the Week 124 Extension Switch population analysis (Section 9.3.1.6), the primary 
efficacy endpoint of interest is the proportion of participants without oral lead-in who 
have HIV-1 RNA ≥50 c/mL at Week 124 (i.e., 24 weeks from initiation of CAB LA + 
RPV LA, ±6-week analysis window, using the FDA Snapshot algorithm).  The endpoint 
will be evaluated descriptively, with no formal statistical comparison to data generated in 
participants receiving oral lead-in by to initiation of CAB LA + RPV LA.  
Table 14 presents the precision in estimation according to sample size and observed 
proportion with HIV-1 RNA ≥ 50 c/mL.  For example, if the observed rate is 3% and 250 
Extension switch participants do not receive oral lead-in, then the upper bound of the 
95% CI would be 5.1%.    
Table 14 
Precision (Upper Limit of 95% CI) for Single Arm Proportion  
Sample Size  
without Oral Lead-In 
Observed Proportion 
HIV-1 RNA ≥ 50 c/mL 
Upper limit of 95% 
Confidence Interval† 
175 
2% 
4.1% 
200 
2% 
3.9% 
225 
2% 
3.8% 
250 
2% 
3.7% 
175 
3% 
5.5% 
200 
3% 
5.4% 
225 
3% 
5.2% 
250 
3% 
5.1% 
175 
4% 
6.9% 
200 
4% 
6.7% 
225 
4% 
6.6% 
250 
4% 
6.4% 
† Two-sided confidence Interval calculated using the Wald normal approximation method 
Section 9.3.1.6.  Extension Switch Population (ES) – New Section 
Rationale for change:  Explanation of population for participants switching from 
ABC/DTG/3TC to CAB LA + RPV LA in the Extension Phase. 
New Text Added: 
The Extension Switch population will include all participants randomized to the 
Maintenance Phase ABC/DTC/3TC arm who switch to and receive at least one dose 
of CAB and/or RPV during the Extension Phase of the study.  The ES population 
will be used to evaluate safety and efficacy of switching to CAB LA + RPV LA, with 
and without oral lead-in. Participants will be assessed according to actual treatment 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 383 - 
 
received during the Extension Phase. 
Section 9.3.3.  Planned Analyses 
Rationale for change:  To describe new Week 124 analysis for participants switching to 
LA during the Extension Phase. 
Original Text: 
At least two analyses will be conducted to evaluate primary and secondary objectives of 
the protocol, one after all subjects have completed their visit at Week 48 and one after 
Week 96.   
Revised Text: 
At least three analyses will be conducted to evaluate the objectives of the protocol: after 
all randomized participants have completed their visits at Week 48 and Week 96, 
respectively, and after all Extension switch participants (Section 9.3.1.6) have 
completed the Week 124 visit.   
Section 9.4.2.  Secondary Analyses 
Rationale for change:  Clarification of planned analyses. 
Original Text: 
Proportion of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL and 
confirmed virologic failure, respectively, over time will be summarized using the 
Snapshot algorithm.   
Revised Text: 
Proportion of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL, and HIV-
1 RNA ≥200 c/mL and ≥50 c/mL, respectively, over time will be summarized using the 
Snapshot algorithm.   
Section 9.4.2.1. Week 124 Extension Switch Analysis (New Section Added) 
Rational for change:  To describe new Week 124 planned analysis. 
New Text Added” 
Section 9.4.2.1.  Week 124 Extension Switch Analysis 
For the Week 124 Extension Switch population analysis (Section 9.3.1.6), antiviral 
response will be assessed according to the proportion of participants with and 
without oral lead-in, respectively, who have HIV-1 RNA ≥50 c/mL at Week 124 (i.e., 
24 weeks from initiation of CAB LA + RPV LA, ±6 week analysis window, using the 
FDA Snapshot algorithm), with corresponding 95% confidence interval.  The 
primary efficacy endpoint of interest for this analysis is the proportion of 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 384 - 
 
participants without oral lead-in who have HIV-1 RNA ≥50 c/mL at Week 124. No 
formal statistical comparison with respect to safety and efficacy outcomes will be 
performed. 
Proportion of participants with plasma HIV-1 RNA <200 c/mL and <50 c/mL and 
confirmed virologic failure, respectively, over time will be summarized. 
Absolute values and change from Extension Baseline CD4+ cell count will be 
summarized over time. 
The proportion of participants reporting AEs will be tabulated for each treatment 
group.  The following summaries of AEs will be provided: 
• Incidence and severity of all AEs 
• Incidence and severity of treatment related AEs 
• Incidence and severity of AEs leading to withdrawal 
• Incidence of SAEs 
Changes from Extension Baseline in laboratory (including fasting lipids) and vital 
signs data will be summarized.  In addition, the number and percentage of 
participants with Extension emergent graded laboratory toxicities (based on DAIDS 
categories) will be summarized by treatment group. 
Further details for secondary efficacy, safety and exploratory analyses will be 
included in the RAP.   
Section 12.7 Appendix 7:  Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential (FRP) and Collection of Pregnancy 
Information 
Rationale for change:  Text updated to be consistent with current template language.  
Original Text: 
Section 12.7.  Appendix 7:  Modified List of Highly Effective Methods for Avoiding 
Pregnancy in Females of Reproductive Potential (FRP) and Collection of Pregnancy 
Information  
The list does not apply to FRP with same sex partners or for participants who are and will 
continue to be abstinent from penile-vaginal intercourse on a long term and persistent 
basis, when this is their preferred and usual lifestyle.  Periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception. 
1. Contraceptive subdermal implantntrauterine device or intrauterine system 
2. Combined estrogen and progestogen oral contraceptive [Hatcher, 2011]) 
3. Injectable progestogen [Hatcher, 2011] 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 385 - 
 
4. Contraceptive vaginal ring [Hatcher, 2011] 
5. Percutaneous contraceptive patches [Hatcher, 2011] 
6. Male partner sterilization with documentation of azoospermia prior to the female 
participant's entry into the study, and this male is the sole partner for that 
participant [Hatcher, 2011].   
7. The documentation on male sterility can come from the site personnel’s: review of 
participant’s medical records, medical examination  and/or semen analysis, or 
medical history interview provided by her or her partner. 
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label.  The investigator is responsible for 
ensuring that participants understand how to properly use these methods of contraception. 
Revised Text: 
Section 12.7.  Appendix 7:  Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
a. Premenarchal 
b. Premenopausal female with ONE of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s: review of participant’s 
medical records, medical examination, or medical history interview. 
c. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-hormonal highly effective contraception methods if they wish 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 386 - 
 
to continue their HRT during the study. Otherwise, they must discontinue HRT 
to allow confirmation of postmenopausal status before study enrollment. 
Section 12.7.1.  Contraception Guidance 
Female participants of childbearing potential are eligible to participate if they agree to 
use a highly effective method of contraception consistently and correctly as described in 
Table 17.  
Table 17 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• oral 
• intravaginal  
• transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulationb  
• injectable  
Highly Effective Methods That Are User Independent  
• Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulationb 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.)  
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.)  
NOTES:  
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants in clinical 
studies.  
b. 
Two highly effective methods of contraception should be utilized from 30 days prior to the first dose of study 
medication, throughout the study, and for at least 52 weeks after discontinuation of CAB LA and RPV LA . 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 387 - 
 
Pregnancy Testing 
o WOCBP should only be included after a confirmed menstrual period and a 
negative highly sensitive serum pregnancy test.  
o Additional pregnancy testing should be performed as per the study Time and 
Events Table. 
o Pregnancy testing will be performed whenever a menstrual cycle is missed or 
when pregnancy is otherwise suspected.  
o Pregnancy testing will be performed and assayed in the central laboratory OR 
using the test kit provided by the central laboratory / provided by the sponsor / 
approved by the sponsor and in accordance with instructions provided in its 
package insert.  
12.14.5. 
Amendment 05 (All Countries) 
Protocol changes for Amendment 05 (20-MAY-2020), from Amendment 04 (24-SEP-
2018).   
12.14.5.1. 
Protocol Amendment Rationale 
The reason for protocol amendment 05 is to include an Appendix with Covid-19 
guidance for clinical trial continuity (participant and study management) during the 
pandemic.  This appendix will replace the previous Appendix 9, and Appendix 9 
“Protocol Amendment History,” will be included as Appendix 10.  
 
12.14.5.2. Protocol Changes/Clarifications 
Section 4.2.7., Section 6.6., Section 6.8., Section 6.8.1., Section 7.0., Section 7.4.3., 
Section 8.0. 
Rationale for change:  Addition of text cross referencing Covid-19 Appendix 9.  
New Text: 
Please refer to Appendix 9 in Section 12.9 for study management information 
during the COVID-19 pandemic. 
Section 12.9. Appendix 9:  COVID-19 Pandemic and Clinical Trial Continuity 
Rationale for change:  To ensure clinical trial continuity added as Appendix 9. 
New Text: 
Background 
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participants ability to attend clinic visits.  In some places, medical 
visits are occurring, and in others, research clinics are operating with only emergency 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 388 - 
 
staff. 
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in HIV-1 
treatment for participants enrolled in this clinical study, through continuous access to 
antiretroviral therapy. 
In order to maintain the scientific integrity of the study, and adhere to updated guidance 
from regulators, procedures have also been put into place to ensure that the actions taken 
to mitigate against any impact of COVID-19 are well documented in the trial database. 
A “Memo to Investigators” was issued on March 18th, 2020 and served as a record of 
approved emergency actions being taken within this clinical trial to manage issues related 
to COVID-19.  That memo continues to serve as record of approved actions which can be 
fully implemented by Investigators, in advance of this protocol guidance.  This appendix 
will remain consistent with the guidance provided within the “Memo to Investigators” 
and will also serve to provide additional protocol documentation requirements and 
procedures. 
This appendix outlines the measures which are approved for implementation within this 
clinical trial, to protect patient safety and to ensure the integrity of the clinical trial, as a 
result of COVID-19 only. These measures may be implemented in accordance with any 
requirements and expectations set out by local Independent Review Boards/Independent 
Ethics Committees and National Competent Authorities, as necessary. 
This appendix does not apply to participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19.  
12.9.1 Changes to Study Visits and Study Procedures 
• Where site staff resource is constrained due to COVID-19, IM dosing visits may 
proceed with limited or no other protocol-defined assessments (e.g. lab tests, 
questionnaires, etc.). If lab tests will be missed for more than one consecutive 
visit, the Medical Monitor must be contacted, to provide guidance for safety 
monitoring.  
• For WOCBP, point of care pregnancy testing should be performed, prior to IM 
dosing. 
• If central laboratory testing cannot be performed at a particular visit, and 
monitoring for safety is required, tests may be performed at an appropriately 
authorised/accredited local laboratory (or other relevant clinical facility), if this 
can be done within local restrictions on physical distancing. The site should 
proactively inform the Sponsor about such instances. Local laboratory results may 
be used to inform safety decisions. Results should be retained in source records. 
• When on-site visits are reduced, it is important that the investigator continue 
collecting relevant clinical information, including adverse events, from the 
participant through alternative means, e.g. by telephone contact. 
• There may be cases where the current principal investigator (PI) of a site is 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 389 - 
 
indisposed for a period and may need to delegate parts of his/her duties 
temporarily, e.g. to a sub-investigator. Any such changes should be documented 
in the site’s source records. Any permanent changes in PI should be 
communicated to the Sponsor. 
• There may also be circumstances where immediate actions are required by the 
Sponsor and/or investigator, outside of what is contemplated in the protocol, in 
order to protect a study participant from immediate hazard. Any such measures 
will be carefully documented and conducted in accordance with the National 
Competent Authority (NCA)/IRB/IEC regulations. 
 
12.9.2. Changes to Informed Consent 
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   
Any updated informed consent form or other subject-facing materials should be provided 
to participants by e-mail, mail or courier before re-consent is obtained. Any consent 
obtained this way should be documented in source records and confirmed by way of 
normal consent procedure at the earliest opportunity when participants attend their next 
on-site study visit. 
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval. 
 
12.9.3. Permissible Use of Antiretroviral Therapy 
In order to minimize the risk of gaps in HIV-1 antiretroviral therapy (ART) for 
participants impacted by COVID-19 in the clinical trial, the following options can be 
considered with regards to ART dosing, in order of preference: 
1. Where possible, and safe to do, please continue to prioritize IM dosing visits in 
order to keep the participants on the protocol-defined regimen. 
 
a. Qualified healthcare professionals (HCPs) trained on study procedures can 
administer IM injections outside of the study clinic setting (e.g. home, 
nursing facility, hospital), assuming this can be done safely, without 
compromising investigational product 
preparation/handling/storage/accountability requirements and done in 
accordance with local requirements. Please seek approval by the study 
team on a case-by-case basis. 
 
2. If a participant is not able to attend an IM injection visit due to COVID-19 related 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 390 - 
 
restrictions, the gap in IM dosing should be covered with oral ART, until IM 
dosing can resume. Participants should be reminded of the importance of adhering 
with daily oral dosing. Two options can be approved for oral bridging therapy in 
consultation with the Medical Monitor, listed in order of preference: 
 
a. Oral CAB + RPV  
i. Investigator should request availability of oral CAB + RPV supplies, 
prior to pursuing option b. 
b. Oral standard of care (SOC) commercial ART (prescribed locally); Note:  
For participants who are HLA-B*5701 negative, if the site has 
investigational product, ABC/DTG/3TC, remaining in study stock that is 
within expiry, this can also be used as the SOC bridging therapy. 
Oral bridging with CAB + RPV 
The protocol permits oral bridging to cover planned missed injections with oral CAB + 
RPV, only until IM dosing can be resumed. The start date of oral bridging should be 
within the dosing window for the missed IM dosing visit. This recommendation can be 
used to accommodate requests for oral dosing due to COVID-19. Oral bridging 
recommendations should be followed as per protocol Section 6.8.1. The process and 
required information for requesting oral bridging can be found in your Study 
Reference/Procedure Manual.  Please continue to reach out to your study Medical 
Monitor for approval of oral bridging, in order to document use and to ensure expeditious 
shipment of oral CAB + RPV to your site.  
Participants who use oral CAB + RPV as short-term oral bridging are permitted to return 
to IM dosing, on protocol, once the COVID-19 conditions permit resumption of site 
activities.  
The investigator should reach out to the Medical Monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with CAB/RPV is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the Medical Monitor to 
continue with oral bridging therapy. Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging. 
Oral bridging with Standard of Care Antiretroviral Therapy (SOC ART) 
For participants impacted by COVID-19, where the participant is unable to receive IM 
injections, and oral CAB + RPV is not available for use, oral bridging with any 
commercially available, guideline-recommended, SOC ART regimen is permitted. The 
start date of oral bridging should be within the dosing window for the missed IM dosing 
visit.  Please reach out to your study Medical Monitor for approval of SOC ART as oral 
bridging, in order to document the use of commercially available SOC ART within the 
study. 
Participants who use oral SOC ART as short-term oral bridging as a result of COVID-19 
will not be considered formally withdrawn insofar as they wish to continue on the study.  
Individuals who bridge with SOC ART will be permitted to return to IM dosing, on 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 391 - 
 
study, once the COVID-19 conditions permit resumption of site activities.   
The investigator should reach out to the Medical Monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with SOC ART is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the medical monitor to 
continue with oral bridging therapy.  Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging. 
12.9.4. Direct-To-Patient (DTP) Shipment of Oral Study IP 
If a participant is unable to travel to the clinic, either to receive IM injections or to be 
dispensed oral bridging, sites are encouraged to consider DTP shipments of drug, from 
the site, to the participant, to ensure access to medicines.  
• If the study site is considering DTP shipment of oral CAB + RPV investigational 
product (IP), the site must first verify if DTP IP dispensing by 
investigators/hospital pharmacies is locally permitted and whether it requires 
regulatory and/or local ethics pre-approval, or post-hoc notification. 
• The study participant should express his/her agreement for DTP shipment and the 
sharing of their personal information with any third-party couriers (as applicable), 
in accordance with local requirements.  This agreement should be documented in 
source records. 
• Oral CAB + RPV IP can be shipped at ambient temperatures via ground transport 
without a temperature monitoring device, with low risk of temperature excursions. 
Sites are encouraged to use discretion in determining the need for in-transit 
temperature monitoring based on the labelled storage requirements and the 
planned mode of transport and apply this as appropriate.  Shipment of oral CAB + 
RPV via air courier continues to require appropriate temperature monitoring.  For 
shipment conditions of oral medications other than oral CAB + RPV, please 
consult the product labelling. 
• In all cases IP accountability must be maintained, and all DTP dispensing 
documentation should be reflected in source records and dispensing logs per GCP. 
• Please refer to your CRA or local study manager for support with the DTP 
process, ensuring reference to current sponsor guidance and arrangement of a 
courier that can support shipment of IMP directly to participants. 
 
12.9.5. COVID-19 Experimental Agents 
If any treatments for COVID-19 are planned for a study participant, please consult with 
the study Medical Monitor to ensure that relevant drug interactions are considered and to 
ensure that continued study participation remains appropriate. 
12.9.6. COVID-19 Specific Data Capture 
12.9.6.1. 
Capturing COVID-19 Specific Protocol Deviations 
In order to summarise the impact of COVID-19 in a systematic way and in line with 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 392 - 
 
regulatory authorities’ recommendations, any study-level impact around COVID-19 will 
be documented as a protocol deviation. This will include the permissible actions 
summarized in this Appendix, which are taken to protect patient safety, including the use 
of CAB + RPV or SOC ART as oral bridging as well as missed visits and assessments as 
a result of logistical challenges resulting from COVID-19. 
Although the conduct of remote visits and the continuity of antiretroviral therapy, via oral 
bridging, are being utilized to protect patient safety, these events fall outside of the intent 
of the original protocol design, may have an impact on data interpretation, and thus will 
be characterized as protocol deviations for the purposes of data summary and analysis. 
 
Any protocol deviations resulting from COVID-19 will be clearly identified as such 
within the protocol deviation description and summarised separately. 
 
Please refer to your study procedure manual for specific details on capturing protocol 
deviations as a result of COVID-19. 
 
12.9.6.2. 
Capturing COVID-19 Specific AEs and SAEs 
It is important for the study team to describe COVID-19 related adverse events/serious 
adverse and their impact on study data and outcomes. Standardization of case definitions 
will facilitate future data analysis.  
Please use the following guidance:  
1. 
AEs should continue to be evaluated as to whether they meet SAE criteria as 
defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. SAEs and AEs should be submitted following usual 
study procedures and timelines.  
 
2. 
When an in-person clinic visit is not possible, please conduct a remote 
telehealth visit to assess for, and document any AEs/SAEs. 
 
3. 
Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released March 20, 2020, represents a time point for 
standardized collection. We recognize definitions are likely to continue to 
evolve. When reporting both serious and non- serious adverse events (related 
to COVID-19 infection, investigators should use the following Verbatim 
terms:  
a) Suspected COVID-19 infection; or  
b) Probable COVID-19 infection; or  
c) Confirmed COVID-19 infection  
 
4. 
Sites should contact the study Medical Monitor for questions related to 
definitions and reporting, and decisions around impact to study drug 
continuation.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 393 - 
 
 
5. 
A new COVID-19 infection Case Report Form will be added to the eCRF to 
collect additional details about the reported COVID-19 AE or SAE data. It is 
important to collect the correct information from each participant reporting a 
COVID-19 AE or SAE.  Therefore, please use the CRF templates to help you 
collect this information, once available. 
 
WHO Case Definition - March 20, 2020 Version (https://www.who.int/publications-
detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov)):  
Suspected case:  
A. A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or 
residence in a location reporting community transmission of COVID-19 disease 
during the 14 days prior to symptom onset;  
OR  
B. A patient with any acute respiratory illness AND in contact (see definition of 
“contact” below) with a confirmed or probable COVID-19 case (see definition of 
contact) in the last 14 days prior to symptom onset;  
OR  
C. A patient with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation.  
 
Probable case:  
A. A suspect case for whom testing for the COVID-19 virus is inconclusive 
(Inconclusive being the result of the test reported by the laboratory).  
OR  
B. A suspect case for whom testing could not be performed for any reason.  
Confirmed case:  
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms.  
Covid-19 Contact: 
A contact is a person who experienced any one of the following exposures during the 2 
days before and the 14 days after the onset of symptoms of a probable or confirmed case:  
1. 
Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes;  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 394 - 
 
2. 
Direct physical contact with a probable or confirmed case;  
3. 
Direct care for a patient with probable or confirmed COVID-19 disease 
without using proper personal protective equipment; OR  
4. 
Other situations as indicated by local risk assessments.  
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken which led to 
confirmation. 
12.14.6. 
Amendment 06 (All Countries) 
Protocol changes for Amendment 06 (05-AUG-2021), from Amendment 05 (20-
MAY-2020).   
12.14.6.1. Protocol Amendment Rationale 
The primary purposes of this amendment are: 
• To allow participants who become pregnant while in the study to remain in the 
study and not be withdrawn due to pregnancy. Allowing pregnant participants to 
continue in the study will negate any additional and subsequent fetal exposures to 
new antiretroviral agents that would occur if the pregnant participant was 
withdrawn from the study and placed on an oral SOC regimen. An appendix, 
“Information and Guidance for Managing Pregnant Participants” was inserted as 
Appendix 10 and all subsequent appendices were renumbered accordingly. 
• Contraceptive methods have been updated to permit the use of progestogen-only 
implantable and injectable contraceptives without the requirement of a second 
highly effective method. 
• Removal of the optional collection of cord blood and/or breast milk after delivery. 
• Removal of the option for study treatment rechallenge following suspected drug-
induced liver injury (DILI). 
• Clarification of which participants enter the LTFU phase when CAB+RPV LA 
marketed product is locally available. 
• Medical Device reporting requirement added. 
• Co-enrolment (only applicable for eligible female participants in South Africa in 
the ACTG A5392 study). 
• Updates to primary and secondary Medical Monitors. 
Other additional edits were made, for clarity and/or correction. 
12.14.6.2. Protocol Changes/Clarifications 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1. Long 
Term Follow-Up 
Phase 
Section 4.1. Overall 
New text added: 
- 
Where the CAB LA + RPV 
LA marketed product is not 
locally available, any 
Transition to 
marketed product. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 395 - 
 
Design 
Section 4.2.6. LTFU 
Phase- IM Regimen 
Only 
Section 5.4. 
Withdrawal/Stopping 
Criteria 
Section 6.10.2. 
Discontinuation of 
CAB LA or RPV LA 
 
participant who receives at 
least a single dose of CAB 
LA and/or RPV LA and 
discontinues the CAB LA + 
RPV LA regimen for any 
reason must enter the 52 
week Long Term Follow-Up 
Phase.  
 
- 
Where CAB LA + RPV LA 
marketed product is locally 
available, only participants 
that discontinue the CAB LA 
+ RPV LA regimen for 
safety-related reasons should 
enter the LTFU Phase. 
Section 4.5. Dose 
Justification 
Text updated to reflect that the 
LATTE study is no longer ongoing. 
For clarification 
purposes. 
Section 4.6. 
Benefit:Risk 
Assessment. 
DTG Data/Rationale for Risk updated. 
Text removed: In one ongoing birth 
outcome surveillance study in 
Botswana, early results from an 
unplanned interim analysis showed that 
4/426 (0.9%) of women who were 
taking DTG when they became 
pregnant had babies with neural tube 
defects compared to a background rate 
of 0.1%. 
Text added: A preliminary analysis of 
an ongoing birth outcome surveillance 
study in Botswana involving women 
exposed to dolutegravir (DTG) 
identified four cases (as of May 2018) 
of neural tube defects in 426 infants 
born to mothers who were exposed to 
DTG-containing regimens from the 
time of conception. In the same study, 
no infant born to a women who started 
DTG during pregnancy had a neural 
tube defect, out of 2,824 women. A 
causal relationship of these events to 
the use of DTG has not been 
established. The incident rate of neural 
tube defects in the general population 
ranges from 0.5-1 cases per 1,000 live 
births. As neural tube defects occur 
within the first 4 weeks of fetal 
Updated safety 
information. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 396 - 
 
development (at which time the neural 
tubes are sealed) this potential risk 
would concern women exposed to DTG 
at the time of conception and in early 
pregnancy. Recently updated data 
(April 2020) for this birth outcome 
study showed that among women who 
were on DTG when they became 
pregnant, 7/3,591 neural tube defects 
(NTD) occurred (0.19%). In 
comparison, NTDs were identified in 
21/19,361 (0.11%) women delivering 
on any non-DTG antiretrovirals. There 
was not a significant difference in the 
number of neural tube defects between 
births to women taking DTG and those 
taking other non-DTG antiretroviral 
treatments (0.09% difference). 
Section 4.6. 
Benefit:Risk 
Assessment 
DTG Mitigation Strategy updated. 
Text removed: Women who become 
pregnant or who desire to be 
pregnant while in the study will 
have study treatment discontinued 
and withdrawn from the study. 
To allow participants 
who become pregnant 
to remain in the 
study. 
Section 4.6.1. Risk 
Assessment 
Updated section Potential Risk of 
Clinical Significance: Drug Induced 
Liver Injury (DILI) 
Summary of Data/Rationale for Risk 
text removed: 
- 
(total exposure >3100 
participants) 
- 
Of the four participants with 
possible or probable cases of 
DILI identified in Phase 2 
studies, all were receiving 
oral CAB. 
Summary of Data/Rationale for Risk 
text added: All participants with 
suspected DILI identified in clinical 
studies to date were receiving oral 
cabotegravir. 
For clarification 
purposes. 
Section 4.6.1 Risk 
Assessment 
Updated section Potential Risk of 
Clinical Significance: Effects in 
pregnancy seen in non-clinical 
To allow participants 
who become pregnant 
to remain in the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 397 - 
 
studies. 
Summary of Data/Rationale for Risk 
Animal reproduction studies data 
updated. 
Mitigation Strategy updated to allow 
participants who become pregnant 
to remain in the study. 
study. 
Section 4.6.1 Risk 
Assessment 
Added new category: Potential 
effects in females exposed to 
dolutegravir during conception and 
early pregnancy.  
Summary of Data/Rationale for Risk 
with data from preliminary analysis 
of an ongoing birth outcome 
surveillance study in Botswana 
involving women exposed to 
dolutegravir (DTG). 
Mitigation Strategy updated to allow 
participants who become pregnant 
to remain in the study. 
To allow participants 
who become pregnant 
to remain in the 
study. 
Section 4.6.1. Risk 
Assessment 
Removed text from RPV risks, Rash 
mitigation strategy: Participants 
with a Grade 1 or 2 rash will be 
allowed to continue treatment or to 
be rechallenged, depending on the 
clinical judgement of the 
investigator. 
Rechallenge option 
removed. 
Section 4.6.2. Other 
Clinically Relevant 
Information 
Seizure information updated. 
For clarification 
purposes. 
Section 4.6.3. 
Benefit Assessment 
Updated list of ongoing studies. 
Addition of Phase 3 studies. 
For clarification 
purposes. 
Section 5.2. 
Diagnostic 
Assessments and 
Other Criteria 
Added text: Participation in other 
interventional studies is generally 
not permitted, however for eligible 
subjects in South Africa co-
enrolment in AIDS Clinical Trial 
Group (ACTG) interventional study 
(A5392) could be exceptionally 
permitted after review and approval 
Co-enrolment in 
study A5392 would 
be permitted in South 
Africa on a case by 
case approval basis. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 398 - 
 
by the Medical Monitor. 
Section 5.4. 
Withdrawal/Stopping 
Criteria 
Removed text: Pregnancy 
(intrauterine), regardless of 
termination status of the pregnancy. 
(If receiving CAB LA + RPV LA, 
the participant would discontinue 
LA study treatment and continue to 
be followed up in the LTFU phase).  
To allow participants 
who become pregnant 
to remain in the 
study. 
Section 5.4.1. Liver 
Chemistry Stopping 
Criteria 
Removed “rechallenge” option 
throughout the sections. 
Rechallenge option 
removed. 
Section 5.4.1.3. 
Liver Chemistry 
Stopping Criteria – 
Restart  
Rechallenge text removed from the 
section title. Rechallenge option 
removed throughout the sections. 
New text updated with the current 
process required in case of restart. 
Rechallenge option 
removed. 
Section 5.4.1.4. 
General Guidance 
Restart 
New section added with the current 
process required in case of restart. 
Rechallenge option 
removed. 
Section 5.4.1.4. 
Liver Chemistry 
Stopping Criteria - 
Restart 
Added text: If definitive non-study 
drug related diagnosis, restart will 
be considered once ALT <3x ULN 
(for participants with baseline ALT 
<1.5x ULN) or <3x baseline ALT 
value (for participants with baseline 
ALT >1.5x UNL). 
For clarification 
purposes. 
Section 5.5. 
Participant and Study 
Completion 
Added Safety Follow-Up visit. 
Transition to 
marketed product. 
Section 6. Study 
Treatment  
New section added: Section 6.14. 
Medical Devices. 
Medical Device 
reporting 
requirement. 
Section 7.1. Time 
and Events Table 
Added new column for Safety 
Follow-Up visit to clarify visit 
requirements. 
Transition to 
marketed product. 
Section 7.4.1. 
Clinical Evaluation 
Added text: Participants who are 
enrolled in the study and have a 
positive pregnancy test during the 
course of the study will be allowed 
To allow participants 
who become pregnant 
to remain in the 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 399 - 
 
to remain in the study, provided a 
pregnancy specific ICF addendum is 
signed by the participant. No IP can 
be continued (oral or LA) in any 
pregnant participant until the 
benefit/risk assessment is discussed 
with the participant and the 
pregnancy specific ICF addendum 
has been signed. See details in 
Appendix 10. Pregnant participants 
who remain in the study do not need 
pregnancy testing during the study, 
for the duration of their pregnancy. 
study. 
Section 7.4.3. 
Adverse Events 
(AEs) and Serious 
Adverse Events 
(SAEs) 
Added text throughout Section 7.4.3 
and Section 7.4.3.1. referring to the 
new requirement to report Medical 
Device incidents. 
Added Medical 
Device incident 
reporting 
requirements. 
Section 7.4.3.4. 
Prompt Reporting of 
Serious Adverse 
Events and Other 
Events 
Added text stating that contacts for 
SAE receipt can be found in the 
Study Reference Manual. 
For clarification 
purposes. 
Section 7.4. Safety 
Added new sections detailing the 
medical device deficiencies 
reporting requirements. New 
sections added: 
7.4.4. Medical Device Deficiencies 
7.4.5. Time Period for Detecting 
Medical Device Deficiencies 
7.4.6. Follow-Up of Medical Device 
Deficiencies. 
7.4.7. Prompt Reporting of Medical 
Device Deficiencies to Sponsor 
7.4.8. Regulatory Reporting 
Requirements for Medical Device 
Deficiencies 
Added medical device 
deficiency reporting 
requirements. 
Section 7.4.9.3. 
Grade 3 
Toxicity/Adverse 
Clarification that a follow-up visit 
should occur 2-4 weeks after the last 
For clarification 
purposes. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 400 - 
 
Event 
dose of IP. 
Section 7.4.10.1. 
Liver Chemistry 
Stopping Criteria 
Removal of rechallenge text. 
Rechallenge option 
removed. 
Section 7.4.10.4. 
Seizures 
Added text: Several cases of seizure 
have occurred during the 
cabotegravir program. These cases 
have had alternative explanations 
for their occurrence. 
ViiV Healthcare has reviewed these 
cases in detail and does not believe 
they constitute a reasonable 
likelihood of causation associated 
with CAB. This assessment is 
supported by the lack of preclinical 
signal, class effect or known CNS 
mechanism, the relatively low 
frequency of seizures relative to 
expected rates in both healthy and 
HIV positive participants and 
clinical cofounders in each case. 
The Sponsor considers the risk of 
developing seizures on the study as 
being no higher than that of the rest 
of the HIV-1 infected population. 
For clarification 
purposes. 
Section 7.4.12. 
Pregnancy 
Added text throughout all sections 
below to allow subjects who 
become pregnant to remain in the 
study: 
 
Added text in Section 7.4.12.1. 
Pregnancy Testing 
Added new Section 7.4.12.2. 
Rationale for Continued Use in 
Pregnancy 
Amended Section 7.4.12.3. Time 
Period for Collecting Pregnancy 
Information 
 
To allow subjects 
who become pregnant 
to remain in the 
study. 
Section 7.4.12.4. 
Removed text: Additionally, there 
Removal of optional 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 401 - 
 
Actions to be taken if 
Pregnancy occurs 
will be an optional umbilical cord 
blood collection at time of delivery, 
requiring additional parental 
consent. Cord blood and breast milk 
samples would be used to better 
understand the level of PK exposure 
to the neonate, if any. 
umbilical cord blood 
and/or breast milk PK 
testing. 
Section 7.5. 
Pharmacokinetics 
Added text: Pregnant participants 
will have additional PK samples 
collected during the duration of the 
pregnancy. See Appendix 10 for 
details. 
Added PK collection 
during pregnancy. 
Section 8. Data 
Management 
Added text: The sponsor or designee 
is responsible for the data 
management of this study including 
quality checking of the data. 
Detailed information about study 
data collection and management 
process including systems used can 
be found in the study Data 
Management Plan. 
For clarification 
purposes. 
Section 10.2. 
Regulatory and 
Ethical 
Considerations, 
Including the 
Informed Consent 
Process 
Added text: If follow-up 
information from a treating 
physician or other licensed medical 
practitioner is required for a medical 
device incident with an AE/SAE 
involving an associated person(s), 
the Associated Person Safety 
Reporting Information and 
Authorization Letter must be signed 
by the associated person to obtain 
consent.  
Added medical device 
deficiency reporting 
requirements.  
Section 12.3. 
Appendix 3 
Removed Appendix 3: Liver Safety 
– Study Treatment Restart or 
Rechallenge Guidelines. 
Added new Appendix 3: Liver 
Safety – Required Actions, Follow 
Up Assessments and Study 
Treatment Restart Guidelines 
Removal of 
rechallenge option. 
Section 12.5. 
Appendix 5 Genetics 
Text updated: In the event that a 
participant withdraws from the 
study and requests destructions of 
To align with the 
most recent template 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 402 - 
 
Research 
their samples then the site staff must 
document this in the site study 
records, complete form F-GRD-001 
and must inform ViiV/GSK via the 
CRA within 5 days of notification 
by the participant to trigger sample 
destruction requests.  
requirements. 
Section 12.7. 
Appendix 7 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Removed footer b of Table 14 
Highly Effective Contraceptive 
Methods: Two highly effective 
methods of contraception should be 
utilized from 30 days prior to the 
first dose of study medication, 
throughout the study, and for at least 
52 weeks after discontinuation of 
CAB LA and RPV LA. 
Permitted 
contraceptive 
methods updated. 
Section 12.7. 
Appendix 7 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Added text throughout section for 
cases of pregnancy during the study. 
To allow patients who 
become pregnant to 
remain in the study. 
Section 12.9.6.1. 
Capturing COVID-
19 Specific Protocol 
Deviations 
Removed text: Please refer to your 
study procedure manual for specific 
details on capturing protocol 
deviations as a result of COVID-19. 
For clarification 
purposes. 
Section 12.10. 
Appendix 10 
New appendix added: Appendix 10: 
Information and Guidance for 
Managing Pregnant Participants. 
To allow participants 
who become pregnant 
to remain in the 
study. 
Section 12.11. 
Appendix 11 
New appendix added: Appendix 11: 
Device Deficiencies: Definition and 
Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting in Medical Device 
Studies. 
Medical Device 
Reporting 
Requirements. 
Section 12.12. 
Appendix 12 
Appendix 12: Protocol Amendment 
History updated. 
 
 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 403 - 
 
12.14.7. 
Amendment 07 (All Countries) 
Protocol changes for Amendment 07 (17 Jun 2022), from Amendment 06 (05-AUG-
2021).   
Amendment 07 17 Jun 2022 
This amendment is considered to be substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment:  
The primary purposes of this amendment are: 
• To include the Sub-Cutaneous Abdominal Injection Sub-Study appendix (only 
applicable for countries participating in the Sub-Study).  
• Clarification added: In Russia, subjects who become pregnant while on study may 
not elect to remain on study treatment and must withdraw and enter the LTFU 
Phase. 
• Inclusion of Appendix 13: Mitigations for Geopolitical Situation in 
Russia/Ukraine. 
Section # and Name 
Description of Change 
Brief Rationale 
Title Page and 
Protocol Amendment 
Summary of 
Changes Table 
Document updated as per the latest GSK 
template. 
Template update. 
Sponsor Signature 
Page 
Provided as separate document. 
Template Update 
Investigator 
Signature Page 
Provided as separate document 
Template Update 
Medical 
Monitor/Sponsor 
Information page 
Removed. Document updated as per the 
latest GSK template. 
Template Update 
Section 4.6. 
Benefit:Risk 
Assessment 
DTG Mitigation Strategy updated. Text 
added: In Russia, women who become 
pregnant or who desire to be pregnant 
while in the study will have study treatment 
discontinued and will be withdrawn from 
the study. 
Russia country 
specific 
pregnancy 
requirements. 
Section 4.6.1. Risk 
Assessment 
Updated section Potential Risk of Clinical 
Significance: Effects in pregnancy seen in 
Russia country 
specific 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 404 - 
 
Section # and Name 
Description of Change 
Brief Rationale 
non-clinical studies. 
Summary of Data/Rationale for Risk text 
added: Not applicable in Russia. 
Mitigation Strategy text added: Not 
applicable in Russia. In Russia, women 
who become pregnant or who desire to 
become pregnant while in the study will 
have study treatment discontinued and will 
be withdrawn from the study. 
pregnancy 
requirements. 
Section 4.6.1. Risk 
Assessment 
Updated section: Potential effects in 
females exposed to dolutegravir during 
conception and early pregnancy.  
Mitigation Strategy text added: Not 
applicable in Russia. In Russia, women 
who become pregnant or who desire to 
become pregnant while in the study will 
have study treatment discontinued and will 
be withdrawn from the study. 
Russia country 
specific 
pregnancy 
requirements. 
Section 5.1. 
Inclusion Criteria 
Informed consent inclusion criteria now 
inclusion criteria number 5 as per 
continuation of numbering format.  
  
French participants informed consent 
criteria now inclusion criteria number 6 as 
per continuation of numbering format. 
Clarification 
purposes.  
Section 5.4. 
Withdrawal/Stopping 
Criteria 
Added text: In Russia, pregnancy 
(intrauterine), regardless of termination 
status of the pregnancy. (If receiving CAB 
LA + RPV LA, the participant would 
discontinue LA study treatment and 
continue to be followed up in the LTFU 
phase). 
Russia country 
specific 
pregnancy 
requirements. 
Section 5.4.1. Liver 
Chemistry Stopping 
Criteria 
Text removed: Figure 10 
Text added: Figure 9 
Correction 
Section 7.4.1. 
Clinical Evaluation 
Added text: Not applicable in Russia. 
Russia country 
specific 
pregnancy 
requirements. 
Section 7.4.12. 
Added text throughout all sections below to 
clarify that subjects who become pregnant 
Russia country 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 405 - 
 
Section # and Name 
Description of Change 
Brief Rationale 
Pregnancy 
in Russia must discontinue LA study 
treatment and continue to be followed up in 
the LTFU phase.  
Added text in Section 7.4.12.1. Pregnancy 
Testing 
Added text in Section 7.4.12.2. Rationale 
for Continued Use in Pregnancy 
Added text in Section 7.4.12.3. Time 
Period for Collecting Pregnancy 
Information 
Added text in Section 7.4.12.4. Action to 
be Taken if Pregnancy Occurs  
specific 
pregnancy 
requirements. 
Section 7.5. 
Pharmacokinetics 
Added text: Not applicable in Russia. 
Russia country 
specific 
pregnancy 
requirements.  
Section 12.1. 
Appendix 1: 
Abbreviations and 
Trademarks 
New abbreviations added: 
DTP – Direct to Patient 
HCP – Healthcare Provider 
LTFU – Long-Term Follow Up 
SVF – Suspected Virological Failure 
For clarification 
purposes. 
Section 12.7. 
Appendix 7: 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Text added throughout to clarify that 
subjects who become pregnant in Russia 
must discontinue LA study treatment and 
continue to be followed up in the LTFU 
phase.  
Section 12.7.1. Contraceptive Guidance 
Section 12.7.2. Collection of Pregnancy 
Information 
Russia country 
specific 
pregnancy 
requirements. 
Section 12.7.1. 
Contraceptive 
Guidance 
Table 15 updated to become Table 16. 
For clarification 
purposes. 
Section 12.8.2. Japan Table 16 updated to become Table 17. 
For clarification 
purposes. 
Section 12.8.3. 
Country specific wording added related to 
Russia country 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 406 - 
 
Section # and Name 
Description of Change 
Brief Rationale 
Russia 
the discontinuation of study treatment for 
participants who become pregnant during 
the study.  
specific 
pregnancy 
requirements. 
Section 12.10. 
Appendix 10 
New text added: Not applicable to 
participants in Russia. In Russia, women 
who become pregnant or who desire to 
become pregnant while in the study will 
have study treatment discontinued and will 
be withdrawn from the study. 
Russia country 
specific 
pregnancy 
requirements. 
Section 12.10. 
Appendix 10 
Table of contents removed. 
As per GSK 
writing guidance, 
document should 
only have one 
table of contents. 
Section 12.12. 
Appendix 12 
New appendix added: Appendix 12: Sub-
Cutaneous Administration PK Sub-Study 
Amendment 
Sub-Study 
information 
Section 12.13. 
Appendix 13 
New appendix added: Appendix 13: 
Mitigations for Geopolitical Situation in 
Russia/Ukraine 
To provide 
approval of 
necessary 
mitigation 
strategies in 
Russia 
Section 12.14. 
Appendix 14 
Appendix 14: Protocol Amendment History 
updated. 
 
Section 12.11. Appendix 14:  Protocol Amendments 
Rationale for change:  Appendix 12 (previously history of protocol amendments) is 
now Appendix 14 to retain this section at the end of the protocol as the final 
appendix of change. 
12.14.8. 
Amendment 08 (All Countries) 
Protocol changes for Amendment 08 (21 Oct 2022) from Amendment 07 (17-Jun-
2022).   
This amendment is considered to be substantial based on the criteria defined in EU 
Clinical Trial Regulation No 536/2014 of the European Parliament and the Council of the 
European Union.  
Overall Rationale for the Amendment:  
The primary purposes of this amendment are: 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 407 - 
 
• To include the Sub-Study Interim Analysis 1: ISR Monitoring Criteria into the 
Sub-Cutaneous Abdominal Injection Sub-Study appendix (only applicable to for 
countries participating in the Sub-Study). 
• To include the Sub-Study Interim Analysis 2: Week 9 Safety and PRO Review 
into the Sub-Cutaneous Abdominal Injection Sub-Study appendix (only 
applicable for countries participating in the Sub-Study).  
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4.6.1. Risk 
Assessment 
Text removed from Oral CAB and CAB 
LA (GSK1265744 / GSK1265744 LA): "is 
at an early stage of clinical development, 
and" 
For clarification 
purposes. 
Section 4.6.1. Risk 
Assessment 
Text removed from Drug Induced Liver 
Injury (DILI) Summary of Data/Rationale 
for Risk:  
 
"A small proportion". 
 
"All participants with suspected DILI 
identified in clinical studies to date were 
receiving oral cabotegravir" 
 
Text added to Drug Induced Liver Injury 
(DILI) Summary of Data/Rationale for 
Risk: "Less than 1%" 
For clarification 
purposes. 
Section 4.6.1. Risk 
Assessment 
Text removed from RPV LA: "Beyond 
what has already been identified with oral 
RPV, no new systemic adverse reactions to 
RPV LA (same active moiety) have been 
observed." 
 
Text added to RPV LA: "Systemic 
reactions following RPV LA injections 
have been observed in clinical trials. These 
occur infrequently (in less than 0.5% of 
participants) and typically begin to resolve 
within minutes of the injection however, 
some participants required supportive care. 
Where timely PK data was available, high 
RPV PK plasma concentrations have been 
Updated safety 
information. 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 408 - 
 
Section # and Name 
Description of Change 
Brief Rationale 
observed which may have resulted from an 
accidental partial IV injection of RPV."   
Section 4.6.1. Risk 
Assessment 
Text added to Inadvertent Intravenous 
Injection (Accidental Maladministration) 
Summary of Data/Rationale for Risk:  
 
"Systemic reactions following RPV LA 
injections have been observed in clinical 
trials. These occur infrequently (in less than 
0.5% of participants) and typically begin to 
resolve within minutes of the injection, 
however, some participants required 
supportive care. Where timely PK data was 
available, high RPV PK plasma 
concentrations have been observed which 
may have resulted from an accidental 
partial IV injection of RPV." 
Updated safety 
information. 
Section 4.6.2. Other 
Clinically Relevant 
Information 
Text removed from Adverse Events of 
Special Interest: Seizure: "Several cases of 
seizure have occurred during the 
cabotegravir program". 
 
Text added to Adverse Events of Special 
Interest: Seizure: "A small number of 
seizure cases have been reported following 
CAB administration (less than 1% of all 
those receiving CAB in clinical studies)". 
For clarification 
purposes. 
Section 5.2. 
Exclusion Criteria 
Correction to the numbering of the 
exclusion criteria. Previously wrong due to 
an error.  
Correction. 
Section 7.4.10.4. 
Seizures 
Text removed: "Several cases of seizure 
have occurred during the cabotegravir 
program".  
 
Text added: "A small number of seizure 
cases have been reported following CAB 
administration (less than 1% of all those 
receiving CAB in clinical studies)". 
For clarification 
purposes. 
Section 12.12.1. 
Sub-Study 
Reference added. 
For clarification 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 409 - 
 
Section # and Name 
Description of Change 
Brief Rationale 
Amendment 
Background 
purposes. 
Section 12.12.2.1. 
Data on CAB/RPV 
Subcutaneous 
Injection Site 
Reactions 
New section added. 
Additional safety 
information.  
Section 12.12.2.2. 
ISR Monitoring 
Criteria Process 
New section added. 
Additional safety 
information. 
Section 12.12.4.1. 
Sub-Study 
Amendment: 
Inclusion and 
Exclusion Criteria 
Correction to the numbering of the 
exclusion criteria. Previously wrong due to 
an error. 
Correction.  
Section 12.12.4.4. 
Return to 
Intramuscular 
Gluteal Injection 
Phase 
Text removed: "Participants will complete 
8 weeks (2 injection cycles) of CAB/RPV 
LA therapy after which the participant's 
participation in the sub-study will 
conclude(after the week 17 assessments 
obtained). The Week 20 injection and all 
assessments obtained at Week 20 and 
beyond will be as part of the parent study 
(FLAIR)." 
 
Text added: "Participants will complete 8 
weeks (2 injection cycles) of CAB/RPV LA 
therapy. After the Week 20 assessments are 
obtained (AEs, SAEs and concomitant 
medications) the participant's participation 
in the sub-study will have concluded." 
For clarification 
purposes. 
Section 12.12.4.5. 
Sub-Study 
Completion 
Text removed: "Participants are considered 
to have completed the sub-study if they 
complete pre-dose assessments at sub-study 
Week 20 visit with the action IM injection 
as part of the parent study." 
 
Text added: "Participants are considered to 
have completed the sub-study once the final 
Week 20 pre-dose assessments (AEs, SAEs 
For clarification 
purposes.  


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 410 - 
 
Section # and Name 
Description of Change 
Brief Rationale 
and concomitant medications) are obtained. 
The IM injection and all other assessments 
will be considered part of the parent study 
and assessments should be completed as 
per the parent study time and events table 
in Section 7.1." 
Section 12.12.4.7. 
Sub-Study Injection 
Site Reactions 
New section added. 
For safety 
purposes. 
Section 12.12.4.9. 
Sub-Study 
Amendment HIV-1 
RNA Blips Guidance 
Text added: "(defined as HIV-1 RNA ≥50 
c/mL and <200 c/mL) " 
For clarification 
purposes.  
Section 12.12.5. 
Sub-Study Time and 
Events Table 
Removed footnote “i” from Week 16 IM 
administration. 
Footnote not 
required for this 
assessment. 
Section 12.12.5. 
Sub-Study Time and 
Events Table 
Removed footnote “i” from Return to IM 
Gluteal Injection Phase. 
Footnote not 
required for this 
assessment.  
Section 12.12.5. 
Sub-Study Time and 
Events Table 
HIVTSQc requirement at Week 17 
removed. 
Not required. 
Section 12.12.5. 
Sub-Study Time and 
Events Table 
Week 20 column added.  
AEs, SAEs concomitant medications to be 
completed at this visit. 
For clarification 
purposes.  
Section 12.12.5. 
Sub-Study Time and 
Events Table 
Removed footnote "n" marker from Pre 
dose PK samples for CAB and RPV. 
Error, there was 
previously no 
footnote n. 
Section 12.12.5. 
Sub-Study Time and 
Events Table 
Footnote "n" added. 
 
"AEs, SAEs and concomitant medications 
to be assessed pre-dose. IM administration 
itself and all other assessments will be 
considered part of the parent study, and 
should be completed as per the parent study 
time and events table in Section 7.1" 
For clarification 
purposes. 
Section 12.12.5. 
Footnote “n” added for Week 20 column 
For clarification 


TMF-16441767 
CONFIDENTIAL 
201584 
 
 
Protocol Amendment 09 
 
- 411 - 
 
Section # and Name 
Description of Change 
Brief Rationale 
Sub-Study Time and 
Events Table 
title.  
purposes. 
Section 12.12.9.6. 
Sub-Study Interim 
Analysis 1: ISR 
Monitoring Criteria 
New section added. 
Sub-Study 
interim analysis 
added. 
Section 12.12.9.7. 
Sub-Study Interim 
Analysis 2: Week 9 
Safety and PRO 
Review 
New section added. 
Sub-Study 
interim analysis 
added. 
Throughout 
Minor editorial and document formatting 
revisions. 
For clarification 
purposes. 
Throughout 
GlaxoSmithKline replaced with GSK due 
to updated branding.  
For clarification 
purposes. 
Section 12.14. 
Appendix 14 
Appendix 14: Protocol Amendment History 
updated.  
For clarification 
purposes. 
 
12.14.9. 
Amendment 09 (All Countries) 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Protocol changes for Amendment 09 (28 Aug 2023), from Amendment 08 (21 Oct 
2022).   
Amendment 08 (All Countries) Protocol changes for Amendment 08 (21-Oct-2022), from 
Amendment 07 (17-Jun2022). 

SAP_001.pdf: 
Statistical Analysis Plan
Main Study ID:  201584
Main Study Official Title: A Phase III, Randomized, Multicenter, Parallel-group, 
Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-
Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic 
Suppression Following Switch from an Integrase Inhibitor Single Tablet Regimen 
in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants
NCT ID for Main Study: NCT02938520
Sub-Study ID:  201584-001
Sub-Study Official Title:  An Amendment to the FLAIR Study to Evaluate the 
Pharmacokinetics, Safety, Tolerability, Maintenance of Virological Suppression 
and Patient Reported Outcomes for Participants Receiving Cabotegravir (CAB 200 
mg/mL) and Rilpivirine (300 mg/mL) Long-Acting Injections Following Sub-
cutaneous (SC) Administration in the Anterior Abdominal Wall SC Tissue 
Compared With Intramuscular (IM) Administration in the Gluteus Medius Muscle 
in Adult Participants Living With HIV-1 Infection in the FLAIR Study
NCT ID for Sub-Study: NCT05896748
Date of Document of Sub-Study: 03-Aug-2023 


 
CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
201584 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: 201584: A Phase III, Randomized, Multicenter, Parallel-
group, Open-Label Study Evaluating the Efficacy, Safety, 
and Tolerability of Long-Acting Intramuscular 
Cabotegravir and Rilpivirine for Maintenance of Virologic 
Suppression Following Switch from an Integrase Inhibitor 
Single Tablet Regimen in HIV-1 Infected Antiretroviral 
Therapy Naive Adult Participants 
Compound Number  : GSK1265744 
Effective Date  
: 03-AUG-23 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Subcutaneous Sub-study Clinical Study Report for Protocol 
201584. Reporting details pertaining to the primary Week 48 and the earlier 
analyses (Week 96 and Week 124) have been retained for completeness.   
• 
This version of the RAP includes amendments to the originally approved RAP. 
 
RAP Author(s): 
Author  
Date 
Lead 
 
03-AUG-23 
Statistician (GSK Clinical Statistics) 
 
 
 
 
 
 
 
Copyright 2023 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
PPD


 
CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
201584 
2 
 
RAP Team Review Confirmations (Method: E-mail) 
Approver 
Date 
 
03-AUG-23 
(Clinical Development Scientist, ViiV Healthcare)  
 
03-AUG-23 
Clinical Study Manager (Global Clinical Sciences & Delivery, 
GSK) 
 
03-AUG-23 
Principle Programmer (GSK Clinical Programming) 
 
Clinical Statistics & Clinical Programming Line Approvals  
(Method: Pharma TMF eSignature) 
Approver 
Date 
 
03-AUG-23 
, Statistics (GSK Clinical Statistics) 
 
03-AUG-23 
 
 
 
, ViiV Healthcare) 
03-AUG-23 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
201584 
3 
 
TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 8 
1.1. 
RAP Amendments ...................................................................................... 11 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION ................................................ 17 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan .......................... 17 
2.2. 
Study Objective(s) and Endpoint(s)............................................................. 17 
2.2.1. 
Subcutaneous Sub-study Objectives and Endpoints .................... 21 
2.3. 
Study Design .............................................................................................. 33 
2.3.1. 
Subcutaneous Sub-Study Design ................................................ 34 
2.4. 
Statistical Hypotheses / Statistical Analyses ............................................... 35 
3. 
PLANNED ANALYSES .......................................................................................... 36 
3.1. 
Interim Analyses ......................................................................................... 36 
3.1.1. 
Subcutaneous Sub-Study Interim Analyses ................................. 36 
3.2. 
Final Analyses ............................................................................................ 37 
4. 
ANALYSIS POPULATIONS ................................................................................... 38 
4.1. 
Protocol Deviations ..................................................................................... 41 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 41 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 41 
5.2. 
Baseline Definitions .................................................................................... 42 
5.3. 
Multicentre Studies ..................................................................................... 43 
5.4. 
Examination of Covariates, Other Strata and Subgroups ............................ 43 
5.4.1. 
Covariates and Other Strata ........................................................ 43 
5.4.2. 
Examination of Subgroups/Covariates ......................................... 44 
5.5. 
Multiple Comparisons and Multiplicity ......................................................... 48 
5.5.1. 
Primary Comparison of Interest ................................................... 48 
5.5.2. 
Other Comparisons of Interest ..................................................... 49 
5.5.3. 
Secondary Comparisons .............................................................. 49 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 50 
6. 
STUDY POPULATION ANALYSES ....................................................................... 52 
6.1. 
Overview of Planned Study Population Analyses ........................................ 52 
6.2. 
Subcutaneous Sub-Study Population Analyses .......................................... 53 
7. 
EFFICACY ANALYSES .......................................................................................... 55 
7.1. 
Primary Efficacy Analyses .......................................................................... 55 
7.1.1. 
Endpoint / Variables ..................................................................... 55 
7.1.2. 
Summary Measure ...................................................................... 55 
7.1.3. 
Population of Interest ................................................................... 55 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 55 
7.1.5. 
Statistical Analyses / Methods ..................................................... 55 
7.2. 
Secondary Efficacy Analyses ...................................................................... 59 
7.2.1. 
Endpoint / Variables ..................................................................... 59 
7.2.2. 
Summary Measure ...................................................................... 60 
7.2.3. 
Population of Interest ................................................................... 60 


 
CONFIDENTIAL 
 
 
201584 
4 
 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 60 
7.2.5. 
Statistical Analyses / Methods ..................................................... 60 
8. 
SAFETY ANALYSES ............................................................................................. 65 
8.1. 
Adverse Events Analyses ........................................................................... 65 
8.2. 
Adverse Events of Special Interest Analyses .............................................. 65 
8.3. 
Clinical Laboratory Analyses ....................................................................... 65 
8.4. 
Other Safety Analyses ................................................................................ 65 
8.5. 
Planned Safety Analysis ............................................................................. 65 
8.5.1. 
Injection Site Reactions ............................................................... 69 
8.5.2. 
Statistical Analyses/Methods ....................................................... 70 
8.6. 
Subcutaneous Sub-Study Safety Analyses ................................................. 71 
9. 
PHARMACOKINETIC AND PHARMACOKINETIC/PHARMACODYNAMIC 
ANALYSES ............................................................................................................ 73 
9.1. 
Primary Pharmacokinetic Analyses ............................................................. 73 
9.1.1. 
Endpoint / Variables ..................................................................... 73 
9.1.2. 
Planned Analyses ........................................................................ 73 
9.1.3. 
Statistical Analyses/Methods ....................................................... 75 
9.2. 
Subcutaneous Sub-Study ........................................................................... 76 
9.2.1. 
Endpoint / Variables ..................................................................... 76 
9.2.2. 
Planned Analyses ........................................................................ 78 
9.2.3. 
Statistical Analyses/Methods ....................................................... 79 
10. PHARMACOKINETIC ANALYSES (DAY 1 JAPAN) ............................................... 81 
10.1. 
Primary Pharmacokinetic Analyses ............................................................. 81 
10.1.1. 
Endpoint / Variables ..................................................................... 81 
10.1.2. 
Summary Measure ...................................................................... 82 
10.1.3. 
Population of Interest ................................................................... 82 
10.1.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 82 
10.1.5. 
Statistical Analyses / Methods ..................................................... 82 
11. HEALTH OUTCOMES ANALYSES ........................................................................ 83 
11.1. 
Endpoint / Variables .................................................................................... 83 
11.1.1. 
Summary Measure ...................................................................... 83 
11.1.2. 
Population of Interest ................................................................... 84 
11.1.3. 
Strategy for Intercurrent (Post-Randomization) Events ................ 84 
11.1.4. 
Planned Health Outcomes Analyses ............................................ 84 
11.1.5. 
Statistical Analyses/Methods ....................................................... 86 
11.2. 
Subcutaneous Sub-Study Endpoint / Variables ........................................... 87 
11.2.1. 
Summary Measure ...................................................................... 88 
11.2.2. 
Statistical Analyses/Methods ....................................................... 88 
12. VIROLOGY ............................................................................................................ 90 
13. REFERENCES ....................................................................................................... 92 
14. APPENDICES ........................................................................................................ 94 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 95 
14.1.1. 
Exclusions from Per Protocol Population ..................................... 95 
14.2. 
Appendix 2: Schedule of Activities .............................................................. 97 
14.2.1. 
Protocol Defined Schedule of Events ........................................... 97 


 
CONFIDENTIAL 
 
 
201584 
5 
 
14.2.2. 
Protocol Defined Schedule of Events for the 
Subcutaneous Sub-Study .......................................................... 109 
14.3. 
Appendix 3: Assessment Windows ........................................................... 115 
14.3.1. 
Definitions of Assessment Windows .......................................... 115 
14.3.2. 
Definitions of Assessment Windows for Data Other than 
Health Outcomes and PK .......................................................... 116 
14.3.3. 
Assessment Window for Study Conclusion ................................ 126 
14.3.4. 
Assessment Window for Health Outcome Data ......................... 126 
14.3.5. 
Assessment Window for PK concentration Data ........................ 130 
14.3.6. 
Multiple assessments within an Analysis Window ...................... 131 
14.4. 
Appendix 4: Study Phases and Treatment State ....................................... 133 
14.4.1. 
Study Phases ............................................................................ 133 
14.4.2. 
Treatment State ......................................................................... 145 
14.4.3. 
Combining Treatment Phases and States .................................. 147 
14.5. 
Appendix 5: Data Display Standards & Handling Conventions .................. 148 
14.5.1. 
Reporting Process ..................................................................... 148 
14.5.2. 
Reporting Standards .................................................................. 148 
14.5.3. 
Reporting Standards for Pharmacokinetic .................................. 149 
14.6. 
Appendix 6: Derived and Transformed Data ............................................. 150 
14.6.1. 
General ...................................................................................... 150 
14.6.2. 
Study Population ........................................................................ 153 
14.6.3. 
Safety ........................................................................................ 158 
14.6.4. 
Efficacy ...................................................................................... 160 
14.6.5. 
Pharmacokinetic ........................................................................ 163 
14.6.6. 
Health Outcome ......................................................................... 166 
14.6.7. 
Viral Genotype and Phenotype .................................................. 173 
14.7. 
Appendix 7: Reporting Standards for Missing Data ................................... 177 
14.7.1. 
Premature Withdrawals .............................................................. 177 
14.7.2. 
Handling of Missing Data ........................................................... 177 
14.8. 
Appendix 8: Values of Potential Clinical Importance ................................. 181 
14.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses .................... 182 
14.10. Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses .................. 183 
14.11. Appendix 11: Snapshot Algorithm Details ................................................. 184 
14.12. Appendix 12: AESI identification ............................................................... 188 
14.12.1. Hepatic Safety Profile ................................................................ 188 
14.12.2. Hypersensitivity Reactions ......................................................... 192 
14.12.3. Rash including severe cutaneous adverse reactions ................. 193 
14.12.4. Prolongation of the Corrected QT Interval of the ECG in 
Supra Therapeutic Doses .......................................................... 195 
14.12.5. Suicidal Ideation/Behaviour ....................................................... 196 
14.12.6. Depression ................................................................................ 197 
14.12.7. Bipolar Disorder ......................................................................... 198 
14.12.8. Psychosis .................................................................................. 199 
14.12.9. Mood Disorders ......................................................................... 202 
14.12.10. Anxiety ....................................................................................... 203 
14.12.11. Sleep Disorders ......................................................................... 207 
14.12.12. Injection site Reactions .............................................................. 211 
14.12.13. Seizures .................................................................................... 212 
14.12.14. Weight Gain ............................................................................... 216 
14.12.15. Rhabdomyolysis ........................................................................ 216 
14.12.16. Pancreatitis ................................................................................ 217 
14.12.17. Impact on Creatinine .................................................................. 218 


 
CONFIDENTIAL 
 
 
201584 
6 
 
14.12.18. Safety During Pregnancy ........................................................... 222 
14.13. Appendix 13: Abbreviations & Trade Marks .............................................. 223 
14.13.1. Abbreviations ............................................................................. 223 
14.13.2. Trademarks ............................................................................... 224 
14.14. Appendix 14: List of Data Displays for Week 48/Week 96 ......................... 225 
14.14.1. Data Display Numbering ............................................................ 225 
14.14.2. Mock Example Shell Referencing .............................................. 225 
14.14.3. Deliverables ............................................................................... 225 
14.14.4. Study Population Tables ............................................................ 226 
14.14.5. Efficacy Tables .......................................................................... 231 
14.14.6. Efficacy Figures ......................................................................... 236 
14.14.7. Safety Tables ............................................................................. 242 
14.14.8. Safety Figures ........................................................................... 268 
14.14.9. Pharmacokinetic Tables ............................................................. 271 
14.14.10. Pharmacokinetic Figures ........................................................... 273 
14.14.11. Pharmacokinetic / Pharmacodynamic Tables ............................ 276 
14.14.12. Pharmacokinetic / Pharmacodynamic Figures ........................... 279 
14.14.13. Health Outcomes Tables ........................................................... 284 
14.14.14. Health Outcomes Figures .......................................................... 289 
14.14.15. Virology Tables .......................................................................... 290 
14.14.16. ICH Listings ............................................................................... 293 
14.14.17. Non-ICH Listings ........................................................................ 297 
14.15. Appendix 15: List of Data Displays for Week 124 ...................................... 301 
14.15.1. Data Display Numbering ............................................................ 301 
14.15.2. Mock Example Shell Referencing .............................................. 301 
14.15.3. Deliverables ............................................................................... 301 
14.15.4. Study Population Tables ............................................................ 302 
14.15.5. Efficacy Tables .......................................................................... 306 
14.15.6. Efficacy Figures ......................................................................... 310 
14.15.7. Safety Tables – Extension Switch Population ............................ 317 
14.15.8. Safety Tables – Maintenance + Extension Phase 
(Randomized Q4W Only) ........................................................... 328 
14.15.9. Safety Tables – Long Term Follow Up ....................................... 337 
14.15.10. Safety Figures – Extension Switch Population ........................... 338 
14.15.11. Safety Figures – Maintenance + Extension Phase 
(Randomized Q4W) ................................................................... 339 
14.15.12. Pharmacokinetic Tables ............................................................. 340 
14.15.13. Pharmacokinetic Figures ........................................................... 342 
14.15.14. Virology Tables .......................................................................... 344 
14.15.15. ICH Listings ............................................................................... 346 
14.15.16. Non-ICH Listings ........................................................................ 349 
14.16. Appendix 16: IDMC ................................................................................... 352 
14.16.1. CVF Monitoring (Adhoc IDMC review) ....................................... 352 
14.17. Appendix 17: Variables Defined for Time to Event Analysis ...................... 353 
14.18. Appendix 18: Japan-Specific Requirements .............................................. 355 
14.18.1. Study Population Tables - Japan ............................................... 356 
14.18.2. Efficacy Tables - Japan .............................................................. 356 
14.18.3. Safety Tables - Japan ................................................................ 357 
14.18.4. Pharmacokinetic Tables - Japan ................................................ 359 
14.18.5. Pharmacokinetic Figures - Japan ............................................... 360 
14.18.6. Health Outcomes Tables - Japan ............................................... 362 
14.18.7. ICH Listings - Japan .................................................................. 363 


 
CONFIDENTIAL 
 
 
201584 
7 
 
14.18.8. Non-ICH Listings - Japan ........................................................... 364 
14.19. Appendix 19: List of Data Displays for Subcutaneous Sub-study 
Analysis .................................................................................................... 365 
14.19.1. Data Display Numbering ............................................................ 365 
14.19.2. Mock Example Shell Referencing .............................................. 365 
14.19.3. Deliverables ............................................................................... 365 
14.19.4. Study Population Tables ............................................................ 366 
14.19.5. Efficacy Tables .......................................................................... 368 
14.19.6. Efficacy Figures ......................................................................... 371 
14.19.7. Safety Tables ............................................................................. 372 
14.19.8. Safety Figures ........................................................................... 381 
14.19.9. Pharmacokinetic Tables ............................................................. 383 
14.19.10. Pharmacokinetic Figures ........................................................... 386 
14.19.11. Health Outcomes Tables ........................................................... 387 
14.19.12. Virology Tables .......................................................................... 390 
14.19.13. ICH Listings ............................................................................... 391 
14.19.14. Non-ICH Listings ........................................................................ 393 
14.20. Appendix 20: Example Mock Shells for Data Displays .............................. 394 
 


 
CONFIDENTIAL 
 
 
201584 
8 
 
1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for protocol 201584. 
GlaxoSmithKline 
Document Number 
Date 
Version 
2015N248866_00 
2016-MAY-26 
Original 
2015N248866_01 
2016-DEC-13 
Amendment No. 1 
The reasons for this amendment were to:  added new primary Medical Monitor contact 
information; added lipid objective and endpoint back in to the table within the 
Synopsis section; added clarification of text for patient reported outcome endpoints; 
added additional clarification regarding provision of CAB LA and RPV LA until 
available through public/government health sectors; new text added to allow use of 
local labs to determine eligibility in exceptional circumstances; updated Time and 
Events Table to provide more clarity around assessments conducted during the 
Extension Phase, added ‘X’ to include collection of cardiovascular risk information at 
Screening, added temperature to Vital Signs row, added row for randomization, and 
clarified timings for completion of patient reported questionnaires relative to other 
clinical assessments in the table footnotes; clarified timing of dosing for 
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC, Triumeq) for the Day 1 visit; 
added additional clarification that participants of child bearing potential must continue 
contraception for at least 52 weeks after the last injection; revised text to say that 
Investigators may provide ‘bridging’ supply after consultation with Medical Monitor 
(vs Medical Monitor authorizing bridging supply); provided clarification that 
cabotegravir and rilpivirine exposure may persist for more than one year in some 
participants after intramuscular administration (with added references); minor edits to 
prohibited medication information; added statement that drugs that cause Torsade de 
Pointes should be used with caution when taking rilpivirine; additional clarification 
that background NRTI therapy is not considered Investigational Product and 
accountability will not be done for NRTI background; changed film coat color for 
Tivicay (dolutegravir) from white (clinical trial material supply) to yellow (commercial 
supply) and removed statement to “protect from light” (for both Triumeq and Tivicay); 
sentence added for collection of additional details for the injection device used for IM 
administration; additional information included regarding randomization schedule; 
added text stating the investigator must discuss long-term commitment for the study 
with potential participants; added statement regarding serofast RPR results; allowed 
serum pregnancy testing where required locally (e.g. when urine testing is not 
available); removed duplicate text regarding monitoring for suicidal related events; 
added option for patient reported outcomes to be collected on paper instrument if 
needed; removed information in Appendix requiring collection of pregnancy 
information for female partners of male study participants; definition of ACCEPT, 
HIVTSQc, and HIVTSQs added to abbreviations table, duplication of ICH 


 
CONFIDENTIAL 
 
 
201584 
9 
 
abbreviation removed; other minor corrections (e.g., updated references, adding cross 
reference to sections, correction of hyperlink to one table). 
2015N248866_02 
2017-JUL-19 
Amendment No. 2 
The reasons for this amendment are as follow:  update of contact information for 
secondary Medical Monitor; modify text to allow dose reduction for participants who 
have a decline in creatinine clearance to <50 mL/min;  clarify that for participants not 
eligible to continue into the Maintenance Phase, only samples with HIV-1 RNA 
> 400 c/mL will be sent for resistance testing; add mitigation for ECG pad removal; 
clarify ± 3 day window is for all oral dosing (both Induction and Maintenance Phase); 
add "LA Arm" back to columns for Week 68, 76, 84, 92 on Time and Events Schedule 
(hidden when column was narrowed); clarify Week 104b visit is specific to those 
participants transitioning from oral IP to CAB LA + RPV LA; clarification added to 
footnote ‘p’ that genetics sample can be collected at any visit after signing informed 
consent, but Week [-20] preferred; correct footnote on Week 5 visit to reflect footnote 
't'; add footnote 'y' back to Time and Events column for Withdrawal Visit (for 
Induction Phase); add clarification to Time and Events column that ISR assessments 
are only conducted for participants receiving injections; remove text from Section 12.2: 
‘In addition, all deaths related to an AE are to be classified as grade 5.’  Administrative 
typographical errors corrected (e.g. clarification provided regarding genetics sample 
taken after participants are enrolled into the study [vs when participants are 
randomized]), and investigator brochure references updated. 
2015N248866_03 
2018-JUN-25 
Amendment No. 3 
Changes for Amendment 3 were made to the protocol to manage and mitigate risks 
following identification of a potential safety issue related to neural tube defect in 
infants born to women with exposure to dolutegravir (DTG) at the time of conception. 
A Risk Assessment table was added to include language regarding risk and mitigation 
of neural tube defects seen with DTG. 
• The withdrawal criteria were updated to include a reminder that females of 
reproductive potential who change their minds and desire to be pregnant should 
also be withdrawn from the study. 
• The Time and Events table was updated to include a reminder for investigators to 
check at every visit that females of reproductive potential are avoiding pregnancy. 
Additionally, clarifications were provided for the following: 
• the DTG IB should be referenced for additional risks, safety information, drug 
interactions, etc.; 
• ‘suspected’ was added to the text prior to the bulleted definition of suspected 
virologic failure in Section 5.4.5.3.; 
• specific storage conditions were removed from the protocol for IP, and a 
statement added to store according to product label; 
• insulin was removed from the section regarding clinical assessments performed 
during the study; 


 
CONFIDENTIAL 
 
 
201584 
10 
 
• timeframe for pregnancy reporting and follow-up were updated to 24 hours to 
align with current reporting process; 
• prescribing information and IB references were updated. 
2015N248866_04 
2018-SEPT-24 
Amendment No. 4 
The primary reason for protocol amendment 04 is to allow an optional (vs mandatory) 
oral lead-in for participants randomized to the ABC/DTG/3TC arm who choose to 
continue into the Extension Phase of the study and receive CAB LA + RPV LA.  The 
Appendix for contraceptive guidance and collection of pregnancy information was 
updated to be consistent with current protocol template text.  Other minor clarifications 
were made as needed, e.g., the eCSSRs timing in the footnote for the Time and Events 
Table, updated abbreviations, etc. 
2015N248866_05 
2020-MAY-20 
Amendment No. 5 
The reason for protocol amendment 05 is to include an Appendix with Covid-19 
guidance for clinical trial continuity (participant and study management) during the 
pandemic.  This appendix will replace the previous Appendix 9, and Appendix 9 
“Protocol Amendment History,” will be included as Appendix 10.  
 
TMF-13030701 
2021-AUG-21 
Amendment No. 6 
The primary purposes of this amendment are: 
• To allow participants who become pregnant while in the study to remain in the 
study and not be withdrawn due to pregnancy. Allowing pregnant participants 
to continue in the study will negate any additional and subsequent fetal 
exposures to new antiretroviral agents that would occur if the pregnant 
participant was withdrawn from the study and placed on an oral SOC regimen. 
An appendix, “Information and Guidance for Managing Pregnant Participants” 
was inserted as Appendix 10 and all subsequent appendices were renumbered 
accordingly. 
• Contraceptive methods have been updated to permit the use of progestogen-
only implantable and injectable contraceptives without the requirement of a 
second highly effective method. 
• Removal of the optional collection of cord blood and/or breast milk after 
delivery. 
• Removal of the option for study treatment rechallenge following suspected 
drug-induced liver injury (DILI). 
• Clarification of which participants enter the LTFU phase when CAB+RPV LA 
marketed product is locally available. 
• Medical Device reporting requirement added. 
• Co-enrolment (only applicable for eligible female participants in South Africa 
in the ACTG A5392 study). 
• Updates to primary and secondary Medical Monitors. 


 
CONFIDENTIAL 
 
 
201584 
11 
 
Other additional edits were made, for clarity and/or correction. 
TMF-147-28112 
2022-JUN-17 
Amendment No. 7 
The primary purposes of this amendment are: 
• To include the Sub-Cutaneous Abdominal Injection Sub-Study appendix (only 
applicable for countries participating in the Sub-Study).  
• Clarification added: In Russia, subjects who become pregnant while on study 
may not elect to remain on study treatment and must withdraw and enter the 
LTFU Phase. 
Inclusion of Appendix 13: Mitigations for Geopolitical Situation in Russia/Ukraine 
TMF-15038148 
2022-OCT-21 
Amendment No. 8 
This amendment is considered to be substantial based on the criteria defined in EU 
Clinical Trial Regulation No 536/2014 of the European Parliament and the Council of 
the European Union. 
Overall Rationale for the Amendment: 
The primary purposes of this amendment are: 
• • To include the Sub-Study Interim Analysis 1: ISR Monitoring Criteria into the 
Sub-Cutaneous Abdominal Injection Sub-Study appendix (only applicable to 
for countries participating in the Sub-Study). 
• • To include the Sub-Study Interim Analysis 2: Week 9 Safety and PRO 
Review into the Sub-Cutaneous Abdominal Injection Sub-Study appendix (only 
applicable for countries participating in the Sub-Study). 
TBD 
TBD 
Amendment No. 9 
This amendment is considered to be substantial based on the criteria in EU Clinical 
Trial Regulation No 536/2014 of the European Parliament and the Council of the 
European Union. 
The primary purposes of this amendment are to update the Potential Risk of Clinical 
Significance of Hypersensitivity Reactions (HSR) when using integrase inhibitors, 
such as CAB. 
1.1. 
RAP Amendments 
Revision chronology:  
RAP Section 
Amendment Details 
Reporting and Analysis Plan_201584_Final_V1 [17-AUG-2018] 
Reporting and Analysis Plan_201584_Amendment_Final_V1 [17-SEPT-2018] 


 
CONFIDENTIAL 
 
 
201584 
12 
 
RAP Section 
Amendment Details 
Reporting and Analysis Plan_201584_Amendment_2_Final_V1  
Japan Specific Reporting Requirements for 
Regulatory Submission 
• 
Added data displays to be generated for 
Japan participants: study population, efficacy, 
safety, and pk.  
• 
Added details for the analysis of PK samples 
for participants in Japan, including estimation 
of PK parameters by non-compartmental 
methods using concentration-time day on Day 
1. 
• 
Added analysis population for Japan PK. 
Adverse Events of Special Interest 
• 
Harmonized list of Adverse Events of Special 
Interest with that used in the Week 48 
integrated analysis of safety summaries (with 
grouping based on clinical review of preferred 
terms and Standardized MedDRA Queries 
(SMQs)) 
Updated PK/PD analysis plan for Week 96 
• 
Removed Last CAB/RPV Trough 
Concentration as a candidate predictor of 
efficacy outcomes at Week 96 (as this 
covariate is confounded with accumulation 
overtime).  
• 
Removed PK/PD efficacy displays related to 
Last CAB/RPV Trough Concentration (as this 
covariate is confounded with accumulation 
overtime). 
• 
Added condition that PK/PD efficacy 
analysis/displays will only be produced if the 
Week 96 dataset includes at least one new 
CVF since the Week 48 analysis  
• 
Clarified that the following PK/PD safety 
figures will not be produced at Week 96 given 
limited PK collection post W48: 
o Scatter Plot of Maximum Change 
from Maintenance Baseline (Day 1) in 
ALT/Bilirubin versus Last Trough 
CAB/RPV PK Concentrations  
o Box Plot of Maximum Toxicity Grades 
of Most Frequently Reported Non-
ISR AEs versus Last Trough 
CAB/RPV PK Concentrations 
Data Handling 
• 
Minor update to the algorithm used to assign 
data to the Extension phase to account for 
direct to inject vs. start with oral lead-in. 
• 
Minor correction to W96 visit window for CD4+ 
cell count data and NRS questionnaire data. 


 
CONFIDENTIAL 
 
 
201584 
13 
 
RAP Section 
Amendment Details 
• 
Added Region (country grouping) and 
Baseline Integrase L74I mutation as subgroup 
variables 
• 
Clarified definition of Hepatitis B and C status 
at Baseline 
• 
Updated imputation rule for adverse events 
with partial end dates (to use last contact date 
instead of treatment stop date). 
• 
Clarified analysis visit assignment for LTFU 
PK samples. 
• 
Update the rationale for the prespecified list of 
mutations associated with resistance to 
integrase strand transfer inhibitors based on 
2019 IAS-US guideline. 
Data Displays 
• 
The following data displays were added for 
Week 96: 
• 
Summary of Change from Plasma HIV-1 RNA 
(log10 c/mL) by Visit (Maintenance Phase) 
• 
Unadjusted Treatment Difference in Proportion 
(95% CI) of Subjects with HIV-1 RNA >= 50 
c/mL (and <50 c/mL) at Week 96 by Selected 
Demographic Subgroups (Maintenance 
Phase) - Snapshot Analysis 
• 
Unadjusted Treatment Difference in Proportion 
(95% CI) of Subjects with HIV-1 RNA >= 50 
c/mL (<50 c/ml) at Week 96 by Selected HIV 
Disease Characteristic Subgroups 
(Maintenance Phase) - Snapshot Analysis 
• 
Summary of Plasma CAB/RPV PK 
Concentration -Time Data by Treatment and 
Visit (Maintenance Phase) – Included Log-
transformed Statistics by Hepatitis C Status at 
Induction Baseline 
• 
Individual Plasma CAB/RPV Concentration-
Time Plots (Semi-Log) -- Post Last Injection 
for Subjects in LTFU 
• 
Listing of Plasma CAB/RPV PK 
Concentration-Time Data (LTFU Phase) 
• 
Listing of Concomitant Medications for 
Subjects with Confirmed Virologic Failure 
• 
Summary of Shift in BMI Categories at Week 
96 
• 
Summary of Shift in BMI from Induction 
Baseline (Week -20) to Maximum Post-
baseline Category (Maintenance Phase) 


 
CONFIDENTIAL 
 
 
201584 
14 
 
RAP Section 
Amendment Details 
• 
Scatter Plot of Maximum vs. Extension 
Baseline (Week 100) for ALT (Extension 
Phase) – Switch Q4W IM 
• 
Scatter Plot of Maximum ALT vs. Maximum 
Total Bilirubin (Extension Phase) – Switch 
Q4W IM 
• 
Matrix Plot of Maximum Liver Chemistries 
(Extension Phase) – Switch Q4W group 
• 
Summary tables for Adverse Events of Special 
Interest 
• 
Listing of All Adverse Events  
• 
Listing of all Subjects Meeting Liver Stopping 
Criteria 
• 
Summary of HIVTSQs - Change from 
Maintenance Baseline (Day 1) in Individual 
Item Score by Visit - LOCF (Maintenance 
Phase) 
• 
Listing of All Genotypic Data 
• 
Summary of Viral load, Genotypic and 
Phenotypic data for Subjects Who Met 
Confirmed Virologic Failure (Maintenance + 
Extension Phase) — Randomized Q4W arm 
• 
Summary of Viral load, Genotypic and 
Phenotypic data for Subjects Who Met 
Confirmed Virologic Failure Criteria (Extension 
Phase) — Switch Q4W IM 
• 
Updated the following table to present 
minimum NCEP Category instead of 
Maximum: 
o Summary of Changes in Maintenance 
Baseline (Day 1) NCEP Fasting Lipid 
Category to Minimum Maintenance 
Phase Category – HDL Cholesterol   
• 
Added further stratification by ‘any history’ vs. 
‘no history’ for the following table:  
o Summary of Depression, Anxiety and 
Suicidal Ideation/Behaviour Adverse 
Events by System Organ Class, 
Maximum DAIDS Toxicity Grade, and 
History of Depression, Anxiety and 
Suicidal Ideation/Behaviour at 
Screening 
• 
Updated some display titles in Appendix 14: 
List of Data Displays.  
Reporting and Analysis Plan_201584_Amendment_3_Final_V1  
Data Handling and Data Displays for Week 124 
• 
Clarified extension phase analyses window for 
AE data in Table 16 


 
CONFIDENTIAL 
 
 
201584 
15 
 
RAP Section 
Amendment Details 
• 
Clarified derivation of Extension Phase extent 
of exposure in Section 14.6.2. 
• 
Added treatment group descriptors for Switch 
Q4W (Direct to Inject) and Switch Q4W (Oral 
Lead-In) in Table 3. 
• 
Added list of specific data displays to be 
produced for the Week 124 analysis to Section 
14.15. 
Reporting and Analysis Plan_201584_Amendment_4 
Data Handling and Data Displays for Sub-study 
• 
Updated visit/phase slotting algorithms to 
handle the newly added sub-study 
assessments and time points in the protocol. 
• 
Added new analysis populations for sub-study 
analysis. 
Defined a separate list of displays for sub-study 
analysis including a cut set of listings due to use of 
the RAPIDO DV. 
Safety Analysis 
• 
Added details of sub-study interim analyses 
including monitoring for ISRs of interest. 
• 
Added calculation methods for extent of 
exposure in sub-study. 
• 
Extended lipid LOCF approach to include both 
SC Injection and Return to Gluteal Injection 
phases in sub-study. 
• 
Added display shells for summaries of COVID-
19 assessments including accommodation of 
possible scenarios of multiple COVID-19 case 
diagnoses per participant. 
PK Analysis 
• 
Added analysis methods for PK parameters 
derived from sub-study concentration-time 
data including interim analyses 
• 
Extended evaluability criteria to include sub-
study PK concentration data. 
Study Population Analysis 
• 
Added windows for evaluating concomitant 
ART/non-ART medications in sub-study. 
• 
Added a/listings for data collected from the 
Transition to CAB + RPV LA Marketed Product 
Status eCRF form. 
Health Outcomes Analysis 
• 
Clarified that LOCF will no longer be used for 
HO analyses 
• 
Added analysis for the newly added 
questionnaires:  
1. Preference Subcutaneous Injection vs Gluteal 
Injection questionnaire. 
2. Reason for switch questionnaire 
• 
Interest in self administration questionnaire 


 
CONFIDENTIAL 
 
 
201584 
16 
 
RAP Section 
Amendment Details 
General Updates 
• 
Added Endpoint & Estimand text for the Sub-
study endpoints 
• 
Added sub-study Schedule of Activities per 
new protocol. 
• 
Added additional minor clarifications and 
corrections to typographical errors/formatting 
to RAP text. 
Reporting and Analysis Plan_201584_Amendment_5 
Data Handling for Sub-study 
• 
Updated visit/phase slotting algorithms to 
appropriately handle Adverse Events within 
the sub-study and clarified algorithm to ensure 
all records are associated with the correct 
visit. 
 
General Updates 
• 
Added additional minor clarifications and 
corrections to typographical errors/formatting 
to RAP text. 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
201584 
17 
 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There is a single deviation planned from protocol amendment #8 [(Dated: 21-OCT-
2022)]. Due to delay in study enrolment for implementation of protocol amendment 8, 
interim analysis 2 will include PK summaries while the protocol indicates that no PK 
analyses will be included.  
Table 1 
Changes to Protocol Defined Analysis Plan 
Protocol 
Reporting & Analysis Plan 
Statistical Analysis Plan 
Statistical Analysis Plan 
Rationale for Changes 
• 
Interim analysis 2 is planned to 
only summarize safety, 
tolerability, and HO data. 
• 
PK data available around 
the Week 9 Safety 
timepoint will also be 
analyzed 
• 
Delay in study start due to 
protocol amendment 8 
necessitated the need for 
an earlier reporting of PK 
data. 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary 
To demonstrate the non-inferior antiviral 
activity of switching to intramuscular CAB LA + 
RPV LA every 4 weeks (monthly) compared to 
continuation of ABC/DTG/3TC over 48 weeks 
in HIV-1 antiretroviral naïve participants. 
• Proportion of participants with a ‘virologic 
failure’ endpoint as per FDA Snapshot 
algorithm at Week 48 (Missing, Switch, or 
Discontinuation = Failure, Intent-to-Treat 
Exposed [ITT-E] population). 
Secondary 
To demonstrate the antiviral and immunologic 
activity of switching to intramuscular CAB LA + 
RPV LA every 4 weeks (monthly) compared to 
continuation of ABC/DTG/3TC. 
• Proportion of participants with plasma 
HIV-1 RNA <50 copies/mL (c/mL) at 
Week 48 using the FDA Snapshot 
algorithm (Intent-to-Treat Exposed [ITT-E] 
population). 
• Proportion of participants with plasma 
HIV-1 RNA <200 c/mL at Week 48 using 
the FDA Snapshot algorithm (ITT-E 
population). 
• Proportion of participants with plasma 
HIV-1 RNA <200 c/mL and HIV-1 RNA 
<50 c/mL at Week 96 using the FDA 
Snapshot algorithm (ITT-E population). 
• Proportion of participants with a ‘virologic 
failure’ endpoint as per FDA Snapshot 
algorithm at Week 96. 
• Proportion of participants with confirmed 


 
CONFIDENTIAL 
 
 
201584 
18 
 
Objectives 
Endpoints 
virologic failure at Week 48 and Week 96. 
• Absolute values and change from Baseline 
in plasma HIV-1 RNA (log10 copies/mL) at 
Week 48 and Week 96. 
• Absolute values and changes from 
Baseline in CD4+ cell counts over time 
including Week 48 and Week 96. 
• Incidence of disease progression (HIV-
associated conditions, acquired 
immunodeficiency syndrome [AIDS] and 
death). 
To evaluate the safety and tolerability of 
switching to CAB LA + RPV LA every 4 weeks 
(monthly) compared to continuation of 
ABC/DTG/3TC over time. 
• 
Incidence and severity of adverse events 
(AEs) and laboratory abnormalities over 
time including Week 48 and Week 96. 
• Proportion of participants who discontinue 
treatment due to AEs over time including 
Week 48 and Week 96. 
• 
Absolute values and changes in laboratory 
parameters over time including Week 48 
and Week 96. 
To evaluate the effects of CAB LA + RPV LA 
every 4 weeks on fasting lipids over time 
compared to continuation of ABC/DTG/3TC 
over time. 
• Change from Baseline in fasting lipids over 
time including Week 48 and Week 96. 
To assess the development of viral resistance 
in participants experiencing protocol-defined 
virologic failure. 
• Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV, 
and other on-study ART at Week 48 and 
Week 96. 
To characterize CAB and RPV concentrations 
and population pharmacokinetics (PK) and 
identify important determinants of variability. 
• Plasma PK parameters for CAB LA and 
RPV LA (when evaluable, Ctrough, 
concentrations post dose [~Cmax], and 
area under the curve [AUC]). 
• Demographic parameters including, but 
not limited to, age, sex, race, body weight, 
body mass index (BMI), and relevant 
laboratory parameters will be evaluated as 
potential predictors of inter- and intra-
participant variability for pharmacokinetic 
parameters.   
To assess the acceptance of pain and injection 
site reactions following injections. 
• Change from Week 5 in Dimension scores 
(e.g., “Bother of ISRs”, “Leg movement”, 


 
CONFIDENTIAL 
 
 
201584 
19 
 
Objectives 
Endpoints 
“Sleep”, and “Injection Acceptance”) and 
individual item scores assessing pain 
during injection, anxiety before and after 
injection, willingness to be injected in the 
future and overall satisfaction with mode of 
administration over time using the 
Perception of iNjection questionnaire 
(PIN).  
• Proportion of participants considering pain 
and local reactions following injection to be 
extremely or very acceptable based on the 
acceptability score over time using the 
Perception of iNjection questionnaire 
(PIN). 
To assess treatment satisfaction of CAB LA + 
RPV LA compared to continuation of 
ABC/DTG/3TC. 
 
• Change from baseline in total “treatment 
satisfaction” score, and individual item 
scores of the HIV Treatment Satisfaction 
Questionnaire (status version) (HIVTSQs) 
at Week 4b, Week 24, Week 44, Week 96 
(or Withdrawal). 
• Change in treatment satisfaction over time 
(using the HIVTSQc change version 
[HIVTSQc]) at Week 48 (or Withdrawal). 
To assess degree of health-related quality of 
life (HR QoL). 
• Change from Baseline in HR QoL using 
the HIV/AIDS targeted quality of life 
questionnaire (HAT-QoL) short format 
Week 24, Week 48, Week 96 (or 
Withdrawal). 
To assess health status. 
• Change from Baseline in health status at 
Week 24, Week 48, and Week 96 (or 
Withdrawal) using the 12-item Short Form 
Survey (SF-12). 
To assess treatment acceptance. 
• Change from Baseline in treatment 
acceptance at Week 8, Week 24, 
Week 48, Week 96 (or Withdrawal) using 
the “General Acceptance” dimension of 
the Chronic Treatment Acceptance 
(ACCEPT) questionnaire. 
To assess tolerability of injections. 
• Change from Week 4b in tolerability of 
injections at Week 5, Week 40, Week 41, 
and Week 96 using the Numeric Rating 
Scale (NRS) within the CAB LA + RPV LA 


 
CONFIDENTIAL 
 
 
201584 
20 
 
Objectives 
Endpoints 
arm. 
To evaluate the antiviral and immunologic 
effects, safety and tolerability, and 
development of viral resistance to CAB LA + 
RPV LA at Week 124 and over time for 
participants switching from ABC/DTG/3TC in 
the Extension Phase, with and without optional 
oral lead-in. 
• Proportion of participants with HIV-1 RNA 
≥ 50 c/mL at Week 124, with and without 
oral lead-in (FDA Snapshot algorithm, 
Extension Switch population). 
• Proportion of participants with plasma HIV-
1 RNA <50 c/mL and HIV-1 RNA 
<200 c/mL time over. 
• Proportion of participants with confirmed 
virologic failure over time. 
• Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB and 
RPV over time. 
• Absolute values and change from Baseline 
in CD4+ cell counts over time. 
• Incidence and severity of AEs and 
laboratory abnormalities over time. 
• Proportion of participants who discontinue 
treatment due to AEs over time. 
• Absolute values and change in laboratory 
parameters over time. 
To evaluate the pharmacokinetics of CAB and 
RPV in the setting of no oral lead-in for 
participants switching from ABC/DTG/3TC in 
the Extension Phase. 
• To evaluate plasma CAB and RPV 
concentrations over time (Week 100 
[direct to inject without oral lead-in] and 
Week 104 [both direct to inject and 
optional oral lead-in participants]) 
Exploratory 
To explore the effect of participant 
characteristics on the virologic and 
immunologic response of CAB LA and RPV LA 
compared to continuation of ABC/DTG/3TC. 
• Proportion of participants by patient 
subgroup(s) (e.g., by age, gender, BMI, 
race, HIV-1 subtype, Baseline CD4+) with 
Virologic Failure over time including Week 
48, and 96 using the Snapshot algorithm 
for the ITT-E population. 
• Proportion of participants by subgroup(s) 
(e.g. by age, gender, BMI, race, HIV-1 
subtype, Baseline CD4+) with plasma 
HIV-1 RNA <50 c/mL at Week 48 and 
Week 96. 
• Change from Baseline in CD4+ cell counts 


 
CONFIDENTIAL 
 
 
201584 
21 
 
Objectives 
Endpoints 
by subgroups at Week 48 and Week 96. 
To explore relationship(s) between plasma 
concentrations of CAB and RPV and 
pharmacodynamic endpoints. 
• Relationship between plasma PK 
concentrations and virologic, immunologic 
responses, and/or occurrence of adverse 
events [AEs] over time may be explored. 
To evaluate renal and bone biomarkers in 
participants receiving CAB LA and RPV LA 
compared to continuation of ABC/DTG/3TC 
over time. 
• Absolute values and change from Baseline 
in renal (in urine and blood) and bone (in 
blood) biomarkers over time including 
Week 48 and Week 96. 
To assess preference for CAB LA + RPV LA 
compared to oral antiretroviral (ARV) therapy 
using a single dichotomous preference 
question. 
• For participants randomized to the “CAB 
LA + RPV LA” arm, preference for CAB 
LA + RPV LA compared to oral ARV 
regimen, at Week 48. 
2.2.1. 
Subcutaneous Sub-study Objectives and Endpoints 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
Pharmacokinetic 
To evaluate PK of monthly dosing of 
CAB LA (200 mg/mL) with RPV LA 
(300 mg/mL) following SC 
administration in the anterior 
abdominal wall SC tissue compared 
with intramuscular administration in 
the gluteus medius muscle in HIV-1 
infected participants currently enrolled 
in the FLAIR Phase 3 study 
Plasma PK parameters for CAB LA 200 mg/mL and RPV 
LA 300 mg/mL (Ctau, concentrations 1-week post dose 
[~Cmax], and area under the curve [AUC (0-tau)]) for SC 
injections during the SC injection phase compared with 
similar PK parameters for gluteal IM injections 
Secondary Objectives 
Secondary Endpoints 
Safety and tolerability 
To assess safety and tolerability of 
monthly dosing of CAB LA 
(200 mg/mL) administered with RPV 
(300 mg/mL) LA following SC 
administration in the anterior 
abdominal wall SC tissue compared 
with intramuscular injections in the 
gluteus medius muscle in HIV-1 
infected participants currently enrolled 
in the FLAIR Phase 3 study 
 
To assess additional safety events 
including other AEs, SAEs, and safety 
labs of monthly dosing of CAB LA and 
RPV LA following SC injections in the 
Incidence and severity of ISRs and AEs of special 
interest during the SC injection phase.  
Proportion of participants who discontinue treatment due 
to ISRs and AEs of special interest during the SC 
injection phase. 
 
Incidence of other AEs not of special interest, SAEs and 
change in laboratory parameters from the last IM gluteal 
injection (prior to the SC abdominal Injection Phase) to 
the end of the SC injection phase (week 12). 


 
CONFIDENTIAL 
 
 
201584 
22 
 
Objectives 
Endpoints 
abdominal wall SC tissue in HIV-1 
infected participants currently enrolled 
in the FLAIR sub-study 
Virologic Response 
To assess the ability to maintain 
virologic suppression (HIV-RNA <50 
copies) in participants who transition 
from IM to SC administrations of CAB 
LA (200 mg/mL) plus RPV LA 
(300 mg/mL) in the FLAIR sub-study. 
To assess virologic non-response 
(HIV-RNA ≥50 c/mL and ≥200 c/mL) 
in participants who transition from IM to 
SC administrations of CAB LA 
(200 mg/mL) 
plus 
RPV 
LA 
(300 mg/mL) in the FLAIR sub-study. 
Proportion of participants with plasma HIV-1 RNA <50 
copies at week 12 during the SC abdominal injection 
phase using the FDA Snapshot algorithm. 
Proportion of participants with plasma HIV-RNA 
≥50 c/mL as per Food and Drug Administration (FDA) 
Snapshot algorithm at week 12 during the SC abdominal 
injection phase. 
Proportion 
of 
participants 
with 
protocol-defined 
confirmed virologic failure (CVF) of ≥200 c/mL at week 
12 during the SC injection phase. 
 
To assess viral resistance in 
participants experiencing protocol-
defined confirmed virologic failure. 
Incidence of treatment emergent genotypic and 
phenotypic resistance to CAB, RPV during the SC 
injection phase. 
Health Outcomes 
To assess patient reported outcomes 
during the SC injection phase by 
administering the following health 
outcome measurements: NRS, 
HIVTSQ (both s and c versions), and 
PIN. 
Numerical Rating Scale (NRS): To assess the 
tolerability of injections during both the SC abdominal 
and IM Gluteal Injection Phases, separate for CAB LA 
and RPV LA.  
HIVTSQ (both s and c versions): To measure levels of 
satisfaction and detect change in satisfaction when 
switching from IM gluteal to SC abdominal injections in 
total “treatment satisfaction” score, and individual item 
scores of the HIV Treatment Satisfaction Questionnaire 
(HIVTSQ) during the SC Injection Phase as well as 
change from SC during the Return to IM Gluteal Phase. 
Perception of injection questionnaire (PIN): To 
assess the acceptance of pain and injection site 
reactions following SC abdominal and IM gluteal 
injections separate for CAB LA and RPV LA. 
To assess participant’s preference of 
SC injections during the SC 
abdominal injection phase compared 
to IM gluteal injections. 
Preference Questionnaire: To assess patient’s 
preference, and reasons for preference, for injections 
received during the SC Injection Phase compared with 
prior IM gluteal injections as well as for injections 
received during the Return to Gluteal phase compared 
with prior SC injections. 


 
CONFIDENTIAL 
 
 
201584 
23 
 
Objectives 
Endpoints 
Exploratory Objectives 
Exploratory Endpoints 
To assess reasons for switch to SC 
from IM injection and interest in a 
potential option for self-administration 
of SC injections 
Reasons for switch and interest for home 
administration options questions: To assess the 
reasons participants agreed to switch to a SC 
abdominal injection from a IM gluteal injection and their 
interest in a potential option for self-administration of 
SC injections. 


 
CONFIDENTIAL 
 
201584 
 
24 
 
2.2.1.1. 
Subcutaneous Sub-study Estimands 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
Primary Objective: To evaluate PK of monthly dosing of CAB LA (200 mg/mL) with RPV LA (300 mg/mL) following SC 
administration in the anterior abdominal wall SC tissue compared with intramuscular administration in the gluteus medius muscle 
in HIV-1 infected participants currently enrolled in the FLAIR Phase 3 study 
• Plasma PK 
parameters for CAB 
LA 200 mg/mL and 
RPV LA 300 mg/mL 
(Ctau, concentrations 
1-week post dose 
[~Cmax], and area 
under the curve 
[AUC (0-tau)]) for 
SC injections during 
the SC injection 
phase compared with 
similar PK 
parameters for gluteal 
IM injections 
Pharmacok
inetic 
Parameter 
& 
Pharmacok
inetic 
Concentrati
on 
 
CAB+R
PV LA 
IM vs. 
CAB+R
PV LA 
SC 
 
Ratio of geometric least squares 
(GLS) means of PK parameters 
between SC and IM injections and 
the corresponding 90% CI estimated 
via a linear mixed-effects model 
PK Concentration: 
Arithmetic mean, median, sd, min, 
max, 90% Confidence Interval (CI) 
for the mean (or 95% CI) 
PK parameters: 
Arithmetic mean, median, sd, min, 
max, 90% CI for the arithmetic 
mean, geometric mean, sd (log), 
• Study treatment discontinuation due 
to any reason: While-on-treatment 
strategy 
Rationale: Discontinuation of planned 
study treatment may bias the evaluation 
of Pharmacokinetic behaviour of study 
treatment so only samples collected 
while on treatment will be summarized.  
 


 
CONFIDENTIAL 
 
201584 
 
25 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
geometric %CV, 90% for the 
geometric mean  
Steady State: 
Point estimate and 90% CI of slope 
of log(concentration) vs. timepoint 
estimated via a linear mixed-effects 
model 
List summary statistics as needed 
Secondary Objective: To assess safety and tolerability of monthly dosing of CAB LA (200 mg/mL) administered with RPV 
(300 mg/mL) LA following SC administration in the anterior abdominal wall SC tissue compared with intramuscular injections in 
the gluteus medius muscle in HIV-1 infected participants currently enrolled in the FLAIR Phase 3 study 
 
To assess additional safety events including other AEs, SAEs, and safety labs of monthly dosing of CAB LA and RPV LA 
following SC injections in the abdominal wall SC tissue in HIV-1 infected participants currently enrolled in the FLAIR sub-study 
• Incidence 
and 
severity of ISRs and 
AEs 
of 
special 
interest during the 
SC injection phase.  
Safety 
 
CAB+R
PV LA 
(SC & 
IM) 
Frequency, 
percentages, 
and 
descriptive statistics 
 
• Study treatment discontinuation due 
to any reason: Treatment policy 
strategy 
Rationale: Safety data will be monitored 
throughout the study after the start of 
treatment. There is interest in evaluating 


 
CONFIDENTIAL 
 
201584 
 
26 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
• Proportion 
of 
participants 
who 
discontinue 
treatment due to 
ISRs and AEs of 
special 
interest 
during 
the 
SC 
injection phase. 
• Incidence of other 
AEs not of special 
interest, SAEs and 
change in 
laboratory 
parameters from the 
last IM gluteal 
injection (prior to 
the SC abdominal 
Injection Phase) to 
the end of the SC 
injection phase 
(week 12). 
and reporting safety events regardless of 
whether participants have completed 
treatment course or not. Safety events 
will be appropriately labeled as 
occurring during the IM or SC phases 
based on injections dates and 
summarized accordingly.   
 


 
CONFIDENTIAL 
 
201584 
 
27 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
Secondary Objective: To assess the ability to maintain virologic suppression (HIV-RNA <50 copies) in participants who transition 
from IM to SC administrations of CAB LA (200 mg/mL) plus RPV LA (300 mg/mL) in the FLAIR sub-study. 
To assess virologic non-response (HIV-RNA ≥50 c/mL and ≥200 c/mL) in participants who transition from IM to SC 
administrations of CAB LA (200 mg/mL) plus RPV LA (300 mg/mL) in the FLAIR sub-study. 
To assess viral resistance in participants experiencing protocol-defined confirmed virologic failure. 
• Proportion 
of 
participants 
with 
plasma HIV-1 RNA 
<50 copies at week 
12 during the SC 
abdominal injection 
phase 
using 
the 
FDA 
Snapshot 
algorithm. 
• Proportion 
of 
participants 
with 
plasma HIV-RNA 
≥50 c/mL as per 
Food 
and 
Drug 
Administration 
(FDA) 
Snapshot 
algorithm at week 
12 during the SC 
Safety 
 
CAB+R
PV LA 
SC 
The proportion of participants with 
plasma HIV-RNA >= or < 50 
copies/mL as per Food and Drug 
Administration (FDA) Snapshot 
algorithm at SC Injection Phase 
Week 12.  
The proportion of participants with 
confirmed virologic failure while on 
CAB+RPV LA SC. 
 
 
• Study treatment discontinuation due 
to lack of efficacy or other reasons 
that impact the viral load outcome: 
Composite strategy 
Rationale: “The presence of missing 
data due to lack of efficacy or 
discontinuation for other reasons on the 
primary endpoint is adequately 
accounted for in the FDA Snapshot 
Algorithm which frames the outcome 
around these events. Please see Section 
14.11 for details.” 
• Rescue medication use/Change in 
Background ART strategy: 
Composite strategy 
Rationale: “The presence of missing 
data due to a change in background 


 
CONFIDENTIAL 
 
201584 
 
28 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
abdominal injection 
phase. 
• Proportion 
of 
participants 
with 
protocol-defined 
confirmed virologic 
failure (CVF) of 
≥200 c/mL at week 
12 during the SC 
injection phase. 
medication is adequately accounted for 
in the FDA Snapshot Algorithm which 
employs a composite strategy in this 
regard, conservatively assuming that 
any participants who changed 
background ART without a current viral 
load and without discontinuing are 
classified as having HIV-1 RNA 
>50c/mL. Please see Section 14.11 for 
details.” 
• Incidence 
of 
treatment emergent 
genotypic 
and 
phenotypic 
resistance to CAB, 
RPV during the SC 
injection phase. 
Safety 
 
CAB+R
PV LA 
SC 
Prevalence of (% of participants 
with) Treatment Emergent 
Resistance Mutations (frequency 
count) 
Prevalence of (% of participants 
with) Phenotype, Replication 
Capacity (frequency count) 
• Missing data for any ICE including 
unevaluable sampling: While-on-
treatment strategy 
Rationale: “Should there be missing 
genetic data, it would be expected that 
any data collected while a participant is 
off study IP would be impacted 
differently that when they are on study 
IP. Therefore, only data collected and 
available while the participant was on 
study IP will be analyzed.” 


 
CONFIDENTIAL 
 
201584 
 
29 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
Secondary Objective: To assess patient reported outcomes during the SC injection phase by administering the following health 
outcome measurements: NRS, HIVTSQ (both s and c versions), and PIN. 
To assess participant’s preference of SC injections during the SC abdominal injection phase compared to IM gluteal injections. 
Exploratory Objective: To assess reasons for switch to SC from IM injection and interest in a potential option for self-
administration of SC injections 
• Numerical 
Rating 
Scale 
(NRS): 
To 
assess the tolerability 
of injections during 
both 
the 
SC 
abdominal and IM 
Gluteal 
Injection 
Phases, separate for 
CAB LA and RPV LA.  
• HIVTSQ (both s and 
c 
versions): 
To 
measure 
levels 
of 
satisfaction and detect 
change in satisfaction 
when switching from 
IM gluteal to SC 
abdominal injections 
Safety 
CAB+R
PV LA 
IM vs. 
CAB+R
PV LA 
SC 
 
Scale scores where prescribed, 
change from Baseline in repeated 
measures, frequency counts, and 
descriptive statistics 
• Missing data for any ICE including 
study treatment discontinuation: 
Treatment policy strategy 
Rationale: “HO assessments are 
administered to align at treatment 
specific timepoints (SC vs LA). They 
also account for differences in treatment 
by design and thus, significant deviation 
from the administration window is not 
expected to impact the outcome and 
data can be assumed to be missing at 
random. There is interest in evaluating 
and reporting HO data regardless of 
whether participants have completed 
treatment course or not. Imputation is 


 
CONFIDENTIAL 
 
201584 
 
30 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
in 
total 
“treatment 
satisfaction” 
score, 
and individual item 
scores of the HIV 
Treatment 
Satisfaction 
Questionnaire 
(HIVTSQ) during the 
SC Injection Phase as 
well as change from 
SC during the Return 
to IM Gluteal Phase. 
• Perception 
of 
injection 
questionnaire (PIN): 
To 
assess 
the 
acceptance of pain 
and 
injection 
site 
reactions following SC 
abdominal and IM 
gluteal 
injections 
separate for CAB LA 
and RPV LA. 
• Preference 
Questionnaire: To 
not considered appropriate for any of 
these measures. “ 
 


 
CONFIDENTIAL 
 
201584 
 
31 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
assess 
patient’s 
preference, 
and 
reasons 
for 
preference, 
for 
injections received 
during 
the 
SC 
Injection 
Phase 
compared with prior 
IM 
gluteal 
injections as well as 
for 
injections 
received during the 
Return to Gluteal 
phase 
compared 
with 
prior 
SC 
injections. 
• Reasons for switch 
and interest for 
home 
administration 
options questions: 
To 
assess 
the 
reasons participants 
agreed to switch to a 
SC 
abdominal 


 
CONFIDENTIAL 
 
201584 
 
32 
 
Endpoint 
Estimand 
Population Treatm
ent 
Summary Measure 
Intercurrent event (IE) / strategy / 
rationale 
injection from a IM 
gluteal injection and 
their interest in a 
potential option for 
self-administration 
of SC injections. 


 
CONFIDENTIAL 
 
201584 
 
33 
 
2.3. 
Study Design 
Overview of Study Design and Key Features 
 
¥ Participants who withdraw from IM CAB LA + RPV LA must enter the 52-week Long Term Follow-Up Phase 
Design 
Features 
• A Phase III, Randomized, Multicenter, Parallel-group, Open-Label, Switch 
from an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected 
Antiretroviral Therapy Naive Adult Participants 
• The FLAIR study comprises a Screening Phase (up to 35 days), an 
Induction Phase (Week [-20] to Day 1), a Maintenance Phase (Day 1 to 
Week 100), followed by an Extension Phase (post Week 100).  Additionally, 
any participant who receives at least a single dose of CAB LA and/or RPV 
LA and discontinues the CAB LA + RPV LA regimen will enter the Long-
term Follow-up Phase and will initiate highly active antiretroviral therapy 
(HAART) for at least 52 weeks after the last dose of CAB LA and/or RPV 
LA. 
Dosing 
• Induction Phase: oral ABC/DTG/3TC 
• Maintenance Phase: 1:1 randomization to CAB LA + RPV LA vs. continue 
oral ABC/DTG/3TC.   
• Extension Phase: CAB LA + RPV LA  
Time & 
Events 
• 
Refer to Appendix 2: Schedule of Activities 
Treatment 
Assignment 
• N =570 randomized at start of Maintenance Phase 
• At Week 100, participants randomised to the oral ABC/DTG/3TC arm 
meeting eligibility requirements will switch to CAB LA + RPV LA 
• GSK RandAll NG used to generate randomization schedules 
• Stratified Randomization by participants’ Induction Baseline HIV-1 RNA 
(<100,000, ≥ 100,000 c/mL) and gender at birth. 


 
CONFIDENTIAL 
 
201584 
 
34 
 
Overview of Study Design and Key Features 
Interim 
Analysis 
• IDMC analyses:  
• Futility analysis at 50% of participants completing Week 24 Continuous 
time monitoring of confirmed virologic withdrawal (CVF) until all 
participants complete Week 24 
• No study summary data according to actual randomized treatment groups 
will be available to sponsor staff prior to the planned Week 48 analysis. 
Planned 
Sponsor 
Analyses 
• The main analysis will be conducted to evaluate the primary objective of the 
study at Week 48.   
• An additional planned analysis at Week 96 will be conducted to evaluate 
long-term antiviral activity, safety, and tolerability and participant 
satisfaction of the regimens. 
• Further data cuts and analyses may be conducted as necessary in order to 
support regulatory submissions and publications. 
 
2.3.1. 
Subcutaneous Sub-Study Design 
The FLAIR amendment (sub-study) will consist of three phases including a Screening/IM 
Gluteal injection Phase (T-4 weeks with 1 gluteal injection interval of 4 weeks), a Sub-
Cutaneous Abdominal Injection Phase (12 weeks with 3 injection intervals of 4 weeks 
each) and a Return to Intramuscular Gluteal Injection Phase (8 weeks with 2 injection 
intervals of 4 weeks each). 80 participants will be targeted for enrollment in order to reach 
the 30-50 necessary to assess the primary PK endpoint as well as to achieve a more robust 
safety conclusion. At the conclusion of the sub-study, participants will have the option to 
continue on the FLAIR parent study or if commercial access is available, the participant 
can transition off the sub-study, complete their participation in the FLAIR study and 
proceed directly to commercially sourced CAB/RPV LA treatment.  
Figure 1 
Sub-Cutaneous Sub-Study Amendment Design (included as part of 
the Parent FLAIR Study) 
 
 


 
CONFIDENTIAL 
 
201584 
 
35 
 
2.4. 
Statistical Hypotheses / Statistical Analyses 
This study is designed to show that the antiviral effect of oral ABC/DTG/3TC followed 
by intramuscular CAB LA + RPV LA regimen is non-inferior to continuation of 
ABC/DTG/3TC at Week 48 of maintenance treatment.  Non-inferiority in the proportion 
of participants with HIV-1 RNA ≥ 50 c/mL at Week 48 for Intent-to-Treat Exposed (ITT-
E) population (per FDA’s snapshot algorithm) can be concluded if the upper bound of a 
two-sided 95% confidence interval for the difference in the proportion of participants 
with HIV-1 RNA ≥ 50 c/mL between the two treatment arms (CAB – ABC/DTG/3TC) is 
less than 6%. 
If fla is the proportion of participants with HIV-1 RNA ≥ 50 c/mL for the Q4W IM arm 
and fc is the proportion of participants with HIV-1 RNA ≥ 50 c/mL (per FDA snapshot 
algorithm) for the ABC/DTG/3TC arm, then the hypotheses can be written as follows: 
Ho: fla – fc ≥ 6% 
H1: fla – fc < 6% 


 
CONFIDENTIAL 
 
201584 
 
36 
 
3. 
PLANNED ANALYSES 
At least three analyses will be conducted to evaluate the objectives of the protocol: after 
all randomized participants have completed their visits at Week 48 and Week 96, 
respectively, and after all Extension switch participants have completed the Week 124 
visit.  The Week 48 analysis will be primary. Additional analysis will be conducted to 
evaluate the objectives of the sub-study after all participants have completed their EOS 
visit at Sub-study Week 20. A final End-of-Study analysis will be conducted when all 
participants have completed the study. 
3.1. 
Interim Analyses 
An Independent Data Monitoring Committee (IDMC) will be instituted to ensure external 
objective medical and/or statistical review of efficacy and safety in order to protect the 
ethical interests and well-being of participants and to protect the scientific validity of this 
study and study 201585.  
An IDMC will evaluate accumulating efficacy, tolerability / safety, and PK of CAB LA + 
RPV LA at predetermined times during the study.  An interim futility analysis will be 
performed with the intent of having approximately 50% of participants reaching Week 24 
and providing sufficient lead time to allow the IDMC to review the data prior to any 
participants reaching the Week 48 visit.  A futility rule based on Bayesian posterior 
predictive probability approach will be applied to assess the probability that CAB LA + 
RPV LA injectable regimen demonstrates non-inferiority to the continued 
ABC/DTG/3TC arm given the partial data set.  The Sponsor will remain blinded to this 
analysis.   
In addition, the IDMC may also monitor the incidence of participants meeting confirmed 
virologic failure criteria until all participants complete Week 24 to ensure that 
participants are not being sub-optimally treated in the CAB + RPV arm. 
Full details of the analyses, estimated timing and the decision criteria that will be used to 
determine regimen performance will be pre-specified in the IDMC Charter. 
3.1.1. 
Subcutaneous Sub-Study Interim Analyses 
The SC Sub-study will contain two interim analyses. Interim analysis 1 for ISR 
monitoring criteria will take place after 50% of participants (equating to 25 out of an 
expected 50) have experienced their first SC injection with a follow-up Week 1 visit. An 
in-stream safety data cut will be performed for ISR data including site reports of details 
of ISRs of interest which include grade 4 ISRs and grade 3 ISRs that include ulceration, 
secondary infection, phlebitis, sterile abscess, or drainage. The posterior probability that 
the rate of ISRs of interest will be calculated based on ISRs of interest collected through 
SC Week1 for each participant. If the Bayesian posterior probability that the true rate of 
ISRs of interest is >0.05 (equating to > 1 participant out of 25) is low (< 5%), then 
individual ISRs will undergo standard safety review. However, if the Bayesian posterior 
probability that the true rate of ISRs of interest is >0.05 is high (≥5%), then a formal 
review of all ISR safety data will take place by the VSLC with the potential consideration 
to pause SC injections. As enrollment will be staggered by country, if 3 participants 


 
CONFIDENTIAL 
 
201584 
 
37 
 
experience an ISR of interest prior to 25 participants reaching the SC Week 1 visit, VSLC 
review will automatically be triggered as 3 out of 25, or a sub-study rate of 0.12, would 
lead to the posterior probability of the rate of ISRs of interest >0.05 being >5%. 
Otherwise, VSLC will only be triggered based on the interim posterior probability being 
>5%. An evidence threshold of 5% gives us 95% confidence that the true rate of ISRs of 
interest is not >0.05 should our interim posterior probability not trigger a decision to 
bring forth formal VSLC review.  For further analysis details, see Section 8.6. 
Interim analysis 2 will take place within the subcutaneous sub-study once 50% of 
enrolled participants have completed their sub-study Week 9 visit. The 50% threshold 
will have been considered reached once 15-20 participants have completed their Week 9 
visit as aligned with the targeted population of 30-50 to assess the primary endpoint. The 
analysis will consist of an internal review of key PK, safety/tolerability, and preference 
endpoints in order to assist in compound development. No formal stopping decisions will 
be made. No formal data cleaning activities will occur. Data will be processed in stream 
with what is available at the time of the data cut. Queries will be issued in extreme 
circumstances. 
3.2. 
Final Analyses 
The primary analysis will be conducted to evaluate the primary objective of the protocol 
at Week 48.  These analyses will be performed after the completion of the following 
sequential steps: 
1. All participants have completed Week 48 and had a re-test if necessary.  
2. All required database cleaning activities have been completed and final database 
release and database freeze has been declared by Data Management. 
3. All criteria for unblinding the randomisation codes have been met. 
4. Randomization codes have been distributed according to Ramos NG procedures. 
Further analyses will be conducted at Week 96, Week 124, a sub-study analysis, and a 
final End-of-Study analysis will be conducted when all participants have completed the 
study. 


 
CONFIDENTIAL 
 
201584 
 
38 
 
4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
All Subjects Screened 
Population 
• Comprised of all participants screened for 
inclusion in the study.  
• Participants may be re-screened once, for 
which they will receive a new subject number.  
• Only the latest re-screening data will be 
included in the screening population 
summaries/analyses.  
• Study Population 
All Participants 
Enrolled 
• All enrolled participants who receive at least 
one dose of study drug in the Induction 
Phase. 
• Secondary 
population for 
some analyses 
Intent-to-Treat 
Exposed Population 
(ITT-E) 
• All randomized participants who receive at 
least one dose of IP during the Maintenance 
Phase of the study (on or after Day 1 visit). 
• Participants will be analyzed according to the 
randomized treatment regardless of what 
treatment was actually received. 
• Study Population 
• Efficacy 
 
Per-Protocol Exposed 
(PP) 
• Consist of all participants in the ITT-E 
Population with the exception of major 
protocol violators.   
• Protocol deviations that would exclude 
participants from the PP-E population are 
defined in Section 4.1 (Protocol Deviations) 
and Appendix 1 (Protocol Deviation 
Management and Definition for Per-Protocol 
Population). 
• This population is not applicable for the W124 
analysis. 
• Efficacy 
(Sensitivity 
Analysis) 
Safety 
• All randomized participants who receive at 
least one dose of IP during the Maintenance 
Phase of the study (on or after Day 1 visit).   
• Participants will be assessed according to 
actual treatment received. 
• Safety 
PK Population 
• All participants who receive CAB and / or RPV 
and undergo PK sampling during the study 
and provide evaluable CAB and /or RPV 
plasma concentration data (i.e., at least 1 
non-missing PK assessment (Non-
quantifiable [NQ] values will be considered as 
non-missing values)). 
• PK 


 
CONFIDENTIAL 
 
201584 
 
39 
 
Population 
Definition / Criteria 
Analyses Evaluated 
Confirmed Virologic 
Failure (CVF) 
• Comprised of all participants in the ITT-E 
population who met Confirmed Virologic 
Failure (CVF) 
*CVF during the Maintenance and Extension 
Phases is defined as: Rebound as indicated by 
two consecutive plasma HIV-1 RNA levels ≥200 
c/mL after prior suppression to <200 c/mL 
• Genotypic 
• Phenotypic 
• IDMC CVF 
Analysis 
All Participants 
Randomized 
Population 
• All randomized participants 
• Secondary 
population for 
some analyses 
Extension Switch 
Population (ES) 
• All randomized subjects from ABC/DTG/3TC 
arm who receive at least one dose of CAB 
and/or RPV during the Extension Phase of 
the study.   
• Participants will be assessed according to 
actual treatment received during the 
Extension Phase. 
• Safety and 
efficacy of 
switching to CAB 
LA + RPV LA, 
with and without 
oral lead-in. 
Long-Term Follow-up 
Population (LTFU) 
• All subjects receiving at least one dose of 
CAB LA and/or RPV LA who have 
discontinued the CAB LA+ RPV LA regimen 
and have a least one Long-Term Follow-up 
Phase clinic visit.    
• Safety and PK 
during LTFU 
Futility analysis 
population 
• Comprised of all participants in the ITT-E 
population who started study treatment at 
least 168 days prior to the IDMC cut-off date 
(in order to account for participants who 
withdrew early but would have achieved 
Week 24). 
• IDMC futility 
analysis 
Japan PK Population 
• All Japanese heritage participants (living in 
Japan) who receive CAB and / or RPV and 
undergo PK sampling and provide evaluable 
CAB and /or RPV plasma concentration data 
(i.e., at least 1 non-missing PK assessment 
(Non-quantifiable [NQ] values will be 
considered as non-missing values)).  PK 
assay results from samples collected from a 
subject with emesis occurring within 4 hours 
of the dose will not be considered as 
evaluable. 
• Japan PK 
displays 
Sub-study Screened 
• Comprised of all participants screened for 
inclusion in the sub-study.  
• Study Population 


 
CONFIDENTIAL 
 
201584 
 
40 
 
Population 
Definition / Criteria 
Analyses Evaluated 
• All screened participants will continue using 
their subject numbers received in the main 
study.  
Sub-study Enrolled 
• All participants who sign informed consent 
into the sub-study, excluding screen failures. 
• Study Population 
Sub-study Safety 
• All enrolled participants who received at least 
one CAB and/or RPV SC injection. 
 
• Study Population 
• Safety 
• Efficacy 
• Health Outcomes 
Sub-study 
Pharmacokinetic 
Concentration (PC) 
• All participants who received at least one 
CAB and/or RPV SC injection and provided at 
least one non-missing CAB and/or RPV 
plasma concentration value during the sub-
study value (non-quantifiable values will be 
considered as non-missing values).  
• PK Concentration 
and individual 
figures  
Sub-study 
Pharmacokinetic 
Parameter (PP) 
• All participants who received at least one 
CAB and/or RPV SC injection and had at 
least one evaluable PK parameter estimated 
during the sub-study. 
• PK Parameters 
NOTES:  
• Please refer to Appendix 14: List of Data Displays for Week 48/Week 96, Appendix 15: List of 
Data Displays for Week 124, Appendix 19: List of Data Displays for the Subcutaneous Sub-
Study, and Appendix 18: Japan-Specific Requirements which details the population to be used 
for each display being generated.   
• In all documents, datasets and data displays the term “Subject” and “Participant” are 
interchangeable. 
 


 
CONFIDENTIAL 
 
201584 
 
41 
 
4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed. 
Important deviations which result in exclusion from the analysis population will also be 
summarised and listed. (Please refer to Appendix 1: Protocol Deviation Management and 
Definitions for Per Protocol Population)]. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations and deviations which may lead to exclusion from the analysis are 
captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF. 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Randomized treatment groups will be displayed as shown in Table 2. 
Table 2 
Data Display Treatment Descriptors for Randomized Arms 
Treatment Group Descriptions 
RandAll NG Randomization System 
Data Displays for Reporting  
Code 
Description 
Description 
Order in TLF  
A 
CAB LA + RPV LA  
Q4W IM 
1 
B 
ABC/DTG/3TC 
ABC/DTG/3TC 
2 
 
Treatment comparisons will be displayed as follows using the descriptors as specified: 
• Q4W IM vs. ABC/DTG/3TC 
 
In data displays of Induction Phase data for the All Enrolled Population and Extension 
Phase data for the Extension Switch population, respectively, study treatment will be 
displayed as shown in Table 3. 


 
CONFIDENTIAL 
 
201584 
 
42 
 
Table 3 
Data Display Treatment Descriptors for All Enrolled Population and 
Extension Switch Population 
Data Type 
Descriptor 
Induction Phase Data for All Enrolled Population 
Induction Phase ABC/DTG/3TC 
Extension Phase Data for Extension Switch Population Switch Q4W IM (Direct to Inject)  
Switch Q4W IM (Oral Lead-In)  
 
5.2. 
Baseline Definitions  
For all assessments evaluated at Screening and/or Week -20 (including labs, vital signs, 
ECGs, virology assessments, etc.), the Induction Baseline (Week -20) value will be the 
latest valid (e.g., fasting for lipids) Pre-treatment value observed. This is generally 
expected to be from the Week -20 visit, although such values may be missing, or 
unscheduled assessments may be performed before treatment start; however, for virology 
data, this is generally expected to be from the Screening visit (except in the case of CVF 
for which virology data is expected at Week -20). 
Electrocardiograms (ECGs) are to be performed in triplicate on Week -20 visit. The 
Induction Baseline (Week -20) value for an ECG parameter will be the mean of the last 
pre-treatment set of assessments from the same date. 
If pre-treatment genotypic/phenotypic results are available from both the central 
laboratory and Monogram Biosciences, then Induction Baseline (Week -20) 
genotype/phenotype will be determined based only upon the data provided by Monogram 
assays.   
The baseline value for each phase of the study is defined as the last valid (e.g., fasting for 
lipids) value observed, up to and including date of first dose of study treatment in the 
respective phase as described in Table 4.  
Baseline values for the sub-cutaneous sub-study will be assigned as the last observation 
prior to the first CAB and/or RPV SC injection in the subcutaneous abdominal phase. 
Table 4 
Baseline Definitions for Each Study Phase 
Definition 
Reporting Details 
Induction Baseline (Week -20) 
Last available recorded value up to and 
including the date of first Induction Phase 
dose of IP 
Maintenance Baseline (Day 1) 
Last available recorded value up to and 
including the date of first Maintenance Phase 
dose of IP 
Extension Baseline (Week 100) 
Last available maintenance phase recorded 
value up to and including the date of first 
Extension Phase dose of IP (Oral CAB/RPV 
or CAB/RPV LA) 


 
CONFIDENTIAL 
 
201584 
 
43 
 
Definition 
Reporting Details 
• only applicable to the Extension Switch 
population participants. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
5.3. 
Multicentre Studies 
Data will be summarized for all centres combined. Country will be treated as an 
exploratory subgroup for analyses of the primary efficacy endpoint as described in 
Section 7.1.5.1. and secondary efficacy endpoint (HIV-1 RNA <50 c/mL) as described in 
Section 7.2.5.1. Some countries may be combined for exploratory subgroup analyses with 
consideration due to the number of participants enrolled.  
5.4. 
Examination of Covariates, Other Strata and Subgroups 
5.4.1. 
Covariates and Other Strata 
The list of covariates and other strata may be used in descriptive summaries and 
statistical analyses, some of which may also be used for subgroup analyses. Additional 
covariates and other strata of clinical interest may also be considered. 
Category 
Details 
Strata 
Randomization Strata: 
• 
For the proportion of participants with plasma HIV-RNA greater than or 
equal to 50 c/mL per FDA Snapshot algorithm at Week 48 (primary 
endpoint), a stratified analysis with Cochran-Mantel Haenszel weights will 
be used to adjust the primary treatment comparison for the randomization 
strata corresponding to sex at birth and Induction Baseline (Week -20) HIV-
1 RNA (<100,000, ≥100,000 c/mL).  A similar approach will be used to 
adjust the analysis of the proportion of participants with HIV-1 RNA <50 
c/mL (per the FDA’s Snapshot algorithm) at Week 48 (key secondary 
endpoint) and repeat analyses of these endpoints at Week 96.   
See Section 7.1.5 for more details on the statistical analysis methodology. 
Other 
Subgroups/Covariates 
See details in Section 5.4.2 
Subcutaneous Sub-Study 
Covariate 
Sub-study Baseline BMI 
The primary endpoint comparison between the SC and IM PK parameters as 
well as ISR incidence between SC and IM will be calculated considering 
Baseline BMI taken at the start of sub-study SC dosing as a covariate to 
account for potential individual differences in compound distribution. The 
following levels will be used: 
• 
BMI ≥ 30 kg/m2 
• 
BMI < 30 kg/m2 


 
CONFIDENTIAL 
 
201584 
 
44 
 
5.4.2. 
Examination of Subgroups/Covariates 
The following is a list of subgroups that may be used in descriptive summaries and 
statistical analyses. Additional subgroups of clinical interest may also be considered. 
• 
If the percentage of participants is small within a particular subgroup, then the 
subgroup categories may be combined prior to unblinding the trial. 
• 
If the category cannot be refined further, then descriptive rather than statistical 
comparisons may be performed for the particular subgroup. 
• 
For subgroup analysis, per European Medicines Agency Guideline on the 
investigation of subgroups in confirmatory clinical trials (EMA, 2013), factors 
defining a subgroup population may be put in three categories:  
EMA Subgroup Category 1: Factors with strong reason to expect a heterogeneous 
response to treatment. In this case separate trials should usually be planned. There 
are no factors falling into this category in this study.  
EMA Subgroup Category 2: Factors with at least some biological plausibility or 
external evidence such that a heterogeneous response might be hypothesized. In this 
study, stratified randomisation strata, key demographic and baseline characteristic 
factors, will fall into this category. For these factors, subgroup analyses will be 
performed but likely underpowered so that a formal proof of efficacy will not be 
available individually in all subgroups. If consistent findings across multiple 
comparisons were observed, then these analyses would still be suggestive of a 
generalizable finding from the overall population.  
EMA Subgroup Guideline Category 3: Factor with good argumentation why 
homogeneity of response to treatment is plausible.  The impact of factors falling into 
this category will be explored.  
Additional covariates of clinical interest may also be considered. 
Category 
Covariates and / or Subgroups 
EMA Subgroup Category 2: 
Stratified Randomisation Strata 
• Induction Baseline (Week -20) HIV-1 RNA (<100,000, 
≥100,000 c/mL) 
• Gender at birth (Male, Female) 
For analysis purposes, randomization strata will be derived 
using eCRF data, even if this differs from the strata captured 
in RAMOS NG. 
All statistical analyses will adjust for the above randomization 
strata, unless stated otherwise. Treatment-by-Strata 
interactions will be assessed as specified in the analysis 
sections. 
Demographic and Baseline 
Characteristic Subgroups  
• Age: 


 
CONFIDENTIAL 
 
201584 
 
45 
 
Category 
Covariates and / or Subgroups 
o <35; 35-<50; ≥50 (for statistical modelling 
analysis, the first two groups will be combined, 
i.e., <50, ≥50) 
• Race: 
o White; Non-White (for statistical modelling 
analysis) 
o Black/ African American; Non- Black/ African 
American 
• Country (not used for statistical modelling) 
o Canada; 
o France; 
o Germany; 
o Italy; 
o Japan  
o The Netherlands; 
o Russian Federation; 
o South Africa; 
o Spain; 
o United Kingdom; 
o United States 
• Region 
o Western/Central Europe and North America 
(grouping of Canada, France, Germany, Italy, 
The Netherlands, Spain, United Kingdom, United 
States) 
o Japan;  
o Russian Federation; 
o South Africa. 
• Induction Baseline (Week -20) HIV-1 RNA c/mL  
o <1000;  
o 1000 to <10,000;  
o 10,000 to <50,000; 
o  50,000 to <100,000; 
o  ≥100,000 to <200,000; 
o  ≥ 200,000 c/mL 
The above subgroup with granular categories for viral load 
will not be used in statistical modelling. 
• Visit of First Suppression (HIV-1 RNA <50 c/mL)a:  
o Week -20 
o Week -16; 
o Week -12; 
o Week -8; 


 
CONFIDENTIAL 
 
201584 
 
46 
 
Category 
Covariates and / or Subgroups 
o Week -4 
• Maintenance Baseline (Day 1) HIV-1 RNA: 
o  <50;  
o ≥ 50 c/mL. 
• Induction Baseline (Week -20) CD4+ cell count: 
o  <200;  
o 200 to <350;  
o 350 to <500;  
o ≥ 500 cells/mm3. 
• Maintenance Baseline (Day 1) CD4+ cell count: 
o  <200;  
o 200 to <350;  
o 350 to <500;  
o ≥ 500 cells/mm3. 
• Derived Maintenance Baseline (Day 1) Centers for 
Disease Control and Prevention (CDC) category: 
o Stage I; 
o Stage II;  
o Stage III  
• HIV-1 Subtype at Induction Baseline (Week -20) 
o A; 
o A1; 
o AE; 
o AG; 
o B; 
o C; 
o Other 
o Missing 
• K103N Mutation at Induction Baseline (Week -20): 
o Yes vs. No 
• Induction Baseline (Week -20) BMI (<30, ≥ 30 kg/m^2) 
• L74I Integrase Mutation at Induction Baseline (Week -
20): 
o Yes vs. No (Note: do not derive is baseline 
integrase genotype is not available) 
EMA Subgroup Category 3: 
Additional subgroup/covariates 
for PK/PD efficacy analysis 
• Week 48 Analysis Only: Last CAB/RPV Trough (pre-
dose) PK concentration by Week 48 (i.e., If pre-dose PK 
concentration at nominal Week 48 is missing, then last 
pre-dose PK concentration prior to Week 48 will be used) 


 
CONFIDENTIAL 
 
201584 
 
47 
 
Category 
Covariates and / or Subgroups 
• Week 8 CAB/RPV Trough PK concentration (i.e., pre-
dose PK concentration at nominal visit of Week 8 
The above two covariates will be dichotomized into two 
subgroup factors as follows:  
• ≤ first Quartile vs > first quartile; 
• ≤ Median vs > Median 
• Needle length for CAB injection at Week 4b: (<2, ≥2 
inch); 
• Needle length for RPV injection at Week 4b: (<2, ≥2 
inch); 
See Section 8.5.1 for additional details regarding attribution 
of ISRs to causal agent (CAB/RPV) and Needle Length. 
• Induction Baseline (Week -20) BMI (<30, ≥ 30 kg/m^2) 
Additional subgroup/covariates 
for PK/PD safety analysis – 
Week 48 Analysis Only 
• Last CAB/RPV trough PK concentration  
For the plot of “Maximum Change from Maintenance 
Baseline (Day 1), CBF, in ALT/Total Bilirubin versus Last 
Trough CAB/RPV PK Concentrations”, Last CAB/RPV 
Trough PK concentration is the most recent trough PK 
concentration prior or equal to the date of the earliest Lab 
assessment corresponding to the maximum CFB during the 
Maintenance Phase. 
For the Plot of “Maximum Toxicity Grades of Most Frequently 
Reported AEs versus Last Trough CAB/RPV PK 
Concentrations”, Last CAB/RPV Trough PK concentration is 
the most recent trough PK concentration prior or equal to the 
earliest onset date of maximum graded AE (for each 
preferred term among non-ISR AEs occurring in ≥5% of 
participants in the Q4W arm during the Maintenance Phase).  
If a participant does not experience the corresponding 
preferred term event during the Maintenance Phase, then the 
last trough value during the Maintenance Phase will be used 
for the plot. 
Additional subgroup for Bone 
Marker analysis 
• 
Induction Baseline (Week -20) BMI (kg/m^2)  
o <30;  
o  ≥ 30  
• Smoking status at Screening: 
o Never; 
o Current; 
o Former 


 
CONFIDENTIAL 
 
201584 
 
48 
 
Category 
Covariates and / or Subgroups 
• Tenofovir Disoproxil Fumarate (TDF) Use at 
Maintenance Baseline (Day 1) 
o Yes; 
o No 
Additional subgroup for ISR 
For each common ISR preferred term (pain, induration, 
nodules and any other ISR with >=5% participants during the 
Maintenance Phase, Maintenance + Extension Phase (for 
Randomized Q4W), and Extension Phase (for Switch Q4W), 
respectively: 
• Needle Length for Last CAB Injection prior to and 
including the onset date of the earliest corresponding 
drug-related CAB ISR with maximum toxicity grade 
during the phase(s) of interest: (<2, ≥2 inch); 
• Needle Length for Last RPV Injection prior to and 
including the onset date of the earliest corresponding 
drug-related RPV ISR with maximum toxicity grade 
during the phase(s) of interest: (<2, ≥2 inch); 
The above subgroup variables will be produced for each 
common ISR preferred term. 
Note: If there is no ISR of interest reported during the 
phase(s) of interest for a participant, these subgroup 
variables will be derived using the needle length of the 
participant’s last injection during the phase(s) of interest. 
Subcutaneous Sub-Study subgroups 
Demographic, Efficacy, Safety, 
PK, & HO Subgroups 
• Age: 
<35; 35-<50; ≥50  
• Sex at birth  
Male, Female 
• Race/Ethnicity  
White: Non-Hispanic, White: Hispanic, Black, Asian, Other 
• Sub-study Baseline BMI 
<30 kg/m2, ≥30kg/m2 
a) Based on any HIV-1 RNA <50 c/mL within the assessment window defined in Table 14. 
 
5.5. 
Multiple Comparisons and Multiplicity 
5.5.1. 
Primary Comparison of Interest 
The primary analysis will be based on the ITT-E population.  The primary comparison 
will be made at a one-sided 2.5% level of significance.  Treatment with Q4W IM will be 
declared non-inferior to ABC/DTG/3TC if the upper end of a two-sided 95% confidence 
interval for the difference between the two groups (Q4W IM– ABC/DTC/3TC) in the 


 
CONFIDENTIAL 
 
201584 
 
49 
 
proportion of participants with HIV-RNA ≥50 c/mL at Week 48 (defined by the US FDA 
snapshot algorithm) lies below 6%. 
The primary comparison of interest is the comparison between Q4W IM and 
ABC/DTC/3TC for the primary endpoint in the ITT-E population. This analysis will be 
adjusted for by the stratification factor applied at randomization. 
If the primary analysis shows non-inferiority, then a superiority hypothesis will be tested 
at the two-sided 5% level of significance. Superiority favoring CAB LA + RPV LA will 
be declared if the upper end of the confidence interval is below 0% for the ITT-E 
population analysis. If superiority is declared, the p-value for superiority will also be 
calculated. 
5.5.2. 
Other Comparisons of Interest 
The analysis described above will also be performed using the PP population and the 
results will be compared for consistency with the results from the ITT-E population.   
5.5.3. 
Secondary Comparisons 
If the primary comparison of interest (Section 5.5.1) using the ITT-E population 
demonstrates non-inferiority of Q4W compared to ABC/DTG/3TC then the following 
key secondary comparisons using the ITT-E population will be tested: 
• Treatment with Q4W IM will be declared non-inferior to ABC/DTG/3TC with 
respect to the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48 
(defined by the US FDA snapshot algorithm) if the lower end of a two-sided 95% 
confidence interval for the difference in response rates (Q4W IM– ABC/DTG/3TC) 
lies above -10%.  
• Superiority of Q4W IM compared to ABC/DTG/3TC with respect to change from 
maintenance baseline (Day 1) HIVTSQs total score at Week 44 using a two-sided 5% 
level of significance. 
• Changes in the PIN acceptance score within the Q4W arm over time using separate 
two-sided 5% level of significance tests for the change from Week 5 to Week 41 and 
change from Week 5 to Week 48, respectively. 
There are no planned adjustments for multiple comparisons or multiplicity.   
For the primary endpoint treatment comparison at Week 48, no multiple comparison 
adjustment is necessary for testing non-inferiority followed by superiority (conditional on 
achieving a significant test for non-inferiority) since testing follows a pre-specified 
sequence of hypothesis such that if the first hypothesis tested is not significant, all 
subsequent tests will not be performed.  This fixed sequence procedure controls the type I 
error rate at the nominal level. 
In addition to the primary and the key secondary comparisons, the comparisons between 
two treatment arms for ACCEPT (general acceptance score), SF-12 (health status), and 


 
CONFIDENTIAL 
 
201584 
 
50 
 
HAT-QoL (Life satisfaction) at timepoints through Week 48 will also be performed as 
supportive analyses. 
Lastly, for the IDMC interim analyses, since the statistical stopping guidelines will not 
result in early stopping for positive efficacy findings, these interim treatment 
comparisons will not inflate the Type I error rate for the primary treatment comparison. 
5.5.3.1. 
Week 124 Extension Switch Analysis 
For the Week 124 Extension Switch population analysis, antiviral response will be 
assessed according to the proportion of participants with and without oral lead-in, 
respectively, who have HIV-1 RNA ≥50 c/mL at Week 124 (i.e., 24 weeks from initiation 
of CAB LA + RPV LA, +/- 6 week analysis window, using the FDA Snapshot 
algorithm), with corresponding 95% confidence interval.  The primary efficacy endpoint 
of interest for this analysis is the proportion of participants without oral lead-in who have 
HIV-1 RNA ≥50 c/mL at Week 124. No formal statistical comparisons with respect to 
safety and efficacy outcomes will be performed. 
5.5.3.2. 
Subcutaneous Sub-Study Analysis 
For the Subcutaneous sub-study analysis, select pharmacokinetic parameters from both 
the gluteal phase and the subcutaneous phase will be informally compared with a 
geometric mean ratio and corresponding 90% confidence interval. No formal statistical 
comparisons with respect to safety and efficacy outcomes will be performed. 
 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 


 
CONFIDENTIAL 
 
201584 
 
51 
 
Section 
Component 
Section 14.2 
Appendix 2: Schedule of Activities 
Section 14.3 
Appendix 3: Assessment Windows 
Section 14.4 
Appendix 4: Study Phases and Treatment State 
Section 14.5 
Appendix 5: Data Display Standards & Handling Conventions 
Section 14.6 
Appendix 6: Derived and Transformed Data 
Section 14.7 
Appendix 7: Reporting Standards for Missing Data 
Section 14.8 
Appendix 8: Values of Potential Clinical Importance 
Section 14.9 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses 
Section 14.10 
Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses 
Section 14.11 
Appendix 11: Snapshot Algorithm Details 
Section 14.14 
Appendix 14: List of Data Displays for Week 48/Week 96 
Section 14.15 
Appendix 15: List of Data Displays for Week 124 
Section 14.16 
Appendix 16: IDMC 
Section 14.17 
Appendix 17: Variables Defined for Time to Event Analysis 
Section 14.18 
Appendix 18: Japan-Specific Requirements 
Section 14.19 
Appendix 19: List of Displays for the Subcutaneous Sub-study 


 
CONFIDENTIAL 
 
201584 
 
52 
 
6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
Details of the planned study population displays for the Week 124 analysis are provided 
in Appendix 15: List of Data Displays for Week 124.The study population analyses will 
be based on the Intent-to-Treat Exposed population, unless otherwise specified. 
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and treatment accountability will be based on GSK Core Data Standards.   
Table 5 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 14: List of Data Displays. 
Table 5 
Overview of Planned Study Population Analyses  
Display Type 
Data Displays Generated 
Table 
Listing 
Randomisation 
Randomisation [1] 
 
Y[2] 
Subject Disposition 
Study Populations [3] 
Y 
 
Study Recruitment [3] 
Y 
 
Reasons for Screening Failures [3] 
Y 
Y 
History of Rescreened Participants [3]   
 
 
Age categories 
Y 
 
Subject Disposition 
Y[4][5] 
 
Reasons for Withdrawal by Visit 
Y[4][5] 
Y 
IP discontinuation 
Y 
Y 
Important Protocol Deviations 
Y 
Y 
Deviations leading to exclusion from PP 
Y 
Y 
Inclusion and Exclusion Criteria Deviations 
Y 
Y  
Demography and Baseline 
Demographics Characteristics [6] 
Y 
Y 
Race & Racial Combinations [7] 
Y 
Y 
Hepatitis Status at Induction Baseline (Week -20) 
Y 
 
CDC Classification of HIV infection (2014) at Maintenance 
Baseline (Day 1) 
Y 
 
Cardiovascular Risk Assessments at Induction Baseline (Week -
20) 
Y 
 


 
CONFIDENTIAL 
 
201584 
 
53 
 
Display Type 
Data Displays Generated 
Table 
Listing 
Distribution of CD4+ Cell Counts at Maintenance Baseline (Day 1) 
Y 
 
Distribution of Quantitative Plasma HIV-1 RNA and CD4+ Cell 
Counts at Screening and Induction Baseline (Week -20) 
Y 
 
HIV-1 Subtype at Induction Baseline (Week -20) 
Y 
 
Medical Conditions, Concomitant Medications & Antiretroviral Therapy 
Medical Conditions (Current/Past) [8] 
Y 
 
Medical Conditions: Sub-conditions (Current/Past) [9, 10] 
Y  
 
Concomitant Medications (non-ART) 
Y[10] 
 
Prior Antiretroviral Therapy 
 
Y 
Concomitant Antiretroviral Therapy during Induction and 
Maintenance Phase, respectively 
 
Y 
ART Regimen at Randomization  
Y 
Y 
Lipid Modifying Agents (Maintenance Baseline (Day 1) and During 
Maintenance Phase) 
Y 
 
Substance use at Screening 
Y 
 
Medical History of Seizure 
 
Y 
Other  
Study Treatment Accountability [11] 
 
Y 
Transition to CAB+RPV LA Marketed Product  
 
Y 
NOTES: 
• 
T = Tables, L = Listings, Y = Display Generated, 
a. 
All Participants Randomized population 
b. 
One listing of participants randomized but not treated, and one listing of planned and actual treatment strata. 
c. 
All Subjects screened population. 
d. 
Participants who have not been recorded as either completing or withdrawing from the study will be categorized 
as “Ongoing at time of the analysis” for summary purposes. 
e. 
Analysis of subject disposition will be performed for each study Phase separately, as well as for overall study 
conclusion. 
f. 
Age and ethnicity collected at Screening; weight and height collected at Baseline (Week -20) 
g. 
The five high level FDA race categories and designated Asian subcategories will be summarised along with all 
combinations of high-level categories which exist in the data. The nine race categories collected will be 
summarised along with categories for mixed race. A by-subject listing of race will also be produced. 
h. 
Medical conditions will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
i. 
Sub conditions are Cardiac, Gastrointestinal, Metabolism and Nutrition, Psychiatric, Renal and Urinary, and 
Nervous System Conditions 
j. 
summarised by, Ingredient combinations  
k. 
Dispensation information (dates and number of tablets dispensed and returned). 
 
6.2. 
Subcutaneous Sub-Study Population Analyses 
Participant sub-study enrollment, protocol deviations, concomitant medications, and sub-
study disposition for the SC injection phase, return to gluteal phase, and overall will be 
summarized for the sub-study screening, enrolled, and safety populations where 


 
CONFIDENTIAL 
 
201584 
 
54 
 
appropriate. Time on prior CAB+RPV treatment though the start of the SC abdominal 
injection phase will be summarized. Oral Bridging will not be summarized as participants 
requiring oral bridging will discontinue the sub-study per the protocol. Transition either 
back to the parent study or to commercial product will be summarized as applicable for 
sub-study participants. See Appendix 19: List of Data Displays for Subcutaneous Sub-
Study Analysis for further details.  


 
CONFIDENTIAL 
 
201584 
 
55 
 
7. 
EFFICACY ANALYSES 
Details of the planned efficacy displays for the Week 124 analysis are provided in 
Appendix 15: List of Data Displays for Week 124. 
7.1. 
Primary Efficacy Analyses 
7.1.1. 
Endpoint / Variables 
Proportion of participants with plasma HIV-RNA greater than or equal to 50 copies/mL  
as per Food and Drug Administration (FDA) Snapshot algorithm at Week 48 (Intent-to-
Treat Exposed [ITT-E] population); see Section 14.11 for additional details. 
7.1.2. 
Summary Measure 
Difference in the proportion of participants with HIV-RNA ≥50 c/mL at Week 48 
(defined by the US FDA snapshot algorithm) between each treatment group (Q4W IM – 
ABC/DTG/3TC). 
7.1.3. 
Population of Interest  
The primary efficacy analyses will be based on the Intent-To-Treat Exposed population, 
unless otherwise specified. 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
As defined by the Snapshot algorithm, HIV-RNA ≥ 50 c/mL is determined by the last 
available HIV-1 RNA measurement while the participant is on treatment within the 
analysis visit window of interest.   
Participants without evaluable HIV-RNA data for the visit of interest and who 
discontinue treatment for reasons not related to adverse event while having HIV-1 RNA 
≥ 50 c/mL at time of discontinuation or who change study treatment not permitted per 
protocol before the analysis window are classified as having HIV-RNA ≥ 50 c/mL. 
7.1.5. 
Statistical Analyses / Methods 
Table 6 provides an overview of the planned efficacy analyses. Details of the planned 
displays are provided in Appendix 14: List of Data Displays and will be based on GSK 
data standards and statistical principles. 


 
CONFIDENTIAL 
 
201584 
 
56 
 
Table 6 
Overview of Planned Primary Efficacy Analyses 
Endpoints 
Stats Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
Proportion of Participants with ‘HIV-1 ≥ 50 c/mL’ at Week 48 – Snapshot 
Primary analysis 
comparison between 
the two groups (Q4W 
IM – ABC/DTG/3TC) in 
‘HIV-1 RNA≥50 c/mL’ 
rates at Week 48  
Y[1] 
 
 
Y[1,2] 
Y[4] 
 
Y[2] 
Treatment 
Heterogeneity across 
randomization strata 
Y 
 
 
 
 
 
 
By Subgroup [3] 
(Exploratory analysis 
to support primary 
analysis) 
 
 
 
Y[5] 
Y[4] 
 
 
NOTES: 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e., modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e., descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data. 
1. 
Generated using the ‘Intent-to-Treat Exposed’ (primary) and ‘Per-Protocol’ (sensitivity) populations.  
2. 
Study outcomes (i.e., response below 50 c/mL, ‘HIV-1 RNA≥50’ or reason for no data in the window) based on 
the snapshot algorithm. 
3. 
Randomisation Strata, Demographic and Baseline Characteristics (refer to Section 5.4.2). 
4. 
Plot of the difference in proportion of participants with HIV-1 RNA ≥50 c/mL (Snapshot algorithm) and its 95% 
confidence intervals for ‘overall’ (on the top of the figure) and by subgroup at Week 48.  
5. 
Study outcomes based on the Snapshot algorithm by subgroup at Week 48 will also be produced. 
7.1.5.1. 
Statistical Methodology Specification 
Primary Statistical Analyses  
Endpoint 
• Proportion of Participants with Plasma HIV-1 ≥ 50 c/mL at Week 48 using the Snapshot 
algorithm for the ITT-E population. ‘HIV-1 RNA≥50’ are based on the Snapshot algorithm 
includes participants who had plasma HIV-1 RNA ≥ 50 c/mL at Week 48, who discontinued for 
lack of efficacy, who discontinued for other reasons while not <50 c/mL, or who changed ART).  
Snapshot Dataset 
• 
Virologic outcome (‘HIV-RNA <50’ or ‘≥ 50 c/mL’) per Snapshot algorithm is determined by the 
last available on-treatment HIV-1 RNA measurement within the analysis visit window of interest 
(please refer to analysis window defined in Table 17). In addition, participants who discontinue 
for reasons not related to adverse event with on-treatment HIV-1 RNA result at the time of 
discontinuation ≥ 50 c/mL or who change study treatment not permitted per protocol during 
Maintenance Phase before the analysis visit are classified as ‘HIV-RNA ≥ 50 c/mL’.   
• Full details of the Snapshot algorithm are provided in Section 14.11.  


 
CONFIDENTIAL 
 
201584 
 
57 
 
Primary Statistical Analyses  
Model Specification 
• The primary efficacy endpoint will be analysed using a stratified analysis with Cochran-Mantel-
Haenszel (CMH) weights, adjusting for Induction Baseline (Week -20) HIV-1 RNA (<100,000, 
≥100,000 c/mL) and gender at birth. 
• The CMH estimate of the adjusted treatment difference will be calculated as a weighted 
average of strata-specific estimates of the treatment difference calculated within each of the 
following four analysis strata: 
o 
Induction Baseline (Week -20) HIV-1 RNA < 100 000 c/mL AND Male gender at birth 
o 
Induction Baseline (Week -20) HIV-1 RNA < 100 000 c/mL AND Female gender at 
birth 
o 
Induction Baseline (Week -20) HIV-1 RNA ≥ 100 000 c/mL AND Male gender at birth 
o 
Induction Baseline (Week -20) HIV-1 RNA ≥ 100 000 c/mL AND Female gender at 
birth 
• If nk is the number of CAB LA + RPV LA treated participants, mk is the number of 
ABC/DTG/3TC control arm treated participants, and Nk = nk + mk is the total number of 
participants in the kth stratum, then the CMH estimate is given by 
 
where 
 
are CMH weights and       are estimates of the differences in proportions between the two 
treatment arms, fla - fc for the kth stratum. 
• The corresponding two-sided 95% CI will be calculated as 
 
where the variance estimator [Sato, 1989] is consistent in both sparse data and large strata 
and is given below   
(
)
(
)
(
)
(
)
(
)2
2
ˆ
ˆ
ˆ
raˆ
v
∑
∑
∑
∑
∑
∑
+
=
+
=
k
k
k
cmh
k
k
k
k
k
cmh
cmh
W
Q
P
d
N
m
n
Q
P
d
d
  
where 
2
2
2
2
/)
(
k
k
k
k
k
k
k
k
k
k
N
n
m
m
n
x
m
y
n
P
−
+
−
=
 
∑
∑
=
k
k
k
cmh
W
d
W
d
ˆ
ˆ
 
k
dˆ
) 
ˆ 
r(
a ˆ 
v 
96 
.1
ˆ
cmh
cmh
d 
d 
×
± 


 
CONFIDENTIAL 
 
201584 
 
58 
 
Primary Statistical Analyses  
2
/
)
(
/
)
(
k
k
k
k
k
k
k
k
k
N
x
n
y
N
y
m
x
Q
−
+
−
=
 
with xk and yk corresponding to the number of participants with Plasma HIV-1 RNA ≥ 50 c/mL 
at Week 48 per FDA Snapshot for CAB LA + RPV LA and ABC/DTG/3TC control arm, 
respectively, for the kth stratum. 
Model Results Presentation 
• Adjusted CMH estimate of the difference in the proportion of participants with ‘HIV-1 RNA≥50’ 
between each treatment group (CAB LA + RPV LA – ABC/DTG/3TC) and corresponding 95% 
confidence interval.  
• Non-inferiority will be concluded if the upper bound of the two-sided 95% confidence interval 
(CI) for the CMH adjusted difference in proportion of participants with ‘HIV-1 RNA≥50’ in the 
CAB LA + RPV LA group minus proportion of participants with ‘HIV-1 RNA≥50’ in the 
ABC/DTG/3TC group is less than 6%.    
• If the analysis shows non-inferiority, then a superiority hypothesis will be tested at the two-
sided 5% level of significance. Superiority favoring CAB LA + RPV LA will be declared if the 
upper end of the confidence interval is below 0% for the ITT-E population analysis. If 
superiority is declared, the p-value for superiority will also be calculated. 
Subgroup Analyses 
1. Treatment Heterogeneity across randomization strata: 
• The weighted least squares chi-squared statistic [Fleiss, 1981] will be used to test for 
one-way homogeneity across the levels of each categorical variable, with each 
categorical variable considered separately.  
• Following Lui and Kelly [Lui, 2000] ½ will be added to each cell in any strata for which 
the stratum-specific rate estimates of either fla or fc are zero or one, and tests will be 
one-sided.  
• Any heterogeneity found to be statistically significant will be explored and if necessary 
results will be reported for each level of the categorical variable. Investigation of 
heterogeneity will be confined to the primary. Tests of homogeneity will be assessed at 
the one-sided 10% level of significance. 
2. Exploration of Subgroups 
• An analysis for demographic and baseline characteristic subgroups listed in Section 
5.4.2 will be performed. This will show the proportion of participants with plasma HIV-1 
RNA ≥50 c/mL at the time of analysis (Week 48) based on the Snapshot algorithm and 
will be presented by treatment group. 
• Unadjusted difference in proportions between treatment groups and corresponding 
two-sided 95% CI will also be presented by subgroups.  The confidence interval will be 
calculated using an unconditional exact method (Chan, 1999) with two inverted one-
sided tests based on the score statistic. These results will also be presented 
graphically.  
• Summary of study outcomes (i.e., response below 50 c/mL, ‘HIV-1 RNA≥50’or reason 
for no data in the window) by subgroup will be produced. 
 


 
CONFIDENTIAL 
 
201584 
 
59 
 
Primary Statistical Analyses  
Note: These subgroup analyses will be exploratory and likely underpowered so that 
interpretation may therefore focus on point estimates as well as the upper bounds of 95% CIs 
for the treatment differences and response rates. Additionally, multiple comparisons are being 
made which inflates the risk of false positive findings. Therefore, if consistent findings across 
the multiple comparisons were observed then these analyses would still be suggestive of a 
generalizable finding of non-inferiority. 
Sensitivity and Supportive Analyses 
1. Per-protocol population analysis: 
To assess the impact of important protocol deviations, statistical analysis will be repeated 
using the Per-protocol population and compared for consistency with the results from the 
primary ITT-E population analysis. 
7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoint / Variables 
Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA 
Snapshot algorithm (Intent-to-Treat Exposed [ITT-E] population). 
Subcutaneous sub-study efficacy endpoints for the study are listed below: 
• Proportion of participants with plasma HIV-1 RNA < 50 c/mL at Week 12 using 
the FDA Snapshot algorithm during the Sub-study Subcutaneous Abdominal 
Injection phase (Sub-study Safety population) 
• Proportion of participants with plasma HIV-1 RNA ≥ 50 c/mL at Week 12 using 
the FDA Snapshot algorithm during the Sub-study Subcutaneous Abdominal 
Injection phase 
• Proportion of participants with protocol-defined confirmed virologic failure 
(CVF) of ≥200 c/mL through Week 12 of the Sub-study Subcutaneous Abdominal 
Injection phase 
• Incidence of treatment emergent genotypic and phenotypic resistance to CAB, 
RPV during the SC injection phase. 
The incidence of observed genotypic and phenotypic resistance to NRTIs and INIs, 
PIs, and NNRTIs will be summarized for subjects meeting confirmed virologic failure 
criteria. 
The proportion of participants with HIV-1 RNA ≥50 c/mL and HIV-1 RNA <50 c/mL 
at Week 12 of the SC injection phase will be summarized using FDA Snapshot 
algorithm for the Safety population in the sub-study. Proportion of participants with 
protocol-defined confirmed virologic failures at Week 12 will also be summarized. 
Summaries will be presented by subgroup as needed where data allow. 
 


 
CONFIDENTIAL 
 
201584 
 
60 
 
7.2.2. 
Summary Measure 
Difference in the proportion of participants with HIV-RNA < 50 c/mL at Week 48 
(defined by the US FDA snapshot algorithm) between each treatment group (Q4W IM – 
ABC/DTC/3TC). 
7.2.3. 
Population of Interest  
The secondary efficacy analyses will be based on the Intent-to-Treat Exposed population, 
unless otherwise specified. 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events 
Participants with last available HIV-1 RNA measurement less than 50 c/mL while the 
participant is on treatment within the analysis visit window of interest are classified as 
HIV-1 RNA < 50 c/mL. 
7.2.5. 
Statistical Analyses / Methods 
Table 7 provides an overview of the planned efficacy analyses. Details of the planned 
displays are provided in Appendix 14: List of Data Displays and will be based on GSK 
data standards and statistical principles. 


 
CONFIDENTIAL 
 
201584 
 
61 
 
Table 7 
Overview of Planned Secondary Efficacy Analyses 
Endpoints 
Stats Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
Proportion of Participants with ‘HIV-1 ≥ 50 c/mL’ at Week 96 – Snapshot [1] 
 
Y[2] 
 
 
Y[2,3] 
Y[5] 
 
Y[3] 
Treatment 
Heterogeneity across 
randomization strata 
Y 
 
 
 
 
 
 
By Subgroup [4] 
(Exploratory analysis) 
 
 
 
Y[6] 
Y[5] 
 
 
Proportion of Participants with Plasma HIV-1 < 50 c/mL at Week 48/Week 96 – Snapshot [1] 
Key Secondary 
Analysis (Week 48)  
Y[2] 
 
 
Y[2, 3] 
Y 
 
Y[3] 
Treatment 
Heterogeneity across 
randomization strata 
Y 
 
 
 
 
 
 
Proportion of Participants without efficacy-related discontinuation (ERDF) or treatment-related 
discontinuation (TRDF) failure at Week 48/Week 96 (refer to Section 14.6.4) 
Kaplan-Meier estimate 
 
 
 
Y 
 
 
 
Proportion of Participants with Plasma HIV-1 RNA ≥ 50 copies/mL over time (Maintenance Phase)– 
Snapshot 
by Visit  
 
 
 
Y 
Y[7] 
 
 
by Visit and 
Subgroup[4] 
 
 
 
Y 
Y[9] 
 
 
Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL over time (Maintenance Phase)– 
Snapshot 
by Visit  
 
 
 
Y 
Y[8]  
 
 
by Visit and Subgroup 
[4] 
 
 
 
Y 
Y[9]  
 
 
Proportion of Participants with Plasma HIV-1 RNA < 200 copies/mL over time (Maintenance Phase)– 
Snapshot  
by Visit 
 
 
 
Y[10] 
Y[11] 
 
 
Proportion of Participants with Plasma HIV-1 RNA ≥ 200 copies/mL over time – Snapshot 
by Visit 
 
 
 
Y[10] 
Y[11] 
 
 
Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 48 by delay in IP injection 
[12] - Snapshot (exploratory analysis) 
by Delay in IP injection   
 
 
Y 
 
 
 
Proportion of Participants with Plasma HIV-1 RNA < 2 copies/mL (exploratory analysis) 
by Visit - Observed 
Case Analysis 
 
 
 
Y[13] 
 
 
 


 
CONFIDENTIAL 
 
201584 
 
62 
 
Endpoints 
Stats Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
Time from First HIV-1 RNA < 50 copies/mL until Initiation of Maintenance Phase Treatment 
 
 
 
 
Y 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e., modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e., descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data. 
1. 
This analysis will be performed using the same approach as described for the primary analysis in Section 7.1. 
2. 
Generated using the ‘Intent-to-Treat Exposed’ (primary) and ‘Per-Protocol’ (sensitivity) populations.  
3. Study outcomes (i.e., response below 50 c/mL, ‘HIV-1 RNA≥50’ or reason for no data in the window) based on 
the snapshot algorithm. 
4. 
Randomisation Strata, Demographic and Baseline Characteristics (refer to Section 5.4.2). 
5. 
Plot of the difference in proportion of participants with HIV-1 RNA ≥50 c/mL (Snapshot algorithm) and its 95% 
confidence intervals for ‘overall’ (on the top of the figure) and by subgroup at Week 96.  
6. 
Study outcomes based on the Snapshot algorithm by subgroup at Week 96 will also be produced. 
7. 
Line plots, with 95% confidence intervals (CIs), for the proportion of participants with HIV-1 RNA ≥50c/mL by 
treatment group at each visit. The 95% CIs will be calculated using Exact (Clopper-Pearson) confidence interval if 
the proportion is 0%; otherwise, they are derived using the normal approximation. 
8. 
Line plots, with 95% confidence intervals, for the proportion of participants with HIV-1 RNA<50c/mL by treatment 
group at each visit. The 95% CIs will be calculated using Exact (Clopper-Pearson) confidence interval if the 
proportion is 100%; otherwise, they are derived using the normal approximation. 
9. 
Plot of the unadjusted treatment difference and its 95% confidence intervals (Snapshot algorithm) overall and by 
subgroup at Week 48/Week 96. 
10. Study outcomes (i.e., HIV-1 RNA< 200 c/mL, HIV-1 RNA≥200c/mL, or reason for no data in the window) based 
on the snapshot algorithm by subgroup for Week 48/Week 96 will also be produced. 
11. Line plots, with 95% confidence intervals, for the proportion of participants with HIV-1 RNA <200c/mL and ≥200 
c/mL by treatment group at each visit. The 95% CIs will be calculated using Exact (Clopper-Pearson) confidence 
interval if the proportion is 0% or 100%; otherwise, they are derived using the normal approximation 
12. Delay in IP injection (days) is defined in Section 14.6.4 
13. Using observed case (OC) data which contains the data that is available at a particular time point, with no 
imputation for missing values and expanded ± 6-week window for W48/W96 and last value in window (see 
Section 14.6.4). 
 
Table 8 
Overview of Additional Secondary Efficacy Analyses 
Endpoints 
Absolute  
Change from Maintenance Baseline  
Stats Analysis 
Summary Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Plasma HIV-1 RNA Over Time  
Observed [1] 
 
 
 
Y[8] 
 
Y[2] 
Y[3] 
 
 
 
Y 
 
 
 
Detected vs Non-
detected by Visit [1,5] 
 
 
 
Y 
 
 
Y[6] 
 
 
 
 
 
 
 
Confirmed Virologic Failure (CVF) 
CVF Overall   
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
CVF by Visit 
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
201584 
 
63 
 
Endpoints 
Absolute  
Change from Maintenance Baseline  
Stats Analysis 
Summary Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
HIV-1 RNA at time of 
suspected and 
confirmed Virologic 
Failure 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
CD4+ & CD8+ Cell Counts Over Time 
CD4+ observed 
 
 
 
Y[7] 
 
 
 
 
 
 
Y[7] 
 
 
 
CD8+ observed 
 
 
 
Y[7] 
 
 
 
 
 
 
Y[7] 
 
 
 
CD4+/CD8+ ratio 
observed 
 
 
 
Y[7] 
 
 
 
 
 
 
 
 
 
 
HIV-1 Conditions and Disease Progression 
HIV Conditions 
including/excluding 
Recurrences as 
recorded in eCRF  
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 
HIV Disease 
Progressions [4] 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e., modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e., descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data. 
1. 
Using observed case (OC) data which contains the data that is available at a particular time point, with no 
imputation for missing values and expanded ± 6 week window for W48/W96 and last value in window (see Section 
14.6.4). 
2. 
Individual plasma HIV-1 RNA only for participants who are in the category of ‘viral load ≥50 c/mL’ at Week 48 per 
Snapshot algorithm or who are CVF participants. The figures will display all HIV-1 RNA values collected. 
3. 
For CVF participants (during the Induction and Maintenance Phase, respectively, and participants with viral load ≥ 
50 c/mL at any time during the Maintenance Phase). 
4. 
HIV disease progressions (Section 14.6.4)  
5. 
See Section 14.6.4 for a definition of “Target Detected” and “Target Non-detected”. 
6. 
Included in the Observed HIV-1 RNA listing 
7. 
Using observed case (OC) data which contains the data that is available at a particular time point, with no 
imputation for missing values 
8. 
Using log10 transformed values 
 


 
CONFIDENTIAL 
 
201584 
 
64 
 
7.2.5.1. 
Statistical Methodology Specification 
Key Secondary Statistical Analyses  
Endpoint 
• Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA 
Snapshot algorithm (Intent-to-Treat Exposed [ITT-E] population) 
Snapshot Dataset 
• As described in Section 7.1.5.1 and Section 14.11 
Model Specification 
• As specified in Section 7.1.5.1 but with Snapshot HIV-1 RNA <50 c/mL replacing Snapshot 
HIV-1 ≥ 50 c/mL   
Model Results Presentation 
• Adjusted CMH estimate of the difference in the proportion of participants with plasma HIV-1 
RNA <50 c/mL at Week 48 between each treatment group (Q4W IM – ABC/DTG/3TC) and 
corresponding 95% confidence interval.  
• Non-inferiority will be concluded if the lower bound of the two-sided 95% confidence interval for 
the CMH adjusted treatment difference (Q4W IM – ABC/DTG/3TC) is greater than -10%.    
Subgroup Analyses 
• Treatment Heterogeneity across randomization strata: 
o As specified in Section 7.1.5.1 but with Snapshot HIV-1 RNA <50 c/mL replacing 
Snapshot HIV-1 RNA ≥ 50 c/mL. 
Sensitivity and Supportive Analyses 
• Per-protocol population analysis: 
To assess the impact of important protocol deviations, statistical analysis will be repeated 
using the Per-protocol population and compared for consistency with the results from the 
primary ITT-E population analysis.  


 
CONFIDENTIAL 
 
201584 
 
65 
 
8. 
SAFETY ANALYSES 
Details of the planned safety displays for the Week 124 analysis are provided in 
Appendix 15: List of Data Displays for Week 124. 
The safety analyses will be based on the Safety population, unless otherwise specified. 
For the Week 48 primary analysis, a set of separate outputs will also be presented for the 
oral lead-in period at Maintenance Phase, including summary of adverse events, SAE, 
AE leading to withdrawal, emergent chemistry/haematology abnormality, participants 
with hepatobiliary abnormality criteria. 
8.1. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs) 
and other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 14: List of Data Displays. 
8.2. 
Adverse Events of Special Interest Analyses 
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
Adverse Events of Special Interest (AESI). [Changes to the MedDRA dictionary may 
occur between the start of the study and the time of reporting and/or emerging data from 
on-going studies may highlight additional adverse events of special interest, therefore the 
list of terms to be used for each event of interest and the specific events of interest will be 
based on the safety review team (SRT) agreements in place at the time of reporting.] The 
details of the current planned grouping, including Standardized MedDRA Query (SMQ) 
values (as applicable), and planned displays are provided in Appendix 12: AESI 
identification and Appendix 14: List of Data Displays. 
8.3. 
Clinical Laboratory Analyses 
Laboratory evaluations including the analyses of Chemistry laboratory tests, Hematology 
laboratory tests, Urinalysis, and liver function tests will be based on GSK Core Data 
Standards. The details of the planned displays are in Appendix 14: List of Data Displays. 
8.4. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. The details of the 
planned displays are presented in Appendix 14: List of Data Displays. 
ECG Values of Potential Clinical Interest are defined as a QTc of > 550ms. 
8.5. 
Planned Safety Analysis 
Table 9 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 14: List of Data Displays. 


 
CONFIDENTIAL 
 
201584 
 
66 
 
Table 9 
Overview of Planned Safety Analyses 
Endpoint 
 
Absolute 
 
Change from 
Maintenance Baseline 
Max Post Maintenance 
BL 
Summary 
Individual 
Summary 
Individual 
Summary 
Individual 
T 
F 
F 
L 
T 
F 
F 
L 
T 
F 
F 
L 
Exposure 
Extent of Exposure[1] 
Y 
 
 
Y[2] 
 
 
 
 
 
 
 
 
Adherence to Q4W 
Dosing Schedule [1] 
Y 
 
 
 
 
 
 
 
 
 
 
 
Injection Needle  
Length and Gauge 
Y 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events[3] 
All AEs by SOC 
Y 
 
 
 
 
 
 
 
 
 
 
 
All AEs by SOC and 
Toxicity[3] 
Y[24] 
 
 
Y[4] 
 
 
 
 
 
 
 
 
Common AEs by freq [5] 
Y 
Y[6] 
 
 
 
 
 
 
 
 
 
 
Common Grade 2-5 
AEs [5] by freq 
Y 
 
 
 
 
 
 
 
 
 
 
 
All Drug-Related AEs by 
SOC and toxicity[3] 
Y 
 
 
 
 
 
 
 
 
 
 
 
Common Drug-related 
Grade 2-5 AEs [5] 
Y 
 
 
 
 
 
 
 
 
 
 
 
All AEs 
 
 
 
Y 
 
 
 
 
 
 
 
 
Serious and other significant adverse events 
All SAEs by SOC 
Y[24] 
 
 
 
 
 
 
 
 
 
 
 
Reason for Considering 
as a Serious Adverse 
Event (FDA) 
 
 
 
Y  
 
 
 
 
 
 
 
 
All Drug-Related SAEs 
by SOC 
Y 
 
 
 
 
 
 
 
 
 
 
 
Fatal SAEs  
 
 
 
Y 
 
 
 
 
 
 
 
 
Non-Fatal SAEs 
Y 
 
 
Y 
 
 
 
 
 
 
 
 
Drug-related non-fatal 
SAEs 
Y 
 
 
 
 
 
 
 
 
 
 
 
Withdrawal AEs 
Y[24] 
 
 
Y 
 
 
 
 
 
 
 
 
Common Non-Serious 
AEs (FDAAA) 
Y 
 
 
 
 
 
 
 
 
 
 
 
Number of occurrences 
of Common Non-serious 
AEs by SOC (EudraCT) 
Y 
 
 
 
 
 
 
 
 
 
 
 
Number of occurrences 
of SAEs, Fatal SAEs, 
Y 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
201584 
 
67 
 
Endpoint 
 
Absolute 
 
Change from 
Maintenance Baseline 
Max Post Maintenance 
BL 
Summary 
Individual 
Summary 
Individual 
Summary 
Individual 
T 
F 
F 
L 
T 
F 
F 
L 
T 
F 
F 
L 
and Drug-related SAEs 
(EudraCT) 
Cumulative AEs by visit 
Y 
 
 
 
 
 
 
 
 
 
 
 
Depression, Suicidal 
and Self-Injury AEs by 
Prior History 
Y[25] 
 
 
 
 
 
 
 
 
 
 
 
Suicidality assessment 
PSRAE 
 
 
 
Y[7] 
 
 
 
 
 
 
 
 
Columbia suicidality (C-
SSR) 
Y 
 
 
 
 
 
 
 
 
 
 
 
Injection Site Reaction Adverse Events [12] 
ISR AEs (Event-Level) 
[17] 
Y 
 
 
 
 
 
 
 
 
 
 
 
ISR AEs (Subject-Level) 
[18]  
Y 
Y 
 
 
 
 
 
 
 
 
 
 
ISR AEs (Subject-Level) 
by Visit and Severity  
Y 
Y[19] 
 
 
 
 
 
 
 
 
 
 
Maximum ISR AE 
Grade by Needle 
Length [21] 
Y 
 
 
 
 
 
 
 
 
 
 
 
Laboratory: Chemistry and Hematology 
Clinical Chemistry & 
Renal Biomarkers [11] 
Y 
 
 
 
Y 
 
 
 
Y [23] 
 
 
 
%Lipids[22]  
 
 
 
 
Y 
 
 
 
 
 
 
 
NCEP shifts in lipids 
 
Y 
 
 
 
 
 
 
Y 
 
 
 
Hematology  
Y 
 
 
 
Y 
 
 
 
Y[23] 
 
 
 
Laboratory: Urinalysis (regardless of fasting status) 
Urine Dipstick 
Y[8] 
 
 
 
 
 
 
 
 
 
 
 
Urine Concentration & 
Renal biomarkers[12] 
 
 
 
 
Y 
 
 
 
 
 
 
 
Laboratory: Hepatobiliary 
Liver Assessment 
 
 
 
Y [14] 
 
 
 
 
 
 
 
 
Hepatobiliary 
Abnormality criteria 
Y[15] 
 
 
Y 
 
 
 
 
 
 
 
 
Liver Chemistries 
 
 
 
Y[16] 
 
 
 
 
 
Y[9] 
 
 
Laboratory: Markers 
Bone markers 
 
 
 
 
Y[10] 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
201584 
 
68 
 
Endpoint 
 
Absolute 
 
Change from 
Maintenance Baseline 
Max Post Maintenance 
BL 
Summary 
Individual 
Summary 
Individual 
Summary 
Individual 
T 
F 
F 
L 
T 
F 
F 
L 
T 
F 
F 
L 
ECG 
ECG findings 
Y 
 
 
Y 
 
 
 
 
 
 
 
 
ECG values 
 
 
 
 
Y 
 
 
 
 
 
 
 
QTC values by 
Category 
Y 
 
 
 
Y 
 
 
 
Y 
 
 
 
Other 
Vital Signs 
 
 
 
 
Y 
 
 
 
 
 
 
 
Weight & BMI 
 
 
 
 
Y[24] 
 
 
 
 
 
 
 
Abacavir HSR 
 
 
 
Y[13] 
 
 
 
 
 
 
 
 
Participants who 
became Pregnant 
 
 
 
Y 
 
 
 
 
 
 
 
 
Patient Profiles 
 
 
 
Y[20] 
 
 
 
 
 
 
 
 
Dosing Errors and IP 
Device Malfunctions 
 
 
 
Y 
 
 
 
 
 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e., modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e., descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data.  
1. 
Refer to Section 14.6.2 for defining Extent of Exposure and adherence to Q4W dosing intervals,  
2. 
Includes reason for any dose change/interruption. 
3. 
For AEs reported more than once by a participant, the most severe intensity will be included.  Separate summary tables 
including and excluding injection site adverse reactions. 
4. 
One listing of all AEs including verbatim text and preferred term, one showing the relationship between verbatim text, 
preferred term and SOC and another giving subject numbers for individual all treatment emergent AEs. 
5. 
Common AEs are those with ≥5% incidence in either treatment group summarised by frequency. 
6. 
Plots of incidence rates and relative risk with 95% CI for Q4W IM vs. ABC/DTG/3TC. 
7. 
Four PSRAE listings: Event and Description (Section 1 and Section 2), Possible Cause (Section 3), Section 4 and 
Section 5 - Section 8. 
8. 
Shift table summarising Maintenance Baseline (Day 1) vs. maximum Maintenance Phase result for urine dipstick 
protein. 
9. 
Scatter plot of baseline vs. maximum post-baseline for ALT. Scatter plot of maximum ALT vs. maximum Bilirubin. Matrix 
plot of maximum liver chemistries. 
10. Bone markers including: Bone-specific alkaline phosphatase, procollagen type 1 N-propeptide, type 1 collagen cross-
linked C-telopeptide, osteocalcin, 25 hydroxy-Vitamin D. 
11. Renal markers: Urine Retinol Binding Protein, Retinol Binding Protein, Cystatin C.  CKD-EP1 GFR using Cystatin C 
(derived in Section 14.6.3) will also be summarized 
12. Repeat for CAB/RPV, CAB, RPV respectively. 
13. Separate listings for exposure to abacavir, history of drug allergies, family conditions, skin rash, symptoms, vital signs, 
individual symptoms, and diagnostic category assignment. 
14. Separate listings for time of event, RUCAM score, biopsy, imaging, past/ current conditions and follow up  
15. One summary of participants and another table showing Subject Ids.  Table of participants  meeting hepatobiliary 
abnormally criteria during the maintenance oral lead-in Phase will also be produced.  
16. Patient profiles for participants meeting protocol defined liver stopping criteria and for patients with virologic failure. 
Patient profiles can also be provided for any other participants, as necessary for medical review. 
17. Event-level summary: Percentages based on total number of ISR events within each treatment group including 
distribution of grade, duration, and event characteristics; 


 
CONFIDENTIAL 
 
201584 
 
69 
 
18. Subject-Level summary: Characteristics of ISR AE (Overall and by Common ISRs); Percentage based on number of 
participants within each treatment group; Includes distribution of grade and max grade, event characteristics, number of 
events per subject, rate of number of events per injection visit; 
19. A corresponding plot of all grades and a separate plot of grade 3-5 events will be produced 
20. Patient profiles are not planned. But it can be produced post hoc, as necessary. 
21. Please refer to Section 5.4.2 “Additional subgroup for ISR” for derivation of needle length used in this summary 
22. Please refer to Section 14.6.3 for defining percentage change from Maintenance Baseline (Day 1) in Lipids 
23. Separate tables will be produced for Maintenance Phase data and Oral Lead-in period data (see Table 28 and Table 29) 
24. Change from Induction Baseline (Week -20) for BMI and Weight. 
25. By SOC and Maximum Toxicity, and history based on prior/current medical conditions collected at Screening 
8.5.1. 
Injection Site Reactions 
For the summary of Injection Site Reaction Adverse Events by Visit and Maximum 
Severity (Overall and by Common ISRs): ISRs will be assigned based on onset date to 
the most recent planned IM injection visit prior or equal to the AE onset date.   
 
Maximum grade at each visit will be derived as the maximum grade among ISRs 
assigned to the particular visit, with consideration for whether the summary applies to a 
particular preferred term (vs. across preferred terms), or drug-related associated to CAB 
and/or RPV. 
 
Drug-related ISRs (based on investigator discretion) will be attributed to the causal agent 
(CAB vs. RPV) when this can be determined specifically based on the side of injection 
administration and the side of the reported ISR (as collected in the eCRF). If we are 
unable to determine the causal agent in those cases where both drugs are given on one 
side and the ISR is reported non-specifically, then the attribution to a specific causal 
agent will remain unknown. 
 
ISRs will be attributed to the needle length when this can be determined specifically 
based on the side of injection administration and the side of the reported ISR (as collected 
in the eCRF). If we are unable to determine the needle length in those events where both 
drugs are given on one side and their needle lengths are different, then the attribution to a 
needle length will remain unknown. 
 
Common ISR includes injection site pain, injection site induration, injection site nodules 
and any other ISR occurring in ≥5% of participants (for Q4W arm only). The same set of 
common terms will be applied to ‘overall’ (CAB and/or RPV), CAB alone, RPV alone. 
 


 
CONFIDENTIAL 
 
201584 
 
70 
 
8.5.2. 
Statistical Analyses/Methods 
Statistical Analyses 
Endpoints 
• Change from Maintenance Baseline (Day 1) in Bone Markers at Week 48 
Covariates 
• Treatment (Q4W IM, ABC/DTG/3TC) 
• Induction Baseline (Week -20) HIV-1 RNA (<100,000, ≥100,000 c/mL), Gender at Birth, TDF 
use at Maintenance Baseline (Day 1), Age, body mass index category at Induction Baseline 
(Week -20), smoking status, and Log-transformed bone marker value at Maintenance 
Baseline (Day 1) (as defined in Section 5.4.2) 
Data Handling 
• All data remains as is (observed). 
Model Specification 
• Bone marker results will be log-transformed. The change in the log-transformed data at week 
48 from Maintenance baseline (i.e., log of ratio of post-baseline value over Maintenance 
baseline value) for each bone marker will be analysed for the comparison between the two 
treatment arms. 
• Analysis of covariance (ANCOVA) model will be used with the above covariates/subgroups. 
Age and Log-transformed bone marker value at Maintenance Baseline (Day 1) will be 
included as continuous variables in the model and all other covariates will be included as 
categorical variables.  
Model Results Presentation 
• The estimated coefficients of the ANCOVA model will be transformed back (exponential 
transform) to reflect the change in the ratio of post-baseline value over Maintenance Baseline 
(Day 1) value rather than the change in the log ratio. The change in the ratio can then be 
translated into percent change from maintenance baseline (Day 1) (e.g., the ratio bb48/bbbl = 
1.3 can be translated into 30% increase from baseline). 
• For each treatment, adjusted (geometric) means of ratio and corresponding confidence 
intervals will be presented. Adjusted point estimates will be derived as LSMEAN S using the 
observed margins (OM) option within PROC MIXED in SAS. 
• The adjusted (geometric mean) difference of the ratio (post-baseline value)/(baseline value) 
between the two treatments with the corresponding confidence interval and p-value will be 
presented 
• Interactions between treatment and each of the covariates will be investigated but not 
included in the main model. If interactions are found to be significant (p-value <0.10), results 
will be presented separately by subgroup. 


 
CONFIDENTIAL 
 
201584 
 
71 
 
NOTES: 
• Statistical analysis will only be performed when all expected data through Week 48 has been 
received from the laboratory. 
8.6. 
Subcutaneous Sub-Study Safety Analyses 
The proportion of participants reporting AEs will be tabulated for each injection type. This 
will include the following AE summaries: 
 
• Incidence and severity of ISRs and AEs of special interest during the SC injection phase 
o This includes incidence of Grade 4 ISRs and Grade 3 ISRs including ulceration, 
secondary infection, phlebitis, sterile abscess, or drainage affecting Interim 1 
monitoring criteria. 
• Proportion of participants who discontinue treatment due to ISRs and proportion of 
AEs of special interest during the SC injection phase 
• Incidence and severity of AEs not of special interest 
• Incidence of SAEs 
• Dimensional characteristics (length & width in mm) of SC ISRs of erythema, redness, 
induration, and swelling 
• Change from baseline (latest non-missing value prior to the first SC injection) in 
laboratory parameters will be summarized by visit through the end of the SC phase. 
 
AE and ISR summaries will be repeated for the following subgroups: Age (<50 vs >=50), 
Sex at Birth (Female vs Male), Race/Ethnicity (White: Non-Hispanic, White: Hispanic, Black, 
Asian, Other), Sub-study Baseline BMI (<30, >=30). 
 
Incidence Rate ratios and their 95% CIs for the incidence of ISRs between SC and IM will 
also be calculated using a Poisson regression model that accounts for within-subject 
variation by using a repeated effect of subject. Categorical Baseline BMI (<30, >=30) will 
be included as a covariate in the model. These informal comparisons will be graphically 
displayed overall and for each subgroup. Results will be repeated for Grade 1+ ISRs as 
well as for Grade 2+ ISRs. Sub-study participant data will be matched to their individual 
IM data via the following comparisons: 
 
1. The first 2 SC injections vs. the two IM injections post-SC dosing 
2. All 3 SC injections vs. the first 3 IM injections in the parent study 
 
ISRs of interest will be simply tabulated (i.e., Grade 3+ ulceration, secondary infection, 
phlebitis, abscess, drainage or a Grade 4 ISR) at interim analysis 1 for ISR monitoring. 
Once counted, the posterior probability that the true rate of ISRs of interest is >0.05 will 
be calculated using a Bayesian Beta-Binomial model to produce posterior hyperparameters 
α´ successes and β´failures as indicated below.  
 
 


 
CONFIDENTIAL 
 
201584 
 
72 
 
𝑎𝑎′ = 𝑎𝑎+ ෍𝑥𝑥𝑖𝑖
𝑛𝑛
𝑖𝑖=1
 
𝛽𝛽′ = 𝛽𝛽+ ෍𝑁𝑁𝑖𝑖
𝑛𝑛
𝑖𝑖=1
 −෍𝑥𝑥𝑖𝑖
𝑛𝑛
𝑖𝑖=1
  
 
Where prior α = 0.001 and prior β = 79 based on previous and ongoing studies mentioned 
in protocol amendment 8, Section 12.12.1.3, 𝑥𝑥𝑖𝑖 is the total number of participants with an 
event, and 𝑁𝑁𝑖𝑖 is the total number of participants with an SC injection at the interim.  
 
The posterior probability that the true rate of ISRs of interest is >0.05 will then be 
calculated from a Beta Distribution CDF using the posterior hyperparameters α´ and β´ and 
summarized for determination of formal VSLC review of all data for ISRs of interest.  
 


 
CONFIDENTIAL 
 
201584 
 
73 
 
9. 
PHARMACOKINETIC AND 
PHARMACOKINETIC/PHARMACODYNAMIC ANALYSES 
Details of the planned PK displays for the Week 124 analysis are provided in Appendix 
15: List of Data Displays for Week 124. 
The GSK Division of Clinical Pharmacology Modelling and Simulation (CPMS) will be 
responsible for the PK analysis of CAB.  The Division of Global Clinical Pharmacology 
at Janssen Research and Development will be responsible for conduct or oversight of the 
PK analysis for RPV. 
All PK and PK/PD displays will be based on the PK Population. 
9.1. 
Primary Pharmacokinetic Analyses 
9.1.1. 
Endpoint / Variables 
9.1.1.1. 
Drug Concentration Measures 
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 14.5.3 
Reporting Standards for Pharmacokinetic) 
9.1.1.2. 
Derived Pharmacokinetic Parameters 
A population-based PK analysis will be described under separate Population-PK 
Reporting and Analysis Plans for CAB LA and RPV LA.  
9.1.2. 
Planned Analyses 
Table 10 provides an overview of the planned analyses based on observed plasma 
CAB/RPV concentration data only with full details being presented in Section Appendix 
14: List of Data Displays. 
Unless otherwise specified, drug concentration and pharmacodynamic measures will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
Table 10 
Overview of Planned Pharmacokinetic Analyses 
 
Stats Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
Pharmacokinetic [5] 
Plasma CAB concentration by Visit 
 
 
 
Y[1][2 
Y[1][3][4] 
Y[3] 
Y 
Plasma RPV concentration by Visit 
 
 
 
Y[1][2] 
Y[1][3][4] 
Y[3] 
Y 
Steady state concentration [8] 
 
 
 
Y[1] 
 
 
 


 
CONFIDENTIAL 
 
201584 
 
74 
 
Pharmacokinetic/Pharmacodynamic 
CAB/RPV last trough and Week 8 
concentrations by Snapshot virologic 
Response at Week 48 
 
 
 
Y 
Y 
 
 
CAB/RPV Week 8 concentrations by 
Snapshot virologic Response at Week 
96 [7] 
 
 
 
Y 
Y 
 
 
Analysis of Snapshot ‘HIV-1 RNA≥50’ at 
Week 48 by last trough CAB/RPV 
concentration, Week 8 trough 
concentration, and subgroups [6] – 
Univariable analysis /multivariable 
analysis 
Y 
 
 
 
 
 
 
Analysis of Snapshot ‘HIV-1 RNA≥50’ at 
Week 96 by Week 8 CAB/RPV trough 
concentration, and subgroups [6] – 
Univariable analysis /multivariable 
analysis [7] 
Y 
 
 
 
 
 
 
Individual CAB/RPV Concentration-Time 
Profiles for Participants with HIV-1 RNA 
≥ 50 c/mL at Week 48 (or Week 96) 
 
 
 
 
Y 
 
 
Change from Maintenance Baseline 
(Day 1) in 2hr post-dose QTc and 2-hour 
post-dose CAB & RPV concentration at 
Week 4b, Week 48, Week 96 
 
 
 
 
 
Y 
 
Maximum Change from Maintenance 
Baseline (Day 1) in ALT/Total Bilirubin 
versus Last Trough CAB/RPV 
Concentrations [8] 
 
 
 
 
 
Y 
 
Maximum Toxicity Grades of Most 
Frequently Reported AEs versus Last 
Trough CAB/RPV PK Concentrations [8] 
 
 
 
 
 
Y 
 
NOTES: 
• 
T = Table, F = Figure, L = Listings, Y = Display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e., modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e., descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data. 
3. 
For both ‘all’ concentration and the ‘evaluable’ concentration. The evaluable concentration is derived from 
samples collected within pre-specified Time window (Section 14.6.5 ) and not affected by dosing errors or oral 
bridging. 
2. 
For both ‘untransformed’ and ‘log –transformed’ statistics.  
3. 
The plots will be produced for the untransformed scale (i.e., a linear plot) and the log transformed scale (i.e., 
log-linear plot), separately. 
4. 
Separate plots will be produced for Mean (SD) and Median concentration. 
5. 
Standard summary statistics for concentration data will be calculated (i.e., mean, standard deviation, median, 
minimum, and maximum).  For Logarithmically transformed data, the summary statistics (i.e., geometric mean, 
coefficient of variation on geometric mean, 95% confidence interval for the geometric mean and standard 
deviation) will also be calculated.  
6. 
Please refer to Section 5.4.2. i.e., randomisation strata, baseline and demographic factors, and additional 
subgroups for PK/PD analyses 
7. 
Will be produced only if at least one new CVF has occurred since Week 48 (randomized Q4W arm). 
8. 
Produced for Week 48 only. 
 


 
CONFIDENTIAL 
 
201584 
 
75 
 
9.1.3. 
Statistical Analyses/Methods 
Planned PK statistical analysis 
Steady State Concentration 
Endpoints 
• loge-transformation of the Trough/Pre-dose plasma concentrations (CAB/RPV) on Week 16-
48  
Covariates 
• Study Week 
Data Handling 
• All data remains as is (observed). 
Model Specification 
• A mixed effects ANOVA model will be fitted with Week (continuous variable) as a fixed effect 
and subject as a random effect for each analysis separately. The Kenward & Roger (KR) 
degrees of freedom approach will be used. The coefficient for the slope of the day effect on 
the loge-scale will be used to evaluate steady state for each drug (CAB/RPV). The 90% 
confidence intervals for the slope for each treatment will be calculated. If it does not appear 
that steady-state has been demonstrated, early weeks (e.g., Week 16, 20, 24, etc...) results 
will be dropped and the analysis repeated. 
Model Checking & Diagnostics 
• The Steady state will be claimed (the coefficient for the slope of the Week effect on the 
(natural) log scale was close to 0 or the 90% CI for the slope estimate included zero. If 
steady-state is not demonstrated, concentrations from early weeks (e.g., Week 16, 20, 24, 
etc.) dropped in sequence and the analysis repeated until either steady state is shown or 
only two timepoints remain. 
Model Results Presentation 
• The coefficient for the slope of the day effect on the loge-scale, its Standard error and 90% 
interval will be presented. 
Population PK Analysis 
• A population-based PK analysis will be done under separate Population-PK Reporting and 
Analysis plans. 
Exposure - antiviral activity analysis (PK/PD) 
Endpoints 
• Snapshot ‘HIV-1 RNA≥50’ at Week 48 (or W96) 


 
CONFIDENTIAL 
 
201584 
 
76 
 
Covariates 
• Randomisation strata, demographic, and baseline characteristics (as specified in Section 
5.4.2), and the following additional subgroup/covariates for PK/PD efficacy analysis 
o  last CAB/RPV trough concentration (Week 48 analysis only) 
o  CAB/RPV trough concentration at the nominal Week 8 visit, Induction Baseline 
(Week -20) BMI, needle length for CAB/RPV injections at Week 4b) 
o See “Additional subgroup/covariates for PK/PD efficacy analysis” in Section 5.4.2 for 
derivation details. 
• For the W96 CSR, this exploratory analysis will be performed only if at least one new CVF 
has occurred since Week 48.  
Data Handling 
• All data remains as is (observed). 
Model Specification 
• Logistic regression will be used to exam the correlation between the endpoint (Snapshot 
‘HIV-1 RNA≥50’) at Week 48 and the covariates/subgroups. This logistic regression analysis 
will be performed for each covariate, separately (univariable analysis), and will also be 
performed with one multivariable analysis using Backward stepwise selection approach to 
identify the covariates potentially affecting virologic response. 
Model Checking & Diagnostics 
• For the multivariable analysis, a logistic regression model that best predicts the dependent 
variable (i.e., ‘HIV-1 RNA≥50’) from the independent variables (i.e., covariates/factors with P 
<0.15 from univariable analysis) will be determined using the backward stepwise selecting 
approach. The last trough and Week 8 trough PK concentration will be logarithmically 
transformed with base of 2 (i.e., one-unit increase of the point estimate of log2 PK 
concentration is equivalent to ‘doubling the concentration’ in the original value). The analysis 
will start with all covariates in the model and remove a covariate with the largest p-value (i.e., 
the least statistically significant) each time and continue until the stopping rule is reached 
when all remaining covariates have p-value <15%. 
• If problems with model convergence occur due to zero event counts or complete/quasi-
complete separation, then alternative methods such as Fisher’s exact test (univariate 
analysis) and exact logistic regression (multivariable analysis) may be used. 
Model Results Presentation 
• The odds ratio, 95% confidence interval, and p-value will be presented. Estimated effect 
represents the change in log odds for a two-unit increase in PK concentration. 
9.2. 
Subcutaneous Sub-Study 
9.2.1. 
Endpoint / Variables 
• Plasma PK parameters for CAB LA 200 mg/mL and RPV LA 300 mg/mL (Ctau, 
concentrations 1-week post dose [~Cmax], and area under the curve [AUC (0-tau)]) 


 
CONFIDENTIAL 
 
201584 
 
77 
 
for SC injections during the SC injection phase compared with similar PK 
parameters for gluteal IM injections 
Plasma CAB and RPV concentration values will be summarized with descriptive statistics 
by dosing interval and planned timepoint for the PK Concentration Population (PC). These 
concentration values will be determined directly from concentration-time data from each 
analyte. Descriptive statistics including the n, mean with associated 95% CI, standard 
deviation, median, minimum, maximum, geometric mean with associated 95% CI, 
standard deviation of logarithmically transformed data, 5th/95th percentiles and the 
geometric coefficient of variation (CV%).  
Individual concentration-time profiles and median/mean profiles from each analyte in each 
dosing interval will be plotted for the PK Concentration (PC) Population.  Each of the 
figures will contain one plot on the untransformed scale (i.e., a linear plot) and one plot on 
the log transformed scale (i.e., semi-log plot).  Actual assessment times will be used in the 
individual concentration-time plots. Nominal times will be used for the purposes of 
summarization and in mean and median plots. See Appendix 4: Data Display Standards & 
Handling Conventions. for details on pharmacokinetic figure and table displays 
Pharmacokinetic parameters will be derived by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin 6.3 or higher (Pharsight, Inc., Cary, NC). All calculations of non-
compartmental PK parameters will be based on actual sampling times. Pharmacokinetic 
parameters listed will be determined from the plasma concentration-time data, as data 
permits. Cτ will be taken from CAB and RPV concentration data at the prescribed timepoint. 
The following PK parameters will be derived and displayed for the PP Population as data 
permits: 
Table 11a 
Derived PK Parameters 
Paramete
r 
Parameter Description 
Gluteal 
Injection 
SC Injection 1 
SC Injection 
2 
SC Injection 3 
Cmax 
Maximum observed 
concentration during the dosing 
interval 
Week-4 - 
Day 1 
Day 1 – 
Week 4 
Week 4 – 
Week 8 
Week 8 – 
Week 12 
tmax 
Time of occurrence of Cmax 
AUC0-τ 
Area under the concentration 
time curve from time zero to 
the end of the dosing interval 
Cτ 
Trough concentrations (Cτ) at 
the end of the dosing interval 
Day 1  
Week 4 
Week 8 
Week 12 
NOTES: NA: Not Applicable 
• 
Additional parameters may be included as required. 
 
 
 
 
 
All the derived pharmacokinetic parameters will be summarized and listed for the PP 
population by study phase and treatment. For each of these PK parameters, with the 
exception of tmax, the following descriptive summary statistics will be calculated for each 
treatment: n, arithmetic mean with associated 95% CI, standard deviation, median, 
minimum, maximum, geometric mean with associated 95% CI, standard deviation of 


 
CONFIDENTIAL 
 
201584 
 
78 
 
logarithmically transformed data, and the geometric coefficient of variation (CVb(%)). 
For tmax, the n, median, minimum, and maximum summary statistics will be provided. 
Where AUC0-τ is collected out of the appropriate window, AUC0-t (the last quantifiable 
concentration) will be used in place of AUC0-τ.  
 
Interim analysis 2 will include descriptive summaries and graphs of PK concentration and 
parameters as data permit. PK summaries will be presented by subgroup as needed where 
data allow. Data display specifications for derived PK parameter summaries and listings 
are given in Appendix 19 of this RAP 
PK samples collected outside the protocol defined time-windows and/or other protocol 
deviations will be reviewed by the study team to determine whether the sample will be 
excluded from PK analyses. 
9.2.2. 
Planned Analyses 
The primary objective of this sub-study is to evaluate the pharmacokinetics of cabotegravir 
LA (200 mg/mL) and rilpivirine (RPV) LA (300 mg/mL) for monthly dosing as a SC 
injection in the anterior abdominal Wall SC Tissue versus an IM injection into the gluteal 
muscle in HIV-1 infected participants currently enrolled in the FLAIR study. 
An estimation approach will be taken and point estimates and confidence intervals will be 
constructed for the ratio of the geometric mean of SC abdominal injection PK parameters 
to the geometric mean of the IM gluteal injection PK parameters. 
The primary analysis is to compare the abdominal SC injection with gluteal IM injection 
using the ratio of the geometric mean of SC injection to the geometric mean of IM injection 
for a PK parameter within each analyte (CAB, RPV). The primary PK parameters of 
interest include concentrations at the end of the dosing interval [Ctau], concentrations 1-
week post dose [~Cmax], and area under the curve for the dosing interval [AUC (0-tau)] 
(Table 24).  CAB and RPV concentrations and parameters will be summarized 
descriptively.   
 
Following log-transformation, Cmax, Ctau and AUC(0-tau) will be separately analyzed by 
analyte using a mixed effects model with fixed effect term for type of injection (SC, gluteal) 
and BMI (≥30 Kg/m2, <30 Kg/m2) in addition to a random effect term for subject. As it is 
suspected that varying participant BMI may impact the PK concentration distribution, BMI 
is being included in the model as a covariate to control for any potential impact beyond the 
effect of injection type. In each model, only participants with PK parameter estimates from 
corresponding both SC and gluteal injections are included. For example, in the model for 
comparing Cmax between the first CAB SC injection vs gluteal CAB injection, only 
participants with Cmax estimates from both first CAB SC injection and CAB gluteal 
injection are included.  
 
Point estimates and their associated 90% confidence intervals will be constructed for the 
differences between the SC injection and the gluteal injection. The point estimates and their 
associated 90% confidence intervals from the log-transformed analysis will then be back-
transformed to provide point estimates and 90% confidence intervals for the ratios between 


 
CONFIDENTIAL 
 
201584 
 
79 
 
the SC injection and the gluteal injection on the original scale. This analysis will be 
performed using the PK Parameter (PP) population for the dosing intervals given in Table 
11b using the Gluteal parameters as the reference variables and each SC injection-based 
set of parameters as the test variables. While no formal bioequivalence testing will be 
performed, parameters can be assumed to be similar if the geometric mean ratio and its 
90% CI fall within 0.80 – 1.25.  
Table 11b 
Parameters and dosing 
Parameters (CAB 
200mg/mL + 
RPV 300mg/mL) 
Q Monthly Dosing  
Cmax (1-week 
post injection), 
Ctau (end of 
dosing interval) 
AUC(0-tau) 
SC Injection 1: 
gluteal injection 
SC Injection 2: 
gluteal injection 
 
SC Injection 3: 
gluteal injection 
The point estimate of the slope of Cτ following the last IM injection through 3rd SC 
injection will also be determined to assess changes in steady state conditions established 
previously. This will be performed using another mixed-effects model with concentration 
timepoint as a predictor variable of concentration and a random effect of subject. The 
model will initially include all concentration values from Day 1 – Week 12 and will then 
be repeated, removing the earliest timepoint in each run until the last two timepoints 
remain, Week 9 – Week 12. Point estimates and 90% confidence intervals for the slope 
will be presented in tabular format. 
9.2.3. 
Statistical Analyses/Methods 
PK Parameters 
Endpoints 
Geometric Mean Ratio: 
• As data permit, Loge-transformation of the PK parameters (Ctau, Cmax and AUC(0-tau) for 
each sub-study dosing interval for participants in the sub-study PK Concentration Population 
Steady State:  
• loge-transformation of the Trough/Pre-dose plasma concentrations (CAB/RPV) on all 
appropriate dosing intervals 
Model Specification 
Geometric Mean Ratio: 
• Following Loge-transformation, PK parameters will be separately analyzed by treatment arm 
and analyte using a mixed effects model with dosing interval (gluteal injection vs 1st, 2nd, and 
3rd SC injection) and Sub-study Baseline BMI (<50 kg/m2, ≥ 30 kg/m2) as fixed effects and 
subject as a random effect. In each model, only subjects with evaluable PK parameter 


 
CONFIDENTIAL 
 
201584 
 
80 
 
estimates in both dosing intervals are included. For example, in the model for comparing 
Cmax estimated from the first CAB SC injection interval with Cmax estimated from the 
gluteal injection interval, only the subjects with evaluable Cmax estimates from both first CAB 
SC injection interval and gluteal injection interval are included. 
Steady State:  
• A mixed effects ANOVA model will be fitted with Day / Week (categorical variable) as a fixed 
effect and subject as a random effect for each analyte. The Kenward & Roger (KR) degrees 
of freedom approach will be used. The coefficient for the slope of the day effect on the loge-
scale will be used to evaluate steady state for each drug (CAB/RPV). The 90% confidence 
intervals for the slope for each treatment will be calculated. The model will be initially run with 
all timepoints from Day 1 – Week 12, removing the earliest timepoint at each iteration until 
the last two timepoints remain, Week 9 - Week 12. Only evaluable concentrations will be 
included in the analysis. 
Model Checking & Diagnostics 
Geometric Mean Ratio: 
• Model assumptions will be applied, but appropriate adjustments may be made based on the 
data. Parameters can be assumed to be similar if the geometric mean ratio and its 90% CI 
fall within 0.80 – 1.25 
Steady State:  
• The Steady state will be claimed (the coefficient for the slope of the Week effect on the 
(natural) log scale was close to 0 or the 90% CI for the slope estimate included zero. 
Concentrations from earlier timepoints (e.g., Day 1, Week 1 etc.) will be dropped in sequence 
and the analysis repeated until only two timepoints remain. 
Model Results Presentation 
Geometric Mean Ratio: 
• The estimated difference and 90% CI obtained on the loge scale will be exponentiated to 
provide an estimate of geometric mean ratio and its associated 90% CI. The estimate of 
within-subject variability (%CVw) will also be provided. 
Steady State:  
• The coefficient for the slope of the day / week effect on the loge-scale, its Standard error and 
90% interval will be presented  


 
CONFIDENTIAL 
 
201584 
 
81 
 
10. 
PHARMACOKINETIC ANALYSES (DAY 1 JAPAN) 
For Japanese participants in the study, blood samples for CAB will be taken at the Day 1 
visit at each of the sampling times shown in Table 11c, in addition to sparse samples 
collected at other visits as specified in the protocol for all CAB LA + RPV LA 
randomized participants. 
Table 11c 
Additional PK Visit and Sample Times for Japanese Participants 
Day 
Time (Related to Dosing of Study agent) 
Oral Cabotegravir 
Day 1 (following first oral dose 
during lead-in phase) 
Pre-dose, 1, 2, 3, 4, 8, and 24 hours post-dose 
10.1. 
Primary Pharmacokinetic Analyses  
Pharmacokinetics of CAB following a single 30 mg dose using the Phase 3 formulation 
in Japanese in 201584 (FLAIR) will be evaluated.  Approximately 20 Japanese 
participants will be enrolled and randomized 1:1 to CAB or ABC/DTG/3TC to achieve 
~10 participants who receive oral CAB.   
The GSK Division of Clinical Pharmacology Modelling and Simulation (CPMS) will be 
responsible for the PK analysis of CAB.  The Division of Global Clinical Pharmacology 
at Janssen Research and Development will be responsible for conduct or oversight of the 
PK analysis for RPV. 
10.1.1. 
Endpoint / Variables 
10.1.1.1. 
Drug Concentration Measures 
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 14.5.3 
Reporting Standards for Pharmacokinetic). 
Assay results from Day 1 samples collected from a subject with emesis occurring within 
4 hours of the dose will not be considered as evaluable and will be excluded from all data 
displays and PK analyses. 
10.1.1.2. 
Derived Pharmacokinetic Parameters 
Pharmacokinetic parameters for Japanese participants randomized to CAB LA + RPV LA 
will be calculated using plasma concentration-time data on Day 1 by standard non-
compartmental analysis according to current working practices and using the currently 
supported version of WinNonlin. All calculations of non-compartmental parameters will 
be based on actual sampling times. Pharmacokinetic parameters listed will be determined 
from the concentration-time data, as data permits. 


 
CONFIDENTIAL 
 
201584 
 
82 
 
Parameter 
Parameter Description 
AUC(0-t) 
The area under the plasma concentration-time curve from time zero to the last quantifiable 
concentration following the first dose, determined using the linear trapezoidal rule for 
increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations 
Cmax 
The first occurrence of the maximum observed plasma concentration determined directly 
from the raw concentration-time data. 
C24 
Concentration observed at 24-hours post dose (±30 mins) determined directly from the raw 
concentration-time data. 
tlag 
The time of sample preceding first quantifiable concentration, determined directly from the 
raw concentration-time data. 
tmax 
The time at which Cmax is observed, determined directly from the raw concentration-time 
data. 
tlast 
The time of last quantifiable concentration 
NOTES: 
• 
Additional parameters may be included as required. 
10.1.2. 
Summary Measure 
For plasma CAB concentrations, the following summary statistics will be calculated by 
planned sampling time: n, mean, standard deviation (SD), coefficient of variation (%CV), 
median, minimum and maximum, geometric mean, 95% confidence interval and the 
between-subject CV (%CVb) based on the geometric mean for the loge-transformed 
values. 
For PK parameters, except for tmax, tlag, and tlast, the following summary statistics will 
be calculated: n, mean, standard deviation (SD), coefficient of variation (%CV), median, 
minimum and maximum, geometric mean, 95% confidence interval and the between-
subject CV (%CVb) based on the geometric mean for the loge-transformed values. For 
tmax, tlag, and tlast, the following summary statistics will be calculated: median, 
maximum, minimum, arithmetic mean, and standard deviation. 
10.1.3. 
Population of Interest  
The primary pharmacokinetic analyses will be based on the Japan Pharmacokinetic 
population, unless otherwise specified. 
10.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
Data following the intercurrent event of randomized treatment discontinuation will not be 
used in the analysis as the concentrations and PK parameters to be estimated is while on-
treatment. 
10.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 1: Japan-Specific Requirements 
and will be based on GSK Data Standards and statistical principles. 


 
CONFIDENTIAL 
 
201584 
 
83 
 
Unless otherwise specified, endpoints / variables defined in Section 9.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
PK parameters that have mass in the units should be reported in µg/mL and µg•h/mL.  
Deviations from planned times will be examined for scheduled assessments. PK 
parameters will be calculated using actual assessment times. Actual assessment times will 
be used in the individual concentration-time plots. Nominal times will be used for the 
purposes of summarization and in mean and median plots. Concentration-time data will 
be listed using actual assessment times. 
All available data will be summarized, with no imputation for missing data. 
10.1.5.1. 
Statistical Methodology Specification 
No formal hypothesis will be tested.  Descriptive statistics will be used to summarize 
data. 
 
11. 
HEALTH OUTCOMES ANALYSES 
11.1. 
Endpoint / Variables 
• Change from Maintenance Baseline (Day 1) in total “treatment satisfaction” score, 
and individual item scores of the HIV Treatment Satisfaction Status Questionnaire 
(HIVTSQs); 
• Change in treatment satisfaction over time (using the HIVTSQc change version) at 
Week 48; 
• Change from Week 5 in Dimension Scores and proportion of participants considering 
pain and local reactions following injection using PIN (Perception of Injection 
Questionnaire) (Q4W arm only); 
• Change from Maintenance Baseline (Day 1) in Subscale of Life satisfaction, HIV 
medication, and disclosure worries using HAT-QoL; 
• Change from Maintenance Baseline (Day 1) in Mental health component (MCS) and 
physical component summary (PCS) using SF-12; 
• Change from Maintenance Baseline (Day 1) in treatment acceptance using ACCEPT; 
• Change from Week 4b in tolerability of injections using NRS (Q4W arm only) 
11.1.1. 
Summary Measure 
Mean treatment difference (Q4W IM – ABC/DTG/3TC) at visits of interest through to 
Week 96 (i.e., the assessment visits detailed in Table 12), excluding PIN and NRS 
endpoints. 
 
Mean change at visits of interest through to Week 96 (i.e., the assessment visits detailed 
in Table 12), for PIN and NRS endpoints. 


 
CONFIDENTIAL 
 
201584 
 
84 
 
11.1.2. 
Population of Interest  
The primary health outcomes analyses will be based on the Intent-to-Treat Exposed 
population, unless otherwise specified. 
11.1.3. 
Strategy for Intercurrent (Post-Randomization) Events 
If a participant discontinues treatment prior to the timepoint of interest such that there is 
no evaluable on-treatment assessment for the timepoint of interest (see Table 30 for 
definition of on-treatment), the data will be computed or imputed (see Section 14.6.6). 
11.1.4. 
Planned Health Outcomes Analyses 
Table 12 provides an overview of the planned analyses. Details of the planned displays 
are provided in Appendix 14: List of Data Displays and will be based on GSK Data 
Standards and statistical principles. 
 
Table 12 
Overview of Planned Health Outcome Analyses 
Endpoints 
Absolute  
Change from Maintenance Baseline  
Stats Analysis Summary Individual Stats Analysis Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Perception of Injection (PIN) at Week 5, 41, 48, 96, Withdrawal (Q4W arm only) 
Individual Item 
Scores 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Domain of ‘Bother 
from injection site 
reactions’, ‘Leg 
movement’, ‘Sleep’, 
‘Acceptability’ 
Y[4] 
 
 
Y 
 
 
 
 
 
 
Y[5] 
 
 
 
 
Health-related quality of life (HATQoL) at Day 1, Week 24, 48, 96, Withdrawal 
Individual Item 
Scores 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Subscale of Life 
satisfaction, HIV 
medication, and 
disclosure worries 
 
 
 
Y 
 
 
 
Y 
Y[1] 
 
Y 
 
 
 
 
Health Status (SF-12) at Day 1, Week 24, 48, 96, Withdrawal 
Individual Item 
Scores 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Mental health 
component (MCS) 
and physical 
component summary 
(PCS)[2] 
 
 
 
Y 
 
 
 
Y 
Y[1] 
 
Y 
 
 
 


 
CONFIDENTIAL 
 
201584 
 
85 
 
Endpoints 
Absolute  
Change from Maintenance Baseline  
Stats Analysis Summary Individual Stats Analysis Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Treatment Satisfaction Score (HIVTSQs) at Day 1, Week 4b, 24, 44, 96, Withdrawal 
Individual Item 
Scores 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
 
Individual Item 
Scores by 
Subgroup[3] 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Treatment 
Satisfaction Score 
Y 
 
 
Y 
 
 
 
Y 
Y[1] 
 
Y 
 
 
 
Treatment Satisfaction Score Change (HIVTSQc) at Week 48, Withdrawal 
Individual Item 
Scores  
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Treatment 
Satisfaction Score 
Change 
Y 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Treatment Acceptance (ACCEPT) at Day 1, Week 8, 24, 48, 96, Withdrawal 
Proportion of 
Individual item score  
 
 
 
Y  
 
 
 
 
 
 
 
 
 
 
 
Acceptance/General 
Dimension Score 
 
 
 
Y 
 
 
 
Y 
Y[1] 
 
Y 
 
 
 
Tolerability of injection (NRS) at Week 4b, 5, 40, 41, 96 (Q4W arm only) 
Proportion of 
Individual item score 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Tolerability Score 
(Q4W IM only) 
 
 
 
Y 
 
 
 
 
 
 
Y 
 
 
 
 
Treatment Preference at Week 48 (Q4W arm only) 
Treatment: Monthly 
injection vs Daily oral 
ART 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
NOTES: 
• 
T = Table, F = Figure, L = Listings, Y = Display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e., modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e., descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data. 
1. 
Line Plot of Adjusted Mean (95% CI) for each treatment arm, as well as the adjusted mean difference (95% CI) 
between the two treatment arms (if questionnaire was used for both arms during Maintenance Phase). 
2. 
Component scores will be calculated form Computer Software purchased from QualityMetric. 
3. 
Subgroups: Induction Baseline (Week -20) HIV-1 RNA (<100,000, ≥100,000 c/mL), gender at birth, age (<35; 35-
<50; ≥50), Maintenance Baseline (Day 1) CD4+ cell count  <200; 200 to <350; 350 to <500; ≥ 500 cells/mm3), 
and race (i.e., white, non-white).  
4. 
Statistical analysis (i.e., p-value) produced only for the acceptance score comparing Week 40/41/96 to Week 5. 
5. 
Change versus Week 5 for PIN. 


 
CONFIDENTIAL 
 
201584 
 
86 
 
11.1.5. 
Statistical Analyses/Methods 
Statistical Analyses 
Endpoints 
• 
Change from Maintenance Baseline (Day 1) in 
• HIVTSQs total treatment satisfaction score 24, 44, and 96 
• ACCEPT general acceptance score at Week 8, 24, 48, and 96 
• 
SF-12: physical component summary (PCS) and mental component summary (MCS) at 
week 24, 48, and 96 
• 
HATQoL (Life satisfaction, HIV medications, disclosure worries) at Week 24, 48, and 96. 
Model Specification 
• An analysis of covariance (ANCOVA) model will be used at each visit at Maintenance Phase 
with covariates: treatment, age (<50, ≥ 50 years old), Induction Baseline (Week -20) HIV-1 
RNA (<100,000, ≥100,000 c/mL), gender at birth, race (i.e., white, non-white) and 
Maintenance Baseline (Day 1) score value (as a continuous variable). 
• Adjusted point estimates will be derived as LSMEANS using the observed margins (OM) 
option within PROC MIXED in SAS. 
• No adjustment for multiplicity will be applied as these analyses will be considered 
supportive. 
• Interactions between treatment and each of the covariates will not be assessed unless the 
exploratory subgroup analyses on the primary endpoint highlights significant interactions. In 
this situation, the interaction(s) of interest will be assessed and, if necessary, results will be 
reported in the clinical study report. Interactions between treatment and the baseline score 
will be investigated but not included in the model. If interactions are found to be significant 
(p<0.10), results may be presented separately by subgroup. 
Dataset 
• LOCF dataset will be used.  
Model Results Presentation 
• Adjusted treatment difference (Q4W IM – ABC/DTG/3TC), its 95% CI and the associated p-
value. The interaction between treatment and the baseline score will be included in a 
footnote. 
• Plots of adjusted mean change from Maintenance Baseline (Day 1) (95% CI) for each 
treatment group, and the adjusted mean difference (95% CI) between the two treatment 
arms from the model will be generated across visit.  
 


 
CONFIDENTIAL 
 
201584 
 
87 
 
Statistical Analyses 
HIVTSQc 
• Treatment Satisfaction Score (Change) at Week 48 
Model Specification 
• An analysis of variance (ANOVA) model will be used with covariates: treatment, age (<50, ≥ 
50 years old), Induction Baseline (Week -20) HIV-1 RNA (<100,000 c/mL, ≥ 100,000 c/mL), 
Gender at birth, and Race (white, non-white) 
• Adjusted point estimates will be derived as LSMEANS using the observed margins (OM) 
option within PROC MIXED in SAS. 
• Interactions between treatment and each of the covariates will not be assessed unless the 
exploratory subgroup analyses on the primary endpoint highlights significant interactions. In 
this situation, the interaction(s) of interest will be assessed and, if necessary, results will be 
reported in the clinical study report. If interactions are found to be significant (p<0.10), results 
may be presented separately by subgroup. 
• No adjustment for multiplicity will be applied as these analyses will be considered supportive. 
Dataset 
• The observed case (OC) dataset uses only the data that is available at Week 48, with no 
imputation for missing values. 
Model Results Presentation 
• Adjusted means, 95% CI, and associated p-value will be presented for the treatment 
difference (Q4W IM – ABC/DTG/3TC).  
Statistical Analyses 
PIN 
• Change from Week 5 in the PIN acceptance score at Week 41 and Week 48 (Q4W arm only) 
Statistical Test 
• The Wilcoxon Signed-Rank Test will be used to evaluable whether the change from Week 5 to 
Week 41 and to Week 48, respectively, is statistically different than zero based on a two-sided 
p<0.05.  Separate tests will be performed for the change from Week 5 to Week 41 and for the 
change from Week 5 to Week 48. 
Dataset 
• LOCF dataset will be used 
Results Presentation 
• Summary statistics at each timepoint (Week 5, Week 41 and W48) and p-value for each 
comparison (W48/W41) versus scores at Week 5  
11.2. 
Subcutaneous Sub-Study Endpoint / Variables 
• Change from gluteal to SC in total “treatment satisfaction” score, and individual 
item scores of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) 
during the SC Injection phase as well as the change from SC to gluteal during the 
Return to Gluteal Injection phase 
• Change from gluteal to SC using the HIV Treatment Satisfaction Change 
(HIVTSQc) questionnaire at Sub-study Week 9 


 
CONFIDENTIAL 
 
201584 
 
88 
 
• Changes in the tolerability of injections (NRS) over time during the sub-study, 
separate for CAB LA and RPV LA 
• Changes in the perception of injections (PIN) over time during the sub-study, 
separate for CAB LA and RPV LA 
• Preference for SC injections compared with prior gluteal injections and the 
injections received during the Return to Gluteal Injection phase respectively. 
• Reasons for switch to SC from IM 
• Interest for home administration options   
11.2.1. 
Summary Measure 
The health outcomes analyses include analyses of data collected from the following 
questionnaires, HIVTSQ (both s and c versions), NRS, PIN, and Preference between SC 
and gluteal injections. The reasons for switch to SC from IM injections will be assessed, 
as well as the interest in a potential option for self-administration of SC injections. Health 
Outcomes assessments will be summarized, where applicable, by study drug (CAB and 
RPV), domain, and item. Summaries will be presented by subgroup as needed where data 
allow. 
 
For the sub-study, the change from sub-study Baseline in Total Treatment Satisfaction 
and Individual Item scores as well as the mean difference between SC injections and 
gluteal injections from visits of interest will be presented for the HIVTSQs (Baseline vs. 
Week 9 and Week 17). Change from sub-study Baseline will be presented for the NRS 
and the PIN (Domain and Individual Item scores). Descriptive statistics and frequency 
counts will be presented as appropriate for all measures.  
Results for the Preference questionnaire, the HIVTSQs, the PIN, and the NRS will be 
displayed by subgroup (age group, sex, race/ethnicity, Baseline BMI).  
Descriptive NRS and Preference score statistics will also be presented at interim analysis 
2.  
11.2.2. 
Statistical Analyses/Methods 
Statistical Analyses 
NRS/PIN/HIVTSQs 
• Change from Sub-study Baseline in the NRS, PIN domain and item scores, and HIVTSQs 
total treatment satisfaction score at all available subsequent sub-study timepoints 
• The mean difference between SC injections and IM injections from all visits in a phase will 
be calculated between all SC results and all return to IM results for the NRS, PIN, and 
HIVTSQs.  
Statistical Test 
• The Wilcoxon Signed-Rank Test will be used to evaluate: 
For HIVTSQs, whether the change from Sub-study Baseline to each post-baseline sub-study 
visit is statistically different from zero based on a two-sided p<0.05. Separate tests will be 


 
CONFIDENTIAL 
 
201584 
 
89 
 
Statistical Analyses 
performed for the change from Baseline to Week 9, for the change from Baseline to Week 
17, and for the change from Week 9 (SC phase) to Week 17 (return to IM phase). 
For the PIN domains, whether the change from Sub-study Baseline to each post-baseline 
sub-study visit is statistically different from zero based on a two-sided p<0.05. Separate 
tests will be performed for the change from Baseline to Week 1, Baseline to Week 9, and 
Baseline to Week 13, and for the change from Week 9 (SC phase) to Week 13 (return to IM 
phase) by treatment (CAB vs RPV). 
Dataset 
• Observed values will be used for all measures 
Results Presentation 
• For HIVTSQs, summary statistics at Sub-study Baseline, Sub-study Week 9, and Sub-study 
Week 17 a p-value for the comparison between scores at each post-baseline sub-study visit 
with scores at Sub-study Baseline will be presented. 
• For the PIN domains, summary statistics at Sub-study Baseline, Sub-study Weeks 1, 9, and 
13 a p-value for the comparison between scores at each post-baseline sub-study visit with 
scores at Sub-study Baseline will be presented. 
 
 


 
CONFIDENTIAL 
 
201584 
 
90 
 
12. 
VIROLOGY 
Details of the planned virology displays for the Week 124 analysis are provided in 
Appendix 15: List of Data Displays for Week 124.  
Virology displays for the subcutaneous sub-study will be produced when data is 
available. Further details available in Appendix 19: List of Data Displays for 
Subcutaneous Sub-Study Analysis. 
The virology analyses will be for the CVF populations using genotype and phenotype 
data based on population sequencing assay, unless otherwise specified.  
Table 13 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 14: List of Data Displays. 
Table 13 
Overview of Planned Virology Analyses 
Endpoint  
Absolute 
Summary 
Individual 
T 
F 
F 
L 
Genotypic resistance at time of CVF[1] 
Prevalence of Resistance Mutations 
Y [2] 
 
 
Y [4] 
Prevalence of Emergent Resistance Mutations – 
Relative to Genotype at Baseline (Week -20) [5] 
Y [2] 
 
 
 
Phenotypic resistance at time of CVF[1] 
Prevalence of Phenotype   
Y [3] 
 
 
Y [4] 
Fold Change for CAB, RPV, DTG  
Y 
 
 
 
Change from Induction Baseline (Week -20) in 
Fold Change to CAB, RPV, DTG. 
Y 
 
 
 
IN, PR/RT Replication Capacity  
 
 
 
Y 
Other 
Viral load, Genotypic and Phenotypic data for 
Participants with genotype and/or phenotype 
data for CVF and non-CVF participants  
 
 
 
Y [4] 
Prevalence of Resistance Mutations at Induction 
Baseline (Week -20) 
Y [2] 
 
 
 
All Genotypic Data 
 
 
 
Y 
 
NOTES: 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e., modelling) conducted. 
• 
Summary = Represents TFL related to any summaries (i.e., descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data.    


 
CONFIDENTIAL 
 
201584 
 
91 
 
1. 
For the CVF as indicated by two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to 
<200 c/mL, the first visit of these two consecutive visits is defined as ‘the suspected visit’, and the 2nd one is the 
confirmed visit. Sample used for resistance testing is taken at the suspected visit date, and only tested once a 
participant confirms virological failure at a subsequent visit.  If the test fails with the sample at the suspected 
visit, we will just report it as ‘no data’. The sample from the confirmed visit will not be tested for resistance. 
2. 
No. and percentage of participants with IN resistance mutations or major mutations in the classes of NNRTI, 
NRTI, PI, respectively, as defined in 14.6.7 
3. 
Separate outputs by phenotypic cut-off and by number of drugs to which participants are resistant. 
4. 
Includes the following at all available timepoints (including screening, Week -20, and all post-baseline samples):  
HIV-1 subtype (Induction Baseline (Week -20)), resistance mutations and fold change to EFV/ETR/RPV, 
DTG/RAL/EVG/CAB and ARTs (for the ABC/DTG/3TC arm) received during the Maintenance Phase.  Non-CVF 
participants may include those with genotype/phenotype data upon withdrawal from treatment with last on-
treatment HIV-1 RNA ≥200 c/mL. 
5. 
Emergent Mutations defined in Section 14.6.7 
 
Additional analyses for HIV-1 resistance may be carried out on peripheral blood 
mononuclear cell (PBMC) samples collected at Day 1 and Week 96 (or withdrawal if 
prior to Week 96). 
If pre-treatment genotypic/phenotypic results are available from both the central 
laboratory and Monogram Biosciences, then Baseline genotype/phenotype will be 
determined based only upon the data provided by Monogram assays.    


 
CONFIDENTIAL 
 
201584 
 
92 
 
13. 
REFERENCES  
Chan, I. S. F. and Zhang, Z. (1999), “Test-Based Exact Confidence Intervals for the 
Difference of Two Binomial Proportions,” Biometrics, 55, 1202–1209. 
Chevat C, Viala-Danten M, Dias-Barbosa C, Nguyen VH. Development and 
psychometric validation of a self-administered questionnaire assessing the acceptance of 
influenza vaccination: the Vaccinees’ Perception of Injection questionnaire. Health Qual 
Life Outcomes. 2008 mar 4; 7:21 
D’Agostino RB, Vasan RS, Pencina MJ, et al. General Cardiovascular Risk Profile for 
Use in Primary Care (The Framingham Heart Study). Circulation 2008; 117: 743-753. 
EMA/CHMP/539146/2013, Guideline on the investigation of subgroups in 4 
confirmatory clinical trials, 23 January 2014 
Fleiss J.L. Statistical Methods for Rates and Proportions. 2nd ed. New York:John Wiley; 
1981. 
Gilet H, Arnould B.  Acceptance by the patients of their treatment (ACCEPT) 
Questionnaire, 2014.  
Grundy S.M., et al. Executive summary of the third report of the National Cholesterol 
Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of 
High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285 
(19):2486-2497.  
HIVTSQ user guidelines, Health Psychology Research Unit, Royal Holloway, University 
of London, 2016 
Holmes WC, HIV/AIDS-Targeted Quality of Life Instrument 1999.  
Kalbfleisch J.D., Prentice R.L. The Statistical Analysis of Failure Time Data. 1st ed. New 
York: John Wiley & Sons; 1980.  
Levey AI, Christopher HS, Hocine T, John HE, Harold IF, Tom G, et al. Estimating 
Glomerular Filtration Rate from Serum Creatinine and Cystatin C. N Engl J Med 2012, 
367: 20-29. 
Lui K.J., Kelly C. A Revisit on Tests for Homogeneity of the Risk Difference, 
Biometrics, 2000;56:309-315. 
Mary E. Nilsson, Shailaja Suryawanshi, Cristiana Gassmann-Mayer, Sarah, Dubrava, 
Paul McSorley, and Kaihong Jiang. Columbia–Suicide Severity Rating Scale, Scoring 
and Data Analysis Guide, 2013 
Nilsson ME, Suryawanshi S, Gassmann-Mayer C et al, Columbia–Suicide Severity 
Rating Scale, Scoring and Data Analysis Guide, 2013. 


 
CONFIDENTIAL 
 
201584 
 
93 
 
Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification 
Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the 
FDA’s pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 
2007;164:1035–1043. 
Ralph B. D’Agostino, Ramachandran S. Vasan, Michael J. Pencina, Philip A. Wolf, Mark 
Cobain, Joseph M. Massaro, William B. Kannel. 2008. General Cardiovascular Risk 
Profile for Use in Primary Care (The Framingham Heart Study). Circulation 2008; 117: 
743-753. 
Sato T. On the variance estimator for the Mantel-Haenszel risk difference. Biometrics. 
1989;42:311-323.  
SF-12 (v2) Health Survey 1994, 2002 Medical Outcomes Trust and QualityMetric 
Incorporated, 2018 
Wensing AM et al, 2019 Update of the Drug Resistance Mutations in HIV-1, Volume 27 
Issue 3 July/August 2019. 


 
CONFIDENTIAL 
 
201584 
 
94 
 
14. 
APPENDICES 
Section 
Appendix 
Analysis Populations 
Section 14.1 
Appendix 1: Protocol Deviation Management and Definitions for Per Protocol 
Population 
General Considerations for Data Analyses & Data Handling Conventions 
Section 14.2 
Appendix 2: Schedule of Activities 
Section 14.3 
Appendix 3: Assessment Windows 
Section 14.4 
Appendix 4: Study Phases and Treatment State 
Section 14.5 
Appendix 5: Data Display Standards & Handling Conventions 
Section 14.6 
Appendix 6: Derived and Transformed Data 
Section 14.7 
Appendix 7: Reporting Standards for Missing Data 
Section 14.8 
Appendix 8: Values of Potential Clinical Importance 
Section 14.9 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses 
Section 14.10 
Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses 
Section 14.11 
Appendix 11: Snapshot Algorithm Details 
Section 14.12 
Appendix 12: AESI identification 
Section 14.17 
Appendix 17: Variables Defined for Time to Event Analysis 
Other RAP Appendices 
Section 14.13 
Appendix 13: Abbreviations & Trade Marks 
Section 14.14 
Appendix 14: List of Data Displays for Week 48/Week 96 
Section 14.15 
Appendix 15: List of Data Displays for Week 124 
Section 14.16 
Appendix 16: IDMC 
Section 14.18 
Appendix 18: Japan-Specific Requirements 
Section 14.19 
Appendix 19: List of Displays for Subcutaneous Sub-study 
Section 14.20 
Appendix 20: Example Mock Shells for Data Displays 
 


 
CONFIDENTIAL 
 
201584 
 
95 
 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population 
14.1.1. 
Exclusions from Per Protocol Population 
Important protocol deviations leading to exclusion from the Per Protocol population are 
those deviations which may 
• directly impact the efficacy endpoint of HIV-1 RNA; or 
• lead to permanent discontinuation of IP/withdrawal and hence indirectly impact 
the efficacy endpoint by causing data to be missing. 
The following criteria define the protocol deviations which, if they occur prior to an 
analysis timepoint of interest (e.g., Week 48/96), will lead to exclusion of a participant 
from the Per-Protocol population for that analysis. Potential protocol deviations leading 
to exclusion from PP population will be reviewed by the study team to confirm that they 
meet these criteria.  A final review will occur before the clinical database has been frozen 
for analysis.  
A participant meeting any of the following criteria will be excluded from the Per Protocol 
population based on case-by-case clinical determination: 
Number 
Exclusion Description 
01 
Participant deviates from inclusion or exclusion criteria that may significantly affect 
exposure, response to therapy or participant safety or that are fundamentally 
inconsistent with the intended study population, as recorded in the Protocol 
Deviation form in the eCRF based on study team review (where indicated in the 
PDMP as case-by-case determination).  
02 
Participant has non-compliance with IP (including IM dosing errors) or took/received 
incorrect IP (i.e., other than the one to which they were randomized) up to an 
analysis timepoint of interest (i.e., Week 48/96), meeting the following conditions: 
Maintenance Phase: 
1. Maintenance Phase Week 48 analysis only: 
• Two or more injection intervals affected by over dosage deviations 
(e.g., extra injection or excessive volume administered, length of 
time between injections less than 3 weeks, excluding split doses) up 
to the analysis visit of interest; or  
2. Week 96 analysis only:  
• For participants discontinuing injections by Week 52: Two or more 
injection intervals affected by over dosage deviations (e.g., extra 
injection or excessive volume administered, length of time between 
injections less than 3 weeks, excluding split doses) up to the 
analysis visit of interest. 
• For participants receiving injections beyond Week 52: Three or 
more injection intervals affected by over dosage deviations (e.g., 
extra injection or excessive volume administered, length of time 


 
CONFIDENTIAL 
 
201584 
 
96 
 
Number 
Exclusion Description 
between injections less than 3 weeks, excluding split doses) up to 
the analysis visit of interest; or 
3. At least 10% of total time on-treatment with under dosing deviations in the 
Maintenance Phase up to the analysis visit of interest (i.e. Week 48/96), 
where the % with non-compliance is derived the ratio of the total number of 
non-compliant under dosing days occurring as of  the date of the last 
analysis timepoint snapshot viral load (i.e. last on-treatment viral load during 
the Maintenance Phase up to Study Day 378 for W48 and up to Study Day 
714 for W96) divided by the number of days on-treatment from start of 
Maintenance Phase treatment to the date of the last analysis timepoint 
snapshot viral load, and non-compliance days are defined as follows: 
ABC/DTG/3TC Arm:  
a. Duration of interruptions in ABC/DTG/3TC arm ART for reasons other 
than treatment-related adverse events/laboratory abnormalities (based 
on Exposure eCRF forms); 
Q4W IM Arm:  
a. Length of time (in days) until next injection from date of 
dosage/administration deviation potentially resulting in under dosage 
(e.g., 1ml administered instead of 2ml) 
b. Length of time (in days) in excess beyond 35 days between injections 
post Week 12 and in excess beyond 28 days for Week 8 and Week 12 
(e.g., missed or late injection visit) 
c. Length of time (in days) in excess beyond 35 days from last injection 
until start of oral bridging post Week 12 and exceeding 4 weeks for 
Week 8 and Week 12 
03 
Prohibited medications: receiving ART medication other than that prescribed/allowed 
by the study (excluding permanent changes in ART regimen; such cases will be 
retained as ‘HIV1-RNA≥50 c/mL’ in the per protocol snapshot analysis) or receiving 
prohibited concomitant medication that would impact exposure or response to 
therapy with duration and route of administration taken into consideration, as 
recorded in the Protocol Deviation form in the eCRF based on study team review 
(where indicated in the PDMP as case-by-case determination) 
04 
Permanent discontinuation of IP/withdrawal due to a reason of “Protocol Deviation” 
(as recorded in the eCRF Conclusion form). 
05 
Other important protocol deviations that exclude participant from Per protocol 
population as recorded in the Protocol Deviation form in the eCRF based on study 
team review (where indicated in the PDMP as case-by-case determination). 


 
CONFIDENTIAL 
 
 
 
201584 
 
97 
 
14.2. 
Appendix 2: Schedule of Activities 
14.2.1. 
Protocol Defined Schedule of Events 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
Clinical and Other Assessments 
Written 
Informed 
Consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Verificatio
n 
(Inclusion 
/ 
Exclusion 
Criteria) 
X 
X 
 
 
X
b 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
b 
 
 
 
 
 
 
 
 
 
 
 
Randomiz
ation 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demogra
phy 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
98 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
Medical 
Historyc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medicatio
n History / 
Prior ART 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom 
Directed 
Physical 
Exam and 
Medical 
Assessme
nt d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight, 
BMI, and 
Height e 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
Cardiovas
cular Risk 
Assessme
nt 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
99 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
Vital 
Signs 
(BP, HR, 
temperatu
re) f 
X 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
12-Lead 
ECG g 
X 
X 
pr
e-
do
se 
x3 
 
 
 
X 
X 
 
X
g 
 
 
 
 
 
 
X
g 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
CDC 
Classificat
ion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV 
Associate
d 
Condition
s 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


 
CONFIDENTIAL 
 
 
 
201584 
 
100 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
AE and 
SAE 
Assessme
nt, Con 
Meds 
X 
h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ISR 
Assessme
nt (LA 
Arm Only) 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
If 
ap
pli-
ca
ble 
Columbia 
Suicide 
Severity 
Rating 
Scale 
(eC-
SSRS) i 
X 
X 
 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
 
X 
W
72 
W8
4 
X 
 
 
 
 
 
 
 
 
 
X 
 
Clinical 
Chemistry  
and 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 


 
CONFIDENTIAL 
 
 
 
201584 
 
101 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
Hematolo
gy 
Rapid 
Plasma 
Reagin 
(RPR) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnanc
y Testingj 
S 
U 
S 
S 
S 
S 
U 
S 
U 
 
S 
S 
S 
S 
 
S 
S 
S 
S 
S 
S 
S 
S 
Uj 
 
S 
S 
U 
S 
S 
S - 
Q4
W 
 
S 
S 
HIV-1 
RNA and 
sample 
for 
storagek  
X
k 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
S
k 
X 
X 
X 
 
X 
Sk 
 
X 
 
X 
X 
X 
 
X 
X 
X 
CD4+  
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
 
 
X 
X 
X 
 
X 
X 
X 
CD8+ 
 
X 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
Urinalysisl  
 
X 
 
 
 
 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
102 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
Fasting 
Lab 
Assessme
nts:  
Glucose, 
Cholester
ol (Total, 
HDL and 
LDL) and 
Triglycerid
es m 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
Hepatitis 
B 
(HBsAg), 
Anti-HBc, 
and Anti-
HBsAG 
 
Hepatitis 
C  
(anti-HCV 
Ab) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
103 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
HLA-
B*5701 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PT/PTT/I
NR 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Renal and 
Bone 
marker 
analytes 
(blood/uri
ne)n 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Peripheral 
Blood 
Mononucl
ear Cells 
(PBMCs) o 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Genetic 
Samplep 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
104 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
Pharmacokinetics (CAB + RPV only) 
PK 
Sample  
(S)= 
Storage 
sample 
 
 
 
 
 
 
 
 
X
v 
w 
Xt  
v 
X 
X 
X 
X 
X
v 
X
v 
X 
X 
X 
S 
 
X
v 
X 
X 
v 
X 
v 
 
X
v 
w 
S 
 
 
 
X 
S 
Investigational Products 
Oral CAB 
and Oral 
RPV 
Dispensat
ion  
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xx 
O
LI 
O
nl
y 
 
 
Xx 
OL
I 
On
ly 
 
 
 
 
 
 
 
ABC/DTG
/3TC 
Dispensat
ion (or 
DTG 
alternate) 
 
X 
X 
X 
X
q r 
 
X 
X 
 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
105 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
Study 
Treatment 
Accounta
bility  
(pill 
counts) 
 
 
X 
X 
Xr 
X 
X 
X 
X
u 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
O
LI 
O
nl
y 
 
 
X 
O
LI 
O
nl
y 
X
u 
 
 
 
 
 
 
IM Study 
Treatment 
Administr
ation – 
Q4W 
throughou
t 
Maintena
nce and 
Extension 
Phase 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X
s 
X 
X 
X 
– 
co
nt 
do
s-
ing 
Q4
W 
 
 
 
Patient Reported Outcomesz 
HAT-QoL 
(short 
form) 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
106 
 
Proced
ures 
Screening a 
Induction Phase by 
Week 
Maintenance Phase by Week 
Extension Phase  
by Week 
WithdrawalY 
Long-Term Follow-Up 
Baseline (-20) 
(-16) 
(-12, -8) 
(-4) 
WDy 
Day 1 
4a 
4b – LA  arm 
5t – LA arm 
8, 12, 16, 20 
24 
28, 32, 36 
40, 44 
41 – LA arm 
48 
52 - LA Arm 
56 
60 – LA Arm 
64, 72, 80, 88 
68,76, 84, 92 
- LA Arm
96 
100 
101 – Direct to Inject Arm 
104a – Direct to Inject Arm 
104a LA and Oral Lead-In Arm 
104b - Oral Lead-In Arm 
108 
112, 116, 120,124 
Q4W after 108 (LA Arm) or 
after 124 (Switch Arm)
Q12W beginning 112 (LA Arm) 
SF-12 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
ACCEPT 
 
 
 
 
 
 
X 
 
 
 
W
8 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
HIVTSQ(s
) 
 
 
 
 
 
 
X 
 
X 
 
 
X 
 
W4
4 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
HIVTSQ(c
) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
PIN (LA 
Arm 
Only)aa 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
NRS (LA 
Arm Only) 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
W4
0 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Preferenc
e (LA Arm 
Only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
107 
 
Follow Up Visit:  Conduct ~4 weeks after the last dose of oral IP.  Required only if the participant has ongoing AEs / lab abnormalities at the last on-study visit.  This visit may be 
conducted by telephone. 
Direct to Inject:  Participants transitioning into the Extension Phase who do not use the optional CAB + RPV oral lead-in beginning at Week 100. 
Oral Lead-In:  Participants transitioning into the Extension Phase who do use the optional CAB + RPV oral lead-in beginning at Week 100. 
LA Arm:  Participants who were originally randomized to CAB LA + RPV LA at Day 1. 
Switch Arm:  All participants who transition into the Extension Phase from ABC/DTG/3TC (or DTG + 2 NRTI’s) at Week 100 – e.g., both direct to inject and oral lead-in participants. 
Note: BMI- Body mass Index, BP – Blood pressure, HR – Heart Rate, HDL – High Density Lipoprotein, LDL – Low Density Lipoprotein, PT – Prothrombin Time / PTT – Partial 
Thromboplastin Time / INR – International Normalized Ratio 
a. 
Complete all Screening assessments within 35 days.  Participants may begin the Induction Phase as soon as all Screening assessments are complete.  Participants may be 
rescreened once and will be assigned a new participant number. Confirmation of eligibility to enter the Maintenance Phase, eligibility to enter the Extension Phase. 
b. 
Collect full routine medical history plus (report at Baseline visit): HIV risk factors (may be collected at a later study visit), cardiovascular risk factors (assessments include smoking 
status and history, family history of cardiac events), recent [≤6 months] illicit drug use, intravenous drug use, gastrointestinal disease, metabolic, psychiatric, renal and neurologic 
disorders. 
c. 
Physical exams should be conducted as part of normal routine clinical care but data will not be collected in the eCRF. Medical assessments include any decisions the study staff 
must make for participant management and / or care.  
d. 
Height collected at Baseline only. 
e. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
f. 
A 12-lead ECG will be performed after resting in a semi-supine position for at least 5 minutes.  Perform ECG at Baseline (Week [-20]) in triplicate prior to dosing.  For participants 
randomized to CAB LA + RPV LA, at Week 4b and Week 48, a second ECG will be obtained approximately 2 hours after the last injection and just prior to the 2 hour post dose PK 
sampling. 
g. 
Collect SAEs at Screen only if associated to study participation. 
h. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  During the Maintenance Phase, the eC-SSRS will be administered at each Q4W visit through the Week 48 
primary endpoint, and then followed by Q12W assessments for CAB LA + RPV LA arm, thereafter through Week 96 (LA:  Week 60, 72, 84, 96).  The ABC/DTG/3TC arm will have 
assessments at Week 72 and Week 96).  Preferably completed at the beginning of the visit following administration of other patient reported questionnaires required prior to 
injections. 
i. 
Conduct pregnancy tests for only women of childbearing potential at every visit throughout the study, including Q4W during the Extension Phase.  Remind females of reproductive 
potential of the need to avoid pregnancy while in study and adherence to the study’s contraception requirements.  A negative urine pregnancy test is required prior to beginning 
the Induction Phase (Week [-20]), on Day 1 (preferably prior to randomization), and at Week 4b (or Week 104b for participants transitioning from ABC/DTG/3TC) prior to the first 
injection. Serum pregnancy test can substitute for urine pregnancy test if locally required but must be appropriately timed to confirm pregnancy status prior to e.g. randomization 
and first IM administration. S=Serum/U=Urine. 


 
CONFIDENTIAL 
 
 
 
201584 
 
108 
 
j. 
Plasma for storage will be used: to determine genotypic eligibility at Screen, for possible future analyses, as back- up in case samples are lost or damaged in transit to the lab and 
for genotypic and phenotypic analyses in cases of virologic failure.  HIV-1 RNA will not be collected for analysis at Week 52 and Week 100 (Week 48 or Week 96 retest will be 
captured as unscheduled visit).  Plasma for storage will be collected at Week 52 and Week 100. 
k. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; and urine phosphate. 
l. 
Overnight fast is preferred; however, a minimum of a 6 hour fast is acceptable. 
m. Blood sample for renal and bone biomarker assessments: Renal: Cystatin C; Retinol Binding Protein (RBP); Bone: bone specific alkaline phosphatase, procollagen type 1-N-
propeptide, type 1 collagen cross-linked C-telopeptide, osteocalcin, 25 hydroxy-Vitamin D 
n. 
Whole blood/Peripheral Blood Mononuclear Cell collection samples may be used for virologic analyses.  PBMCs will be collected at Day 1, Week 96, Withdrawal visits. 
o. 
Informed consent for genetic research must be obtained before sample collection.  Sample may be collected at any visit after signing informed consent, but preferably at the 
Week [-20] visit. 
p. 
Instruct participants to continue to take the ABC/DTG/3TC regimen until Day 1 of the Maintenance Phase.  Participants will be randomized at Day 1 to continue on ABC/DTG/3TC 
arm or begin oral CAB + oral RPV.  Day 1 dosing should occur after randomization to determine defined treatment for the Maintenance Phase. 
q. 
Remind participants of the potential change in study treatment and visit frequency beginning at Day 1. 
r. 
Visit Week 104b is only required for participants transitioning from the ABC/DTG/3TC arm. 
s. 
The Week 5 visit should be performed approximately 7 days after the first injections at Week 4b (3 to 10-day window allowed). 
t. 
For oral CAB + RPV only. 
u. 
Take PK samples pre-dose.  At Week 4b (and Week 104b for participants transitioning to LA from ABC/DTG/3TC using the optional oral lead-in), the pre-dose PK sample should 
be taken after review of the PK diary and prior to the final oral CAB + RPV dose.  A sample will be also be taken at Week 4b, Week 48, and Week 96 (and Week 100 [direct to 
inject] or Week 104b [using CAB + RPV oral lead-in]), approximately 2 hours post-injections.  The Week 5, Week 41, and Week 101 visit can be performed at any time from 3 to 
10 days after the Week 4b, Week 40, and Week 100 injection, respectively. PK samples at Week 5, Week 41, and Week 101 can be taken at any time during the visit. 
v. 
Participants should take the last dose of oral CAB+RPV at Week 4b (and Week 104b for participants transitioning to LA from ABC/DTG/3TC if using the optional oral lead-in) in the 
clinic after PK sampling. Participants should take the last dose of ABC/DTG/3TC at Week 100 if transitioning directly to injections at Week 100.  Injections should be administered 
within 2 hours of the last oral dose where possible. 
w. For participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC only. 
x. 
Follow Up Visit:  Conduct approximately 4 weeks after the last dose of oral IP.  Required only if the participant has ongoing AEs or lab abnormalities at the last on-study visit.  This 
visit may be conducted by telephone. 
y. 
With the exception of the NRS questionnaire, patient reported questionnaire/surveys are recommended to be administered at the beginning of the visit before any other clinical 
assessments are conducted, and prior to completion of the eCSSRs assessments.  Only conduct questionnaires/surveys at Withdrawal if occurring prior to Week 96 (The NRS will 
not be collected at Withdrawal). 
z. 
The PIN, Preference, and NRS questionnaires are to be administered only to participants receiving CAB LA + RPV LA injections. The NRS should be collected 30 to 60 minutes 
post-injection (and at Week 5 and Week 41, one-week post-injections) - the participant should record the maximum level of pain experienced with the most recent injections. 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
109 
 
14.2.2. 
Protocol Defined Schedule of Events for the Subcutaneous Sub-Study 


 
CONFIDENTIAL 
 
 
 
201584 
 
110 
 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d 
Screening 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20  
IM Gluteal 
Administration 
X 
 
 
 
 
 
 
 
X k 
 
X 
 
 
SC Abdominal 
Administration k 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Written 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Verification  
 
Inclusion / 
Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom 
directed 
physical exam 
and medical 
assessment a 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Height, Weight 
and BMI 
 
 
X 
 
 
 
 
 
X 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
111 
 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d 
Screening 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20  
Vital Signs, BP, 
HR, temp b 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12 EKG c 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
HIV associated 
conditions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
AEs, SAEs, 
concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ISR 
assessments 
for IM injections 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
 
ISR 
assessments 
for SC 
injections 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Clinical 
Chemistry and 
Hematology 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Pregnancy 
testing, serum e 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
112 
 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d 
Screening 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20  
HIV-1 RNA and 
sample for 
storage (S) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
CD4+ cell count 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
CD8+ cell count 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Urinalysis f 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
Fasting lab 
assessments: 
glucose, 
cholesterol 
(total, HDL and 
LDL) and 
triglycerides g 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
PK Sample Collection j 
Pre dose PK 
samples for 
CAB and RPV  
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Post dose PK 
sampling 
(~Cmax) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 


 
CONFIDENTIAL 
 
 
 
201584 
 
113 
 
Procedures 
Screening Phase d 
SC Abdominal Injection Phase d 
Return to IM Gluteal Injection Phase d 
Screening 
Week -4 
Week -3 
Day 1 
Week 1 
Week 4 
Week 5 
Week 8 
Week 9 
Week 12 
Week 13 
Week 16 
Week 17 
Week 20  
PROs m 
HIVTSQC 
 
 
 
 
 
 
 
X 
 
 
 
 
 
HIVTSQS l 
 
X m 
 
 
 
 
 
X 
 
 
 
X 
 
NRS h 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
PIN i 
 
X 
 
X 
 
 
 
X 
 
X 
 
 
 
Preference SC 
Abdominal 
injection vs IM 
Gluteal injection 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Reason for 
switch 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Interest for 
home 
administration 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
a. Physical exams should be conducted as part of normal routine clinical care. 
b. Measure vital signs about 5 minutes of rest in a semi-supine position. 
c. A 12-lead ECG will be performed after resting in a semi-supine position for at least 5 minutes. ECGs will be performed pre-dose. 


 
CONFIDENTIAL 
 
 
 
201584 
 
114 
 
d. All injection visits during the sub-study should be kept to the same projected visit schedule as in the parent study. 
e. Women of childbearing potential only. SR = serum, UR = urine. Urine pregnancy test can be performed at study visits where other 
blood draws are not required in order to limit needle sticks.  
f. A morning specimen is preferred. 
g. An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
h. Should be collected 30 to 60 minutes post injection. To be assessed separately for CAB LA and RPV LA 
i. To be assessed separately for CAB LA and RPV LA. 
j. PK window allowed for sample collection: For 1-week post dose sample (3 to 10 days post dose). 
k. During the SC phase (and for the first IM injection in the return to IM injection phase), the dosing window can be -7 days, however, it 
cannot be +7 days from the projected visit date. Once SC injections begin, the next SC administration can be 3-4 weeks later, however, 
SC administration may not take place 5 weeks later. See details in Section 12.12.1.2. and Section 12.12.4.3. 
l.  All Patient Reported Outcome Questionnaires/Surveys will be administered via paper instrument (in exception circumstances, the 
questionnaires could be completed via telephonic interview, please refer to the COVID19 appendix for additional details) at the 
beginning of the visit before any other assessments are conducted, with the exception of the NRS. 
m. For HIVTSQS, we want to measure satisfaction with IM gluteal injection prior to switch to sub-cutaneous. This will be assessed at week 
-3 (questionnaire can be administered at any time during the visit). 


 
CONFIDENTIAL 
 
 
201584 
 
115 
 
14.3. 
Appendix 3: Assessment Windows 
14.3.1. 
Definitions of Assessment Windows 
AEs, SAEs and concomitant medications to be assessed pre-dose. IM administration 
itself and all other assessments will be considered part of the parent study, and should be 
completed as per the study time and events tables in Section 14.2. 
Laboratory data, vital signs, ECGs, NRS questionnaire (health outcomes) assessments, 
protocol deviations, and genotypic/phenotypic data will be assigned to assessment 
windows according to actual dates rather than the nominal visit labels as recorded on the 
eCRF or in the laboratory database. 
In most cases the window around an assessment will include all dates from the midpoints 
between the target day and that of the previous and the proceeding visits.  In general, the 
nominal target study day for week w is (7*w) +1.   
For parameters which are not scheduled to be assessed at particular visits, the all-
inclusive assessment windows will still be used; however, data summaries will only 
report scheduled visits. Assessments at unscheduled visits will be included for ‘any time 
On-treatment’ time points and in data listings, as well any algorithms that make use of 
additional data (e.g., Snapshot). 
Prior to visit slotting, assessments are first assigned to a study Phase (screening, 
induction, maintenance, extension, sub-study screening, SC injection, return to gluteal 
injection, or Long Term Follow Up) based on the tables in Section 14.4.1 and treatment 
state based on Section 14.4.2. 
Induction Phase and Maintenance Phase assessments are assigned based on the Induction 
Phase Study Day and Maintenance Phase Study Day, respectively, as shown in Table 14 
and Table 15. The analysis visits from Week 4 to Week 100 should be only applied to the 
assessments that are already assigned to Maintenance Phase (on-treatment).   
Extension Phase assessments are assigned based on the Maintenance Phase Study day for 
participants continuing Q4W IM dosing into the Extension Phase and based on the 
Extension Phase Study Day for participants switching from the control arm to Q4W IM 
dosing for the Extension Phase as shown in in Table 16.  The analysis visits from Week 
104 (except for Follow-up) in the Extension Phase should be only applied to the 
assessments that are already assigned to Extension Phase (on-treatment).   
Assessment windows at key analysis time points for the snapshot efficacy data are shown 
in Table 17. 
The sub-study assessments other than health outcome, PK and HIV-1 RNA are assigned 
analysis visits based on Study Day as shown in Table A. The assessment visit windows 
for HIV-1 RNA data are defined in Table B, and the snapshot windows for visits up to 
Sub-study Week 12 are defined in Table C.Long-term Follow-up Phase assessments are 
assigned based on the LTFU study day as shown in Table 20.  See Section 14.6.1 for 
derivation of Induction, Maintenance, Extension and LTFU Study Day. 


 
CONFIDENTIAL 
 
 
201584 
 
116 
 
14.3.2. 
Definitions of Assessment Windows for Data Other than Health 
Outcomes and PK 
Table 14 
Assessment Windows for Screening and Induction Phase Data 
Analysis Set 
/ Domain 
Parameter      Target 
Study 
Day 
Analysis Window 
Analysis Timepoint 
 
All 
All 
The day 
of earliest 
record 
Induction Study Day ≤1  
Screening 
 
 
1 
Last available recorded value up to 
and including the date of first 
Induction Phase dose of IP 
Induction 
Baseline (Week -20) 
 
 
29 
2 ≤ Induction Study Day ≤ 42 
Week -16 
 
 
57 
43 ≤ Induction Study Day ≤ 70 
Week -12 
 
 
85 
71 ≤ Induction Study Day ≤ 98 
Week -8 
 
 
113 
99 ≤ Induction Study Day ≤ 126 
Week -4 
 
 
141 
127 ≤ Induction Study Day ≤ 
Induction ART Stop Day[a] + 1  
Day 1 
 
 
 
For Participants not continuing 
into Maintenance Phase: 
 
Induction Study Day > (Induction 
ART Stop Day[a] +1) 
Follow-up 
NOTES: 
• 
For parameters which are not scheduled to be assessed at particular visits, the all-inclusive windows defined 
will still be used. Assessments at unscheduled visits will be included for ‘any time On-treatment’ time points 
and in data listings. 
 
a. 
ABC/DTG/3TC stop day: the last permanently stop day among all ARTs taken during Induction Phase. 
 
 


 
CONFIDENTIAL 
 
 
201584 
 
117 
 
Table 15 
Assessment Windows Maintenance Phase Data 
All Parameters expect where noted f    
Analysis Window 
Target 
Study Day 
Analysis 
Timepoint 
 
 
 
Last available recorded value 
up to and including the date of 
first Maintenance Phase dose 
of IP 
1 
Maintenance 
Baseline (Day 1) 
ECG, CD8, CD4/CD8 ratio 
2 ≤ Study Day ≤ 70 
29 
Week 4 
 
2 ≤ Study Day ≤ 42 
 
43 ≤ Study Day ≤ 70 
57 
Week 8 
 
71 ≤ Study Day ≤ 98 
85 
Week 12 
 
99 ≤ Study Day ≤ 126 
113 
Week 16 
 
127 ≤ Study Day ≤ 154 
141 
Week 20 
CD8, CD4/CD8 ratio 
155 ≤ Study Day ≤ 210 
169 
Week 24 
 
155 ≤ Study Day ≤ 182 
 
183 ≤ Study Day ≤ 210 
197 
Week 28 
 
211 ≤ Study Day ≤ 238 
225 
Week 32 
 
239 ≤ Study Day ≤ 266 
253 
Week 36 
 
267 ≤ Study Day ≤ 294 
281 
Week 40 
 
295 ≤ Study Day ≤ 322 
309 
Week 44 
ECG, CD8, CD4/CD8 ratio,  
Urinalysis [c], 
Renal and Bone marker analytes [d],  
Lipids [e], Weight, Height, Vital Signs 
323 ≤ Study Day ≤ 378 
337 
Week 48  
 
323 ≤ Study Day ≤ 350 
 
 
 
351 ≤ Study Day ≤ 378 
365 
Week 52 
 
379 ≤ Study Day ≤ 406 
393 
Week 56 
 
407 ≤ Study Day ≤ 434 
421 
Week 60 
 
435 ≤ Study Day ≤ 476 
449 
Week 64 
 
477 ≤ Study Day ≤ 532 
505 
Week 72 
 
533 ≤ Study Day ≤ 588 
561 
Week 80 
 
589 ≤ Study Day ≤ 644 
617 
Week 88 
ECG, CD4, CD8, CD4/CD8 ratio,  
Urinalysis [c], 
Renal and Bone marker analytes [d],  
Lipids [e], Weight, Height, Vital Signs 
645 ≤ Study Day ≤ 714 
673 
Week 96 
 
645 ≤ Study Day ≤ 686 


 
CONFIDENTIAL 
 
 
201584 
 
118 
 
All Parameters expect where noted f    
Analysis Window 
Target 
Study Day 
Analysis 
Timepoint 
 
 
ECG, CD4, CD8, CD4/CD8 ratio,  
Urinalysis [c], 
Renal and Bone marker analytes [d],  
Lipids [e], Weight, Height, Vital Signs 
For ‘ABC/DTG/3TC’ arm: 
 
715  ≤ Study Day ≤ 
Maintenance 
ABC/DTG/3TCStop Day[b] + 1 
 
For ‘Q4W’ arm: 
 
715  ≤ Study Day ≤ Max (Day 
of Last Q4W IM Dose + 35, 
Last Oral dose Day + 1) [a] 
701 
Week 100 
 
For ‘ABC/DTG/3TC’ arm: 
 
687  ≤ Study Day ≤ 
Maintenance 
ABC/DTG/3TCStop Day[b] + 1 
 
For ‘Q4W’ arm: 
 
687 ≤ Study Day ≤ Max (Day 
of Last Q4W IM Dose + 35, 
Last Oral dose Day + 1) [a] 
701 
Week 100 
 
For ‘Q4W’ arm: 
 
a) For participants who 
discontinued from oral 
lead-in during 
Maintenance Phase: 
 
Study Day > (Day of last oral 
lead-in dose+1) 
 
b) For participants who are 
not continuing into the 
extension phase and who 
received at least one 
CAB/RPV injection: 
 
Study Day > Max (Day of Last 
Q4W IM Dose + 35, Last Oral 
dose Day + 1)  
 
For ‘ABC/DTG/3TC’ arm: 
 
Participants discontinued from 
ABC/DTG/3TC’ and not 
continuing into the Extension 
Phase: 
 
Study Day > (Maintenance 
ABC/DTG/3TC Stop Day[b] +1) 
 
Follow-up 
 


 
CONFIDENTIAL 
 
 
201584 
 
119 
 
NOTES: 
• 
For parameters which are not scheduled to be assessed at particular visits, the all-inclusive windows defined will 
still be used.  Assessments at unscheduled visits will be included for ‘any time On-treatment’ time points and in 
data listings, as well as algorithms that make use of additional data (e.g., Snapshot). 
a. 
Last Q4W IM / last oral dose is only applied to participants who permanently discontinue from study treatment 
b. 
ABC/DTG/3TCstop day: the last permanently stop day among all ARTs taken during Maintenance Phase. 
c. 
Urinalysis: All parameters provided by the central laboratory under the category of urinalysis, including Urine 
Albumin/Creatinine, Urine Creatinine, Urine pH, Urine Protein/Creatinine, Urine Erythrocytes, Urine Specific 
Gravity, Urine Leukocytes, Urine Retinol Binding Protein, Urine Phosphate, Urine Creatinine. 
d. 
Bone Marker: Bone Specific Alkaline Phosphatase, Osteocalcin, Procollagen 1 N-Terminal Propeptide, Vitamin 
D, Type I C-Telopeptides.  Renal marker: Cystatin C, Retinol Binding Protein. 
e. 
Lipids: Cholesterol, HDL Cholesterol Direct, LDL Cholesterol Calculation, LDL Cholesterol Direct, Total 
Cholesterol/HDL Cholesterol Ratio, Triglycerides 
f. 
Analysis windows for parameters with sparse collection are noted.   
 
Table 16 
Assessment Windows for Extension Phase Data 
All Parameters 
expect where noted b   
Analysis Window 
Target 
Extension 
Phase  
Study 
Day  
Target 
Study 
Day 
Analysis 
Timepoint 
Participants Continuing Randomized Q4W IM Regimen 
Adverse Events [c] 
Study day of Nominal Week 100 
visit ≤ Study Day ≤ 742 
 
729 
Week 104 
 
Urinalysis [a] 
 
Study day of Nominal Week 100 
visit < Study Day ≤ 770 
 
 
Study day of Nominal Week 100 
visit < Study Day ≤ 742 
 
743≤ Study Day ≤770 
 
757 
Week 108 
 
771≤ Study Day ≤826 
 
785 
Week 112 
 
(7*w - 41) 
≤ Study Day ≤ (7*w + 42) 
 
7*w + 1 
Week w 
w = 124,136, 
148,… 
 
 
For participants who permanently 
discontinue extension phase study 
treatment: 
 
Study Day > Max (Day of Last 
Q4W IM Dose + 35, Day of Last 
Oral Dose Day + 1)  
 
 
 
Follow-up 
Participants Switching to Q4W IM Dosing 
 
Last available recorded value up to 
and including the date of first 
Extension Phase dose of IP 
1 
 
Extension Baseline 
(W100) 
ECG, CD4, CD8, 
CD4/CD8 ratio,  
2 ≤ Extension Study Day ≤ 70 
29 
 
Week 104  


 
CONFIDENTIAL 
 
 
201584 
 
120 
 
All Parameters 
expect where noted b   
Analysis Window 
Target 
Extension 
Phase  
Study 
Day  
Target 
Study 
Day 
Analysis 
Timepoint 
Urinalysis [a], 
Weight, Vital Signs 
 
2 ≤ Extension Study Day ≤ 42 
Excluding: ECG, CD4, 
CD8, CD4/CD8 ratio,  
Urinalysis [a], Weight, 
Vital Signs 
43 ≤ Extension Study Day ≤ 70 
57 
 
Week 108 
 
71 ≤ Extension Study Day ≤ 98 
85 
 
Week 112 
 
99 ≤ Extension Study Day ≤ 126 
113 
 
Week 116 
 
127 ≤ Extension Study Day ≤ 154 
141 
 
Week 120 
 
155 ≤ Extension Study Day ≤ 210 
169 
 
Week 124 
 
211 ≤ Extension Study Day ≤ 294 
253 
 
Week 136 
 
(7*(w-100) - 41) 
≤ Study Day ≤ (7*(w-100) + 42) 
7*(w-100) + 
1 
 
Week w 
w = 148, 160,… 
 
 
For participants who permanently 
discontinue extension phase study 
treatment: 
 
Study Day > Max (Day of Last 
Q4W IM Dose + 35, Day of Last 
Oral Dose Day + 1)  
 
 
 
Follow-up 
NOTES: 
• 
For parameters which are not scheduled to be assessed at particular visits, the all-inclusive windows defined 
will still be used. Assessments at unscheduled visits will be included for ‘any time On-treatment’ time points 
and in data listings, as well as algorithms that make use of additional data (e.g., Snapshot). 
• 
Nominal Week 100 visit is the original visit from eCRF (i.e., the VISIT variable as opposed to AVISIT) 
a. 
Urinalysis: All parameters provided by the central laboratory under the category of urinalysis, including Urine 
Albumin/Creatinine, Urine Creatinine, Urine pH, Urine Protein/Creatinine, Urine Erythrocytes, Urine Specific 
Gravity, Urine Leukocytes, Urine Retinol Binding Protein, Urine Phosphate, Urine Creatinine. 
b. 
Analysis windows for parameters with sparse collection are noted. 
c. 
For ISR specific displays, ISRs will be assigned to analysis timepoints based on onset date to the most recent 
planned IM injection visit prior or equal to the AE onset date.   


 
CONFIDENTIAL 
 
 
201584 
 
121 
 
Table 17 
Assessment Windows for Summary of Snapshot Data — Data 
assigned to Maintenance Phase Only  
Snapshot Analysis Windows 
(if no viral load data in default window, expand upper bound to + 6 weeks) 
 
 
 
 
Analysis 
Timepoint 
Default (midpoint between planned visits) a 
Expanded +6 Week upper window 
Last available recorded value up to and 
including the date of first Maintenance Phase 
dose of IP 
Last available recorded value up to and 
including the date of first Maintenance Phase 
dose of IP 
Maintenance 
Baseline (Day 1) 
2 ≤ Study Day ≤ 42 
2 ≤ Study Day ≤ 70 
Week 4 
43 ≤ Study Day ≤ 70 
43 ≤ Study Day ≤ 98 
Week 8 
71 ≤ Study Day ≤ 98 
71 ≤ Study Day ≤ 126 
Week 12 
99 ≤ Study Day ≤ 126 
99 ≤ Study Day ≤ 154 
Week 16 
127 ≤ Study Day ≤ 154 
127 ≤ Study Day ≤ 182 
Week 20 
155 ≤ Study Day ≤ 182 
155 ≤ Study Day ≤ 210 
Week 24 
183 ≤ Study Day ≤ 210 
183 ≤ Study Day ≤ 238 
Week 28 
211 ≤ Study Day ≤ 238 
211 ≤ Study Day ≤ 266 
Week 32 
239 ≤ Study Day ≤ 266 
239 ≤ Study Day ≤ 294 
Week 36 
267 ≤ Study Day ≤ 294 
267 ≤ Study Day ≤ 322 
Week 40 
295 ≤ Study Day ≤ 322 
295 ≤ Study Day ≤ 350 
Week 44 
295 ≤ Study Day ≤ 378 
295 ≤ Study Day ≤ 378 
Week 48 
379 ≤ Study Day ≤ 406 
379 ≤ Study Day ≤ 434 
Week 56 
407 ≤ Study Day ≤ 434 
407 ≤ Study Day ≤ 462 
Week 60 
435 ≤ Study Day ≤ 476 
435 ≤ Study Day ≤ 490 
Week 64 
477 ≤ Study Day ≤ 532 
477 ≤ Study Day ≤ 546 
Week 72 
533 ≤ Study Day ≤ 588 
533 ≤ Study Day ≤ 602 
Week 80 
589 ≤ Study Day ≤ 644 
589 ≤ Study Day ≤ 658 
Week 88 
631 ≤ Study Day ≤ 714 
631 ≤ Study Day ≤ 714 
Week 96 
NOTES: 
Apply Snapshot analysis windows only to viral load data that is on-treatment (per Table 30) within the Maintenance 
Phase (Per Table 25) 
a. 
± 6 Week window always used at key analysis timepoints (Week 48 and Week 96) 
 


 
CONFIDENTIAL 
 
 
201584 
 
122 
 
Table 18 
For W124 Analysis: Extension Switch Population Assessment 
Windows for Snapshot Viral Load Data up to Week 124 — Data 
assigned to Extension Phase Only  
Snapshot Analysis Windows 
(if no viral load data in default window, expand upper bound to + 6 weeks) 
 
 
 
 
Analysis 
Timepoint 
Default (midpoint between planned visits) a 
Expanded +6 Week upper window 
Last available recorded value up to and 
including the date of first Extension Phase 
dose of IP (oral lead-in or injection, whichever 
occurs first) 
Last available recorded value up to and 
including the date of first Extension Phase 
dose of IP (oral lead-in or injection, 
whichever occurs first) 
Extension 
Baseline (Week 
100) 
2 ≤ Extension Study Day ≤ 42 
2 ≤ Extension Study Day ≤ 70 
Week 104  
43 ≤ Extension Study Day ≤ 70 
43 ≤ Extension Study Day ≤ 98 
Week 108 
71 ≤ Extension Study Day ≤ 98 
71 ≤ Extension Study Day ≤ 126 
Week 112 
99 ≤ Extension Study Day ≤ 126 
99 ≤ Extension Study Day ≤ 154 
Week 116 
127 ≤ Extension Study Day ≤ 154 
127 ≤ Extension Study Day ≤ 182 
Week 120 
127 ≤ Extension Study Day ≤ 210 
127 ≤ Extension Study Day ≤ 210 
Week 124 
 
For participants who permanently discontinue 
extension phase study treatment: 
 
Extension Study Day > Max (Day of Last Q4W 
IM Dose + 35, Day of Last Oral Dose Day + 1)  
 
 
Follow-up 
NOTES: 
Apply Snapshot analysis windows only to viral load data that is on-treatment (per Table 30) within the Extension 
Phase (Per Table 25) 
a. 
± 6 Week window always used at key analysis timepoints (Week 124) 
 


 
CONFIDENTIAL 
 
 
201584 
 
123 
 
Table 19 
For W124 Analysis: ITT-E (Randomized Q4W arm) Assessment 
Windows for Snapshot Viral Load Data up to Week 124 — Data 
assigned to Maintenance and Extension Phase  
Snapshot Analysis Windows 
(if no viral load data in default window, expand upper bound to + 6 weeks) 
 
 
 
 
Analysis 
Timepoint 
Default (midpoint between planned visits) a 
Expanded +6 Week upper window 
Last available recorded value up to and 
including the date of first Maintenance Phase 
dose of IP 
Last available recorded value up to and 
including the date of first Maintenance Phase 
dose of IP 
Maintenance 
Baseline (Day 1) 
2 ≤ Study Day ≤ 42 
2 ≤ Study Day ≤ 70 
Week 4 
43 ≤ Study Day ≤ 70 
43 ≤ Study Day ≤ 98 
Week 8 
71 ≤ Study Day ≤ 98 
71 ≤ Study Day ≤ 126 
Week 12 
99 ≤ Study Day ≤ 126 
99 ≤ Study Day ≤ 154 
Week 16 
127 ≤ Study Day ≤ 154 
127 ≤ Study Day ≤ 182 
Week 20 
155 ≤ Study Day ≤ 182 
155 ≤ Study Day ≤ 210 
Week 24 
183 ≤ Study Day ≤ 210 
183 ≤ Study Day ≤ 238 
Week 28 
211 ≤ Study Day ≤ 238 
211 ≤ Study Day ≤ 266 
Week 32 
239 ≤ Study Day ≤ 266 
239 ≤ Study Day ≤ 294 
Week 36 
267 ≤ Study Day ≤ 294 
267 ≤ Study Day ≤ 322 
Week 40 
295 ≤ Study Day ≤ 322 
295 ≤ Study Day ≤ 350 
Week 44 
295 ≤ Study Day ≤ 378 
295 ≤ Study Day ≤ 378 
Week 48 
379 ≤ Study Day ≤ 406 
379 ≤ Study Day ≤ 434 
Week 56 
407 ≤ Study Day ≤ 434 
407 ≤ Study Day ≤ 462 
Week 60 
435 ≤ Study Day ≤ 476 
435 ≤ Study Day ≤ 490 
Week 64 
477 ≤ Study Day ≤ 532 
477 ≤ Study Day ≤ 546 
Week 72 
533 ≤ Study Day ≤ 588 
533 ≤ Study Day ≤ 602 
Week 80 
589 ≤ Study Day ≤ 644 
589 ≤ Study Day ≤ 658 
Week 88 
631 ≤ Study Day ≤ 714 
631 ≤ Study Day ≤ 714 
Week 96 
715 ≤ Study Day ≤ 770 
715 ≤ Study Day ≤ 798 
Week 108 
771 ≤ Study Day ≤ 826 
771 ≤ Study Day ≤ 826 
Week 112 
827 ≤ Study Day ≤ 910 
827 ≤ Study Day ≤ 910 
Week 124 
NOTES: 
Apply Snapshot analysis windows only to viral load data that is on-treatment (per Table 30) within the Maintenance 
Phase and Extension Phases (Per Table 25) 
a. 
± 6 Week window always used at key analysis timepoints (Week 48 and Week 96) 
 
Table A Assessment Windows for Sub-study Baseline, SC Injection Phase and 
Return to Gluteal Injection Phase Data (Excluding HIV-1 RNA Data) 
All Parameters 
except for where 
noted[a] 
Target 
Study Day 
Analysis Window 
Analysis Timepoint 
 
First Sub-
study record 
Study Day <7*w + 1 
Sub-study 
Screening 
All except ECG, 
Labs, Vitals 
7*w + 1 
Study Day = 7*w + 1 
Sub-study Day 1 


 
CONFIDENTIAL 
 
 
201584 
 
124 
 
All Parameters 
except for where 
noted[a] 
Target 
Study Day 
Analysis Window 
Analysis Timepoint 
ECG, Labs, Vitals 
7*w + 1 
Last available recorded value up to and 
including the date of first SC injection. 
Sub-study 
Baseline[b] 
 
7*(w+1) +1 
7*w + 2 ≤ Study Day ≤ 7*(w+2) 
Sub-study Week 1 
 
7*(w+4) +1 
7*(w + 2) + 1≤ Study Day ≤ 7*(w+4) +1 
Sub-study Week 4 
Labs,CD4 
7*w + 2 ≤ Study Day ≤ 7*(w+6) 
 
7*(w+5) +1 
7*(w + 4) + 2 ≤ Study Day ≤ 7*(w+6) 
Sub-study Week 5 
 
7*(w+8) +1 
7*(w + 6) + 1 ≤ Study Day ≤ 7*(w+8) + 1 
Sub-study Week 8 
Labs, CD4 
7*(w + 6) + 1 ≤ Study Day ≤ 7*(w+10) 
 
7*(w+9) +1 
7*(w + 8) + 2 ≤ Study Day ≤ 7*(w+10) 
Sub-study Week 9 
 
7*(w+12) +1 
7*(w + 10) + 1 ≤ Study Day ≤ 7*(w+12) + 
1 
Sub-study Week 12 
Labs, CD4 
7*(w + 10) + 1 ≤ Study Day ≤ 7*(w+14) 
ECG, Weight, CD8, 
CD4/CD8 ratio 
Urinalysis, Fasting 
labs/lipids 
7*w + 2 ≤ Study Day 
 
7*(w+13) +1 
7*(w + 12) + 2 ≤ Study Day ≤ 7*(w+14) 
Sub-study Week 13 
 
7*(w+16) +1 
7*(w + 14) + 1 ≤ Study Day ≤ 7*(w+16) + 
1 
Sub-study Week 16 
Labs, CD4 
7*(w + 14) + 1 ≤ Study Day ≤ 7*(w+18) 
 
7*(w+17) +1 
7*(w + 16) + 2 ≤ Study Day ≤ 7*(w+18) 
Sub-study Week 17 
 
7*(w+20) +1 
7*(w+18) + 1  ≤ Study Day 
Sub-study Week 20 
If a participant permanently discontinued study treatment: 
 
 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 35) 
Follow-up 
NOTES: 
• 
The “w” in the target study day calculation refers to the week number within the Sub-study, starting with Week 
0. For example, the Sub-study Day 1 Analysis Timepoint would have a “w” of 0, to allow for a Target Study Day 
of 1. 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
• 
Sub-study Day 1 (Post Dose), Sub-study Week 4 and Sub-study Week 8 visits are SC Injection phase visits, 
Sub-study Week 12 and Week 16 are Return to Gluteal Injection phase visits. 
[a] Analysis windows for parameters with sparse collection are noted.  
[b] The values considered for deriving Sub-study Baseline value include both Extension phase and sub-study data. 
 
Table B Assessment Windows for Sub-study Baseline, SC Injection Phase and 
Return to Gluteal Injection Phase HIV-1 RNA Data 


 
CONFIDENTIAL 
 
 
201584 
 
125 
 
Phase 
Target Study 
Day 
Analysis Window 
Analysis Timepoint 
Sub-study Screening 
7*w + 1 
Last available recorded value up to 
and including the date of first SC 
injection 
Sub-study Baseline 
SC Injection 
7*(w+4) + 1 
7*w + 2 ≤ Study Day ≤ 7*(w+6) 
Sub-study Week 4 
7*(w+8) + 1 
7*(w+6) + 1 ≤ Study Day ≤ 7*(w+10) 
Sub-study Week 8 
Return to Gluteal 
Injection 
7*(w+12) + 1 
7*(w+10) + 1 ≤ Study Day ≤ 7*(w+14) 
Sub-study Week 12 
7*(w+16) + 1 
7*(w+14) + 1 ≤ Study Day ≤ 7*(w+18) 
Sub-study Week 16 
If a participant permanently discontinued study treatment: 
 
 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 
35) 
Follow-up 
NOTES: 
• 
The “w” in the target study day calculation refers to the week number within the Sub-study, starting with Week 
0, Day 0 being the day prior to the first SC injection. For example, the Sub-study Day 1 Analysis Timepoint 
would have a “w” of 0, to allow for a Target Study Day of 1. 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
 
Table C 
Assessment Windows for Summary of Snapshot Data Up to Week 12 
in Sub-study— Data Assigned to SC Injection Phase 
Snapshot Analysis Windows 
(If no on-treatment viral load data in default window, use expanded 
window) 
Analysis Timepoint 
Default 
Expanded +6 Week Upper Window 
Last available recorded value up to 
and including the date of first SC 
injection 
Last available recorded value up to and 
including the date of first SC injection 
Sub-study Baseline 
7*w + 2 ≤ Study Day ≤ 7*(w+6) 
7*w + 2  ≤ Study Day ≤ 7*(w+10) 
Sub-study Week 4 
7*(w+6) + 1 ≤ Study Day ≤ 7*(w+10) 
7*(w+6) + 1 ≤ Study Day ≤ 7*(w+14) 
Sub-study Week 8 
7*(w+10) + 1 ≤ Study Day ≤ 
min( 7*(w+14), Day of First Return to 
Gluteal IM Injection) 
7*(w+10) + 1 ≤ Study Day ≤ min(7*(w+18), 
Day of First Return to Gluteal IM Injection) 
Sub-study Week 12 
NOTES: 
• 
The “w” in the target study day calculation refers to the week number within the Sub-study, starting with 
Week 0, Day 0 being the day prior to the first SC injection. For example, the Sub-study Day 1 Analysis 
Timepoint would have a “w” of 0, to allow for a Target Study Day of 1. 
• 
For post-baseline visits (i.e., Week 4 and afterwards), apply Snapshot analysis windows only to viral load 
data that is on-treatment (per Table 30) within the SC Injection Phase (per Table 24). 
• 
An on-treatment viral load assessment may be assigned to more than one snapshot analysis window, 
e.g., on-treatment assessment taken on 7*(w+14) will be in both Sub-study Week 8 and Sub-study Week 
12 visits. 
• 
± 6 Week window is always used at the key analysis timepoint, Sub-study Week 12 visit with the 
exclusion of HIV-1 RNA values collected on or after resuming IM injections. Only results collected while 
on SC injections will be considered. 
 


 
CONFIDENTIAL 
 
 
201584 
 
126 
 
Table 20 
Assessment Windows for Summaries of Long-Term Follow Up 
Phase Data for Participants Who Received At least One Injection of 
CAB+RPV and Permanently Discontinued from Study Treatment 
Day of Assessment 
Assessment 
Window 
Target Study 
Day of 
Window 
1 ≤ LTFU Study Day ≤ 60 
LTFU Month 1 
30 
61 ≤ LTFU Study Day ≤ 135 
LTFU Month 3 
90 
136 ≤ LTFU Study Day ≤ 225 
LTFU Month 6 
180 
226 ≤ LTFU Study Day ≤ 315 
LTFU Month 9 
270 
316 ≤ LTFU Study Day ≤ 405 
LTFU Month 12 
360 
(30*m - 44) ≤ LTFU Study Day≤ (30*m + 45) 
LTFU Month m 
m = 15, 18, 21,… 
30*m 
NOTES: 
• 
An assessment may be slotted to both LTFU and Maintenance /Extension Phase 
 
14.3.3. 
Assessment Window for Study Conclusion 
The study conclusion and Phase conclusion records in disposition data will be slotted 
based on Table 14 (for Induction Phase conclusion records), Table 15 (for Maintenance 
Phase conclusion records) and Table 16 (for extension Phase conclusion records). 
However, if the discontinuation date is post-treatment (based on  Table 30), then the 
discontinuation will be slotted to the participants the last attained on-treatment analysis 
visit across all assessments (e.g., analysis visit corresponding to the last on-treatment lab 
assessment), rather than follow up. 
14.3.4. 
Assessment Window for Health Outcome Data  
14.3.4.1. 
NRS 
NRS questionnaire assessments are assigned to analysis visits based on the windows 
defined in Table 21. 


 
CONFIDENTIAL 
 
 
201584 
 
127 
 
Table 21 
Assessment Windows for Maintenance Phase NRS Questionnaire 
Data 
Domain Parameter Target Date 
Analysis Window 
Analysis 
Timepoint 
 
NRS 
All 
Date of 1st 
Injection 
Assessment Date ≤ Date of 1st injection + 2 
Week 4B 
 
 
Date of 1st 
injection+7 
Date of 1st injection +3 ≤ Assessment Date 
≤ Date of 1st injection + 42 
Week 5 
 
 
Date of W40 
Injection 
If participant received Week 40 injection: 
Date of WK40 injection - 42 ≤ Assessment 
Date ≤ Date of W40 Injection + 2 
Week 40 
Date of 1st 
Injection + 
252 
If participant did not receive Week 40 
injection: 
Date of 1st injection + 210 ≤ Assessment 
Date ≤ Date of 1st injection + 280 
 
 
Date of W40 
Injection + 7 
If participant received Week 40 injection: 
Date of W40 Injection + 3 ≤ Assessment 
Date ≤  Date of W40 Injection + 28 
Week 41 
Date of 1st 
Injection + 
644 
Date of 1st Injection + 602 < Assessment 
Date ≤ Date of 1st Injection + 686 
Week 96 
Note: Apply NRS analysis windows only to assessments that are on-treatment (per Table 30) 
within the Maintenance Phase (Per Table 25) 
14.3.4.2. 
PIN/HATQoL/SF-12/HIVTSQs/HIVTSQc/ACCEPT/Treatment Preference 
PIN, HATQoL, SF-12, HIVTSQs, HIVTSQc, ACCEPT, and Treatment Preference 
questionnaire assessments will be assigned to analysis visits as follows: 
1. Maintenance Baseline (Day 1) will be defined as last available recorded value up 
to and including the date of first Maintenance Phase dose of study treatment 
(expected to be collected at Day 1). 
2. If the nominal visit identifier as captured in the source dataset corresponds to a 
scheduled collection per the Time and Events Schedule (see Section 14.2 and 
Table 22) and the assessment is collected in the Maintenance Phase (per Table 
25), then the nominal visit identifier will be kept as the analysis visit (excluding 
Day 1 which will normally be assigned to Maintenance Baseline (Day 1). 
3. If the nominal visit identifier is unscheduled or withdrawal, then the following 
procedure will be used: 
a) Assign the assessment to a study Phase according to Table 25.  Proceed to 
step b if the assessment is assigned to the Maintenance Phase. 
b) Identify the ‘last nominal visit’ with the HO assessment performed prior to 
the unscheduled/withdrawal visit to be slotted.  
c) The unscheduled/withdrawal visit will be slotted to the planned nominal 
visit subsequent to the ‘last nominal visit’. If the ‘last nominal visits’ does 


 
CONFIDENTIAL 
 
 
201584 
 
128 
 
not exist (e.g., no records originate from a planned nominal visit), then the 
unscheduled/withdrawal visit will be slot to the first planned nominal visit 
after Day 1. 
Example 1, for HATQoL, the planned nominal visits are Week 24, 48, and 96. If a 
participant has the ‘last nominal visit’ (with HATQoL assessment) at Week 24 prior to 
withdrawal at Week 36, the withdrawal assessment will be slotted to the subsequent 
planned nominal visit of Week 48.  
Example 2, for HATQoL, if there is unscheduled visit between Week 24 and Week 48. 
This unscheduled visit will be slotted to Week 48 per the rule.  In this case, there are two 
assessments with analysis visit equal to Week 48 (i.e., the slotted value and the value at 
original nominal week 48 visit). The original nominal value will be selected for summary 
per the rule below for multiple records—see Section 14.3.6. 
Table 22 
Planned Nominal Visit of Health Outcome Data  
Endpoints 
Day1 W4b 
W5 W8 W24 W40 W41 W44 W48 W52 W96 
PIN (Q4W) 
 
 
x 
 
 
 
x 
 
x 
 
x 
HATQoL 
x 
 
 
 
x 
 
 
 
x 
 
x 
SF-12 
x 
 
 
 
x 
 
 
 
x 
 
x 
HIVTSQs 
x 
x 
(Q4W 
arm 
only) 
 
 
x 
 
 
x 
 
 
x 
HIVTSQc 
 
 
 
 
 
 
 
 
x 
 
 
ACCEPT 
x 
 
 
x 
x 
 
 
 
x 
 
x 
NRS (Q4W) 
 
x 
x 
 
 
x 
x 
 
 
 
x 
Treatment 
preference 
(Q4W) 
 
 
 
 
 
 
 
 
x 
 
14.3.4.3. 
Evaluable Criteria for Observed Case Displays — NRS and PIN 
Post the visit slotting as described above, data that is assessed outside of 5-9 days post 
injection (relative to date of injection at Week 4b/40, respectively) at Week 5/41 for 
NRS/PIN, and data at Week 4b/40 for NRS that is not assessed on the same day as 
CAB+RPV injections (at Week 4b/40, respectively) are received will be excluded from 
Observed Case Displays (see Table 23). However, these data will still be used for LOCF 
displays. 


 
CONFIDENTIAL 
 
 
201584 
 
129 
 
Table 23 
Evaluable Time Windows for Observed Cases Summary Tables 
Endpoints 
W4b 
W5 
W40 
W41 
W96 
PIN  
(Q4W) 
 
Within Day 
5-9 post W4b 
injection 
 
Within Day 5-9 
post W40 
injection 
 
NRS 
(Q4W) 
On the same 
Day of W4b 
injection 
Within Day 
5-9 post W4b 
injection 
On the same 
day of W40 
injection 
Within Day 5-9 
post W40 
injection 
On the same day 
of W96 injection 
 
14.3.4.4. 
HIVTSQs/HIVTSQc/PIN/Preference/Reason for Switch/Interest in Sub-
study 
HIVTSQs, HIVTSQc, PIN, Preference SC Injection vs Gluteal Injection, Reason for 
Switch, and Interest questionnaire assessments will be assigned to analysis visits as 
follows: 
1. Sub-study Baseline will be defined as last available recorded value prior to the 
date of first SC injection. Baseline is not applicable for HIVTSQc, Preference SC 
Injection vs Gluteal Injection, Reason for Switch, or Interest assessments as they 
are not planned to be collected during the Sub-study Baseline.  
2. For post-baseline visits, if the nominal visit identifier as captured in the source 
dataset corresponds to a scheduled collection per the Time and Events Schedule 
(see Section 14.2.2) and the assessment is collected in the planned phase (per 
Table 24, visits at/before Sub-study Week 12 belong to SC Injection phase, and 
visits after Sub-study Week 12 belong to Return to Gluteal Injection phase), then 
the nominal visit identifier will be kept as the analysis visit. 
3. For post-baseline visits, if the nominal visit identifier is unscheduled or it is 
scheduled however not conducted in the planned phase (e.g., the sub-study Week 
9 HIVTSQs assessment is conducted after the Week 12 gluteal injection and 
therefore belong to Return to Gluteal Injection phase), then this visit will be 
assigned to the planned visit in the same phase. 
14.3.4.5. 
Tolerability of Injections (NRS) in Sub-study 
After assigning the phases per Table 24, the NRS assessments will be slotted to analysis 
visits per Table D. 
Table D Assessment Window for NRS Data 
Phase 
Assessment Window 
Visit 
Sub-study 
Screening 
Q4W: post-dose and on the Week -4 injection date 
Sub-study Week -4 
Q4W: (Week -4 injection date+1, Week -4 injection 
date+14), inclusive 
Sub-study Week -3 
 
SC 
Injection 
Post-dose and on the Day 1 injection date 
Sub-study Day 1 
(Day 1 injection date+1, Day 1 injection date+14), 
inclusive 
Sub-study Week 1 
Post-dose and on the Week 8 injection date 
Sub-study Week 8 


 
CONFIDENTIAL 
 
 
201584 
 
130 
 
Phase 
Assessment Window 
Visit 
 (Week 8 injection date+1, Week 8 injection date+14), 
inclusive 
Sub-study Week 9 
Return to 
Gluteal 
Post-dose and on the Week 12 injection date 
Sub-study Week 12 
(Week 12 injection date+1, Week 12 injection 
date+14), inclusive 
Sub-study Week 13 
 
14.3.5. 
Assessment Window for PK concentration Data  
14.3.5.1. 
Maintenance/Extension Phase Assessments 
For PK concentration data at a nominal withdrawal/unscheduled/LTFU Month1 visits 
during Maintenance or Extension Phase (after assignment to study phase according to 
Table 25), the visit will be slotting to the analysis visit per the following steps: 
1. Identify the ‘last nominal PK visit’ with the PK assessment performed prior to the 
visit to be slotted during the same study Phase 
2. The unscheduled/withdrawal/LTFU Month1 visit will be slotted to the earliest 
nominal visit from the following: 
• nominal visit corresponding to the next planned pre-dose PK assessment visit 
(excluding timepoints with storage PK collection in which samples have not 
been analysed for all participants), that is subsequent to the ‘last nominal PK 
visit’ during the same study phase. 
• nominal visit of the next planned injection visit within the study phase 
occurring on or after the date of the PK assessment. 
During the Maintenance or Extension Phase, the planned nominal visits for PK Pre-dose 
are Week 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 80, 88, 96, 100 for the 
Q4W arm; and Week 100 (direct to inject group), Week 101 (direct to inject group),Week 
104a (direct to inject group), and Week 104b (oral lead-in group) for the Switch Q4W IM 
group .  Planned Injection visits are Week 4, Week 8, continuing every 4 weeks for the 
Q4W arm and every 4 weeks for the ABC/DTG/3TC arm starting at Week 100 (for direct 
to inject group) and Week 104b for oral lead-in group. 
There will be no slotting for planned nominal visits (i.e., analysis visit =visit).  
Example 1: If a participant has the ‘last nominal PK visit’ at Week 24 and then withdraws 
(around Week 28) with a Maintenance Phase PK assessment labelled as ‘LTFU Month 1’ 
Phase, this assessment will be slotted to the subsequent planned PK assessment visit of 
Week 28.  
Example 2: If a participant has the ‘last nominal PK visit’ at Week 60 and then withdraws 
(around Week 88, with last injection at W84) with a Maintenance Phase PK assessment 
labelled as ‘LTFU Month 1’, then this assessment will be slotted the subsequent planned 
injection visit of Week 88 (next injection visit).  


 
CONFIDENTIAL 
 
 
201584 
 
131 
 
14.3.5.2. 
Long-Term Follow-up Phase Assessments: 
PK concentration data at nominal visits other than LTFU MONTH 1/LTFU MONTH 
3/LTFU MONTH 6/LTFU MONTH 9/LTFU MONTH 12/LIVER EVENT which have 
been assigned to the Long-Term Follow-up phase (according to according to Table 27) 
will be slotting to analysis visits per the following steps: 
• Identify the ‘last nominal PK visit’ with the PK assessment performed prior to the 
visit to be slotted during the LTFU phase; 
• The unscheduled/withdrawal visit will be slotted to the nominal visit corresponding to 
the next planned LTFU PK assessment visit that is subsequent to the ‘last nominal PK 
visit’ during the LTFU phase. 
There will be no slotting for planned PK nominal visits (i.e., analysis visit =visit): LTFU 
Month 1, LTFU Month 3, LTFU Month 6, LTFU Month 9 and LTFU Month 12. 
14.3.5.3. 
Sub-study Assessments 
PK concentration plots based on Sub-Study Day as appropriate for each phase where 
concentration data is collected. Unscheduled sub-study assessments will not be slotted to 
any analysis visit, however, will be displayed based on Sub-Study Day in individual PK 
plots. There will be no slotting for planned nominal visits (i.e., analysis visit=visit). 
Unscheduled assessments will not be summarized outside of individual plots, however, 
will be listed.  
14.3.6. 
Multiple assessments within an Analysis Window 
If after window assignment there are multiple valid assessments of a parameter within the 
same window, then the following hierarchy will be used to determine the value to be used 
for summary statistics of observed values: 
 
For data other than health outcome/PK concentration:  
• the assessment closest to the window target Study Day. 
• if there are multiple assessments equidistant from the target Study Day, then the 
mean of these values will be used. For HIV-1 RNA, the geometric mean of the 
number of copies will be used as opposed to the arithmetic mean. 
NRS questionnaire health outcomes assessments:  
• the assessment closest to the window target Study Day will be used. 
• if there are multiple assessments equidistant from the target Day, then the earliest 
assessment will be used. 
Other health outcome assessments (i.e., apart from NRS) and PK concentration data: 
• 
if there are multiple assessments assigned to the same analysis visit, the 
assessment from the original planned nominal visit will be used for summary 
statistics.  
• 
if there are multiple assessments assigned to the same analysis visit and none 
originate from a planned nominal visit (e.g., two unscheduled/withdrawal nominal 
visits), then 
a. the assessment closest to the window target Study Day will be used; 


 
CONFIDENTIAL 
 
 
201584 
 
132 
 
b. if there are multiple assessments equidistant from the target Study Day, 
then the earliest assessment will be used. 
Assessments not chosen for use in summary statistics by this algorithm will still appear in 
the associated listings. Also, all applicable assessments, irrespective of proximity to the 
target study day, will be used when categorizing values across visits, such as ‘maximum 
grade’ or ‘at any time’, and for any algorithm that has specific rules for which 
observation to use (e.g., snapshot algorithm or LOCF). 


 
CONFIDENTIAL 
 
 
201584 
 
133 
 
14.4. 
Appendix 4: Study Phases and Treatment State 
14.4.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
the Treatment Start Date defined in Section 14.6.1. 
AEs will be assigned to study Phases as defined in Table 24.  For example, adverse 
events prior to start of Extension Phase IP/LTFU ART will be assigned to the 
Maintenance Phase. 
Laboratory data (efficacy, safety, and virology), HIV associated/ AIDS-defining 
conditions, health outcomes assessments, vital signs, PK, and ECGs will be assigned to 
study phases as defined as in Table 25.  For example, assessments/events occurring up to 
and including start of extension phase IP/LTFU ART will be assigned to the Maintenance 
Phase. 
Assessments/events are assigned to study phases sequentially, starting from the top of 
each table, except for the assessments/events occurring after returning to Extension phase 
from the sub-study participation. 
Table 24 
Assignment of Study Phases for AEs 
Study Phase 
Date range 
Screen 
Date < Induction Treatment Start Date 
Induction 
For participants continuing into Maintenance Phase: 
 
Induction Treatment Start Date ≤ Date < Maintenance Treatment Start Date 
 
For participants not continuing into Maintenance Phase: 
 
Date ≥Induction Treatment Start Date 
Maintenance 
DTG/ABC/3TC Arm: 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date ≤ Date < min (Start Date of Extension 
Phase with Oral lead-in of CAB + RPV, Date of first CAB/RPV injection) 
 
For participants not continuing into Extension Phase: 
 
Date ≥Maintenance Treatment Start Date  


 
CONFIDENTIAL 
 
 
201584 
 
134 
 
Study Phase 
Date range 
Q4W IM Arm: 
 
For participants continuing into Extension Phase: 
 
Maintenance Treatment Start Date ≤ Date < Date of Nominal Week 100 Visit  
 
For participants not continuing into Extension Phase: 
 
Maintenance Treatment Start Date ≤ Date < LTFU ART Start Date  


 
CONFIDENTIAL 
 
 
201584 
 
135 
 
Study Phase 
Date range 
Extension 
For participants continuing into the Extension Phase and not entering 
the Sub-study: 
- Participants continuing into LTFU Phase: 
   - Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W: 
min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) ≤ Date < LTFU ART Start Date  
   - Participants continuing maintenance Q4W into Extension Phase: 
Date of Nominal Week 100 Visit ≤ Date < LTFU ART Start Date  
- Participants transitioning to marketed product/alternative HAART and 
did not withdraw the study for safety related reasons: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W 
IM: 
Min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) ≤ Date < Date of end of study +35 days 
   - Participants continuing maintenance Q4W IM into Extension Phase: 
Date of Nominal Week 100 Visit ≤ Date < Date of end of study +35 days 
 
For participants continuing into the Extension Phase, entering the Sub-
study but not returning to the Extension Phase: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W 
IM: 
Min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) ≤ Date < Date of First Sub-study Record 
- Participants continuing maintenance Q4W IM into Extension Phase: 
Date of Nominal Week 100 Visit ≤ Date < Date of First Sub-study Record 
 
For participants continuing into the Extension Phase, entering the Sub-
study and returning to the Extension Phase: 
- Before the sub-study: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W 
IM: 
Min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) ≤ Date < Date of First Sub-study Record 
- Participants continuing maintenance Q4W IM into Extension Phase: 
Date of Nominal Week 100 Visit ≤ Date < Date of First Sub-study Record 
 
After the sub-study: 
- Participants continuing into LTFU Phase after return to extension 
phase: 
End of sub-study date ≤ Date < LTFU ART Start Date 
- Participants transitioning to marketed product/alternative HAART and 
did not withdraw the study for safety related reasons: 
End of sub-study date ≤ Date < Date of end of study +35 days 


 
CONFIDENTIAL 
 
 
201584 
 
136 
 
Study Phase 
Date range 
Sub-study 
Screening 
For participants entering the sub-study and not receiving any SC 
injection: 
If participants continued into Extension Phase after the sub-study, then 
Date of First sub-study record ≤ Date ≤ End of Sub-study Date 
For participants entering the sub-study and receiving SC injection(s): 
Date of First sub-study record ≤ Date < Date of First SC Injection 
SC Injection 
For participants continuing into Return to Gluteal Injection Phase: 
Date of First SC Injection ≤ Date < Date of Nominal Sub-study Week 12 Visit 
For participants not continuing into Return to Gluteal Injection Phase: 
- Participants continued into Extension Phase after the sub-study: 
Date of First SC Injection ≤ Date ≤ End of Sub-study Date 
- Participants continuing into LTFU Phase after the sub-study: 
Date of First SC Injection ≤ Date < LTFU ART Start Date 
- Participants transitioning to marketed product/alternative HAART and 
did not withdraw the study for safety related reasons: 
Date of First SC Injection ≤ Date ≤ End of Sub-study Date +35 days 
Return to 
Gluteal 
Injection 
For participants continuing into Extension Phase after the sub-study: 
Date of Nominal Sub-study Week 12 Visit ≤ Date ≤ End of Sub-study Date 
For participants not continuing into Extension Phase after the sub-
study: 
- Participants continuing into LTFU Phase after the sub-study: 
Date of Nominal Sub-study Week 12 Visit ≤ Date < LTFU ART Start Date 
- Participants transitioning to marketed product/alternative HAART and 
did not withdraw the study for safety related reasons: 
Date of Nominal Sub-study Week 12 Visit ≤ Date ≤ End of Sub-study Date 
+35 days 
• 
Date = AE Start date 
• 
Maintenance Treatment Start Date: refer to Treatment Start Date in Section 14.6.1 
• 
End of Sub-study Date and nominal Week 12 Visit Date are defined in Section 14.6.1. 
Table 25 
Assignment of Study Phases for Lab assessments, ECG, Vital Signs, 
PK, Health Outcomes, PDs, and HIV associated/AIDS-defining 
conditions  
Study Phase 
Date range 
Screen 
Date ≤ Induction Treatment Start Date 
Induction 
For participants continuing into Maintenance Phase: 
 
Induction Treatment Start Date < Date ≤ Maintenance Treatment Start Date 
 
For participants not continuing into Maintenance Phase: 
 
Date > Induction Treatment Start Date 


 
CONFIDENTIAL 
 
 
201584 
 
137 
 
Study Phase 
Date range 
Maintenance 
DTG/ABC/3TC Arm: 
 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date < Date ≤ min (Start Date of Extension 
Phase Oral lead in of CAB + RPV, Date of first CAB/RPV injection) (expected 
to be nominal Week 100) 
 
For participants not continuing into Extension Phase: 
Date >Maintenance Treatment Start Date   
Q4W IM Arm: 
 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date < Date ≤ Date of Nominal Week 100 visit 
 
For participants not continuing into Extension Phase: 
Maintenance Treatment Start Date < Date ≤ LTFU ART Start Date 


 
CONFIDENTIAL 
 
 
201584 
 
138 
 
Study Phase 
Date range 
Extension 
For participants continuing into the Extension Phase and not entering 
the Sub-study: 
- Participants continuing into LTFU Phase: 
   - Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W: 
min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) < Date ≤ LTFU ART Start Date  
   - Participants continuing maintenance Q4W into Extension Phase: 
Date of Nominal Week 100 Visit < Date ≤ LTFU ART Start Date  
- Participants transitioning to marketed product/alternative HAART and 
did not withdraw the study for safety related reasons: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W 
IM: 
Min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) < Date ≤ Date of end of study +35 days 
   - Participants continuing maintenance Q4W IM into Extension Phase: 
Date of Nominal Week 100 Visit < Date ≤ Date of end of study +35 days 
 
For participants continuing into the Extension Phase, entering the Sub-
study but not returning to the Extension Phase: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W 
IM: 
Min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) < Date ≤ Date of First Sub-study Record 
- Participants continuing maintenance Q4W IM into Extension Phase: 
Date of Nominal Week 100 Visit < Date ≤ Date of First Sub-study Record 
 
For participants continuing into the Extension Phase, entering the Sub-
study and returning to the Extension Phase: 
- Before the sub-study: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to Q4W 
IM: 
Min (Start Date of Extension Phase Oral lead-in of CAB + RPV, Date of first 
CAB/RPV injection) < Date ≤ Date of First Sub-study Record 
- Participants continuing maintenance Q4W IM into Extension Phase: 
Date of Nominal Week 100 Visit < Date ≤ Date of First Sub-study Record 
 
After the sub-study: 
- Participants continuing into LTFU Phase after return to extension 
phase: 
End of sub-study date < Date ≤ LTFU ART Start Date 
- Participants transitioning to marketed product/alternative HAART and 
did not withdraw the study for safety related reasons: 
End of sub-study date < Date ≤ Date of end of study +35 days 


 
CONFIDENTIAL 
 
 
201584 
 
139 
 
Study Phase 
Date range 
Sub-study 
Screening 
For participants entering the sub-study and not receiving any SC 
injection: 
If participants continued into Extension Phase after the sub-study, then 
Date of First sub-study record < Date ≤ End of Sub-study Date  
For participants entering the sub-study and receiving SC injection(s): 
Date of First sub-study record < Date ≤ Date of First SC Injection 
SC Injection 
For participants continuing into Return to Gluteal Injection Phase: 
Date of First SC Injection < Date ≤ Date of Nominal Sub-study Week 12 Visit 
For participants not continuing into Return to Gluteal Injection Phase: 
- Participants continued into Extension Phase after the sub-study: 
Date of First SC Injection < Date ≤ End of Sub-study Date 
- Participants continuing into LTFU Phase after the sub-study: 
Date of First SC Injection < Date LTFU ART Start Date 
- Participants transitioning to marketed product/alternative HAART and 
did not withdraw the study for safety related reasons: 
Date of First SC Injection < Date ≤ Date of end of Sub-study +35 days 
Return to 
Gluteal 
Injection 
For participants continuing into Extension Phase after the sub-study: 
Date of Nominal Sub-study Week 12 Visit < Date ≤ End of Sub-study Date 
For participants continuing into LTFU Phase after the sub-study: 
Date of Nominal Sub-Study Week 12 Visit < Date ≤ LTFU ART Start Date 
For Participants transitioning to marketed product/alternative HAART 
and did not withdraw the study for safety related reasons: 
Date of Nominal Sub-Study Week 12 Visit < Date ≤ Date of end of Sub-study 
+35 days 
• 
Date = start or assessment date 
• 
Maintenance Treatment Start Date: refer to Treatment Start Date in Section 14.6.1 
• 
End of Sub-study Date and nominal Week 12 Visit Date are defined in Section 14.6.1. 
• 
The post-dose assessments (e.g., 2-hour post-dose PK and NRS) taken on the date of first SC 
injection will be assigned SC Injection Phase, instead of Sub-study Screening Phase. 
• 
The post-dose assessment (e.g., NRS) taken on the date of Sub-study Week 12 injection will be 
assigned Return to Gluteal Injection Phase, instead of SC Injection Phase. 
Table 26 
Assignment of Study Phases for Concomitant medication/ART 
Concomitant during: 
Date range 
Prior  
Medication Taken < Induction Treatment Start Date 


 
CONFIDENTIAL 
 
 
201584 
 
140 
 
Concomitant during: 
Date range 
Induction 
For participants continuing into Maintenance Phase: 
 
Induction Treatment Start Date ≤ Medication Taken < Maintenance 
Treatment Start Date 
 
For participants not continuing into Maintenance Phase: 
 
Medication Taken ≥ Induction Treatment Start Date 
 
Note: ART stopped on the start date of Induction Treatment will be 
considered Prior ART and will not be considered concomitant during the 
Induction Phase. 
Maintenance 
DTG/ABC/3TC Arm: 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date ≤ Medication Taken < Start Date of 
Extension Phase CAB + RPV (expected to be WK100) 
 
For participants not continuing into Extension Phase: 
 
Medication Taken ≥ Maintenance Treatment Start Date 
 
Note: ART stopped on the start date of Maintenance Treatment will be 
considered concomitant during the Induction Phase and will not be 
considered concomitant during the Maintenance Phase. 
Q4W IM Arms: 
 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date ≤  Medication Taken < Date of 
Nominal Week 100 visit 
 
For participants not continuing into Extension Phase: 
Maintenance Treatment Start Date ≤  Medication Taken < LTFU ART 
Start Date  
 
Note: ART stopped on the start date of Maintenance Treatment will be 
considered concomitant during the Induction Phase and will not be 
considered concomitant during the Maintenance Phase. 


 
CONFIDENTIAL 
 
 
201584 
 
141 
 
Extension 
For Participants continuing into the Extension Phase and not 
entering the Sub-study: 
- Participants continuing into LTFU Phase: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to 
Q4W IM: 
Start Date of Extension Phase CAB + RPV[a] ≤ Medication Taken < 
LTFU ART Start Date 
- Participants continuing maintenance Q4W IM into Extension 
Phase: 
Date of Nominal Week 100 Visit[b] ≤ Medication Taken < LTFU ART 
Start Date 
- Participants transitioning to marketed product/alternative HAART 
and did not withdraw the study for safety related reasons: 
- Participants Switching from Maintenance DTG/ACB/3TC Arm to 
Q4W IM: 
Start Date of Extension Phase CAB + RPV[a] ≤ Medication Taken < 
Date of end of study +35 days 
-Participants continuing maintenance Q4W IM into Extension 
Phase: 
Date of Nominal Week 100 Visit[b] ≤ Medication Taken < Date of end 
of study +35 days 
 
For participants continuing into the Extension Phase, entering the 
Sub-study but not returning to the Extension Phase: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to 
Q4W IM: 
Start Date of Extension Phase CAB + RPV[a]  ≤ Medication Taken < 
Date of First Sub-study Record 
- Participants continuing maintenance Q4W IM into Extension 
Phase: 
Date of Nominal Week 100 Visit[b] ≤ Medication Taken < Date of First 
Sub-study Record 
 
For participants continuing into the Extension Phase, entering the 
Sub-study and returning to the Extension Phase: 
- Before the sub-study: 
- Participants Switching from Maintenance DTG/ABC/3TC Arm to 
Q4W IM: 
Start Date of Extension Phase CAB +RPV[a] ≤ Medication Taken < 
Date of First Sub-study Record 
- Participants continuing maintenance Q4W IM into Extension 
Phase: 
Date of Nominal Week 100 Visit[b] ≤ Medication Taken < Date of First 
Sub-study Record 
 
After the sub-study: 


 
CONFIDENTIAL 
 
 
201584 
 
142 
 
Concomitant during: 
Date range 
- Participants continuing into LTFU Phase after return to extension 
phase: 
End of sub-study date[c] ≤ Medication Taken < LTFU ART Start Date 
- Participants transitioning to marketed product/alternative HAART 
and did not withdraw the study for safety related reasons: 
End of sub-study date[c] ≤ Medication Taken < Date of end of study 
+35 days 
Long-Term Follow-Up 
For participants who received at least one CAB and/or RPV 
Injection: 
 
Medication Taken ≥ LTFU ART Start Date 
Sub-study Screening 
For participants entering the sub-study and not receiving any SC 
injection: 
If participants continued into Extension Phase after the sub-study, then 
Date of First sub-study record[d] ≤ Medication Start Date < End of Sub-
study Date 
For participants entering the sub-study and receiving SC 
injection(s): 
Date of First sub-study record[d] ≤ Medication Start Date < Date of First 
SC Injection 
SC Injection 
For participants continuing into Return to Gluteal Injection Phase: 
Date of First SC Injection[e] ≤ Medication Start Date < Date of Nominal 
Sub-study Week 12 Visit 
For participants not continuing into Return to Gluteal Injection 
Phase: 
- Participants continued into Extension Phase after the Sub-study: 
Date of First SC Injection[e] ≤ Medication Start Date < End of Sub-
study Date 
- Participants continuing into LTFU Phase after the sub-study: 
Date of First SC injection[e] ≤ Medication Start Date < LTFU ART Start 
Date 
- Participants transitioning to marketed product/alternative HAART 
and did not withdraw the study for safety related reasons: 
Date of First SC Injection[e] ≤ Medication Start Date < Date of end of 
Sub-Study +35 days 
Return to Gluteal 
Injection 
For participants continuing into Extension Phase after the sub-
study: 
Date of Nominal Sub-study Week 12 Visit[f] ≤ Medication Start Date < 
End of Sub-study Date 
For participants continuing into LTFU Phase after the sub-study: 
Date of Nominal Sub-study Week 12 Visit[f] ≤ Medication Start Date < 
LTFU ART Start Date 
For participants transitioning to marketed product/alternative 
HAART and did not withdraw the study for safety related reasons: 
Date of Nominal Sub-study Week 12 Visit[f] ≤ Medication Start Date < 
Date of end of Sub-study +35 days 


 
CONFIDENTIAL 
 
 
201584 
 
143 
 
• 
[a] ART stopped on the start date of Extension Phase CAB + RPV will not be assigned to the Extension 
Phase. 
• 
[b] ART taken stopped on the date of nominal Week 100 visit will be considered concomitant during the 
Maintenance Phase and will not be considered concomitant during the Extension Phase. 
• 
[c] ART taken stopped on the end of Sub-study date will be considered concomitant during the previous sub-
Study Phase and will not be considered concomitant during the Extension Phase. 
• 
[d] ART stopped on the date of first Sub-study record not be assigned to the Sub-study Screening Phase. 
• 
[e] ART stopped on the date of first SC Injection will not be assigned to the SC Injection Phase. 
• 
[f] ART stopped on the date of Nominal Sub-study Week 12 Visit will not be assigned to the Return to Gluteal 
Injection Phase. 
 
If a partial date for medication/ART is recorded in the eCRF, the following convention will be used 
to assign the medication: 
• 
if the partial date is a start date, a '01' will be used for missing days and 'Jan' will be 
used for missing months; 
• 
if the partial date is a stop date, a '28/29/30/31' will be used for the missing day 
(dependent on the month and year) and 'Dec' will be used for the missing month; for 
medications recorded separately in the eCRF as prior ART, the earlier of this 
imputed date or the day before IP start will be used. 
The recorded partial date will be displayed in listings. 
Table 27 
Assignment to Long-Term Follow-Up Phase  
Study Phase 
Date range 
Long-Term 
Follow-Up 
Date > max (Last IM Injection Date, Last Oral Bridging End Date) 
• 
Date = Assessment/Start Date 
Note that the long-term follow-up Phase and maintenance/extension Phases are not 
necessarily mutually exclusive and are to be defined with separate Phase variables in the 
datasets.  For example, an Q4W IM participant who has Week 44 injection and 
withdrawal at Week 48 without receiving Week 48 injection, the “Week 48 withdrawal 
visit” belongs to both the Maintenance Phase and long-term follow-up Phase.   
14.4.1.1. 
Study Periods 
Certain displays will be produced for data collected during the oral-lead-in and during the 
first 52 weeks of the Maintenance Phase, respectively.  These period variables are 
defined in Table 28 and Table 29 and will be reflected in the datasets in separate 
variables. 
Table 28 
Assignment of Study Period for AE Data 
Study Period 
Date range 


 
CONFIDENTIAL 
 
 
201584 
 
144 
 
Maintenance 
Phase up to 
Week 52 
ABC/DTG/3TC Arm: 
 
For participants continuing beyond Week 52: 
Maintenance Treatment Start Date ≤ Date < Date of Study Day 378 (Upper 
Assessment Window for Week 52)  
 
For participants not continuing beyond Week 52: 
Date ≥ Maintenance Treatment Start Date 
Q4W IM Arm: 
 
For participants continuing beyond Week 52: 
Maintenance Treatment Start Date ≤ Date < Date of Study Day 378 (Upper 
Assessment Window for Week 52)  
 
For participants not continuing beyond Week 52: 
Maintenance Treatment Start Date ≤ Date < LTFU ART Start Date 
Maintenance 
Phase Oral 
lead-in 
Q4W IM Arm: 
 
For participants receiving at least one Maintenance Phase Injection: 
Maintenance Treatment Start Date ≤ Date < Date of First IM injection  
 
For participants withdrawing prior to first Maintenance Phase Injection: 
Date ≥ Maintenance Treatment Start Date 
Extension 
Phase Oral 
lead-in 
Switch Q4W (Oral Lead-In Arm): 
 
For participants receiving at least one Extension Phase Injection: 
Extension Oral CAB/RPV Start Date ≤ Date < Date of First IM injection  
 
For participants withdrawing prior to first Extension Phase Injection: 
Date ≥ Extension Oral CAB/RPV Start Date 
 
Table 29 
Assignment of Study Period for Lab assessments: 
 Period 
Date range 
Maintenance 
up to Week 52  
[Note: this is derived for 
LAB assessments only] 
ABC/DTG/3TC Arm: 
 
For participants continuing beyond Week 52: 
Maintenance Treatment Start Date < Date ≤ Date of Study Day 
378 (Upper Assessment Window for Week 52)  
 
For participants not continuing beyond Week 52: 
Date >Maintenance Treatment Start Date 


 
CONFIDENTIAL 
 
 
201584 
 
145 
 
Q4W IM Arm: 
 
For participants continuing beyond Week 52: 
Maintenance Treatment Start Date < Date ≤ Date of Study Day 
378 (Upper Assessment Window for Week 52)  
 
For participants not continuing beyond Week 52: 
Maintenance Treatment Start Date < Date ≤ LTFU ART Start Date 
Maintenance Oral lead-in 
[Note: this is derived for 
LAB assessments only] 
Q4W IM Arm: 
 
For participants receiving at least one Maintenance Phase 
Injection: 
 
Maintenance Treatment Start Date < Date ≤ Date of First IM 
injection  
 
For participants withdrawing prior to first Maintenance Phase 
Injection: 
 
Date >Maintenance Treatment Start Date 
 
Extension Phase Oral 
lead-in 
[Note: this is derived for 
LAB assessments only] 
Switch Q4W (Oral Lead-In) Arm: 
 
For participants receiving at least one Extension Phase 
Injection: 
 
Extension Oral CAB/RPV Start Date < Date ≤ Date of First IM 
injection  
 
For participants withdrawing prior to first Extension Phase 
Injection: 
 
Date > Extension Oral CAB/RPV Start Date 
 
 
14.4.2. 
Treatment State 
Within each treatment study Phase (i.e., Induction, Maintenance and Extension—based 
on assignment of study Phase described in Section 14.4.1), only those assessments which 
occur within the ranges shown in Table 30 will be considered ‘on-treatment’ for the given 
Phase. 
Table 30 
Treatment State within Study Phases 
Study Phasea 
Treatment State Date Range 
Screen 
Pre-treatment 
All assessments/events within Phase 
Induction 
On-treatment 
Date ≤ Induction Treatment Stop Date + 1 


 
CONFIDENTIAL 
 
 
201584 
 
146 
 
Post-treatment 
Date > Induction Treatment Stop Date + 1 
Maintenance 
On-treatment 
ABC/DTG/3TC ART arm: 
Date ≤ Maintenance ART Stop Date + 1 
IM Q4W arm:  
 
Date ≤ max (Date of Last Q4W IM Dose + 35, 
Last Oral Dose Date + 1) 
 
Post-treatment 
ABC/DTG/3TC arm: 
Date > ABC/DTG/3TC Stop Date + 1 
IM Q4W arm:  
Date > max (Date of Last Q4W IM Dose + 35, 
Last Oral Dose Date + 1) 
Extension 
On-treatment 
Date ≤ max (Date of Last Q4W IM Dose + 35, 
Last Oral Dose Date + 1) 
Post-treatment 
Date > Date of Last Q4W IM Dose + 35, Last 
Oral Dose Date + 1) 
Long-Term 
Follow-up 
On-treatment 
Date ≤ min (LTFU ART start date, max (Last 
Injection Date + 35, Last Oral Dose Date + 1)) 
Post-treatment 
Date > min (LTFU ART start date, max (Last 
Injection Date + 35, Last Oral Dose Date + 1)) 
Note1: Treatment State is determined after data has been assigned to the study Phases as defined 
in Section 14.4.1 
Note2: Last Q4W IM / last oral dose / Induction Treatment stop date/Maintenance ART Stop Date is 
only applied to participants who permanently discontinue from study treatment 
Note3: Date = Assessment/Start Date. 
• 
For Sub-study Screening, SC Injection and Return to Gluteal Injection phases, the same on-
treatment and post-treatment algorithms as those in Extension Phase will be applied. 
 
14.4.2.1. 
Treatment States for AE Data 
For adverse events, partial AE start date will use imputation as described in Section 
14.7.2.1. In the case of a completely missing start date, the event will be considered to 
have started On-treatment at Maintenance Phase unless an end date for the AE is 
provided which is before start of study treatment at Maintenance Phase; in such a case the 
AE is assigned as Pre-treatment.  
Within each treatment study Phase, only those AE with onset date within the ranges 
shown in Table 30 will be considered ‘on-treatment’ for the given Phase. The onset date 
will be derived based on Table 31.  


 
CONFIDENTIAL 
 
 
201584 
 
147 
 
Table 31 
AE onset date, AE duration and relation to study treatment 
 
Definition 
Onset 
date/study day 
Since 1st Dose 
of each study 
Phase (Days) 
If Treatment Start Date ˃ AE Onset Date = AE Onset Date - Treatment 
Start Date 
If Treatment Start Date ≤ AE Onset Date = AE Onset Date - Treatment 
Start Date +1 
Missing otherwise. 
Duration 
(Days)  
AE Resolution Date – AE Onset Date + 1 
Drug-related 
If relationship is marked ‘YES’ on Inform/CRF OR value is missing. 
NOTES: 
• 
Onset date/study day will be derived for each study Phase, respectively (refer to Section 
14.6.1) 
14.4.3. 
Combining Treatment Phases and States 
On-treatment and Post-treatment assessments and events will be classified as occurring 
during the Induction, Maintenance Phase, Extension, or Long-term follow up Phase. 


 
CONFIDENTIAL 
 
 
201584 
 
148 
 
14.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
14.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: us1salx00259 
HARP Area 
\ARPROD\GSK1265744\mid201584\primary_01 (W48 analysis) 
\ARPROD\GSK1265744\mid201584\primary_07 (W96 analysis) 
\ARPROD\GSK1265744\mid201584\primary_09 (Day 1 Japan PK analysis) 
\ARPROD\GSK1265744\mid201584\primary_17 (Week 124 analysis) 
 
 
QC Spreadsheet : \ARWORK\GSK1265744\mid201584\documents\qc\ 
Analysis Datasets  
• Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.1.3 & 
AdaM IG Version 1.0). 
• 
For creation of ADaM datasets (ADCM/ADAE), the same version of dictionary datasets will 
be implemented for conversion from SI to SDTM. 
Generation of RTF Files 
• 
RTF files will be generated for every reporting effort described in the RAP. 
14.5.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
 
• 
All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects CDISC and 
GSK Data Display Standards terminology. 
Formats 
• 
GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 


 
CONFIDENTIAL 
 
 
201584 
 
149 
 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
• 
The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the subject listings displays.  
Unscheduled Visits 
• Unscheduled visits will be assigned to a study visit using the all-inclusive windows defined in 
Section 14.3.2. 
• However, data summaries will only report visits that are planned assessment time points for 
each parameter (according to the Time and Events table). 
• 
Assessments at unscheduled visits will be included for ‘any time On-treatment’ time points 
and in data listings, as well any algorithms that make use of additional data (e.g., Snapshot). 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
14.5.3. 
Reporting Standards for Pharmacokinetic 
Pharmacokinetic Concentration Data 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical Principle 6.06.1. 
 
NQ concentration values will be assigned a numeric value equal to the low 
limit of quantification (LLQ) (Refer to GUI_51487 for further details) for 
descriptive summary statistics/analysis and summarized graphical displays only.  
 
For Japan Day 1 PK concentrations, refer to the standard operating procedure, 
SOP-CPK-0001 and R&D Guideline: Non-Compartmental Analysis of 
Pharmacokinetic Data, GUI_51487 (3.0), for more information regarding the 
handling of plasma concentrations below the assay’s lower limit of 
quantification (LLQ). 
Geometric mean, 95% CI of geometric mean, standard deviation (SD) of 
logged data and between geometric coefficient of variation (CVb (%)) will be 
reported. 
o CVb (%) = √ (exp(SD2) - 1) * 100, SD = SD of log transformed data) 
 


 
CONFIDENTIAL 
 
 
201584 
 
150 
 
14.6. 
Appendix 6: Derived and Transformed Data 
14.6.1. 
General 
Multiple Measurements at One Time Point 
• If after window assignment there are multiple valid assessments of a parameter within the 
same window, then the following hierarchy will be used to determine the value to be used for 
summary statistics of observed values: 
o the assessment closest to the window target Study Day; 
o if there are multiple assessments equidistant from the target Study Day, then for 
continuous variables the mean of these values will be used and for categorical 
variables the worse assessment. For HIV-1 RNA, the geometric mean of the 
number of copies will be used as opposed to the arithmetic mean 
• Assessments not chosen for use in summary statistics by this algorithm will still appear in 
the associated listings. Also, such valid assessments will be used when determining values 
of potential clinical concern for the ‘any time On-treatment’ time point, and for any algorithm 
that has specific rules for which observation to use (e.g., Snapshot). 
Treatment Start Date 
Treatment start date is defined by Phase as follows: 
Induction Phase 
• Start date of DTG regimen entered onto the Induction Phase IP exposure CRF 
Maintenance Phase 
• For participants randomised to Q4W IM, maintenance treatment start date is the date of 
oral lead-in of CAB+RPV entered onto the Maintenance Phase IP exposure CRF  
• For participants randomised to ABC/DTG/3TC, maintenance treatment start is DTG 
regimen start date entered onto the Maintenance Phase IP exposure CRF 
Extension Phase 
• For participants randomised to Q4W IM, extension treatment start date is the date of 
Nominal Week 100 injection date. 
For participants randomised to ABC/DTG/3TC, extension treatment start date is the 
start date of oral lead-in of CAB+RPV entered onto the Extension Phase IP exposure 
CRF.  
SC Sub-Study 
• For participants enrolled in the SC sub-study, treatment start date is the date of their 
screening injection. For purposes of exposure calculations, the date of the first SC 
injection will be used. 
• For participants who received Sub-study Week 12 injection, nominal Sub-study Week 
12 visit date is defined by the Sub-study Week 12 injection date. Otherwise, nominal 
Sub-study Week 12 visit date is defined by the date of latest Sub-study Week 12 
assessment. 
• For participants who continued into Return to Gluteal Injection Phase however missed 
Sub-study Week 12 visit, nominal Sub-study Week 12 visit date is defined by the end of 
SC Injection Phase date (i.e., date for the SC Injection Phase conclusion record in the 
SDTM DS domain) for the analysis purpose. 


 
CONFIDENTIAL 
 
 
201584 
 
151 
 
• For sub-study screen failures, the end of sub-study date is defined by the date they 
failed to meet the inclusion/exclusion criteria in the sub-study. For other sub-study 
participants, the end of sub-study date is defined by the date of completion or 
withdrawal available in the sub-study conclusion eCRF form or the Week 20 visit date, 
whichever comes first. 
Induction Phase Study Day 
The Induction Phase Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of 
AE or HIV associated/AIDS-defining condition) will be derived as the number of days between 
the date of the event and the initial start date of DTG in the Induction Phase as follows: 
if date of event ≥ start date of Induction Phase DTG, then 
1 
IP
 
phase
Induction 
 
of
 
date
start 
 -
event 
 
of
 
date
 
Day 
Study 
 
Phase
Induction 
+
=
 
if date of event < start date of Induction Phase DTG, then 
IP
 
phase
Induction 
 
of
 
date
start 
 -
event 
 
of
 
date
 
Day 
Study 
 
Phase
Induction 
=
 
if date of event > start date of Maintenance Phase DTG, then  
Induction Phase Study Day will not be derived (i.e., will be set to missing). 
Note that the initial start date of Induction Phase DTG is considered to be on Induction Phase 
Study Day 1 and the day before this is Induction Phase Study Day -1; i.e., there is no Induction 
Phase Study Day 0.  
Study Day 
The Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of AE or HIV 
associated/AIDS-defining condition) will be derived as the number of days between the date of 
the event and the start date of study treatment on Maintenance Phase as follows: 
if date of event ≥ start date of study treatment, then 
• Study Day = Date of Event – Start Date of Maintenance Phase IP + 1 
if date of event < start date of study treatment, then 
• Study Day = Date of Event – Start Date of Maintenance Phase IP  
Note that the start date of study treatment on Maintenance Phase is considered to be on Study 
Day 1 and the day before this is Study Day -1; i.e., there is no Study Day 0. 
Extension Phase Study Day 
The Extension Phase Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of 
AE or HIV associated/AIDS-defining condition) will be derived as the number of days between 
the date of the event and the initial start date of Extension Phase IP as follows: 
if date of event ≥ start date of extension Phase IP, then 


 
CONFIDENTIAL 
 
 
201584 
 
152 
 
1 
IP
 
phase
 
 Extension
of
 
date
start 
 -
event 
 
of
 
date
 
Study Day 
 
 Phase
Extension
+
=
 
if date of event < start date of Extension Phase IP, then 
IP
 
phase
 
 Extension
of
 
date
start 
 -
event 
 
of
 
date
 
Study Day 
 
 Phase
Extension
=
 
Note that the start date of Extension Phase IP is considered to be on Extension Phase Study 
Day 1 and the day before this is Extension Phase Study Day -1; i.e., there is no Extension 
Phase Study Day 0.  
Long-Term Follow Up Study Day 
The Long-Term Follow Up (LTFU) Study Day of an event (e.g., lab assessment, start date of AE 
or HIV associated/AIDS-defining condition) will be derived as the number of days between the 
date of the event and the end of IP treatment [i.e., max (Last IM Injection Date, Last Oral 
Bridging End Date)] 
as follows: 
If the onset of event falls in Long-term Follow up Phase, then 
• 
IP
 
of
 
date
 
end
 -
event 
 
of
 
date
 
Study Day 
 
LTFU
=
 
Sub-study Phase Study Day 
Each phase Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of AE or 
HIV associated condition) will be derived as the number of days between the date of the event 
and the reference date for each phase of the sub-study as follows: 
if date of event ≥ reference date, then 
• 
 Study Day=date of event - reference date + 1 
 
if date of event < reference date, then 
• Study Day=date of event - reference date 
 
The reference dates for each Phase are as follows: 
• SC Injection Phase: Date of first SC injection 
• Return to Gluteal Injection Phase: Date of the nominal sub-study Week 12 visit date 
The SC injection date will serve as the reference date for the overall study day. 
Study treatment/drugs 
• Refers to either investigation product (CAB+RPV oral /CAB+ RPV LA) or ABC/DTG/3TC or 
DTG plus alternate NRTIs. 
 


 
CONFIDENTIAL 
 
 
201584 
 
153 
 
14.6.2. 
Study Population 
Demographics 
Age 
• Age, in whole years, will be calculated with respect to the participant’s Screening visit.   
• GSK standard IDSL algorithms will be used for calculating age where birth date will be 
imputed as follows: 
o Any participant with a missing date and month will have this imputed as ‘30th June’. 
• Birth date will be presented in listings as ‘YYYY’. 
• Completely missing dates of birth will remain as missing, with no imputation applied. 
Consequently, the age of the participant will not be calculated and will remain missing. 
Body Mass Index (BMI) 
• Calculated as Weight (kg) / Height (m)2, using Height collected at Day 1. 
Hepatitis B Status 
• A participant will be considered positive for hepatitis B virus (HBV) if they have a positive 
surface antigen (i.e., “REACTIVE”) and/or detectable HBV DNA (“HBV DNA DETECTED” or 
HBV DNA ≥ 116 copies/mL, with “HBV DNA DETECTED” taking precedence over HBV 
DNA reported as <116 copies/mL). If DNA result is available, then this will be used to qualify 
as positive or negative; otherwise, Hepatitis B status will be determined using the surface 
antigen result. 
Hepatitis C Status 
• Hepatitis C status will be determined using antibody (IgM or IgG) and/or hepatitis C virus 
(HCV) RNA assessments performed during screening or during the conduct of the study.  
• If both antibody and virus RNA assessments are available, then the latter will take 
precedence and positive/negative status will be based on whether HCV RNA is ≥15 
IU/mL.  In the absence of an HBV RNA result, Hepatitis C antibody of “REACTIVE” or 
“BORDERLINE” will qualify as Hep C positive. 
Lipid-modifying Agents 
• The following ATC codes correspond to lipid-modifying agents: 
• ATC Level 2: C10 
• ATC Level 3: C10A, C10B (if Level 2 is not available) 
• ATC Level 4: C10AA, C10AB, C10AC, C10AD, C10AX, C10BA, C10BX (if level 2, 3 are 
not available) 
• Participants are considered to have used a lipid-modifying agent at baseline if they are 
taking the medication at the time of their baseline lipid testing date. 
• Participants are also considered to have used a lipid-modifying agent at baseline if they 
stopped their lipid modifying medication within 12 weeks prior to their baseline lipid testing 
date. 
Framingham Risk Equation 
• The predicted probability, 𝑝𝑝̂, of having a cardiovascular disease (CVD) within the next 10-
years according to the Framingham formula [D’Agostino, 2008] is 
for females: 
𝑝𝑝̂F = 1 – S0(t)exp{ 2.32888 × log(age) + 1.20904 × log(TC) – 0.70833 × log(HDL) + 2.76157 × log(SBPu) + 2.82263 × log(SBPt) +  


 
CONFIDENTIAL 
 
 
201584 
 
154 
 
Demographics 
0.52873 × Is + 0.69154 × Id – 26.1931}, 
 
for males: 
𝑝𝑝̂M = 1 – S0(t)exp{ 3.06117 × log(age) + 1.12370 × log(TC) – 0.93263 × log(HDL) + 1.93303 × log(SBPu) + 1.99881 × log(SBPt) 
+  
0.65451 × Is + 0.57367 × Id – 23.9802}, 
 
where 
S0(t) = ൜0.95012, females
0.88936, males  
 
TC = total serum cholesterol (mg/dL), 
HDL = serum HDL cholesterol (mg/dL), 
SBPu = systolic blood pressure (mmHg) if participant is not treated for high blood pressure  
(note that if a participant is treated for high blood pressure, then log(SBPu) = 0) 
SBPt = systolic blood pressure (mmHg) if participant is treated for high blood pressure 
 (note that if a participant is not treated for high blood pressure, then log(SBPt) = 0) 
 



=
otherwise
smo
current
Is
,0
ker
,1
 



=
otherwise
diabetic
Id
,0
,1
 
•  A participant will be considered as treated for high blood pressure if during screening it 
has specified that is suffering from hypertension. 
• A participant is classified as diabetic if current or past is indicated in the medical 
conditions eCRF for Type 1 or Type 2 diabetes mellitus, or if baseline fasting glucose 
≥7.00 mmol/L (126 mg/dL).  
• Smoking status is collected in the eCRF at Induction Baseline (Week -20). A current 
smoker is defined as currently smoking/using tobacco or has smoked/used tobacco 
within the previous 6 months; a former smoker is defined as previously smoked/used 
tobacco products and has not smoked/used tobacco products within the previous 6 
months. 
• This calculation will not be performed for participants who have indicated current or past 
myocardial infarction conditions on the eCRF. These participants will not be included in 
summary statistics of risk but will be counted in the highest category of risk in the 
summary by category. 
 


 
CONFIDENTIAL 
 
 
201584 
 
155 
 
Extent of Exposure 
• Exposure to CAB+RPV (oral lead-in), CAB LA+RPV LA, ABC/DTG/3TC (or DTG if 
alternate NRTI is used) will be calculated from the IP eCRF pages.   
Maintenance Phase: Q4W IM arm 
Exposure to CAB + RPV (oral lead-in) 
= 
Oral lead-in CAB/RPV Stop Date – Oral lead-in 
CAB/RPV Start Date +1 
Exposure to CAB LA + RPV LA = Number of IP injections received during 
Maintenance Phase (up to but not including 
Injections administered at Week 100) 
Overall Exposure to IP = min [Date of latest Maintenance Phase visit up to 
and including Week 100, max (Date of last IP 
injection +35 [a], Date of last oral CAB/RPV [a] ) ] – 
Oral lead-in CAB/RPV Start Date +1 
Maintenance + Extension Phase: Q4W IM arm 
Exposure to CAB LA + RPV LA = Number of IP injections received during 
Maintenance Phase + Extension Phase 
Overall Exposure to IP = min [Min(Date of Last Study Contact, Long Term 
Follow Up HAART Start Date), max (Date of last IP 
injection +35 [a], Date of last oral CAB/RPV [a] )] – 
Oral lead-in CAB/RPV Start Date +1 
a. Last Q4W IM / last oral dose is only applied to participants who permanently discontinue from study 
Maintenance Phase: ABC/DTG/3TC arm 
Exposure = Min (Date of latest Maintenance Phase visit up to and including Week 100, 
Maintenance Phase Treatment Stop Date, Date of Maintenance Phase Discontinuation) – 
Maintenance Treatment Start Date + 1 
Extension Phase: Switch Q4W IM group (Extension Switch Population only) 
Exposure to CAB + RPV (oral lead-in) 
= 
min (Date of Last Study Contact, Long Term Follow 
Up HAART Start Date, Oral lead-in CAB/RPV Stop 
Date) – Oral lead-in CAB/RPV Start Date +1 
Exposure to CAB LA + RPV LA = Number of IP injections received during Extension 
Phase 
Overall Exposure to CAB + RPV = min [min(Date of Last Study Contact, Long Term 
Follow Up HAART Start Date), max (Date of last IP 
injection +35 [a], Date of last oral CAB/RPV [a] ) ] – 
min(Oral lead-in CAB/RPV Start Date, Date of First 
IP Injection) +1 
a. Last Q4W IM / last oral dose is only applied to participants who permanently discontinue from study 
• Duration of dosing in subject years will be calculated as the sum of subject duration of 
dosing in days (across all participants)/365.25 


 
CONFIDENTIAL 
 
 
201584 
 
156 
 
Extent of Exposure 
• Participants who were randomised to CAB LA+RPV LA but did not report an IP start date 
will be categorised as having zero days of exposure.  
SC Sub-study 
• For SC Injection Phase 
• Exposure to CAB LA + RPV LA = Number of IP injection visits received during 
SC Injection Phase. Note that the planned Sub-study Week 12 injections belong 
to Return to Gluteal Injection Phase. 
• The SOC or CAB+RPV oral bridging are not allowed in this phase.  
• Overall exposure to IP:  
min [Date of Latest SC Injection Phase Visit up to the Nominal Sub-study Week 
12 Visit Date, max (Date of Last Injection + 35[a], Date of Last Dose of Oral 
CAB+RPV, Date of Last Dose of SOC Oral Bridging)] – Date of First SC 
Injection) + 1 
Note that the Nominal Sub-study Week 12 visit date is defined in Section 
14.6.1. 
• Overall exposure to IP = Overall exposure to Study Treatment. 
• For SC Injection + Return to Gluteal Injection Phase 
• Exposure to CAB LA + RPV LA = Number of IP injection visits received during 
SC Injection or Return to Gluteal Injection Phase. Note that the injections 
received on the date of Sub-study Week 20 visit belong to the Extension Phase 
in main study. 
• The SOC or CAB+RPV oral bridging are not allowed in these two phases.  
• Overall exposure to IP:  
min [End of Sub-study Date, max (Date of Last Injection + 35[a], Date of Last 
Dose of Oral CAB+RPV, Date of Last Dose of SOC Oral Bridging)] – Date of 
First SC Injection) + 1 
Note that the End of Sub-study Date is defined in Section 14.6.1. 
• Overall exposure to IP = Overall exposure to Study Treatment. 
[a] Last Injection/ last oral dose is only applied to participants who permanently discontinue the study. 
Adherence to CAB/RPV Injection Schedule  
For participants in the randomized Q4W arm, Timeliness of Injections Relative to Date of 
Projected Dosing Visits are assessed by using "actual injection visit date - projected visit date 
from Week 4b".  
For participants in the Switch Q4W Oral Lead-in group, Timeliness of Injections Relative to Date 
of Projected Dosing Visits are assessed by using "actual injection visit date - projected visit date 
from Week 104b".  
For participants in the Switch Q4W Direct to Inject group, timeliness of Injections Relative to 
Date of Projected Dosing Visits are assessed by using "actual injection visit date - projected visit 
date from Week 100".  


 
CONFIDENTIAL 
 
 
201584 
 
157 
 
Extent of Exposure 
For participants in the Sub-Study, timeliness of Injections Relative to Date of Projected Dosing 
Visits are assessed by using “actual injection visit date - projected visit date from Sub-study 
Week -4”. 
Each injection visit is counted only once. Individual CAB and RPV injections administered at the 
same visit are not counted twice. "Extra" unscheduled injections are excluded from all 
derivations. For example, if during a scheduled visit a participant receives 1 ml of injection 
instead of 2 ml due to a dosing error but returns one week later for the remaining 1 ml injection, 
then the additional visit is excluded. If a participant receives an extra injection at an unscheduled 
visit by mistake, this visit will also be excluded. 
 
The categories of Timeliness of Injections Relative to Date of Projected Dosing Visits for 
summary are listed below: 
 
< -14 days 
-14 to   - 8 days 
-7   to   - 4 days  
-3   to   -2 days -1 
 0 day  
1  
2 to 3 days  
4 to 7 days  
8 to 14 days 
>14 days 
Missed Injection without Oral Bridging 
Missed Injection with Oral Bridging 
Corrected QTC 
When not entered directly in the eCRF, corrected QT intervals by Bazett’s (QTcB) and 
Fridericia’s (QTcF) formulas will be calculated, in msec, depending on the availability of other 
measurements. 
If RR interval (in msec) is provided, then missing QTcB and/or QTcF will be derived as 
1000
RR
QT
QTcB =
  
3
1000
RR
QT
QTcF =
 
where uncorrected QT interval is also measured in msec. 
If RR interval is not provided directly and one of QTcB or QTcF has been entered, then RR 
interval can be obtained from the above formulas and used to calculate the other correction 
method value; i.e., 


 
CONFIDENTIAL 
 
 
201584 
 
158 
 
Extent of Exposure 
QT
QTcF
QTcB
3
=
 
 
3
2
QTcB
QT
QTcF
⋅
=
 
 
14.6.3. 
Safety 
Adverse Events– DAIDS Grading 
• Clinical adverse events will be graded based on the Division of AIDS Table for Grading the 
Severity of Adult and Pediatric Adverse Events Version 2.0, November 2014, as specified in 
the protocol Appendix 12.2.  
Laboratory Parameters 
• If a laboratory value which is expected to have a numeric value for summary purposes, has 
a non-detectable level reported in the database, where the numeric value is missing, but 
typically a character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than 
x in the comment field) is present, the number of significant digits in the observed values will 
be used to determine how much to add or subtract in order to impute the corresponding 
numeric value. If a character value starting with “<=x”, then the numeric value will be x. 
o Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01 
o Example 2: 1 Significant Digit   =  ‘> x’ or ‘>=x’ becomes x + 0.1 
o Example 3: 0 Significant Digits = ‘< x’ becomes x – 1     


 
CONFIDENTIAL 
 
 
201584 
 
159 
 
Estimate of Glomerular Filtration Rate (GFR) (Levey, 2012) 
• Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [Levey, 2012]. be 
used by the central laboratory to provide an estimate of GFR, in mL/min per 1.73 m2, as 
follows: 
 
where age (in years) is at time of assessment, κ = 0.7 if female or 0.9 if male, α = -0.329 if 
female and -0.411 if male, min() indicates the minimum of CRT/κ or 1, max() indicates the 
maximum of CRT/κ or 1, and CRTmg/dL is serum creatinine concentration in mg/dL. The serum 
creatinine concentration in mg/dL is obtained from GSK standard units of µmol/L as CRTmg/dL 
=0.0113x CRTµmol/L.  
• The CKD-EPI GFR will also be calculated using Cystatin C, as follows 
 
133 X min(Scys/0.8, 1) -0.499 X max (Scys/0.8, 1)-1.328 X 0.996 Age X[0.932 if female] 
Where Scys is serum cystatin C mg/Liter, min indicates the minimum of Scr/0.8 or 1, and max 
indicates the maximum of Scys/0.8 or 1 
• Lab Toxicities – DAIDS Grading based on Version 2.0, November 2014, as specified in 
the protocol of Appendix 12.2 
• Toxicities will be based on the Division of AIDS (DAIDS) grading system, Version 2.0, 
November 2014, as specified in the protocol of Appendix 12.2. Toxicity grades provided by 
the central laboratory do not distinguish between abnormally high or low criteria, when both 
are relevant for a particular parameter. 
• When summarising toxicity grades for such parameters, they will be categorised as to 
whether they are above or below the midpoint of normal range. 
 
Parameter 
Below Midpoint for 
those ≥Grade 1 
Above Midpoint for 
those ≥Grade 1  
Fasted glucose 
Hypoglycemia 
Hyperglycemia 
Sodium 
Hyponatremia 
Hypernatremia 
Potassium 
Hypokalemia 
Hyperkalemia 
National Cholesterol Education Program (NCEP) Lipid Categories 
• In addition to DAIDS toxicity grades (see protocol), lipid values will be categorized according 
to the 2001 NCEP Adult Lipid Guidelines [Grundy, 2001] 
 
Parameter 
Value Range (mmol/L) 
Value Range (mg/dL) Category 
Triglycerides 
<1.70 
<150 
Normal 
1.70 to <2.26 
150 to <200 
Borderline High 
2.26 to <5.65 
200 to <500 
High 
≥5.65 
≥500 
Very High 
Total Cholesterol 
<5.18 
<200 
Desirable 


 
CONFIDENTIAL 
 
 
201584 
 
160 
 
5.18 to <6.21 
200 to <240 
Borderline High 
≥6.21 
≥240 
High 
HDL Cholesterol 
<1.04 
<40 
Low 
1.04 to <1.56 
40 to <60 
Normal 
≥1.56 
≥60 
High 
LDL Cholesterol 
<2.59 
<100 
Optimal 
2.59 to <3.37 
100 to <130 
Near/Above Optimal 
3.37 to <4.14 
130 to <160 
Borderline High 
4.14 to <4.92 
160 to <190 
High 
≥4.92 
≥190 
Very High 
 Total Cholesterol / HDL Cholesterol Ratio 
• When both total cholesterol and HDL cholesterol results are available from the same date 
for a participant, then the ratio will be calculated by dividing the total cholesterol result by the 
HDL cholesterol result. The ratio can be classified as follows: 
 
Parameter 
Value Range 
Total Cholesterol 
/ HDL Ratio 
< 3.5 
3.5 to < 4.4 
4.4 to < 5 
≥ 5 
 Percentage change for lipids 
The percentage change from Maintenance Baseline (Day 1) is calculated as: 
% Change from Maintenance BL 
= 
 
Value at Week 48/Week 96 – Maintenance BL 
value 
X 100 % 
Maintenance BL value 
The percentage change from Extension Baseline (Week 100) is calculated as: 
% Change from Maintenance BL 
= 
 
Value at Week 104 – Extension BL value 
X 100 % 
Extension BL value 
Other Safety Endpoints 
Columbia Suicide Severity Rating Scale (C-SSRS) (Posner, 2007) 
• Missing data will not have any imputation performed (Nilsson, 2013) 
 
14.6.4. 
Efficacy 
Snapshot 
• The Snapshot algorithm is intended to be primarily a virologic assessment of the endpoint, 
and as such follows a “virology first” hierarchy. ‘HIV-1 RNA <50 c/mL’ or ‘HIV-1 RNA ≥50 
c/mL’ within an analysis window (see Table 17) is determined by the last available HIV-1 
RNA measurement in that window while the participant is On-treatment in the applicable 
phase(s), e.g., Maintenance Phase (as assigned based on Table 30). 


 
CONFIDENTIAL 
 
 
201584 
 
161 
 
Snapshot 
• When no HIV-1 RNA data is available within a window, a participant cannot be assigned to 
the category of ‘HIV-1 RNA < 50 c/mL’.  Depending on the reason for lack of data, the 
participant will be classified as a ‘HIV-1 RNA≥50’ or reported as ‘No Virologic Data at Week 
X’; in the latter case, the algorithm further classifies the nature of the missing data. Typically, 
a participant withdrawn (i) due to AE or, (ii) for another reason yet was suppressed at the 
time, will be counted as ‘No Virologic Data at Week X’.  Should a participant withdraw for 
reasons other than AE and was not suppressed at the time, they will be a ‘HIV-1 RNA≥50 
c/mL’. 
• Full details of the algorithm, including the handling of special cases, are included in Section 
14.11. 
Plasma HIV-1 RNA 
• For summaries and analyses which use HIV-1 RNA level as a continuous measure, the 
logarithm to base 10 of the value will be used. 
• HIV-1 RNA results may be provided as censored values, such as <40 or >9,999,999 c/mL. 
For the purposes of summary statistics, such values will be replaced by the next value 
beyond the limit of detection, e.g., 39 or 10,000,000 c/mL, respectively, for the given 
examples. Data listings will show the censored values as provided. 
Target Detected / Target Non- Detected/Super low viral load testing 
• When a measurement of plasma HIV-1 RNA is below the limit of quantification (i.e., 40 
c/mL) and is qualitatively observable that will be denoted as a “Target Detected” measure, 
while HIV-1 RNA below the limit of quantification that is not qualitatively observable that will 
be denoted as “Target Not Detected”. Any measurements <40 c/mL characterised as 
“Target Not Detected” or “Target Detected” will be captured in the database. 
• Super low viral load will also be tested by BioMNTR lab for Viral loads below the limit of 
quantification (i.e., <2 c/mL) at some visits (e.g., Week 48). 
Treatment (TRDF) and Efficacy Related (ERDF) Discontinuation = Failure 
• The analysis of time to confirmed virologic failure (CVF) or discontinuation due to treatment 
related reasons (i.e., drug-related AE, intolerability of injections, protocol defined safety 
stopping criteria, or lack of efficacy) will censor participants who, at the end of the Week 48 
analysis window per Table 15 (i.e., study day 350), have not met CVF criteria and are 
ongoing in the study, or who have discontinued for reasons other than those related to 
treatment. This will be the Treatment Related Discontinuation = Failure (TRDF) data. 
• Participants who, at the end of the Week 48 analysis window per Table 15 (i.e., study day 
350), have not met CVF criteria and are ongoing in the study, or who have discontinued for 
reasons other than lack of efficacy, will be censored in the analysis of the Efficacy Related 
Discontinuation = Failure (ERDF) data. 
• Proportion of Participants without virologic (ERDF) or tolerability (TRDF) failure will be 
estimated using the Kaplan-Meier nonparametric method based on the time to ERDF or 
TRDF. The estimated proportion at Week 48 (i.e., study day 350) will be presented by 
treatment group, along with estimated difference in proportions between treatment groups 


 
CONFIDENTIAL 
 
 
201584 
 
162 
 
Snapshot 
and its associated two-sided 95% CI. The estimate of the standard error used to derive 
confidence intervals will be based on Greenwood’s formula [Kalbfleisch,1980]. 
• See Appendix 1: Variables Defined for Time to Event Analysis  
Observed Case Viral Load (HIV-1 RNA) Category by Visit Summary Tables  
• For each visit with scheduled viral load collection (per time and events schedule in the 
protocol), the Observed Case proportion is defined using available data, with no imputation 
for missing values.  
• Week 48 and Week 96: 
o Numerator: Number of participants with on-treatment HIV-1 RNA in the respective 
category (e.g., < 50 c/mL) based on the last viral load assessment collected within 
the analysis Snapshot window for Week 48 and Week 96, respectively. (i.e., Week 
48 ±6 weeks and Week 96 ±6 weeks).    
o Denominator: Number of participants with on-treatment HIV-1 within the analysis 
Snapshot window for Week 48 and Week 96, respectively. (i.e., Week 48 ±6 weeks 
and Week 96 ±6 weeks).    
• Other Visits: 
o Numerator: Number of participants with on-treatment HIV-1 RNA in the respective 
category (e.g., < 50 c/mL) based on the last viral load assessment collected within 
the default analysis visit windows for Maintenance phase assessments (Table 15).    
o Denominator: Number of participants with on-treatment HIV-1 RNA collected within 
the default analysis visit windows for Maintenance phase assessments (Table 15).    
• Observed case proportions will be derived for the following HIV-1 RNA categories: RNA 
<40, 40 <= RNA <50, RNA < 40 & Target Detected, RNA <40 & Target Not Detected.  
• For Maintenance Baseline (Day 1), the last viral load collected prior to or equal to the date of 
first Maintenance Phase study treatment dose will be selected for determining the observed 
case proportion at this timepoint. 
Confirmed Virologic Failure (CVF) 
• The definition of CVF is provided in the Protocol, Section 5.4.4 – Definition of Virologic 
Failure 
HIV-1 Disease progression Stage 
• Categories: 
• CDC Stage I at Maintenance Baseline (Day 1) to CDC Stage II; 
• CDC Stage I at Maintenance Baseline (Day 1) to CDC Stage III;  
• CDC Stage II at Maintenance Baseline (Day 1) to CDC Stage III;  
• CDC Stage III at Maintenance Baseline (Day 1) to new CDC Stage III event; 
• CDC Stage I, II, III at Maintenance Baseline (Day 1) to Death.  
 
Please refer to Protocol (Appendix 4: CDC Classification for HIV-1 Infection) for defining Stage. 
• For the purpose of analysis, the CDC at Maintenance Baseline (Day 1) and at post-Day 1 


 
CONFIDENTIAL 
 
 
201584 
 
163 
 
Snapshot 
during Maintenance Phase will be derived as below: 
• At Baseline (Week -20), the ‘Baseline CDC stage’ for each participant was assessed by 
investigator and recorded in the eCRF. However, for the analysis, Maintenance Baseline 
(Day 1) CDC stage will be derived based on Maintenance Baseline (Day 1) CD4+ 
values as well as whether any HIV-associated/AIDS-defining conditions present on the 
start date of maintenance treatment (i.e., started/stopped on Study Day 1 or ongoing 
through Study Day 1) per the Criteria’s thresholds (Appendix 4 in Protocol).  
• To analyse disease progression, the most advanced Maintenance CDC stage will be 
derived based on the occurrences of new AIDs-defining conditions (please refer to 
Appendix 4 in Protocol for the list of AIDs-defining Conditions) as well as the nadir value 
of Maintenance Phase CD4+.  
• For example, If a participant with CDC ‘Stage I’ at Maintenance Baseline (Day 1) had the 
lowest Maintenance Phase CD4+ =120 cell/mm3 without new AIDs-defining conditions, then 
HIV disease progression for this participant would be considered as ‘CDC stage I at 
Maintenance Baseline (Day 1) to CDC stage III’.If a participant with CDC ‘Stage II’ at 
Maintenance Baseline (Day 1) had the lowest Maintenance Phase CD4+ =220 cell/mm3 
AND had at least one new AIDs-defining condition, then HIV disease progression for this 
participant would be considered as ‘CDC stage II at Maintenance Baseline (Day 1) to CDC 
stage III’. 
Delay in IP Injection 
IM dosing is expected to occur every 4 weeks from Week 4b onwards (for the Q4W arm).  The 
Delay in IP injection (days) will be calculated as: 
• Delay in IP injection(days) =   Injection date - date of preceding injection – 28 days  
Delay in IP injection will be grouped into: ≤1, 2-3, 4-7, >7 days.  
The proportion of participants with HIV-1 RNA≥50 c/mL at Week 48 (Snapshot) will be 
summarized by last delay in IP Injection. The last delay in IP injection will be the delay in IP 
injection at Week 48, or the delay in last IP injection prior to Week 48 if a participant does not 
receive Week 48 injection (i.e., missing visit or withdrawal).  
14.6.5. 
Pharmacokinetic 
This document is intended for planning analysis of PK concentration data only. 
Population pharmacokinetics and identification of important determinants of variability 
will be described in a separate document. 
Plasma CAB and RPV concentration-time data 
Plasma samples for determination of CAB and RPV concentration will be collected throughout 
the Maintenance and Extension Phases of the study. Additional samples will be collected for 
storage during the Long-Term Follow-Up Phase.   


 
CONFIDENTIAL 
 
 
201584 
 
164 
 
Plasma CAB and RPV concentration-time data 
PK analysis of the plasma CAB concentration-time data on Day 1 and Week 4b for Japan 
participants will be conducted using non-compartmental methods with WinNonlin (Version 5.2 or 
higher).  Actual sampling and dosing times as recorded in the eCRF will be used for analysis.   
Evaluable concentration 
PK concentration will be summarized in two ways: ‘all data’ without regard to timing relative to 
scheduled time and ‘evaluable data’. 
The ‘evaluable data’ are from the samples that met sample collection window criteria, excluding 
samples affected by dosing errors/oral bridging. Sampling windows are determined relative to 
the previous dose as follows:  
• 1-5 hours for 2-hour post dose samples; 
• ± 3-10 days post last injection for 1-week post injection visits;  
• ±4 day for pre-dose sample.  
• Samples affected by dosing errors (e.g., wrong dose) or oral bridging will also be 
excluded. 
 
Timepoint 
Evaluable window 
For Programming: 
PRE-DOSE: 
WK4b/104b 
only 
20-28 hrs after 
last oral dose 
taken and the last 
3 oral doses 
administered 
properly 
20 hrs ≤ Days Since Last Oral Dose ≤ 28 hrs and the 
last 3 oral doses administered on the three 
consecutive days prior to WK4b/104b. 
2-HR-POST:  
1-5 hrs 
 1 hr ≤ Hours Since Last Injection Dose ≤ 5 hrs 
1-WK-POST:  
 3-10 days post 
last injection 
3 d ≤ Days Since Last Dose ≤ 10 d 
PRE-DOSE:  
±4 days 
24 d ≤ Days Since Last Dose ≤ 32d 
 
Relative Time is calculated relative to the date and time of last previous dose. For example, if 
the time of the last previous dose (e.g., oral lead-in/oral-bridging) is missing, then the relative 
time for pre-dose PK sample will be set to missing and the sample will not be considered 
‘evaluable’.  
If a pre-dose sample is collected on the same day as the first dose of oral bridging, and the time 
of the first dose (not recorded in eCRF) is confirmed to be ‘after’ the collection of pre-dose 
sample (by medical monitor or Data querying), then this PK sample will not be impacted by the 
oral bridging. 
At Week 4b/104b, the evaluable window and relative time for 2-HR-POST will be derived based 
on last injection dose (not the last oral dose). The timing of last oral dose will not affect 
‘evaluable’ status with the exception of the last oral dose taken after the 1st injection, i.e., if a 
participant took the last oral dose after the 1st injection, the 2-HR-POST will not be considered 
‘evaluable’, because of the deviation from the IP administration sequence per protocol. 
The time-deviation (hours) from the targeted timepoint will be calculated for the following 
timepoints: 


 
CONFIDENTIAL 
 
 
201584 
 
165 
 
Plasma CAB and RPV concentration-time data 
Time_deviation (hrs) for ‘1-Week-POST’ =Sample date.time-last previous injection date.time -
7*24 hours 
Time_deviation (hrs) for ‘1-HR-POST’ =Sample date.time-last previous injection date.time -1 
hours 
Time_deviation (hrs) for ‘2-HR-POST’ =Sample date.time-last previous injection date.time -2 
hours 
Time_deviation (hrs) for ‘4-HR-POST’ =Sample date.time-last previous injection date.time -4 
hours 
Time_deviation (hrs) for ‘5-HR-POST’ =Sample date.time-last previous injection date.time -5 
hours Time_deviation (hrs) for ‘8-HR-POST’ =Sample date.time-last previous injection date.time 
-8 hours 
Time_deviation (hrs) for ‘24-HR-POST’ =Sample date.time-last previous injection date.time -24 
hours 
For Long-term Follow-up Phase PK concentrations: 
LTFU RPV concentrations for participants receiving oral RPV during the LTFU phase will be 
excluded from LTFU PK summary tables and mean/median concentration plot but will be 
included in data listings and PK concentration-time profiles plots (with footnotes indicate which 
participants were receiving oral RPV).  Participants receiving inducers during the LTFU phase 
may also be excluded.  
 
The following windows are for defining ‘evaluable’ Long-term Follow-up Phase PK 
concentrations.  
TIMEPOINT 
EVALUABLE WINDOW FOR PROGRAMMING: 
LTFU MONTH 1 
± 4 days 
24d ≤ Days Since Last Injection ≤ 32d 
LTFU MONTH 3 
± 1 Week 
77d ≤ Days Since Last Injection ≤ 91d 
LTFU MONTH 6 
± 2 Week 
154d ≤ Days Since Last Injection ≤ 
182d 
LTFU MONTH 9 
± 2 Week 
238d ≤ Days Since Last Injection ≤ 
266d 
LTFU MONTH 12 
± 2 Week 
322d ≤ Days Since Last Injection ≤ 
350d 
Pharmacokinetic Parameters 
• Population pharmacokinetics and identify important determinants of variability will be 
described in a separate document. 
  


 
C O N FI D E N TI A L  
 
 
2 0 1 5 8 4  
 
1 6 6  
 
1 4. 6. 6.  
H e alt h O ut c o m e  
HI V T S Q s  
Tr e at m e nt S atisf a cti o n Sc or e  
•  T ot al Tr e at me nt S atisfacti on Sc or e is c o m p ut e d wit h ite ms 1 -1 1. It e ms 1 -1 1 ar e su m m e d t o 
pr o d uce a scor e wit h a possi bl e r a n ge of 0 t o 6 6.  
•  It e m 1 2 will n ot b e i ncl ud ed i n T ot al Tr eat m e nt S atisf actio n Scor e. Inst ea d, it will b e tr e at ed as a 
st a n d-alo n e it e m only.  
•  Hi g h er sc or es r epr es ent great er tr eat m e nt s atisfacti o n as c o m p ar e d t o t h e p ast f e w w e eks.  
•  A m axi m u m of 5 it e ms c an b e missi n g, whic h c an be i m p ut e d t o refl ect th e me a n of t he 
c o m pl et ed it e m sc or es. If 6 or m or e it e ms ar e missi n g, th e n t h e tr e at m ent satisf actio n sc ale 
sc or e s h oul d n ot b e co m p ute d an d inst e ad be i m p ute d usi n g L O C F.  
I n di vi d u al It e m Sc or e s 
•  It e ms ar e r at e d as 6 (v ery satisfi e d, c o nve ni ent, flexi bl e, etc.) to 0 (v ery diss atisfi ed, 
i nc o nv eni e nt, i nfl exibl e, etc.).  
•  Hi g h er sc or es r epr es ent great er s atisfacti on wit h e ac h as p ect of tr eat m e nt  
•  F or i n divi d u al ite m sc or es out p uts, missi n g sc ores will not be c o m put ed ( acc or di ng to P ag e 7 of 
t h e [HI V T S Q  Us er G ui d eli nes , 20 1 6]) a nd i nste a d b e i m p ut e d usi ng L O C F. 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


 
C O N FI D E N TI A L  
 
 
2 0 1 5 8 4  
 
1 6 7  
 
HI V T S Q c  
Tr e at m e nt S atisf a cti o n Sc or e ( c h a n g e)  
•  T ot al Tr e at me nt S atisfacti on Sc or e is c o m p ut e d wit h ite ms 1 -1 1. It e ms 1 -1 1 ar e su m m e d t o 
pr o d uce a scor e wit h a possi bl e r a n ge of -3 3 t o 3 3 
•  It e m 1 2 will b e c o m put ed as a n i ndivi d u al ite m o nly. 
•  T h e hi gh er th e scor e, th e gr e at er th e i m pr ove m e nt i n s atisf acti o n with tr eat m e nt; t he l o w er t h e 
sc or e, t he gr eat er t h e d et eri or ati o n  in s atisfacti o n wit h tre at m e nt.  A sc or e of 0 r e pr es e nts n o 
c h a ng e.  
•  A m axi m u m of 5 it e ms c an b e missi n g, t h e missi n g sc or es will b e i m p ut ed wit h t h e m e a n of t he 
c o m pl et ed it e m sc or es. If 6 or m or e it e ms ar e missi n g, th e n t h e ov er all tr eat m ent s atisf acti o n 
sc al e sc or e sh oul d not be co m p ut ed an d will r e m ai n missi n g. 
I n di vi d u al Tre at m e nt C h a n g e It e m Sc or e s 
•  It e ms ar e r at e d as +3 (‘ m uc h m or e s atisfi e d’, ‘ m uc h m or e c o nv eni e nt’, ‘ m uc h m or e fl exi bl e’, 
etc.) t o -3 (‘ m uc h l ess satisfie d’, ‘ m uc h less c o nve ni ent’, ‘ m uc h l ess fl exi ble’, etc.).  
•  T h e hi gh er th e scor e, th e gr e at er th e i m pr ove m e nt i n s atisf acti o n with eac h as p ect of tr e at m e nt 
a n d t h e l o w er t he sc or e, t he gr e ater t he det eri or ati on i n s atisf acti on wit h e ac h as pect of 
tr e at m e nt. 
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


 
C O N FI D E N TI A L  
 
 
2 0 1 5 8 4  
 
1 6 8  
 
PI N  
Di m e n si o n Sc or e (C hev at , 2 0 08) 
•  D o m ai ns a nd Cl usters  
o  B ot her fr o m i nj ecti on sit e r eacti o ns:  it e ms 3, 4, 5, 6, 7, 8  
o  L e g m ove m e nt: it e ms 11, 12, 15, 16  
o  Sl e e p: it e ms 9, 1 0, 13, 14  
o  Acc e pta bility: it e ms 1 7, 1 8  
•  5 it e ms not i ncl ud e d i n any of t hes e d o m ai ns a nd m ai ntai n e d as i ndivi d u al ite ms (it e ms 1, 2, 19, 
2 0, 2 1) ( a nxi ety bef or e, pai n, s atisf actio n, a nxi ety aft er, willi n g n ess) 
•  N o ov er all sc or e is c alc ul at ed p er th e g ui da nce  
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


 
C O N FI D E N TI A L  
 
 
2 0 1 5 8 4  
 
1 6 9  
 
•  T h e sc or e of a do m ai n is c alc ul at e d as th e m ea n of all ite ms wit h t he do m ai n. Hi gh er sc or es 
r e pr es e nt w ors e p erc e pti o n of i nj ecti on. 
•  A m axi m u m of <5 0 % ite ms c a n be missi n g wit hi n a d o m ai n, w hic h ca n b e i m p ut e d t o r efl ect t he 
m e a n of t he c o m plet ed it e m sc or es wit hi n t h e d o m ain. Th us, if t h e n u m ber of missi ng it e ms is 
≥3 ( B oth er fr o m i nj ecti o n site r e acti ons), ≥2 ( L e g m ov e m e nt/ Sl ee p), ≥1 ( Acc ept ability), t h e n t he 
t ot al scor e f or th e d o m ai n sh o ul d n ot b e c o m put ed a nd i nst e ad be i m p ute d usi n g L O C F 
(S ecti o n 1 4.7. 2.2 ) 
•  L O C F will n ot be use d f or t he S C s ub -st u dy 
I n di vi d u al It e m Sc or e s 
•  It e ms ar e r at e d o n a 5-p oi nt sc al e, r an gi ng fr o m 1( v ery s atisfi e d, n ot at all, etc.) t o 5 (v ery 
diss atisfi e d, extr e m ely, etc. ).  
•  Hi g h er  sc or es r epr es ent w ors e p erc epti o n of i njecti o n 
•  F or i n divi d u al ite m sc or es out p uts, missi n g sc ores will not be c o m put ed an d i nste ad b e i m p ut e d 
usi n g L O C F  ( S ecti on 14. 7. 2. 2 ). O bserv e d val u es will be us e d i n th e S C S u b -stu dy.  
S F -1 2  
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


 
C O N FI D E N TI A L  
 
 
2 0 1 5 8 4  
 
1 7 0  
 
Di m e n si o n Sc or e  
•  C h a n ges fr o m Bas eli ne at  W e ek 4 8 i n he alt h -r el at e d qu ality of lif e ( usi ng S F -1 2) for t h e physic al 
c o m p o ne nt su m m ary ( P C S) a n d t he m e ntal c o m po n ent s u m m ary ( M C S) w er e ass ess e d for t h e 
t w o tr e at me nt gr o ups. Scor es ar e cr eat ed accor di n g t o t h e m an u al [S F -1 2 (v2)  H e alt h S urv ey 
1 9 94, 20 02 M e dic al Outc o m es Tr ust a nd Qu ality M etric I nc or por at ed ] an d t h e c o mp o ne nt scor es 
w er e c alc ul ate d usi n g c o m put er s oft w ar e p urc h ase d fr o m 
Q u ality M etric.( http:// w w w. qu ality m etric.c o m/)  
•  Missi n g c o m p o ne nt sc or es will b e i m p ut ed usi ng L O C F  ( S ecti o n 1 4. 7. 2. 2 ). 
I n di vi d u al It e m Sc or e s 
•  It e ms ar e r at e d as 5 exc ept f or Q u esti o n 2. Qu esti on 2a a n d 2 b ar e r at e d as 3 
•  I n divi d ual it e m missi n g sc ores will b e i m p ute d usi n g L O C F ( S ecti o n  1 4.7. 2.2 ). 
H A T Q o L ( H ol m e s , 1 99 9) 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


 
C O N FI D E N TI A L  
 
 
2 0 1 5 8 4  
 
1 7 1  
 
I n di vi d u al It e m Sc or e s 
•  F or i n divi d u al ite m sc or es out p uts, missi n g sc ores will not be c o m put ed an d i nste ad b e i m p ut e d 
usi n g L O C F ( S ecti on  14. 7. 2. 2 ). 
A C C E P T ( A c c e pt a n ce/ G e n er al Di me n si o n) ( Gilet , 20 1 4) 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


 
C O N FI D E N TI A L  
 
 
2 0 1 5 8 4  
 
1 7 2  
 
T ol er a bilit y of I nj ecti o n ( N R S)  
Q u e sti o n n aire wit h o n e si n gl e q u e sti o n f or Q4 W I M ar m o nl y  
•  M axi m u m l ev el of pai n ex p eri e nc e d wit h t he m ost r ece nt i nj ecti o ns. R a nkin g fr o m no p ain ( 0) t o 
extr e m e pai n ( 10).  
•  Missi n g sc or es will  b e i m p ute d usin g L O C F ( S ecti on 14.7. 2.2). O bserv e d val u es will b e us e d i n 
t h e S C S ub-st u dy 
Pr ef er e nc e q u esti o n  
Q u esti on n air e wit h on e si ngl e dic h ot o m o us pr efer e nc e q u estio n at W e ek 4 8 ( Q4 W I M ar m)  
•  Ass ess t he tr eat m e nt pr efer e nc e: M o nths i nj ecti on vs daily or al c urr e nt A R T at W eek 4 8 f or 
‘ Q 4 W I M’ ar m 
•  A ny missi n g v alu es will r e m ai n missi n g ( i. e., n o i m p ut ati o n)  
•  A pr efer e nc e q uesti on n air e will als o b e ad mi nist er ed t o s u b -st u dy p artici pa nts. It asks 
p artici p a nts t o st ate t heir pref er e nce bet w ee n I M a n d S C i nj ecti o ns a n d t o ch eck off p ote ntial 
r e as o ns why.  
R e a s o n s f or S wit c h  Q ue sti o n n air e  
R e as o n f or S witch q uesti onn air e is c oll ecte d f or s ub-st udy p artici pa nts a nd asks th e r e as o ns t hey 
a gr e ed t o s witc h to S C i nj ecti o ns . 
A ny missi n g v alu es will r e m ai n missi n g ( i. e., n o i m p ut ati o n).  
I nt er e st Q u esti o n n aire  
T h e I nt er est  q uesti o nn air e is c oll ect e d f or su b-st udy partici p a nts an d asks ho w i nt er est e d th ey 
w o ul d be to s witc h to S C i njecti o ns at ho m e o n a 5 p oi nt sc al e r an gi ng fr o m ‘ N ot at all i nt er este d’ to 
‘ Extr e m ely i nt er este d.’. 
A ny missi n g v alu es will r e m ai n missi n g ( i. e., n o i m p ut ati o n).  
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


 
CONFIDENTIAL 
 
 
201584 
 
173 
 
14.6.7. 
Viral Genotype and Phenotype 
Genotype  
Amino Acid Changes 
• A mutation is considered present whenever the encoded amino acid residue differs from the 
amino acid that would have been encoded by the wild-type (e.g., HXB2, NL43) comparator 
gene; e.g., Q148K.  
• If the encoded amino acid is seen as a mixture of wild-type and mutant amino acid, e.g., 
Q148Q/K, the mutated amino acid is considered present at the codon of interest.  
• If the encoded amino acid is seen as a mixture of two or more amino acids, which may or may 
not include wild type, e.g., Q184K/H or Q184K/H/Q, etc., for the purposes of calculating the 
number of mutated amino acids, only one mutation is considered to be present at the codon of 
interest. 
Representation of Amino Acid Changes 
 
 
Mutations 
Amino acid change 
T69S 
Single mutation from amino acid 'T' (vendor reference) to 'S' (sample) at codon '69'  
Q148H/K/R Mixture of amino acid mutations ‘H’, ‘K’ and ‘R’ (sample) from amino acid ‘Q’ 
(vendor reference) at codon ‘148’ 
_69_1T 
First insertion of amino acid 'T' (sample) at codon '69' 
_69_2S 
Second insertion of amino acid 'S' (sample) at codon '69' 
_69_3S/A 
Third insertion of a mixture of amino acids 'S' and 'A' (sample) at codon '69' 
L74L/- 
Mixture of amino acid 'L' (sample) and a deletion at codon '74' 
V75- 
Single deletion of amino acid (sample) at codon '75' 
Resistance Associated Mutations 
• Known INI mutations associated with the development of resistance to Integrase Strand 
Transfer Inhibitors: 
 
Amino Acids in 
HIV Integrase for 
Analysis 
H51Y, T66A/I/K, L68V/I, L74I/M, E92Q/V/G, Q95K, T97A, G118R, F121Y/C, 
E138A/D/K/T, G140A/C/R/S, Y143C/H/R/K/S/G/A, P145S, Q146P, S147G, 
Q148H/K/R/N, V151/IL/A, S153F/Y, N155H/S/T, E157Q, G163R/K, G193E, 
S230R, R263K 
NOTES: 
o 
Draft listing; may be modified in case of additional substantive data availability. 
o 
Based on the IAS-USA list of mutations associated with resistance to Bictegravir, Cabotegravir, 
Dolutegravir, Elvitegravir, or Raltegravir (IAS-USA 2019 resistance mutations update volume 27 issue 3, 
2019): T66A/I/K, L74M, E92Q/G, T97A, G118R, F121Y, E138A/K/T, G140A/C/R/S, Y143C/H/R, S147G, 
Q148H/K/R, S153F/Y, N155H, R263K) and observed mutations during in vitro passage of DTG or seen in a 
previous DTG study in INI-experienced subjects (study ING112574): H51Y, L74I, L68V/I, E92V, Q95K, 
E138D, Y143K/S/G/A, P145S, Q146P, V151I/L/A, N155S/T, E157Q, G163R/K, G193E, S230R.  
o 
Major USA-IAS mutations associated with resistance to INSTI are bolded. 
 
• Major resistance mutations to other classes (i.e., NRTI, NNRTI, PI) as defined by the 
International Antiviral Society-USA (IAS-USA). The most up to date IAS-USA guidelines 
available at the time of DBF will be used in the analysis [Wensing, 2019]. 
 


 
CONFIDENTIAL 
 
 
201584 
 
174 
 
Genotype  
Class 
Mutations 
NRTIs 
M41L, A62V, K65R/E/N, D67N, 69 insert, K70E/R, L74V, V75I, F77L, Y115F, F116Y, 
Q151M, M184V/I, L210W, T215Y/F, K219Q/E 
NNRTIs 
L100I, K101E/P, K103N/S, V106A/M, V108I, E138/A/G/K/Q/R, V179L, 
Y181C/I/V, Y188C/L/H, G190S/A, H221Y, P225H, F227C, M230I/L 
PIs 
D30N, V32I, M46I/L, I47A/V, G48V, I50V/L, I54V/M/L, Q58E, T74P, L76V, 
V82A/T/F/L/S, N83D, I84V, N88S, L90M 
Note: List generated from IAS_USA Guideline, [Wensing, 2019] 
 
Treatment-Emergent Mutations Relative to Induction Baseline (Week -20) 
• Treatment-emergent genotypic mutations are defined as mutations that appear between 
Induction Baseline (Week -20), i.e., prior to the start of Induction Phase study drug (inclusive), 
and an on-treatment assessment (e.g., at time of confirmed virologic failure).  Note: If 
Monogram is not able to produce genotype at Week -20, then treatment-emergent will be 
determined relative to the screening genotype provided by the central laboratory. 
Phenotypic Susceptibility  
• Phenotypic susceptibility to all licensed antiretroviral drugs and CAB will be determined using 
PhenoSense HIV assays from Monogram Inc. and will be reported as fold change (FC) in IC50 
relative to wild-type control virus NL4-3, i.e., FC of sample virus = IC50 of sample virus/IC50 of 
control virus.   
• Since the maximum assay limit for FC for each ART varies from assay to assay, FC values that 
are greater than the maximum assay limit (e.g., ‘>100’) will be interpreted as having a value 
equal to the smallest maximum assay limit for that ART in the study population for data 
analysis. Censored values will be presented ‘as is’ in the listings.  Phenotypic susceptibilities 
will be categorized according to FC as shown below (based on Monogram PhenoSense assay).  
Clinical cutoffs (where available) or biological cutoffs by PhenoSense will be used to define the 
phenotypic susceptibility of ART therapy by Monogram.  
• Replication capacity is generated as part of standard phenotypic assays 
PhenoSense Algorithm 
Drug 
Abbreviation 
Class 
PhenoSense cutoff 
Abacavir 
ABC 
NRTI 
(4.5 – 6.5)a 
Lamivudine 
3TC 
NRTI 
3.5 a 
Didanosine 
ddI 
NRTI 
(1.3 – 2.2) a 
Stavudine 
d4T 
NRTI 
1.7 a 
Zidovudine 
AZT (ZDV) 
NRTI 
1.9 
Emtricitabine 
FTC 
NRTI 
3.5 
Tenofovir 
TDF (TAF) 
NRTI 
(1.4 – 4) a 
Delavirdine 
DLV 
NNRTI 
6.2 
Efavirenz 
EFV 
NNRTI 
3 
Nevirapine 
NVP 
NNRTI 
4.5 


 
CONFIDENTIAL 
 
 
201584 
 
175 
 
Genotype  
Etravirine 
ETR 
NNRTI 
(2.9-10) a 
Rilpivirine 
RPV 
NNRTI 
2.0 
Fosamprenavir/r 
FPV/r 
PI 
(4-11) a 
Atazanavir/r 
ATV/r 
PI 
5.2 a 
Indinavir/r 
IDV/r 
PI 
10 a 
Lopinavir/r 
LPV/r 
PI 
(9 – 55) a 
Nelfinavir 
NFV 
PI 
3.6 
Saquinavir/r 
SQV/r 
PI 
(2.3 – 12) a 
Tipranavir/r 
TPV/r 
PI 
(2 – 8) a 
Darunavir/r 
DRV/r 
PI 
(10 – 90) a 
Ritonavir 
RTV 
PI 
2.5 
Enfuvirtide 
T20 
FI 
6.48 
Cabotegravir 
CAB 
INI 
2.5 
Raltegravir 
RAL 
INI 
1.5 
Elvitegravir 
EVG 
INI 
2.5  
Dolutegravir 
DTG 
INI 
(4-13) a 
a. 
clinical cutoff (lower cutoff – higher cutoff).  
 
Phenotypic susceptibility to each drug in a participant’s background regimen is determined by 
applying drug-associated cutoffs as defined by the PhenoSense algorithm to the phenotypic fold 
resistance as below:  
 
Full Sensitivity  
Fold Change 
Interpretation 
> clinical lower cutoff or biologic cutoff 
resistance 
≤ clinical lower cutoff or biologic cutoff 
sensitive 
 
Partial Sensitivity  
Fold Change 
Interpretation 
> clinical higher cutoff 
resistance 
≤ clinical higher cutoff and > clinical lower cutoff partially sensitive 
≤ clinical lower cutoff 
sensitive 
 
PHENOTYP dataset from Monogram contains the phenotypic susceptibility for each drug derived 
from the cutoff listed above. Thus, phenotypic susceptibility (i.e., full sensitivity and partial 
sensitivity) will not be re-derived for our analysis. 
Genotypic and Net Assessment Susceptibility 
• Genotypic and Net assessment susceptibility to all licensed antiretroviral drugs and CAB will be 
determined from Monogram Inc. and will be reported with the categories of ‘resistance’, 
‘partially sensitive’, and ‘sensitive’ as what will be performed for phenotypic susceptibility.  
Genotypic and Net assessment susceptibility will be assessed at time of CVF using plasma 
sample, Genotypic susceptibility may be assessed at baseline using PBMC. 
Induction Baseline (Week -20) HIV-1 Subtype 
• For participants without confirmed virologic failure: Screening visit subtype from Q SQUARED, 
unless a subtype from MONOGRAM is available on the same date. 


 
CONFIDENTIAL 
 
 
201584 
 
176 
 
Genotype  
• For participants with confirmed virologic failure:  Select last pre-treatment subtype (expected to 
be the Week -20 result from MONOGRAM). 


 
CONFIDENTIAL 
 
 
201584 
 
177 
 
14.7. 
Appendix 7: Reporting Standards for Missing Data 
14.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• Subject study completion (i.e., as specified in the protocol) was defined as: 
o Randomly assigned to either treatment group, completed the 
randomized Maintenance Phase including the Nominal Week 100 
visit, and did not enter the Extension Phase; 
o Randomly assigned to either treatment group, completed the 
randomized Maintenance Phase including the Nominal Week 100 
visit, and entered and completed the Extension Phase (defined as 
remaining on study until commercial supplies of CAB LA + RPV LA 
become locally available, or development of CAB LA + RPV LA is 
terminated). 
Participants who withdraw from CAB LA + RPV LA and go into the Long-Term 
Follow Up Phase will be considered to have prematurely withdrawn from the 
study, even if they complete the 52-week follow-up Phase. In addition to the 52-
week Long-Term Follow-Up Phase required for participants randomized to CAB 
LA + RPV LA, an in-clinic Follow-Up visit will be conducted approximately 4 weeks 
after the last dose of study medication for participants randomized to the 
ABC/DTG/3TC arm with ongoing AEs, SAEs, and also any laboratory 
abnormalities that are considered to be AEs or potentially harmful to the 
participant, at the last on-study visit. Assessments at the Follow-up visit should 
reflect any ongoing complaints (e.g., blood draws to follow a laboratory 
abnormality). Follow-Up visits are not required for successful completion of the 
study. 
• Withdrawn participants were not replaced in the study. 
• All available data from participants who were withdrawn from the study will be 
listed and all available planned data will be included in summary tables and 
figures, unless otherwise specified.  
• Withdrawal visits will be slotted as per Appendix 3: Assessment Windows or 
will be summarised as withdrawal visits. 
 
14.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• Missing data occurs when any requested data is not provided, leading to 
blank fields on the collection instrument: 
o These data will be indicated by the use of a “blank” in subject listing 
displays. Unless all data for a specific visit are missing in which case the 
data is excluded from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered 
to be missing data and should be displayed as such. 


 
CONFIDENTIAL 
 
 
201584 
 
178 
 
Element 
Reporting Detail 
Outliers 
• Any participants excluded from the summaries and/or statistical analyses will 
be documented along with the reason for exclusion in the clinical study report. 
 
14.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• Partial dates will be displayed as captured in subject listing displays. 
Adverse Events 
• The eCRF allows for the possibility of partial dates (i.e., only month and 
year) to be recorded for AE start and end dates; that is, the day of the 
month may be missing. In such a case, the following conventions will be 
applied for calculating the time to onset and the duration of the event: 
o Missing Start Day: First of the month will be used unless this is 
before the start date of study treatment; in this case the study 
treatment start date will be used and hence the event is considered 
On-treatment as per Appendix 4: Study Phases and Treatment 
State. 
o Missing Stop Day: Last day of the month will be used unless this is 
after the last contact date; in this case the last contact date will be 
used. 
o Completely missing start or end dates will remain missing, with no 
imputation applied. Consequently, time to onset and duration of 
such events will be missing. 
Concomitant 
Medications/ 
Medical History 
• Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 
'Jan' will be used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the 
day (dependent on the month and year) and 'Dec' will be used for 
the month. 
o For medications recorded in the eCRF as prior ART, the earlier of 
this imputed date or the day before Screening date will be used. 
• The recorded partial date will be displayed in listings. 
Health 
outcomes  
• For the health outcomes questionnaire data, please refer to Section 14.6.6. 
• For the summary of individual item scores outputs, missing scores will not 
be computed. 
• For the SC Sub-study going forward, missing data for all HO assessments 
will not be imputed using the LOCF technique. Observed values will be used 
unless otherwise specified. 


 
CONFIDENTIAL 
 
 
201584 
 
179 
 
14.7.2.2. 
Handling of Missing data for Statistical Analysis 
Element 
Reporting Detail 
Snapshot 
• In the Snapshot dataset, participants without HIV-1 RNA data in the assessment 
window for the visit of interest (due to missing data or discontinuation of IP prior 
to the visit window) do not belong to ‘HIV-1 RNA < 50 c/mL (or <200 c/mL)’.  
The nature of this missing data will be further classified in Snapshot summaries 
as either ‘HIV-1 RNA≥50’ or ‘No Virologic Data at Week X’; Appendix 11: 
Snapshot Algorithm Details for full details. 
LOCF 
• In the LOCF dataset, missing values will be carried forward from the previous, 
non-missing on-treatment assessment. 
Lipid LOCF 
1. Maintenance (both arms) and Maintenance + Extension Phase 
(randomized Q4W arm only): 
Maintenance Baseline (Day 1) for Lipids LOCF Analyses: 
• Last evaluable lipids assessment up to and including the start of 
Maintenance Phase IP, where ‘evaluable’ is defined as: Lipid modifying 
agents not taken within 12 weeks of the date of assessment and Lipids are 
collected in a fasting state.  Participants with unevaluable Maintenance 
Baseline (Day 1) for Lipids (as defined above) will be excluded from the 
analysis of Maintenance phase values and Maintenance + Extension phase 
values (Randomized Q4W arm). 
During Maintenance + Extension phases 
• If participants initiate serum lipid-lowering agents during the Maintenance + 
Extension Phase, then the last available fasted On-treatment lipid values 
prior to the initiation will be used in place of future, observed On-treatment 
values.  
• Imputation at visits with observed on-treatment values will continue even if 
the participant discontinues the lipid-lowering agent.  Missing assessments 
will not be imputed. 
Analyses Evaluated with Lipid LOCF dataset: 
• This dataset will be used to summarize fasting lipids parameters in the 
following displays:  
o Summary of Chemistry Values by visit  
o Summary of Chemistry Change from Maintenance Baseline (Day 1) by 
visit 
o Summary of Fasting TC/HDL Ratio Change from Maintenance Baseline 
(Day 1) 
All other displays of lipids (i.e., toxicity tables and NCEP tables) will use 
observed fasting data, without LOCF imputation. 
2. Extension Phase (Q4W Switch IM group): 
Extension Baseline (Week 100) for Lipids LOCF Analyses: 
• 
Last evaluable lipids assessment up to and including the first dose of 
Extension phase CAB and/or RPV, where ‘evaluable’ is defined as: Lipid 
modifying agents not taken within 12 weeks of the date of assessment and 


CONFIDENTIAL 
201584 
180 
Element 
Reporting Detail 
Lipids are collected in a fasting state.  Participants with unevaluable 
Extension Baseline (Week 100) for Lipids (as defined above) will be 
excluded from the analysis of Extension phase values (Extension Switch 
population). 
During Extension phase 
•
If participants initiate serum lipid-lowering agents during the Extension
Phase, then the last available fasted On-treatment lipid values prior to the
initiation will be used in place of future, observed On-treatment values.
•
Imputation at visits with observed on-treatment values will continue even if
the participant discontinues the lipid-lowering agent.  Missing assessments
will not be imputed.
Baseline for Lipids LOCF Analyses in sub-study: 
•
Last evaluable lipids assessment up to and including the start of SC injection,
where ‘evaluable’ is defined as: Lipid-modifying agents not taken within 12
weeks of the date of assessment and Lipids are collected in a fasting state.
During the SC Injection or Return to Gluteal Injection Phase: 
•
If participants initiate serum lipid-modifying agents during the SC injection or
Return to Gluteal Injection Phase, then the last available fasted on-treatment
lipid values prior to the initiation will be used in place of future, observed on-
treatment values in sub-study.
•
Imputation at planned visits will continue even if the participant discontinues the
lipid-modifying agent.  Missing assessments will not be imputed if there is no
last available fasting on-treatment lipid value prior to the initiation of serum lipid-
modifying agent.
•
If participants take lipid modifying agents within 12 weeks prior to the start of the
SC injection, all the post-baseline values in sub-study will be missing.
Analyses Evaluated with Lipid LOCF dataset:
•
This dataset will be used to summarize fasting lipids parameters in the
following displays:
o
Summary of Chemistry Values by Visit (Extension Switch population)
o
Summary of Chemistry Change from Extension Baseline (Week 100) by
Visit
o
Summary of Fasting TC/HDL Ratio Change from Extension Baseline
(Week 100)
o
Summary of Chemistry Changes from Sub-study Baseline by Visit (SC
Injection + Return to Gluteal Injection Phase)
o
Summary of Chemistry Values by Visit (SC Injection + Return to Gluteal
Injection Phase)
All other displays of lipids (i.e., toxicity tables and NCEP tables) will use 
observed fasting data, without LOCF imputation. 


 
CONFIDENTIAL 
 
 
201584 
 
181 
 
14.8. 
Appendix 8: Values of Potential Clinical Importance 
Element 
Reporting Detail 
Laboratory 
Values and 
Adverse 
Events 
• The central laboratory will flag lab parameter toxicities directly in the 
provided datasets based on Division of AIDS Table for Grading the 
Severity of Adult and Pediatric Adverse Events Version 2.0, November 
2014. 


 
CONFIDENTIAL 
 
 
201584 
 
182 
 
14.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses 
PopPK will be described in a separate document. 


 
CONFIDENTIAL 
 
 
201584 
 
183 
 
14.10. 
Appendix 10: Pharmacokinetic / Pharmacodynamic 
Analyses 
PK/PD dataset specification and methodology will be described in a separate document. 


 
CONFIDENTIAL 
 
 
201584 
 
184 
 
14.11. 
Appendix 11: Snapshot Algorithm Details 
Detailed Algorithm Steps 
• 
Consider an analysis visit window for Week X (e.g., Week4, …Week 24, Week 48 et al). The 
Window for Week 24/48 visit is defined in Table 17 (e.g., window for Week 48 is ± 6 Week: 
295 ≤ Study Day ≤ 378) and in Table 15 for other visits through to Nominal Week 52 at 
Maintenance Phase. The Snapshot Analysis at post Maintenance Phase will not be 
appropriate because a large portion of responders will be switched to other studies and not 
all participants would have the chance to reach same timepoint.  
• 
The HIV1-RNA threshold of 50, 200 copies/mL will be analysed, respectively, in this study  
• 
The analysis window ‘Week 48’ and HIV1-RNA threshold of ’50 copies/mL’ are used for the 
purpose of illustration. A participant’s Snapshot response and reason at Week 48 are 
categorized as below. 
o HIV1-RNA < 50 copies/mL  
o HIV1-RNA ≥ 50 copies/mL  
Data in window not below 50 
Discontinued for lack of efficacy 
Discontinued for other reason while not below 50 
Change in background therapy* 
o No Virologic Data at Week 48 Window 
Discontinued study due to AE or death 
Discontinued study for other reasons 
On study but missing data in window 
 
* Note: since changes in ART are not permitted in this protocol, all such participants who change 
ART during the Maintenance Phase will be considered ‘HIV1-RNA ≥ 50 copies/mL’. if the change 
in ART is made prior to an analysis timepoint.  Participants with protocol permitted oral bridging 
treatment will not be considered ‘HIV1-RNA ≥ 50 copies/mL’ due to ‘change in ART’. 
• 
The steps in determining response and reasons are indicated in Table below, in the order 
stated. 
 
Detailed steps 
Please note that the following scenarios will NOT be penalized Per Snapshot algorithm (i.e., 
please excluding these scenarios from Condition 1-4). 
Dose reduction, dropping a component, or change in formulation (e.g. ‘Tivicay + Kivexa’ to 
‘Triumeq’ with the identical ingredients)  
Condition (‘Week 48’ indicates Week 48 window) 
Response  
Reasons 
1. If non-permitted change in background therapy prior to 
Week 48  
HIV1-RNA ≥ 
50  
Change in 
background 
therapy 


 
CONFIDENTIAL 
 
 
201584 
 
185 
 
2.  If permitted change[a] in background therapy prior to 
Week 48 AND the latest on-treatment VL prior to/on the 
date of change is ≥ 50 c/m (NA to this study) 
HIV1-RNA ≥ 
50  
Change in 
background 
therapy 
3:  If non-permitted change in background therapy during 
Week 48    
 
 
• Last on-treatment VL during Week 48 prior to/on 
the date of change ≥ 50 c/mL 
HIV1-RNA ≥ 
50  
Data in window 
not below 50 
• Last on-treatment VL during Week 48 prior to/on 
the date of change <50   c/mL 
HIV1-RNA < 
50  
 
• No VL during Week 48 prior to/on the date of 
change     
HIV1-RNA ≥ 
50  
Change in 
background 
therapy 
4: If permitted change[a] in background therapy during 
Week 48 AND the last on-treatment VL prior to/on the 
date of change is ≥ 50 c/mL (NA to this study) 
 
 
4.1    this last on-treatment VL occurs prior to Week 48  HIV1-RNA ≥ 
50  
Change in 
background 
therapy  
4. 2   this last on-treatment VL occurs during Week 48 
but prior to/on the date of change 
HIV1-RNA ≥ 
50  
Data in window 
not below 50 
5: If none of the above conditions met 
 
 
5.1 VL available during Week 48  
 
 
• Last on-treatment VL during Week 48 ≥ 50 
c/mL 
HIV1-RNA ≥ 
50  
Data in window 
not below 50 
• Last on-treatment VL during Week 48 <50 
c/mL 
HIV1-RNA < 
50  
 
5.2 No VL during Week 48    
 
 
5.2.1 if participants still on study i.e. the upper bound 
of analysis snapshot window is prior to the following 
date:   
 
For ABC/DTG/3TC arm: 
Min (ABC/DTG/3TC Stop Date + 1, withdrawal date) 
No virologic 
data at Week 
48 Window  
On study but 
missing data in 
window 


 
CONFIDENTIAL 
 
 
201584 
 
186 
 
For Q4W arm:  
Min[max(Date of last Q4W IM Dose + 35, Date of last oral 
dose+1), withdrawal date] 
 
5.2.2 If participants withdraw before/during Week 48 
due to 
 
 
5.2.2.1 Safety reasons (e.g. AE/death, liver 
chemistry stopping criteria, renal toxicity 
withdrawal criteria, QTc withdrawal criteria et al, 
as recorded in eCRF Conclusion form) 
No virologic 
data at Week 
48 Window 
Disc due to 
AE/death 
5.2.2.2  Non-safety related reasons (e.g. Lack of 
efficacy, protocol deviation, withdrew consent, 
loss to follow-up, study closed/terminated, 
investigator discretion et al, as recorded in 
eCRF Conclusion Form) 
 
 
• Last on-treatment VL <50 c/mL OR no on-
treatment VL available during study   
No virologic 
Data at Week 
48 Window 
Disc for other 
reasons 
• Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to Lack of efficacy 
HIV1-RNA ≥ 
50  
Disc. for lack of 
efficacy 
• Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to all other non-safety related 
reasons 
HIV1-RNA ≥ 
50  
Dis. for other 
reason while not 
below 50 
a: Excluding permitted change in background therapy where change or decision to change is 
made prior to/on the first on-treatment viral result  
Examples from FDA guidance 
1. Data in Window 
Virologic outcome should be determined by the last available measurement while the patient is on 
treatment and continued on trial within the time window: 
• HIV-RNA = 580 copies/mL at Day 336, HIV-RNA below 50 copies/mL on Day 350. This 
should be categorized as HIV-RNA below 50 copies/mL. 
2.No Data in Window 
Discontinued study due to Adverse Event or Death: 
• Any patient who discontinues because of an AE or death before the window should be 
classified as Discontinued due to AE or Death (as appropriate), regardless of the HIV-
RNA result, even if the HIV-RNA is below 50 copies/mL at the time of discontinuation.  
• However, if a patient has an HIV-RNA value in the time window and also discontinues in 
the time window, the viral load data should be used to classify the patient’s response. 
This is the Virology First hierarchy: 


 
CONFIDENTIAL 
 
 
201584 
 
187 
 
a. HIV-RNA below 50 copies/mL at Day 336 and discontinues because of AE or 
even dies on Day 360 — this person is categorized as having HIV-RNA below 
50 copies/mL.  
b. HIV-RNA is 552 copies/mL on Day 336 and the patient discontinues on Day 
360, the patient is categorized as having HIV-RNA greater than or equal to 50 
copies/mL. 
Discontinued for Other Reasons: 
• Only patients who have achieved virologic suppression can be counted as Discontinued 
for Other Reasons. 
• If a patient discontinues the study before the time window because of lack of efficacy, 
then the patient should be included in the HIV-RNA greater than or equal to 50 row and 
not in the Discontinued for Other Reasons row. 
• If a patient discontinues because of participant withdrew consent and his or her HIV-1 
RNA result at the time of discontinuation was equal to or above 50 copies/mL, then he or 
she should be categorized as HIV-RNA greater than or equal to 50 and NOT as 
Discontinued for Other Reasons.  
• If a patient discontinued because of Lost to Follow-Up and the last HIV-RNA result was 
49 copies/mL, then the patient can be categorized as Discontinued for Other Reasons. 
• If patients changed background treatment — not permitted by protocol— they should be 
captured in the HIV-RNA greater than or equal to 50 copies/mL row. 
3.On study but missing data in window: 
• If there are no data during Days 294 to 377, but there is an HIV-RNA below 50 
copies/mL on Day 380, this patient should be considered On Study but Missing Data in 
Window. 
• If there are no data during Days 294 to 377, but there is an HIV-RNA equal to or above 
50 copies/mL on Day 280, this patient also should be classified as On Study but Missing 
Data in Window. 
 


 
CONFIDENTIAL 
 
 
201584 
 
188 
 
14.12. 
Appendix 12: AESI identification 
SMQ and PT codes based on MedDRA dictionary version 22.0 for Week 96 CSR. 
14.12.1. 
Hepatic Safety Profile 
Medical concept of hepatic failure and hepatitis. Sub- SMQs (1) 'Hepatic failure, fibrosis 
and cirrhosis and other liver damage-related conditions' and (2) 'Hepatitis, non-
infectious', both of parent SMQ 'Hepatic Disorders'; only narrow terms selected from 
sub-SMQs. Some preferred terms e.g. PT 'hepatitis fulminant' are duplicated. 
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005 
Sub-SMQ: 'Hepatic failure, fibrosis and cirrhosis and other liver damage-related 
conditions' 
Category: A 
Scope: Narrow 
Preferred Term 
PT Code 
Acquired hepatocerebral degeneration 
10080860 
Acute hepatic failure 
10000804 
Acute on chronic liver failure 
10077305 
Acute yellow liver atrophy 
10070815 
Ascites 
10003445 
Asterixis 
10003547 
Bacterascites 
10068547 
Biliary cirrhosis 
10004659 
Biliary fibrosis 
10004664 
Cardiohepatic syndrome 
10082480 
Cholestatic liver injury 
10067969 
Chronic hepatic failure 
10057573 
Coma hepatic 
10010075 
Cryptogenic cirrhosis 
10063075 
Diabetic hepatopathy 
10071265 
Drug-induced liver injury 
10072268 
Duodenal varices 
10051010 
Gallbladder varices 
10072319 
Gastric variceal injection 
10076237 


 
CONFIDENTIAL 
 
 
201584 
 
189 
 
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005 
Sub-SMQ: 'Hepatic failure, fibrosis and cirrhosis and other liver damage-related 
conditions' 
Category: A 
Scope: Narrow 
Preferred Term 
PT Code 
Gastric variceal ligation 
10076238 
Gastric varices 
10051012 
Gastric varices haemorrhage 
10057572 
Hepatectomy 
10061997 
Hepatic atrophy 
10019637 
Hepatic calcification 
10065274 
Hepatic cirrhosis 
10019641 
Hepatic encephalopathy 
10019660 
Hepatic encephalopathy prophylaxis 
10066599 
Hepatic failure 
10019663 
Hepatic fibrosis 
10019668 
Hepatic hydrothorax 
10067365 
Hepatic infiltration eosinophilic 
10064668 
Hepatic lesion 
10061998 
Hepatic necrosis 
10019692 
Hepatic steato-fibrosis 
10077215 
Hepatic steatosis 
10019708 
Hepatitis fulminant 
10019772 
Hepatobiliary disease 
10062000 
Hepatocellular foamy cell syndrome 
10053244 
Hepatocellular injury 
10019837 
Hepatopulmonary syndrome 
10052274 
Hepatorenal failure 
10019845 
Hepatorenal syndrome 
10019846 
Hepatotoxicity 
10019851 


 
CONFIDENTIAL 
 
 
201584 
 
190 
 
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005 
Sub-SMQ: 'Hepatic failure, fibrosis and cirrhosis and other liver damage-related 
conditions' 
Category: A 
Scope: Narrow 
Preferred Term 
PT Code 
Intestinal varices 
10071502 
Intestinal varices haemorrhage 
10078058 
Liver dialysis 
10076640 
Liver disorder 
10024670 
Liver injury 
10067125 
Liver operation 
10062040 
Liver transplant 
10024714 
Lupoid hepatic cirrhosis 
10025129 
Minimal hepatic encephalopathy 
10076204 
Mixed liver injury 
10066758 
Nodular regenerative hyperplasia 
10051081 
Nonalcoholic fatty liver disease 
10082249 
Non-alcoholic steatohepatitis 
10053219 
Non-cirrhotic portal hypertension 
10077259 
Oedema due to hepatic disease 
10049631 
Oesophageal varices haemorrhage 
10030210 
Peripancreatic varices 
10073215 
Portal fibrosis 
10074726 
Portal hypertension 
10036200 
Portal hypertensive colopathy 
10079446 
Portal hypertensive enteropathy 
10068923 
Portal hypertensive gastropathy 
10050897 
Portal vein cavernous transformation 
10073979 
Portal vein dilatation 
10073209 
Portopulmonary hypertension 
10067281 


 
CONFIDENTIAL 
 
 
201584 
 
191 
 
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005 
Sub-SMQ: 'Hepatic failure, fibrosis and cirrhosis and other liver damage-related 
conditions' 
Category: A 
Scope: Narrow 
Preferred Term 
PT Code 
Primary biliary cholangitis 
10080429 
Regenerative siderotic hepatic nodule 
10080679 
Renal and liver transplant 
10052279 
Retrograde portal vein flow 
10067338 
Reye’s syndrome 
10039012 
Reynold’s syndrome 
10070953 
Splenic varices 
10067823 
Splenic varices haemorrhage 
10068662 
Steatohepatitis 
10076331 
Subacute hepatic failure 
10056956 
Varices oesophageal 
10056091 
Varicose veins of abdominal wall 
10072284 
White nipple sign 
10078438 
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005 
Sub-SMQ: 'Hepatitis, non-infectious’ 
Category: A 
Scope: Narrow 
Preferred Term 
PT Code 
Acute graft versus host disease in liver 
10066263 
Allergic hepatitis 
10071198 
Alloimmune hepatitis 
10080576 
Autoimmune hepatitis 
10003827 
Chronic graft versus host disease in liver 
10072160 
Chronic hepatitis 
10008909 
Graft versus host disease in liver 
10064676 
Hepatitis 
10019717 


 
CONFIDENTIAL 
 
 
201584 
 
192 
 
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005 
Sub-SMQ: 'Hepatic failure, fibrosis and cirrhosis and other liver damage-related 
conditions' 
Category: A 
Scope: Narrow 
Preferred Term 
PT Code 
Hepatitis acute 
10019727 
Hepatitis cholestatic 
10019754 
Hepatitis chronic active 
10019755 
Hepatitis chronic persistent 
10019759 
Hepatitis fulminant 
10019772 
Hepatitis toxic 
10019795 
Immune-mediated hepatitis 
10078962 
Ischaemic hepatitis 
10023025 
Lupus hepatitis 
10067737 
Non-alcoholic steatohepatitis 
10053219 
Radiation hepatitis 
10051015 
Steatohepatitis 
10076331 
14.12.2. 
Hypersensitivity Reactions  
Medical concept of hypersensitivity reactions/DRESS. Only narrow terms selected from 
Category A of SMQ 'Drug reaction with eosinophilia and systemic symptoms syndrome'. 
Algorithmic approach for this SMQ not used due to complexity in applying and poor 
specificity of remaining categories. Category A selected as PTs because more specific for 
concept (only narrow terms) and a pre-requisite for any combination in algorithmic 
search. Overlap of some preferred terms with SMQ 'Severe Cutaneous Adverse 
Reactions'. Plus, additional preferred terms selected from HGLT 'Allergic conditions' 
under SOC 'Immune system disorders. 
SMQ: Drug reaction with eosinophilia and systemic symptoms syndrome 
SMQ Code: 20000225 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Drug reaction with eosinophilia and systemic symptoms 
10073508 
Pseudolymphoma 
10037127 


 
CONFIDENTIAL 
 
 
201584 
 
193 
 
SMQ: Drug reaction with eosinophilia and systemic symptoms syndrome 
SMQ Code: 20000225 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Additional preferred terms selected from HLGT 'Allergic conditions' 
under SOC 'Immune system disorders' 
Preferred Term 
PT Code 
Drug hypersensitivity 
10013700 
Hypersensitivity 
10020751 
Type IV Hypersensitivity reaction 
10053613 
Eosinophillia 
10014950 
Eye swelling 
10015967 
Eyelid oedema 
10015993 
Lip swelling 
10024570 
Angioedema 
10002424 
Circumoral oedema 
10052250 
Face oedema 
10016029 
Idiopathic angioedema 
10073257 
Lip oedema 
10024558 
Mouth swelling 
10075203 
Oedema mouth 
10030110 
Periorbital oedema 
10034545 
Swelling face 
10042682 
Periorbital swelling 
10056647 
Swelling of eyelid 
10042690 
14.12.3. 
Rash including severe cutaneous adverse reactions 
Medical concept of rash including severe cutaneous adverse reactions. Only narrow terms 
from SMQ 'Severe cutaneous adverse reactions' selected. Plus several additional 
preferred terms selected from HLTs 'Rashes, eruptions and exanthems NEC', 'Pruritus 


 
CONFIDENTIAL 
 
 
201584 
 
194 
 
NEC', 'Pustular conditions', 'Dermatitis ascribed to specific agent' all under SOC 'Skin 
and subcutaneous tissue disorders'. 
SMQ: Severe Cutaneous Adverse Reactions 
SMQ Code: 20000020 
Category: A 
Scope: Narrow 
 
SMQ 
PT Code 
Acute generalised exanthematous pustulosis 
10048799 
Cutaneous vasculitis 
10011686 
Dermatitis bullous 
10012441 
Dermatitis exfoliative 
10012455 
Dermatitis exfoliative generalised 
10012456 
Drug reaction with eosinophilia and systemic symptoms 
10073508 
Epidermal necrosis 
10059284 
Erythema multiforme 
10015218 
Exfoliative rash 
10064579 
Oculomucocutaneous syndrome 
10030081 
Skin necrosis 
10040893 
Stevens-Johnson syndrome 
10042033 
Target skin lesion 
10081998 
Toxic epidermal necrolysis 
10044223 
Toxic skin eruption 
10057970 
Additional preferred terms selected from HLTs 'Rashes, eruptions and 
exanthems NEC', 'Pruritus NEC', 'Pustular conditions', 'Dermatitis 
ascribed to specific agent' all under SOC 'Skin and subcutaneous tissue 
disorders'. 
 
Preferred Term 
PT Code 
Eyelid rash 
10074620 
Genital rash 
10018175 
Mucocutaneous rash 
10056671 
Nodular rash 
10075807 


 
CONFIDENTIAL 
 
 
201584 
 
195 
 
SMQ: Severe Cutaneous Adverse Reactions 
SMQ Code: 20000020 
Category: A 
Scope: Narrow 
 
SMQ 
PT Code 
Perineal rash 
10075364 
Rash 
10037844 
Rash erythematous 
10037855 
Rash generalised 
10037858 
Rash macular 
10037867 
Rash maculo-papular 
10037868 
Rash maculovesicular 
10050004 
Rash morbilliform 
10037870 
Rash papular 
10037876 
Rash rubelliform 
10057984 
Rash scarlatiniform 
10037890 
Rash vesicular 
10037898 
Rash pruritic 
10037884 
Rash follicular 
10037857 
Rash pustular 
10037888 
Drug eruption 
10013687 
14.12.4. 
Prolongation of the Corrected QT Interval of the ECG in Supra 
Therapeutic Doses 
Notes: Medical concept of QT prolongation and complications. Only narrow terms from 
SMQ 'Torsade de pointes/QT prolongation' selected plus one additional PT under HLT 
‘ECG investigations'. 
SMQ: Torsade de pointes/QT prolongation 
SMQ Code: 20000001 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 


 
CONFIDENTIAL 
 
 
201584 
 
196 
 
Electrocardiogram QT interval abnormal 
10063748 
Electrocardiogram QT prolonged 
10014387 
Long QT syndrome 
10024803 
Long QT syndrome congenital 
10057926 
Torsade de pointes 
10044066 
Ventricular tachycardia 
10047302 
Additional preferred terms selected from HGLT ' ECG investigations' 
under SOC ‘Investigations’. 
Preferred Term 
PT Code 
Electrocardiogram repolarisation abnormality 
10052464 
14.12.5. 
Suicidal Ideation/Behaviour  
Medical concept of suicidal ideation and behaviour. Sub-SMQ 'Suicide/self-injury' 
(SMQ) from parent SMQ of 'Depression and Suicide/Self Injury'. Only narrow terms 
from the sub-SMQ selected. 
 
SMQ: 'Depression and Suicide/Self Injury' 
SMQ Code: 20000035 
Sub-SMQ: 'Suicide/self-injury' 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Assisted suicide 
10079105 
Columbia suicide severity rating scale abnormal 
10075616 
Completed suicide 
10010144 
Depression suicidal 
10012397 
Intentional overdose 
10022523 
Intentional self-injury 
10022524 
Poisoning deliberate 
10036000 
Self-injurious ideation 
10051154 
Suicidal behaviour 
10065604 


 
CONFIDENTIAL 
 
 
201584 
 
197 
 
Suicidal ideation 
10042458 
Suicide attempt 
10042464 
Suicide threat 
10077417 
Suspected suicide 
10082458 
Suspected suicide attempt 
10081704 
14.12.6. 
Depression  
Medical concept of Depression. Sub-SMQ 'Depression (excl suicide and self injury)' 
(SMQ) from parent SMQ of 'Depression and Suicide/Self Injury'. Only narrow terms 
from the sub-SMQ selected. 
SMQ: ‘'Depression and Suicide/Self Injury' 
SMQ Code: 20000035 
Sub-SMQ: 'Depression (excl suicide and self injury)'  
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Activation syndrome 
10066817 
Adjustment disorder with depressed mood 
10001297 
Adjustment disorder with mixed anxiety and depressed mood 
10001299 
Agitated depression 
10001496 
Anhedonia 
10002511 
Antidepressant therapy 
10054976 
Childhood depression 
10068631 
Decreased interest 
10011971 
Depressed mood 
10012374 
Depression 
10012378 
Depression postoperative 
10012390 
Depressive symptom 
10054089 
Dysphoria 
10013954 
Electroconvulsive therapy 
10014404 
Feeling guilty 
10049708 


 
CONFIDENTIAL 
 
 
201584 
 
198 
 
SMQ: ‘'Depression and Suicide/Self Injury' 
SMQ Code: 20000035 
Sub-SMQ: 'Depression (excl suicide and self injury)'  
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Feeling of despair 
10016344 
Feelings of worthlessness 
10016374 
Helplessness 
10077169 
Major depression 
10057840 
Menopausal depression 
10067371 
Mixed anxiety and depressive disorder 
10080836 
Perinatal depression 
10078366 
Persistent depressive disorder 
10077804 
Post stroke depression 
10070606 
Postictal depression 
10071324 
14.12.7. 
Bipolar Disorder 
Medical concept of bipolar disorder. All preferred terms from HLGT ‘Manic and Bipolar 
mood disorders and disturbances’ under SOC ‘Psychiatric disorders’. 
Preferred Term 
PT Code 
Bipolar I disorder 
10004939 
Bipolar II disorder 
10004940 
Bipolar disorder 
10057667 
Cyclothymic disorder 
10011724 
Hypomania 
10021030 
Mania 
10026749 


 
CONFIDENTIAL 
 
 
201584 
 
199 
 
14.12.8. 
Psychosis 
Medical concept of psychosis. Only narrow terms from SMQ 'Psychosis and psychotic 
disorders' selected. 
SMQ: 'Psychosis and psychotic disorders' 
SMQ Code: 20000117 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Acute psychosis 
10001022 
Alcoholic psychosis 
10001632 
Alice in wonderland syndrome 
10001666 
Brief psychotic disorder with marked stressors 
10048549 
Brief psychotic disorder without marked stressors 
10056395 
Brief psychotic disorder, with postpartum onset 
10006362 
Charles Bonnet syndrome 
10063354 
Childhood psychosis 
10061040 
Clang associations 
10009232 
Cotard’s syndrome 
10059591 
Delusion 
10012239 
Delusion of grandeur 
10012241 
Delusion of reference 
10012244 
Delusion of replacement 
10012245 
Delusional disorder, erotomanic type 
10012249 
Delusional disorder, grandiose type 
10012250 
Delusional disorder, jealous type 
10012251 
Delusional disorder, mixed type 
10012252 
Delusional disorder, persecutory type 
10053195 
Delusional disorder, somatic type 
10012254 
Delusional disorder, unspecified type 
10012255 
Delusional perception 
10012258 


 
CONFIDENTIAL 
 
 
201584 
 
200 
 
SMQ: 'Psychosis and psychotic disorders' 
SMQ Code: 20000117 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Dementia of the Alzheimer’s type, with delusions 
10012295 
Depressive delusion 
10063033 
Derailment 
10012411 
Epileptic psychosis 
10059232 
Erotomanic delusion 
10015134 
Flight of ideas 
10016777 
Hallucination 
10019063 
Hallucination, auditory 
10019070 
Hallucination, gustatory 
10019071 
Hallucination, olfactory 
10019072 
Hallucination, synaesthetic 
10062824 
Hallucination, tactile 
10019074 
Hallucination, visual 
10019075 
Hallucinations, mixed 
10019079 
Hypnagogic hallucination 
10020927 
Hypnopompic hallucination 
10020928 
Hysterical psychosis 
10062645 
Ideas of reference 
10021212 
Illusion 
10021403 
Jealous delusion 
10023164 
Loose associations 
10024825 
Mixed delusion 
10076429 
Neologism 
10028916 
Neuroleptic-induced deficit syndrome 
10075295 
Paranoia 
10033864 


 
CONFIDENTIAL 
 
 
201584 
 
201 
 
SMQ: 'Psychosis and psychotic disorders' 
SMQ Code: 20000117 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Paranoid personality disorder 
10033869 
Parkinson’s disease psychosis 
10074835 
Paroxysmal perceptual alteration 
10063117 
Persecutory delusion 
10034702 
Postictal psychosis 
10070669 
Post-injection delirium sedation syndrome 
10072851 
Posturing 
10036437 
Psychosis postoperative 
10065617 
Psychotic behaviour 
10037249 
Psychotic disorder 
10061920 
Psychotic disorder due to a general medical condition 
10061921 
Reactive psychosis 
10053632 
Rebound psychosis 
10074833 
Schizoaffective disorder 
10039621 
Schizoaffective disorder bipolar type 
10068889 
Schizoaffective disorder depressive type 
10068890 
Schizophrenia 
10039626 
Schizophreniform disorder 
10039647 
Schizotypal personality disorder 
10039651 
Senile psychosis 
10039987 
Shared psychotic disorder 
10040535 
Somatic delusion 
10041317 
Somatic hallucination 
10062684 
Substance-induced psychotic disorder 
10072388 
Tangentiality 
10043114 


 
CONFIDENTIAL 
 
 
201584 
 
202 
 
SMQ: 'Psychosis and psychotic disorders' 
SMQ Code: 20000117 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Thought blocking 
10043495 
Thought broadcasting 
10052214 
Thought insertion 
10043496 
Thought withdrawal 
10043497 
Transient psychosis 
10056326 
Waxy flexibility 
10047853 
14.12.9. 
Mood Disorders 
Medical concept of mood disorders. All preferred terms from HLGT 'Mood disorders and 
disturbances NEC', under SOC 'Psychiatric disorders'. 
Preferred Term 
PT Code 
Affect lability 
10054196 
Affective ambivalence 
10077173 
Affective disorder 
10001443 
Alexithymia 
10077719 
Anger 
10002368 
Apathy 
10002942 
Blunted affect 
10005885 
Boredom 
10048909 
Constricted affect 
10010778 
Crying 
10011469 
Diencephalic syndrome of infancy 
10012774 
Dysphoria 
10013954 
Emotional disorder 
10014551 
Emotional distress 
10049119 


 
CONFIDENTIAL 
 
 
201584 
 
203 
 
Preferred Term 
PT Code 
Emotional poverty 
10014557 
Euphoric mood 
10015535 
Flat affect 
10016759 
Frustration tolerance decreased 
10077753 
Inappropriate affect 
10021588 
Irritability 
10022998 
Laziness 
10051602 
Lethargy 
10024264 
Listless 
10024642 
Moaning 
10027783 
Mood altered 
10027940 
Mood disorder due to a general medical condition 
10027944 
Mood swings 
10027951 
Morose 
10027977 
Neuroleptic-induced deficit syndrome 
10075295 
Premenstrual dysphoric disorder 
10051537 
Premenstrual syndrome 
10036618 
Screaming 
10039740 
Seasonal affective disorder 
10039775 
Steroid withdrawal syndrome 
10042028 
Substance-induced mood disorder 
10072387 
14.12.10. Anxiety 
Notes: Medical concept of anxiety disorders. All preferred terms from HLGT “Anxiety 
disorders and symptoms”, under SOC “Psychiatric disorders”. 
Preferred Terms 
PT Code 
Acrophobia 
10000605 
Activation syndrome 
10066817 
Acute stress disorder 
10001084 


 
CONFIDENTIAL 
 
 
201584 
 
204 
 
Preferred Terms 
PT Code 
Aerophobia 
10080300 
Agitation 
10001497 
Agitation postoperative 
10049989 
Agoraphobia 
10001502 
Akathisia 
10001540 
Algophobia 
10078056 
Animal phobia 
10002518 
Anniversary reaction 
10074066 
Anticipatory anxiety 
10002758 
Anxiety 
10002855 
Anxiety disorder 
10057666 
Anxiety disorder due to a general medical condition 
10002859 
Arachnophobia 
10051408 
Astraphobia 
10078372 
Autophobia 
10071070 
Body dysmorphic disorder 
10052793 
Burnout syndrome 
10065369 
Catastrophic reaction 
10082329 
Cibophobia 
10082413 
Claustrophobia 
10009244 
Compulsions 
10010219 
Compulsive cheek biting 
10076510 
Compulsive handwashing 
10071263 
Compulsive hoarding 
10068007 
Compulsive lip biting 
10066241 
Compulsive shopping 
10067948 
Dermatillomania 
10065701 
Dysmorphophobia 
10049096 


 
CONFIDENTIAL 
 
 
201584 
 
205 
 
Preferred Terms 
PT Code 
Emetophobia 
10070637 
Fear 
10016275 
Fear of animals 
10016276 
Fear of closed spaces 
10016277 
Fear of crowded places 
10050365 
Fear of death 
10066392 
Fear of disease 
10016278 
Fear of eating 
10050366 
Fear of falling 
10048744 
Fear of injection 
10073753 
Fear of open spaces 
10016279 
Fear of pregnancy 
10067035 
Fear of weight gain 
10016280 
Fear-related avoidance of activities 
10080136 
Generalised anxiety disorder 
10018075 
Glossophobia 
10080077 
Haemophobia 
10073458 
Haphephobia 
10067580 
Herpetophobia 
10081809 
Hydrophobia 
10053317 
Hyperarousal 
10080831 
Immunisation anxiety related reaction 
10075205 
Kinesiophobia 
10078430 
Limited symptom panic attack 
10024511 
Mysophobia 
10078769 
Nail picking 
10066779 
Nervousness 
10029216 
Neurosis 
10029333 


 
CONFIDENTIAL 
 
 
201584 
 
206 
 
Preferred Terms 
PT Code 
Noctiphobia 
10057946 
Nocturnal fear 
10057948 
Nosophobia 
10063546 
Obsessive need for symmetry 
10077179 
Obsessive rumination 
10056264 
Obsessive thoughts 
10029897 
Obsessive-compulsive disorder 
10029898 
Obsessive-compulsive symptom 
10077894 
Ochlophobia 
10050095 
Osmophobia 
10060765 
Paediatric autoimmune neuropsychiatric disorders associated with 
streptococcal infection 
10072147 
Panic attack 
10033664 
Panic disorder 
10033666 
Panic reaction 
10033670 
Paruresis 
10069024 
Performance fear 
10034432 
Phagophobia 
10050096 
Pharmacophobia 
10069423 
Phobia 
10034912 
Phobia of driving 
10056676 
Phobia of exams 
10034913 
Phobic avoidance 
10034918 
Phonophobia 
10054956 
Photaugiaphobia 
10064420 
Postpartum anxiety 
10082233 
Postpartum neurosis 
10036419 
Postpartum stress disorder 
10056394 


 
CONFIDENTIAL 
 
 
201584 
 
207 
 
Preferred Terms 
PT Code 
Post-traumatic stress disorder 
10036316 
Procedural anxiety 
10075204 
Pseudoangina 
10056610 
Selective mutism 
10039917 
Separation anxiety disorder 
10040045 
Sitophobia 
10080170 
Social anxiety disorder 
10041242 
Social fear 
10041247 
Stress 
10042209 
Tension 
10043268 
Terminal agitation 
10077416 
Thanatophobia 
10064723 
Thermophobia 
10075147 
Trichotemnomania 
10072752 
Trichotillomania 
10044629 
14.12.11. Sleep Disorders 
Medical concept of sleep disorders. All preferred terms from (1) HLGT 'Sleep Disorders 
and Disturbances', 'Psychiatric disorders' SOC plus (2) HLGT 'Sleep disturbances 
(including subtypes)', 'Nervous system' SOC. Numerous duplicated preferred terms e.g. 
middle insomnia. 
HLGT Sleep Disorders and Disturbances, HLGT Code 10040991 
 
Preferred Term 
PT Code 
Abnormal dreams 
10000125 
Abnormal sleep-related event 
10061613 
Advanced sleep phase 
10001423 
Behavioural induced insufficient sleep syndrome 
10081938 
Behavioural insomnia of childhood 
10072072 
Breathing-related sleep disorder 
10006344 


 
CONFIDENTIAL 
 
 
201584 
 
208 
 
HLGT Sleep Disorders and Disturbances, HLGT Code 10040991 
 
Preferred Term 
PT Code 
Cataplexy 
10007737 
Circadian rhythm sleep disorder 
10009191 
Confusional arousal 
10067494 
Delayed sleep phase 
10012209 
Dyssomnia 
10061827 
Exploding head syndrome 
10080684 
Hypersomnia 
10020765 
Hypersomnia related to another mental condition 
10020767 
Hypersomnia-bulimia syndrome 
10053712 
Hypnagogic hallucination 
10020927 
Hypnopompic hallucination 
10020928 
Hyposomnia 
10067530 
Initial insomnia 
10022035 
Insomnia 
10022437 
Insomnia related to another mental condition 
10022443 
Irregular sleep phase 
10022995 
Irregular sleep wake rhythm disorder 
10080301 
Loss of dreaming 
10065085 
Middle insomnia 
10027590 
Narcolepsy 
10028713 
Nightmare 
10029412 
Non-24-hour sleep-wake disorder 
10078086 
Parasomnia 
10061910 
Periodic limb movement disorder 
10064600 
Pickwickian syndrome 
10035004 
Poor quality sleep 
10062519 
Rapid eye movement sleep behaviour disorder 
10077299 


 
CONFIDENTIAL 
 
 
201584 
 
209 
 
HLGT Sleep Disorders and Disturbances, HLGT Code 10040991 
 
Preferred Term 
PT Code 
Rapid eye movements sleep abnormal 
10037841 
Shift work disorder 
10078088 
Sleep apnoea syndrome 
10040979 
Sleep attacks 
10040981 
Sleep disorder 
10040984 
Sleep disorder due to a general medical condition 
10063910 
Sleep disorder due to general medical condition, hypersomnia type 
10040985 
Sleep disorder due to general medical condition, insomnia type 
10040986 
Sleep disorder due to general medical condition, mixed type 
10040987 
Sleep disorder due to general medical condition, parasomnia type 
10040988 
Sleep inertia 
10067493 
Sleep paralysis 
10041002 
Sleep sex 
10067492 
Sleep talking 
10041009 
Sleep terror 
10041010 
Sleep-related eating disorder 
10067315 
Somnambulism 
10041347 
Somnolence 
10041349 
Somnolence neonatal 
10041350 
Sopor 
10058709 
Stupor 
10042264 
Terminal insomnia 
10068932 
Upper airway resistance syndrome 
10063968 
HLGT Sleep disturbances (incl subtypes), HLGT code 10040998 
 
Abnormal dreams 
10000125 
Abnormal sleep-related event 
10061613 
Advanced sleep phase 
10001423 


 
CONFIDENTIAL 
 
 
201584 
 
210 
 
HLGT Sleep Disorders and Disturbances, HLGT Code 10040991 
 
Preferred Term 
PT Code 
Behavioural induced insufficient sleep syndrome 
10081938 
Behavioural insomnia of childhood 
10072072 
Breathing-related sleep disorder 
10006344 
Cataplexy 
10007737 
Central-alveolar hypoventilation 
10007982 
Circadian rhythm sleep disorder 
10009191 
Confusional arousal 
10067494 
Delayed sleep phase 
10012209 
Dyssomnia 
10061827 
Fatal familial insomnia 
10072077 
Hypersomnia 
10020765 
Hyposomnia 
10067530 
Initial insomnia 
10022035 
Insomnia 
10022437 
Irregular sleep phase 
10022995 
Irregular sleep wake rhythm disorder 
10080301 
Loss of dreaming 
10065085 
Microsleep 
10076954 
Middle insomnia 
10027590 
Narcolepsy 
10028713 
Non-24-hour sleep-wake disorder 
10078086 
Periodic limb movement disorder 
10064600 
Pickwickian syndrome 
10035004 
Poor quality sleep 
10062519 
Rapid eye movement sleep behaviour disorder 
10077299 
Rapid eye movements sleep abnormal 
10037841 
Shift work disorder 
10078088 


 
CONFIDENTIAL 
 
 
201584 
 
211 
 
HLGT Sleep Disorders and Disturbances, HLGT Code 10040991 
 
Preferred Term 
PT Code 
Sleep apnoea syndrome 
10040979 
Sleep deficit 
10080881 
Sleep inertia 
10067493 
Sleep paralysis 
10041002 
Sleep sex 
10067492 
Sleep talking 
10041009 
Sleep terror 
10041010 
Sleep-related eating disorder 
10067315 
Somnambulism 
10041347 
Sudden onset of sleep 
10050014 
Terminal insomnia 
10068932 
Upper airway resistance syndrome 
10063968 
14.12.12. Injection site Reactions 
Use eCRF terms for ISR. 


 
CONFIDENTIAL 
 
 
201584 
 
212 
 
14.12.13. Seizures  
Medical concept of seizures. Only narrow terms from SMQ 'Convulsions' selected plus 
selected PTs of possible seizure events from HLT 'Disturbances in consciousness NEC' 
under SOC 'Nervous systems disorders' and HLT 'Confusion and disorientation' under 
SOC 'Psychiatric disorders'. 
SMQ: ‘Convulsions’  
SMQ Code: 20000079 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
1p36 deletion syndrome 
10082398 
2-Hydroxyglutaric aciduria 
10078971 
Acquired epileptic aphasia 
10052075 
Acute encephalitis with refractory, repetitive partial seizures 
10076948 
Alcoholic seizure 
10056347 
Aspartate-glutamate-transporter deficiency 
10079140 
Atonic seizures 
10003628 
Atypical benign partial epilepsy 
10056699 
Automatism epileptic 
10003831 
Autonomic seizure 
10049612 
Baltic myoclonic epilepsy 
10054895 
Benign familial neonatal convulsions 
10067866 
Benign rolandic epilepsy 
10070530 
Biotinidase deficiency 
10071434 
Change in seizure presentation 
10075606 
Clonic convulsion 
10053398 
Convulsion in childhood 
10052391 
Convulsions local 
10010920 
Convulsive threshold lowered 
10010927 
CSWS syndrome 
10078827 
Deja vu 
10012177 


 
CONFIDENTIAL 
 
 
201584 
 
213 
 
SMQ: ‘Convulsions’  
SMQ Code: 20000079 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Double cortex syndrome 
10073490 
Dreamy state 
10013634 
Drug withdrawal convulsions 
10013752 
Early infantile epileptic encephalopathy with burst-suppression 
10071545 
Eclampsia 
10014129 
Epilepsy 
10015037 
Epilepsy surgery 
10079824 
Epilepsy with myoclonic-atonic seizures 
10081179 
Epileptic aura 
10015049 
Epileptic psychosis 
10059232 
Febrile convulsion 
10016284 
Febrile infection-related epilepsy syndrome 
10079438 
Focal dyscognitive seizures 
10079424 
Frontal lobe epilepsy 
10049424 
Generalised non-convulsive epilepsy 
10018090 
Generalised tonic-clonic seizure 
10018100 
Glucose transporter type 1 deficiency syndrome 
10078727 
Grey matter heterotopia 
10082084 
Hemimegalencephaly 
10078100 
Hyperglycaemic seizure 
10071394 
Hypocalcaemic seizure 
10072456 
Hypoglycaemic seizure 
10048803 
Hyponatraemic seizure 
10073183 
Idiopathic generalised epilepsy 
10071081 
Infantile spasms 
10021750 


 
CONFIDENTIAL 
 
 
201584 
 
214 
 
SMQ: ‘Convulsions’  
SMQ Code: 20000079 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Juvenile myoclonic epilepsy 
10071082 
Lafora’s myoclonic epilepsy 
10054030 
Lennox-Gastaut syndrome 
10048816 
Migraine-triggered seizure 
10076676 
Molybdenum cofactor deficiency 
10069687 
Multiple subpial transection 
10079825 
Myoclonic epilepsy 
10054859 
Myoclonic epilepsy and ragged-red fibres 
10069825 
Neonatal epileptic seizure  
10082068 
Neonatal seizure 
10082067 
Partial seizures 
10061334 
Partial seizures with secondary generalisation 
10056209 
Petit mal epilepsy 
10034759 
Polymicrogyria 
10073489 
Post stroke epilepsy 
10076982 
Post stroke seizure 
10076981 
Postictal headache 
10052470 
Postictal paralysis 
10052469 
Postictal psychosis 
10070669 
Postictal state 
10048727 
Post-traumatic epilepsy 
10036312 
Schizencephaly 
10073487 
Seizure 
10039906 
Seizure anoxic 
10039907 
Seizure cluster 
10071350 


 
CONFIDENTIAL 
 
 
201584 
 
215 
 
SMQ: ‘Convulsions’  
SMQ Code: 20000079 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Seizure like phenomena 
10071048 
Severe myoclonic epilepsy of infancy 
10073677 
Simple partial seizures 
10040703 
Status epilepticus 
10041962 
Sudden unexplained death in epilepsy 
10063894 
Temporal lobe epilepsy 
10043209 
Tonic clonic movements 
10051171 
Tonic convulsion 
10043994 
Tonic posturing 
10075125 
Topectomy 
10073488 
Transient epileptic amnesia 
10081728 
Tuberous sclerosis complex 
10080584 
Uncinate fits 
10045476 
Additional selected preferred terms from HLT 'Disturbances in 
consciousness NEC' under SOC 'Nervous systems disorders' and HLT 
'Confusion and disorientation' under SOC 'Psychiatric disorders'. 
Preferred Term 
PT Code 
Confusional state 
10010305 
Loss of consciousness 
10024855 
Syncope 
10042772 
Sopor 
10058709 
Stupor 
10042264 
Altered state of consciousness 
10001854 
Depressed level of consciousness 
10012373 
Consciousness fluctuating 
10050093 


 
CONFIDENTIAL 
 
 
201584 
 
216 
 
14.12.14. Weight Gain 
Medical concept of weight gain. Selected PTs from HLT 'General nutritional disorders 
NEC', under SOC 'Metabolism and nutrition disorders', and HLT 'Physical examination 
procedures and organ system status', under SOC 'Investigations' and HLT 'General signs 
and symptoms NEC', under SOC 'General disorders and administration site conditions'. 
Preferred Term 
PT Code 
Abdominal fat apron 
10077983 
Overweight 
10033307 
Abnormal weight gain 
10000188 
Central obesity 
10065941 
Obesity 
10029883 
Weight abnormal 
10056814 
Weight increased 
10047899 
Waist circumference increased 
10064863 
Body mass index abnormal 
10074506 
Body mass index increased 
10005897 
Fat tissue increased 
10016251 
14.12.15. Rhabdomyolysis 
Medical concept of rhabdomyolysis. Only narrow terms only for SMQ 
'Rhabdomyolysis/myopathy' plus 2 additional preferred terms selected from HGLT 
'muscle disorders' under SOC 'Musculoskeletal and connective tissue disorders' 
SMQ: 'Rhabdomyolysis/myopathy' 
SMQ Code: 20000002 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Muscle necrosis 
10028320 
Myoglobin blood increased 
10028625 
Myoglobin blood present 
10059888 
Myoglobin urine present 
10028631 
Myoglobinaemia 
10058735 


 
CONFIDENTIAL 
 
 
201584 
 
217 
 
SMQ: 'Rhabdomyolysis/myopathy' 
SMQ Code: 20000002 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Myoglobinuria 
10028629 
Myopathy 
10028641 
Myopathy toxic 
10028648 
Necrotising myositis 
10074769 
Rhabdomyolysis 
10039020 
Thyrotoxic myopathy 
10081524 
Additional selected preferred terms from HLGT 'muscle disorders' under 
SOC 'Musculoskeletal and connective tissue disorders' 
Preferred Term 
PT Code 
Myalgia 
10028411 
Myositis 
10028653 
14.12.16. Pancreatitis  
Medical concept of acute pancreatitis. Only narrow terms of SMQ 'Acute pancreatitis' 
selected. Algorithmic approach for this SMQ not used due to complexity in applying and 
poor specificity of remaining categories. Category A selected as PTs because more 
specific for concept (only narrow terms). 
SMQ: 'Acute pancreatitis'  
SMQ Code: 20000022  
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Cullen’s sign 
10059029 
Grey Turner’s sign 
10075426 
Haemorrhagic necrotic pancreatitis 
10076058 
Hereditary pancreatitis 
10056976 
Ischaemic pancreatitis 
10066127 
Oedematous pancreatitis 
10052400 


 
CONFIDENTIAL 
 
 
201584 
 
218 
 
SMQ: 'Acute pancreatitis'  
SMQ Code: 20000022  
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Pancreatic abscess 
10048984 
Pancreatic cyst drainage 
10082531 
Pancreatic haemorrhage 
10033625 
Pancreatic necrosis 
10058096 
Pancreatic phlegmon 
10056975 
Pancreatic pseudoaneurysm  
10081762 
Pancreatic pseudocyst 
10033635 
Pancreatic pseudocyst drainage 
10033636 
Pancreatitis 
10033645 
Pancreatitis acute 
10033647 
Pancreatitis haemorrhagic 
10033650 
Pancreatitis necrotising 
10033654 
Pancreatitis relapsing 
10033657 
Pancreatorenal syndrome 
10056277 
14.12.17. Impact on Creatinine 
Medical concept of worsening renal function/renal failure in the context of impact on 
creatinine. Only narrow terms from SMQ 'Acute renal failure' plus all PTs from HLT 
'Renal failure and impairment', under SOC 'Renal and urinary disorders'. Numerous 
duplicated preferred terms e.g. renal failure 
SMQ: ‘Acute renal failure’ 
SMQ Code: 20000003 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Acute kidney injury 
10069339 
Acute phosphate nephropathy 
10069688 


 
CONFIDENTIAL 
 
 
201584 
 
219 
 
SMQ: ‘Acute renal failure’ 
SMQ Code: 20000003 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Anuria 
10002847 
Azotaemia 
10003885 
Continuous haemodiafiltration 
10066338 
Dialysis 
10061105 
Foetal renal impairment 
10078987 
Haemodialysis 
10018875 
Haemofiltration 
10053090 
Neonatal anuria 
10049778 
Nephropathy toxic 
10029155 
Oliguria 
10030302 
Peritoneal dialysis 
10034660 
Prerenal failure 
10072370 
Renal failure 
10038435 
Renal failure neonatal 
10038447 
Renal impairment 
10062237 
Renal impairment neonatal 
10049776 
Subactute kidney injury  
10081980 


 
CONFIDENTIAL 
 
 
201584 
 
220 
 
SMQ: ‘Acute renal failure’ 
SMQ Code: 20000003 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Plus, all PTs from HLT 'Renal failure and impairment' under 
SOC 'Renal and urinary disorders' 
Preferred Term 
PT Code 
Acute Kidney injury 
10069339 
Anuria 
10002847 
Atypical haemolytic uraemic syndrome 
10079840 
Cardiorenal syndrome 
10068230 
Chronic kidney disease 
10064848 
Crush syndrome 
10050702 
Diabetic end stage renal disease 
10012660 
End stage renal disease 
10077512 
Foetal renal impairment 
10078987 
Haemolytic uraemic syndrome 
10018932 
Hepatorenal failure 
10019845 
Hepatorenal syndrome 
10019846 
Nail-patella syndrome 
10063431 
Neonatal anuria 
10049778 
Oliguria 
10030302 
Pancreatorenal syndrome 
10056277 
Postoperative renal failure 
10056675 
Postrenal failure 
10059345 
Prerenal failure 
10072370 
Propofol infusion syndrome 
10063181 
Renal failure 
10038435 
Renal failure neonatal 
10038447 


 
CONFIDENTIAL 
 
 
201584 
 
221 
 
SMQ: ‘Acute renal failure’ 
SMQ Code: 20000003 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Renal impairment 
10062237 


 
CONFIDENTIAL 
 
 
201584 
 
222 
 
SMQ: ‘Acute renal failure’ 
SMQ Code: 20000003 
Category: A 
Scope: Narrow 
 
Preferred Term 
PT Code 
Renal impairment neonatal 
10049776 
Renal injury 
10061481 
Scleroderma renal crisis 
10062553 
Traumatic anuria 
10044501 
14.12.18. Safety During Pregnancy 
Use AE terms co-reported in pregnancy exposures to CAB. 
 


 
CONFIDENTIAL 
 
 
201584 
 
223 
 
14.13. 
Appendix 13: Abbreviations & Trade Marks  
14.13.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
BMD 
Bone Mineral Density 
BMI 
Body Mass Index 
CAB 
Cabotegravir 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale  
CTR 
Clinical Trial Register 
CVb 
Coefficient of Variation (Between) 
CVb / CVw 
Coefficient of Variation (Between) / Coefficient of Variation (Within) 
CVD 
Cardiovascular Disease  
CVF 
Confirmed Virologic Failure 
DAIDS 
Division of AIDS  
DBF 
Database Freeze 
DBR 
Database Release 
DOB 
Date of Birth 
DP 
Decimal Place 
DTG 
Dolutegravir 
eCRF 
Electronic Case Record Form 
eGFR 
Estimated Glomerular Filtration Rate 
EMA 
European Medicines Agency 
ERDF 
Efficacy Related Discontinuation Failure 
ES 
Extension Switch Population 
FDA 
Food and Drug Administration  
FSFV 
First Subject First Visit 
GSK 
GlaxoSmithKline 
GUI 
Guidance 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus  
HSR 
Hypersensitivity Reaction 
IA 
Interim Analysis 
ICH 
International Conference on Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 


 
CONFIDENTIAL 
 
 
201584 
 
224 
 
Abbreviation 
Description 
INI 
Integrase Inhibitors 
IP 
Investigational Product 
ITT 
Intent-To-Treat 
ITT-E 
Intent-To-Treat Exposed 
LOCF 
Last Observation Carries Forward 
MMRM 
Mixed Model Repeated Measures 
NCEP 
National Cholesterol Education Program  
NNRTI 
Non-Nucleoside Reverse Transcriptase Inhibitors  
NQ 
Non Quantifiable 
NRTI 
Nucleoside Reverse Transcriptase Inhibitors  
OC 
Observed Case 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamic 
PDMP 
Protocol Deviation Management Plan 
PI 
Protease Inhibitors 
PK 
Pharmacokinetic 
PopPK 
Population PK 
PP 
Per Protocol 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAMOS 
Randomisation & Medication Ordering System 
RAP 
Reporting & Analysis Plan 
RPV 
Rilpivirine 
SAE 
Serious Adverse Event 
SAC 
Statistical Analysis Complete 
SD 
Standard Deviation 
SDAC 
Statistics Data Analysis Centre  
SDTM 
Study Data Tabulation Model 
SMQ 
Standardized MedDRA Queries 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings 
TRDF 
Treatment Related Discontinuation Failure  
 
14.13.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
Dolutegravir 
 
NONMEM 
Triumeq 
 
Rilpivirine 
 
 
SAS 
 
 
WinNonlin 


 
CONFIDENTIAL 
 
 
201584 
 
225 
 
14.14. 
Appendix 14: List of Data Displays for Week 48/Week 96 
All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects 
CDISC and GSK Data Display Standards terminology. 
14.14.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.01 to 1.n 
1.01 to 1.n 
Efficacy 
2.01 to 2.n 
2.01 to 2.n 
Safety 
3.01 to 3.n 
3.01 to 3.n 
Pharmacokinetic 
4.01 to 4.n 
4.01 to 4.n 
Pharmacokinetic / Pharmacodynamic 
5.01 to 5.n 
5.01 to 5.n 
Health Outcomes 
6.01 to 6.n 
6.01 to 6.n 
Virology 
7.01 to 7.n 
7.01 to 7.n 
Section 
Listings 
ICH Listings 
1 to x 
Other Listings 
y to z 
 
14.14.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided a separate document. 
14.14.3. 
Deliverables 
Delivery [1] 
Description 
HL 
Headline at Week 48 
W48 
Week 48 
W96 
Week 96  
EOS 
End of study 
NOTES: 
1. 
Indicates priority (i.e. order) in which displays will be generated for the reporting effort. 
 


 
CONFIDENTIAL 
 
 
201584 
 
226 
 
14.14.4. 
Study Population Tables 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
Subject Disposition 
1.1.  
All Subjects 
Screened  
SA1 
Summary of Study Populations 
CS CORE 
 
For W96: add column for ‘Switch 
Q4W’ 
HL, W48, 
W96, EOS 
1.2.  
All Subjects 
Screened 
Shell TSP1 
Summary of Subjects by Country and Investigator 
For W96: add column for ‘Switch 
Q4W’ 
W48, W96, 
EOS 
1.3.  
All Subjects 
Screened 
ES6 
Summary of Screening Status and Reasons for 
Screening Failures 
CS CORE 
W48, W96, 
EOS 
1.4.  
All Enrolled 
EudraCT age 
Summary of Age Categories 
CS CORE 
W48, W96, 
EOS 
1.5.  
ITT-E 
ES1 
Summary of Subject Accountability: Study Conclusion 
Record  
ICH E3, GSK CTR, FDAAA, 
EudraCT 
For W96: add column for ‘Switch 
Q4W’ 
W48, W96, 
EOS 
1.6.  
ITT-E 
ES1 
Summary of Study Drug Discontinuation 
CS CORE 
For W96: add column for ‘Switch 
Q4W’ 
W48, W96, 
EOS 
1.7.  
ITT-E 
ES1 
Summary of Subject Accountability: Maintenance 
Phase Conclusion Record  
ICH E3, GSK CTR, FDAAA, 
EudraCT 
HL, W48, 
W96 
1.8.  
LTFU 
ES1 
Summary of Subject Accountability: Long-term follow 
up Phase Conclusion Record  
ICH E3, GSK CTR, FDAAA, 
EudraCT 
For W96: add column for ‘Switch 
Q4W’ 
W48, W96, 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
227 
 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
1.9.  
ITT-E 
HIV_ES1 
Summary of Subject Accountability: Withdrawals by 
Visit - Maintenance Phase 
 
W48, W96 
1.10. 
ITT-E 
ES1 
Summary of Subject Accountability: Maintenance and 
Extension Phase Conclusion Record (Randomized 
Q4W) 
For Randomized Q4W arm only 
Add the following subcategories 
under subject status:  a) 
Completed Maintenance and did 
not enter Extension b) Completed 
Extension c) Withdrawn from 
Maintenance d) Withdrawn from 
Extension. 
W96, EOS 
1.11. 
ITT-E 
HIV_ES1 
Summary of Subject Accountability: Withdrawals by 
Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
For Randomized Q4W arm only 
W96, EOS 
1.12. 
ES 
ES1 
Summary of Subject Accountability: Extension Phase 
Conclusion Record (Extension Switch Population) 
Switch Q4W IM group only 
 
W96, EOS 
1.13. 
ES 
HIV_ES1 
Summary of Subject Accountability: Withdrawals by 
Visit – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 
1.14. 
All 
Participants 
Enrolled 
ES4 
Summary of Subject Disposition at Each Study Epoch 
See Mid200056//wk96cdisc/Table 
6.1006 
For W96: add column for ‘Switch 
Q4W’ 
W48, W96, 
EOS 
1.15. 
All 
Participants 
Enrolled 
ES5 
Summary of Reasons for Withdrawal at Each Epoch 
See Mid200056//wk96cdisc/Table 
6.1007 
For W96: add column for ‘Switch 
Q4W’ 
W48, W96, 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
228 
 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
1.16. 
ITT-E 
DV1a 
Summary of Important Protocol Deviations 
(Maintenance Phase) 
CS CORE  
W48, W96 
1.17. 
ITT-E 
DV1a 
Summary of Important Protocol Deviations - 
Maintenance and Extension Phase (Randomized 
Q4W) 
CS CORE 
For Randomized Q4W arm only  
W96, EOS 
1.18. 
ES 
DV1a 
Summary of Important Protocol Deviations – 
Extension Phase (Extension Switch Population) 
CS CORE 
Switch Q4W IM group only 
W96, EOS 
1.19. 
ITT-E 
SP2 
Summary of Protocol Deviations Leading to Exclusion 
from the Per-Protocol Population (Week X Analysis) 
[X =Week 48 or Week 96, depending on the 
deliverable)]  
CS CORE 
Exclude deviations occurring 
during the Extension phase 
W48, W96 
1.20. 
ITT-E 
IE1 
Summary of Inclusion/Exclusion Criteria Deviations 
 
W48, W96, 
EOS 
1.21. 
All 
Participants 
Enrolled 
ES1 
Summary of Subject Accountability: Induction Phase 
Conclusion Record 
ICH E3, GSK CTR, FDAAA, 
EudraCT 
W48 
Demography and Baseline 
1.22. 
ITT-E 
Shell TSP2 
Summary of Demographic Characteristics 
See also DM1 in IDSL 
Age categorization will include:  
<=18, 19-64, >=65 (FDAAA 
requirement) 
18-64, 65-84, >=85 (EMA 
requirement) 
 
HL, W48, 
W96, EOS 
1.23. 
ITT-E 
DM5 
Summary of Race and Racial Combinations 
CS CORE 
W48, W96, 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
229 
 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
1.24. 
ITT-E 
DM6 
Summary of Race and Racial Combinations Details 
CS CORE 
W48, W96, 
EOS 
1.25. 
ITT-E 
Shell TSP3 
Summary of Hepatitis Status at Induction Baseline 
(Week -20) 
 
W48, W96, 
EOS 
1.26. 
ITT-E 
CDC1 
Summary of Derived CDC Stages of HIV Infection at 
Maintenance Baseline (Day 1) 
 
W48, W96, 
EOS 
1.27. 
ITT-E 
Shell TSP4 
Summary of Induction Baseline (Week -20) 
Cardiovascular Risk Assessments 
 
W48, W96, 
EOS 
1.28. 
ITT-E 
Shell TSP5 
Distribution of CD4+ Cell Count Results at 
Maintenance Baseline (Day 1) 
Same presentation as shown in 
the mock shell for induction 
baseline. 
W48, W96, 
EOS 
1.29. 
ITT-E 
Shell TSP5 
Distribution of Quantitative Plasma HIV-1 RNA and 
CD4+ Cell Count Results at Screening and Induction 
Baseline (Week -20) 
 
W48, W96, 
EOS 
Medical Conditions, Concomitant Medications & Antiretroviral Therapy 
1.30. 
ITT-E 
MH1 
Summary of Current Medical Conditions 
CS CORE 
W48, W96, 
EOS 
1.31. 
ITT-E 
MH1 
Summary of Past Medical Conditions 
CS CORE 
W48, W96, 
EOS 
1.32. 
ITT-E 
MH4 
Summary of Current Cardiac, Gastrointestinal, 
Metabolism and Nutrition, Psychiatric, Renal and 
Urinary, Nervous System Conditions, and 
Hepatobiliary disorders 
 
W48, W96, 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
230 
 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
1.33. 
ITT-E 
MH4 
Summary of Past Cardiac, Gastrointestinal, 
Metabolism and Nutrition, Psychiatric, Renal and 
Urinary, Nervous System Conditions, and 
Hepatobiliary disorders 
 
W48, W96, 
EOS 
1.34. 
ITT-E 
CM8 
Summary of Concomitant Medication Ingredient 
Combinations (Maintenance Phase) 
 
W48, W96 
1.35. 
ITT-E 
CM8 
Summary of Concomitant Medication Ingredient 
Combinations - Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only  
W96, EOS 
1.36. 
ES 
CM8 
Summary of Concomitant Medication Ingredient 
Combinations – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only  
W96, EOS 
1.37. 
ITT-E 
Shell TSP11 
Summary of Alternate Background NRTI Therapy at 
End of Induction Phase  
 
W48, W96, 
EOS 
1.38. 
ITT-E 
Shell TSP9 
Summary of Lipid Modifying Agent Use at 
Maintenance Baseline (Day 1) 
taken during the 12 weeks before 
the first Maintenance Phase dose 
of study drug 
W48, W96, 
EOS 
1.39. 
ITT-E 
Shell TSP10 
Summary of Lipid Modifying Agent Use Started During 
Maintenance 
 
W48, W96, 
EOS 
1.40. 
ITT-E 
SU1 
Summary of Substance Use at Entry 
 
W48, W96, 
EOS 
1.41. 
ITT-E 
Shell TSP12 
Summary of HIV Risk Factor 
 
W48, W96, 
EOS 
1.42. 
ITT-E 
Shell TSP13 
Summary of Time from First HIV-1 RNA < 50 
copies/mL until Initiation of Maintenance Phase 
Treatment 
 
W48, W96, 
EOS 
1.43. 
ITT-E 
Shell CLAD1 
Summary of the Prevalence of HIV-1 Subtype 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
231 
 
14.14.5. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
Primary Efficacy Analyses  
2.1.  
ITT-E 
Shell TPEF1 
Summary of Analysis for Proportion of Subjects with Plasma HIV-
1 RNA ≥50 c/mL at Week 48 (Maintenance Phase) – Snapshot 
Analysis  
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
HL, W48, 
W96 
2.2.  
Per-Protocol  Shell TPEF1 
Summary of Analysis for Proportion of Subjects with Plasma HIV-
1 RNA ≥50 c/mL at Week 48 (Maintenance Phase) – Snapshot 
Analysis (Per-Protocol Population) 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
HL, W48, 
W96 
2.3.  
ITT-E 
Shell TPEF2 
Summary of Study Outcomes (50 c/mL cut-off) at Week 48 
(Maintenance Phase) – Snapshot Analysis 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
HL, W48, 
W96 
2.4.  
ITT-E 
Shell TPEF3 
Treatment by Strata Tests of Homogeneity for Proportion of 
Subjects with Plasma HIV-1 RNA ≥50 c/mL at Week 48 
(Maintenance Phase) - Snapshot Analysis 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
HL, W48, 
W96 
2.5.  
ITT-E 
Shell TPEF4 
Summary of Analysis for Proportion of Subjects with Plasma HIV-
1 RNA ≥50 c/mL at Week 48 by Subgroup (Maintenance Phase) - 
Snapshot Analysis 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
W48, W96 
2.6.  
ITT-E 
Shell TPEF5 
Summary of Study Outcomes (50 c/mL cut-off) at Week 48 by 
Subgroup (Maintenance Phase) – Snapshot Analysis  
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
W48, W96 
Secondary Efficacy Analyses  
2.7.  
ITT-E 
Shell TPEF1 
Summary of Analysis for Proportion of Subjects with Plasma HIV-
1 RNA <50 c/mL at Week 48 (Maintenance Phase) – Snapshot 
Analysis  
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
HL, W48, 
W96 
2.8.  
Per-Protocol Shell TPEF1 
Summary of Analysis for Proportion of Subjects with Plasma HIV-
1 RNA <50 c/mL at Week 48 (Maintenance Phase) – Snapshot 
Analysis (Per-Protocol Population) 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
HL, W48, 
W96 


 
CONFIDENTIAL 
 
 
201584 
 
232 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.9.  
ITT-E 
Shell TPEF3 
Treatment by Strata Tests of Homogeneity for Proportion of 
Subjects with Plasma HIV-1 RNA <50 c/mL at Week 48 
(Maintenance Phase) - Snapshot Analysis 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
W48, W96 
2.10. 
ITT-E 
Shell TPEF4 
Summary of Analysis for Proportion of Subjects with Plasma HIV-
1 RNA <50 c/mL at Week 48 by Subgroup (Maintenance Phase) - 
Snapshot Analysis 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
W48, W96 
2.11. 
ITT-E 
Shell TSEF2 
Proportion of Subjects with Plasma HIV-1 RNA ≥50 c/mL by Visit 
(Maintenance Phase) – Snapshot Analysis 
 
W48, W96  
2.12. 
ITT-E 
Shell TSEF2.1 
Proportion of Subjects with Plasma HIV-1 RNA ≥50 c/mL by 
Subgroup and Visit (Maintenance Phase) – Snapshot Analysis 
 
W48 
2.13. 
ITT-E 
Shell TSEF7.0 
Summary of Kaplan-Meier Estimates of Proportion of Subjects 
Without Confirmed Virologic Failure at Week 48 - Treatment 
Related Discontinuation = Failure  
For W96 deliverable, replace ‘Week 
52’ with ‘Week 100’ 
W48, W96 
2.14. 
ITT-E 
Shell TSEF7.1 
Summary of Kaplan-Meier Estimates of Proportion of Subjects 
Without Confirmed Virologic Failure at Week 48 - Efficacy Related 
Discontinuation = Failure 
For W96 deliverable, replace ‘Week 
52’ with ‘Week 100’ 
W48, W96 
2.15. 
ITT-E 
Shell TSEF2.1 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL by Visit 
(Maintenance Phase) – Snapshot Analysis 
 
W48, W96 
2.16. 
ITT-E 
Shell TSEF2 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL by 
Subgroup and Visit (Maintenance Phase) – Snapshot Analysis 
 
W48, W96 
2.17. 
ITT-E 
Shell TSEF2 
Proportion of Subjects with Plasma HIV-1 RNA <200 c/mL by Visit 
(Maintenance Phase) – Snapshot Analysis 
 
W48, W96  
2.18. 
ITT-E 
Shell TSEF9 
Proportion of Subjects with HIV-1 RNA≥50 c/mL at Week 48 
(Snapshot) by Last Delay in IP Injection (Maintenance Phase) 
For Q4W IM arm only. 
The last delay in IP injection is the 
delay in IP injection at Week 48, or 
delay in last IP injection prior to 
Week 48 if a subject has no injection 
at WK48 (e.g., missing visit or early 
withdrawal) 
W48 


 
CONFIDENTIAL 
 
 
201584 
 
233 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.19. 
ITT-E 
Shell TSEF8 
Summary of Plasma HIV-1 RNA (log10 c/mL) by Visit 
(Maintenance Phase) 
 
W48, W96 
 EOS 
2.20. 
ITT-E 
Shell TSEF8 
Summary of Change from Maintenance Baseline (Day 1) in 
Plasma HIV-1 RNA (log10 c/mL) by Visit (Maintenance Phase) 
 
W96, EOS 
2.21. 
ITT-E 
Shell TSEF3 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria by Visit During the Maintenance Phase (Up to 
Week 52)  
For Week 96 deliverable, show all 
visit up to Week 100. 
HL, W48, 
W96 
2.22. 
ITT-E 
Shell TSEF3.1 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria During the Maintenance Phase 
 
HL, W48, 
W96 
2.23. 
ITT-E 
Shell TSEF3.1 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria During the Maintenance and Extension Phase 
(Randomized Q4W) 
For Randomized Q4W arm only 
W96, EOS 
2.24. 
ES 
Shell TSEF3.1 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria During the Extension Phase (Extension Switch 
Population) 
 
Switch Q4W IM group only 
W96, EOS 
2.25. 
CVF 
Shell TSEF4 
Distribution of Quantitative Plasma HIV-1 RNA Results at 
Suspected and Confirmation of Confirmed Virologic Failure – 
Maintenance Phase 
 
W48, W96 
2.26. 
ITT-E 
Shell TSEF5 
Summary of Change from Maintenance Baseline (Day 1) in CD4+ 
Cell Count (cells/mm^3) by Visit -Maintenance Phase 
Visits starting from Maintenance 
Baseline (Day 1), Week 4, … 
W48, W96 
2.27. 
ITT-E 
Shell TSEF5 
Summary of Change from Maintenance Baseline (Day 1) in CD4+ 
Cell Count (cells/mm^3) by Visit - Maintenance and Extension 
Phase (Randomized Q4W) 
Visits starting from Maintenance 
Baseline (Day 1), Week 4, … 
EOS 
2.28. 
ES 
Shell TSEF5 
Summary of Change from Extension Baseline (Week 100) in 
CD4+ Cell Count (cells/mm^3) by Visit – Extension Phase 
(Extension Switch Population) 
 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
234 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.29. 
ITT-E 
Shell TSEF5 
Summary of Change from Maintenance Baseline (Day 1) in CD4+ 
Cell Count (cells/mm^3) at Week 48 by Subgroup (Maintenance 
Phase) 
Visits starting from Maintenance 
Baseline (Day 1), Week 4, … 
For W96 deliverable, replace ‘Week 
48’ with ‘Week 96’ 
W48, W96 
2.30. 
ITT-E 
Shell TSEF5 
Summary of CD4+ Cell Count (cells/mm^3) by Visit– Induction 
and Maintenance Phase 
Visits starting from Induction 
Baseline (Week -20), Week -16, 
W48, W96, 
EOS 
2.31. 
ITT-E 
Shell TSEF5 
Summary of CD4+ Cell Count (cells/mm^3) by Visit – 
Maintenance and Extension Phase (Randomized Q4W) 
Visits starting from Induction 
Baseline (Week -20), Week -16, 
EOS 
2.32. 
ES 
Shell TSEF5 
Summary of CD4+ Cell Count (cells/mm^3) by Visit – Extension 
Phase (Extension Switch Population) 
 
EOS 
2.33. 
ITT-E 
Shell TSEF5 
Summary of CD8+ Cell Count (cells/mm^3) by Visit – Induction + 
Maintenance Phase 
Visits starting from Induction 
Baseline (Week -20), Week -16, 
W48, W96, 
EOS 
2.34. 
ITT-E 
Shell TSEF5 
Summary of CD8+ Cell Count (cells/mm^3) by Visit – 
Maintenance and Extension Phase (Randomized Q4W) 
Visits starting from Induction 
Baseline (Week -20), Week -16, 
EOS 
2.35. 
ES 
Shell TSEF5 
Summary of CD8+ Cell Count (cells/mm^3) by Visit– Extension 
Phase (Extension Switch Population) 
 
EOS 
2.36. 
ITT-E 
Shell TSEF5 
Summary of Change from Maintenance Baseline (Day 1) in CD8+ 
Cell Count (cells/mm^3) by Visit – Maintenance Phase) 
Visits starting from Induction 
Maintenance Baseline, Week 4, … 
W48, W96, 
2.37. 
ITT-E 
Shell TSEF5 
Summary of Change from Maintenance Baseline (Day 1) in CD8+ 
Cell Count (cells/mm^3) by Visit – Maintenance and Extension 
Phase (Randomized Q4W) 
Visits starting from Maintenance 
Baseline (Day 1), Week 4, … 
EOS 
2.38. 
ES 
Shell TSEF5 
Summary of Change from Maintenance Baseline (Day 1) in CD8+ 
Cell Count (cells/mm^3) by Visit – Extension Phase (Extension 
Switch Population) 
 
EOS 
2.39. 
ITT-E 
Shell TSEF5 
Summary of CD4+/CD8+ Ratio Cell Count (cells/mm^3) by Visit –
Induction and Maintenance Phase 
While both CD4+ and CD8+ are 
available on the same date  
W48, W96  


 
CONFIDENTIAL 
 
 
201584 
 
235 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.40. 
ITT-E 
Shell TSEF5 
Summary of CD4+/CD8+ Ratio Cell Count (cells/mm^3) by Visit –
Induction, Maintenance and Extension Phase (Randomized Q4W) For Randomized Q4W arm only 
EOS 
2.41. 
ES 
Shell TSEF5 
Summary of CD4+/CD8+ Ratio Cell Count (cells/mm^3) by Visit – 
Extension Phase (Extension Switch Population) 
 
EOS 
2.42. 
ITT-E 
HIV1/Shell 
TSEF 6.0 
Summary of Maintenance Phase HIV-1 Associated Conditions 
Including Recurrences  
 
W48, W96 
2.43. 
ITT-E 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Including Recurrences - 
Maintenance and Extension Phase (Randomized Q4W) 
For Randomized Q4W arm only 
EOS 
2.44. 
ES 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Including Recurrences 
– Extension Phase (Extension Switch Population) 
 
EOS 
2.45. 
ITT-E 
HIV1/Shell 
TSEF 6.0 
Summary of Maintenance Phase HIV-1 Associated Conditions 
Excluding Recurrences  
 
W48, W96 
2.46. 
ITT-E 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Excluding Recurrences 
- Maintenance and Extension Phase (Randomized Q4W)  
For Randomized Q4W arm only 
EOS 
2.47. 
ES 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Excluding Recurrences 
– Extension Phase (Extension Switch Population) 
 
EOS 
2.48. 
ITT-E 
HIV2/Shell 
TSEF6.1 
Summary of HIV-1 Disease Progression and/or Deaths 
(Maintenance Phase)  
 
W48, W96 
2.49. 
ITT-E 
HIV2/Shell 
TSEF6.1 
Summary of HIV-1 Disease Progressions and/or Deaths -
Maintenance and Extension Phase (Randomized Q4W) 
For Randomized Q4W arm only 
EOS 
2.50. 
ES 
HIV2/Shell 
TSEF6.1 
Summary of HIV-1 Disease Progressions – Extension Phase 
(Extension Switch Population) 
 
EOS 
2.51. 
ITT-E 
TSEF12 
Proportion of Subjects with Plasma HIV-1 RNA <2 copies/mL by 
Visit - Observed Case Analysis (Maintenance Phase) 
 
W48, W96 
2.52. 
ITT-E 
Shell TPEF2 
Summary of Study Outcomes (200 c/mL) at Week 48 
(Maintenance Phase) – Snapshot Analysis 
For W96 analysis, replace ‘Week 48’ 
with ‘Week 96’ 
W48, W96 
2.53. 
ITT-E 
Shell TSEF11 
Summary of Subjects per Viral Load Category by Visit – 
Maintenance Phase) 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
236 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.54. 
All 
Participants 
Enrolled 
Shell TSEF12 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL by Visit 
(Observed data) – Induction Phase 
Induction Baseline (Week -20), 
Week -16, Week -8, Week -4 and 
Day 1.  Single arm for Induction 
ABC/DTG/3TC 
W48 
14.14.6. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Primary Efficacy Analyses   
2.1.  
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA ≥50 c/mL by 
Visit (Maintenance Phase) – Snapshot Analysis 
 
W48, W96 
2.2.  
ITT - E 
Shell FPEF2 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA ≥50 c/mL at Week 48 by Subgroup – 
Snapshot Analysis 
For W96 deliverable, replace 
‘Week 48’ with ‘Week 96’ 
W48, W96 
2.3.  
ITT-E 
SNAPSHOT9B 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA >= 50 c/mL at Week 96 by Selected 
Demographic Subgroups (Maintenance Phase) - Snapshot 
Analysis 
Include: Overall, Gender at Birth 
(Female, Male), Age (<35, 35-<50, 
>=50), Induction Baseline (Week -
20) BMI (<30, >=30), Region 
(Western/Central Europe and North 
America, Russian Federation, 
Japan, South Africa). 
W96 


 
CONFIDENTIAL 
 
 
201584 
 
237 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.4.  
ITT-E 
SNAPSHOT9B 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA >= 50 c/mL at Week 96 by Selected 
HIV Disease Characteristic Subgroups (Maintenance Phase) - 
Snapshot Analysis 
Include: Overall, Induction BL 
(Week -20) HIV-1 RNA (<100,000, 
>=100,000), Induction BL (Week -
20) CD4+ cell count (<200, 200 to 
<350, 350 to <500, >=500), HIV-1 
Subtype (A, A1, AE, Ag, B, C, 
Other) 
W96 
Secondary Efficacy Analyses  
2.5.  
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA <50 c/mL by 
Visit (Maintenance Phase) – Snapshot Analysis 
 
W48, W96 
2.6.  
ITT-E 
SNAPSHOT9B 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA < 50 c/mL at Week 96 by Selected 
Demographic Subgroups (Maintenance Phase) - Snapshot 
Analysis 
Include: Overall, Gender at Birth 
(Female, Male), Age (<35, 35-<50, 
>=50), Induction Baseline (Week -
20) BMI (<30, >=30), Region 
(Western/Central Europe and North 
America, Russian Federation, 
Japan, South Africa). 
W96 
2.7.  
ITT-E 
SNAPSHOT9B 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA < 50 c/mL at Week 96 by Selected 
HIV Disease Characteristic Subgroups (Maintenance Phase) - 
Snapshot Analysis 
Include: Overall, Induction BL 
(Week -20) HIV-1 RNA (<100,000, 
>=100,000), Induction BL (Week -
20) CD4+ cell count (<200, 200 to 
<350, 350 to <500, >=500), HIV-1 
Subtype (A, A1, AE, Ag, B, C, 
Other) 
W96 
2.8.  
ITT - E 
Shell FPEF2 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA <50 c/mL at Week 48 by Subgroup – 
Snapshot Analysis 
For W96 analysis, replace ‘Week 
48’ with ‘Week 96’ 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
238 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.9.  
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA <200 c/mL by 
Visit (Maintenance Phase) – Snapshot Analysis 
 
W48, W96 
2.10. 
ITT-E 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA (log10 copies/mL) Profiles by 
Visit– for CVF subjects (Randomized Q4W)  
The first vertical line indicates start 
of Induction phase investigational 
product (ABC/DTG/3TC or DTG). 
The second vertical line indicates 
start of Maintenance phase 
investigational product (oral CAB + 
oral RPV). The third vertical 
reference line indicates last on-
treatment study day, i.e. min 
(max(day of last IP injection 
dose+35 days, day of last oral 
CAB+RPV+1), day of LTFU 
HAART start date).  This line is 
only for participants who withdraw 
from the Maintenance/Extension 
phase. 
HL, W48, 
W96, EOS  


 
CONFIDENTIAL 
 
 
201584 
 
239 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.11. 
ITT-E 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA (log10 copies/mL) Profiles by 
Visit – for CVF subjects (Randomized ABC/DTG/3TC arm)  
The first vertical line indicates start 
of Induction phase investigational 
product (ABC/DTG/3TC or DTG). 
The second vertical line indicates 
start of Maintenance phase 
investigational product 
(continuation of ABC/DTG/3TC or 
DTG). The third vertical reference 
line indicates last Maintenance 
phase on-treatment study day, i.e. 
day of last ABC/DTG/3TC (or DTG) 
dose + 1. This line is only for 
participants who withdraw or 
complete the Maintenance phase. 
The fourth vertical reference line 
indicates last Extension Phase on-
treatment study day, i.e. min (max 
(day of last IP injection dose+35 
days, day of last oral 
CAB+RPV+1), day of LTFU 
HAART start date).  This line is 
only for participants who withdraw 
from the Extension phase. 
HL, W48, 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
240 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.12. 
ITT - E 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA for subjects who are in the 
category of ‘HIV-1 RNA ≥50 c/mL’ at Week 48 per Snapshot 
algorithm (Randomized Q4W arm) 
The first vertical line indicates start 
of Induction phase investigational 
product (ABC/DTG/3TC or DTG). 
The second vertical line indicates 
start of Maintenance phase 
investigational product (oral CAB + 
oral RPV). The third vertical 
reference line indicates last on-
treatment study day, i.e. min 
(max(day of last IP injection 
dose+35 days, day of last oral 
CAB+RPV+1), day of LTFU 
HAART start date).  This line is 
only for participants who withdraw 
from the Maintenance/Extension 
phase. 
For W96 analysis, replace ‘Week 
48’ with ‘Week 96’ 
 
HL, W48, 
W96 


 
CONFIDENTIAL 
 
 
201584 
 
241 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.13. 
ITT - E 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA for subjects who are in the 
category of ‘viral load ≥50 c/mL’ at Week 48 per Snapshot 
algorithm (Randomized ABC/DTG/3TC arm) 
The first vertical line indicates start 
of Induction phase investigational 
product (ABC/DTG/3TC or DTG). 
The second vertical line indicates 
start of Maintenance phase 
investigational product 
(continuation of ABC/DTG/3TC or 
DTG). The third vertical reference 
line indicates last Maintenance 
phase on-treatment study day, i.e. 
day of last ABC/DTG/3TC (or DTG) 
dose + 1. This line is only for 
participants who withdraw or 
complete the Maintenance phase. 
The fourth vertical reference line 
indicates last Extension Phase on-
treatment study day, i.e. min 
(max(day of last IP injection 
dose+35 days, day of last oral 
CAB+RPV+1), day of LTFU 
HAART start date).  This line is 
only for participants who withdraw 
from the Extension phase. 
For W96 analysis, replace ‘Week 
48’ with ‘Week 96’ 
HL, W48, 
W96 
2.14. 
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA >=200 c/mL 
by Visit – Snapshot Analysis 
 
W48, W96 
 


 
CONFIDENTIAL 
 
 
201584 
 
242 
 
14.14.7. 
Safety Tables 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Exposure  
3.1.  
Safety 
Shell TS1.1 
Summary of Extent of Exposure to Investigational Product – 
Maintenance Phase 
CS Core  
W48, W96, 
EOS 
3.2.  
Safety 
Shell TS1.1 
Summary of Extent of Exposure to Investigational Product – 
Maintenance Phase and Extension Phase (Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
W96, EOS 
3.3.  
ES 
Shell TS1.1 
Summary of Extent of Exposure to Investigational Product –
Extension Phase (Extension Switch Population) 
CS Core  
Switch Q4W IM group only 
W96, EOS 
3.4.  
Safety 
Study 201584 
(primary_02): 
Table 3.114 
Summary of Categorized Needle Length and Gauge for CAB 
Injection - Maintenance Phase  
Randomized Q4W arm only 
W48, W96 
3.5.  
Safety 
Study 201584 
(primary_02): 
Table 3.115 
Summary of Categorized Needle Length and Gauge for RPV 
Injection - Maintenance Phase  
Randomized Q4W arm only 
W48, W96 
3.6.  
Safety 
Shell TS1.3 
Summary of Adherence to Q4W IM Dosing Schedule - 
Maintenance Phase 
(only for randomized Q4W arm) 
please refer to Section 14.6.2-- 
Adherence to CAB/RPV Injection 
Schedule 
W48, W96 
Adverse Events  
3.7.  
Safety 
AE1 
Summary of All Adverse Events by System Organ Class – 
Maintenance Phase 
CS Core  
W48, W96  
3.8.  
Safety 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Maintenance Phase 
CS Core 
HL, W48, W96 
3.9.  
Safety 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
243 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.10. 
ES 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Extension Phase (Extension Switch 
Population) 
CS Core  
Switch Q4W IM group only 
W96, EOS 
3.11. 
Safety 
AE5B 
Summary of All On-treatment Adverse Events by System 
Organ Class and Maximum Toxicity – Maintenance Phase 
CS Core 
W48, W96 
3.12. 
LTFU 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Long-term Follow-up Phase 
CS Core 
EOS 
3.13. 
Safety  
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Oral Lead-in Period at Maintenance 
Phase 
CS Core  
Randomized Q4W arm only 
HL, W48 
3.14. 
Safety 
AE3 
Summary of Common Adverse Events (>=5%) by Overall 
Frequency – Maintenance Phase 
CS Core 
W48, W96 
3.15. 
Safety 
AE3 
Summary of Common Grade 2-5 Adverse Events (>=1%) by 
Overall Frequency – Maintenance Phase 
 
W48, W96 
3.16. 
Safety 
AE1 
Summary of All Drug-Related Adverse Events by System 
Organ Class– Maintenance Phase 
 
W48, W96 
3.17. 
Safety 
AE5B 
Summary of All Drug-Related Adverse Events by System 
Organ Class and Maximum Toxicity – Maintenance Phase 
CS Core 
HL, W48, W96 
3.18. 
Safety 
AE5B 
Summary of All Drug-Related Adverse Events by System 
Organ Class and Maximum Toxicity – Maintenance and 
Extension Phase (Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
W96, EOS 
3.19. 
ES 
AE5B 
Summary of All Drug-Related Adverse Events by System 
Organ Class and Maximum Toxicity – Extension Phase 
(Extension Switch Population) 
CS Core  
Switch Q4W IM group only 
W96, EOS 
3.20. 
Safety 
AE3 
Summary of All Drug-Related Grade 2-5 Adverse Events by 
Overall Frequency – Maintenance Phase 
 
W48, W96 
Serious and Other Significant Adverse Events  
3.21. 
Safety 
AE1 
Summary of Serious Adverse Events by System Organ Class 
– Maintenance Phase 
CS Core 
HL, W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
244 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.22. 
Safety 
AE1 
Summary of Serious Adverse Events by System Organ Class 
– Maintenance and Extension Phase (Randomized Q4W) 
CS Core 
Randomized Q4W arm only 
W96, EOS 
3.23. 
ES 
AE1 
Summary of Serious Adverse Events by System Organ Class 
– Extension Phase (Extension Switch Population) 
CS Core  
Switch Q4W IM group only 
W96, EOS 
3.24. 
LTFU 
AE1 
Summary of Serious Adverse Events by System Organ Class 
– Long term follow up 
CS Core 
W48, W96, 
EOS 
3.25. 
Safety 
AE1 
Summary of Serious Adverse Events by System Organ Class 
–– Oral Lead-in Period at Maintenance Phase 
CS Core 
Randomized Q4W arm only 
HL, W48 
3.26. 
Safety 
AE1 
Summary of Drug-Related Serious Adverse Events by System 
Organ Class – Maintenance Phase 
CS Core 
W48, W96 
3.27. 
Safety 
AE1 
Summary of Drug-Related Serious Adverse Events by System 
Organ Class – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
W96, EOS 
3.28. 
ES 
AE1 
Summary of Drug-Related Serious Adverse Events by System 
Organ Class – Extension Phase (Extension Switch Population) 
CS Core  
Switch Q4W IM only 
W96, EOS 
3.29. 
Safety 
AE3 
Summary of Non-Fatal Serious Adverse Events by Overall 
Frequency – Maintenance Phase 
 
W48, W96 
3.30. 
Safety 
AE3 
Summary of Drug-Related Non-Fatal Serious Adverse Events 
by Overall Frequency – Maintenance Phase 
 
W48, W96 
3.31. 
Safety 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by System Organ Class – Maintenance Phase 
CS Core 
HL, W48, W96 
3.32. 
Safety 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by SOC – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
245 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.33. 
ES 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by SOC – Extension Phase (Extension Switch 
Population) 
CS Core  
Switch Q4W IM group only 
W96, EOS 
3.34. 
Safety  
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by SOC – Oral Lead-in Period at Maintenance Phase 
CS Core  
Randomized Q4W arm only 
W48, W96 
3.35. 
Safety 
AE3 
Summary of Common (>=5%) Non-Serious Adverse Events by 
Overall Frequency – Maintenance Phase 
CS Core 
W48, W96 
3.36. 
Safety 
EudraCT Non-
serious AE 
AE15 
Summary of Subjects and Number of Occurrences of 
Common (>=5%) Non-Serious Adverse Events by System 
Organ Class – Maintenance Phase 
CS Core for FDAAA and EMA 
disclosure requirements. EudraCT 
Use macro TD_AE4VCTR for New 
Data Disclosure HARP Reporting 
Tools 
W48, W96 
3.37. 
Safety 
EudraCT SAE 
AE16 
Summary of Subjects and Number of Occurrences of SAEs, 
Fatal SAEs, and Drug-related SAEs – Maintenance Phase 
CS Core for FDAAA and EMA 
disclosure requirements.  EudraCT  W48, W96 
3.38. 
Safety 
Shell TS2.1 
Summary of Cumulative Adverse Events by Visit – 
Maintenance Phase 
Please note this table only display 
AEs occurring >=5% subjects 
during Maintenance Phase 
W48, W96 
3.39. 
All 
Participants 
Enrolled 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by System Organ Class – Induction Phase  
CS Core 
W48 
Injection Site Reaction Adverse Events 
3.40. 
Safety 
Shell TS2.2 
Summary of Injection Site Reaction Adverse Events (Event-
Level Summary) – Maintenance Phase 
Randomized Q4W arm only 
HL, W48, W96 
3.41. 
Safety 
Shell TS2.2 
Summary of Injection Site Reaction Adverse Events (Event-
Level Summary) – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
246 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.42. 
ES 
Shell TS2.2 
Summary of Injection Site Reaction Adverse Events (Event-
Level Summary) – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 
3.43. 
Safety 
Shell TS2.3 
Summary of Subject-Level Characteristics of Injection Site 
Reaction Adverse Events (Overall and Common) – 
Maintenance Phase 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W48, W96 
3.44. 
Safety 
Shell TS2.3 
Summary of Subject-Level Characteristics of Injection Site 
Reaction Adverse Events (Overall and Common) – 
Maintenance and Extension Phase (Randomized Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W96, EOS 
3.45. 
ES 
Shell TS2.3 
Summary of Subject-Level Characteristics of Injection Site 
Reaction Adverse Events (Overall and Common) – Extension 
Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (Switch 
Q4W IM group only) 
W96, EOS 
3.46. 
Safety 
Shell TS2.4 
Summary of Injection Site Reaction Adverse Events by Visit 
and Maximum Severity (Overall and Common) – Maintenance 
Phase 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W48, W96 
3.47. 
Safety 
Shell TS2.2 
Summary of CAB Drug-Related Injection Site Reaction 
Adverse Events (Event-Level Summary) – Maintenance Phase  Randomized Q4W arm only 
W48, W96 
3.48. 
Safety 
Shell TS2.3 
Summary of CAB Drug-Related Subject-Level Characteristics 
of Injection Site Reaction Adverse Events (Overall and 
Common) – Maintenance Phase 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for Q4W 
arm only) 
W48, W96 
3.49. 
Safety 
Shell TS2.4 
Summary of CAB Drug-Related Injection Site Reaction 
Adverse Events by Visit and Maximum Severity (Overall and 
Common) – Maintenance Phase  
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for Q4W 
arm only) 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
247 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.50. 
Safety 
Shell TS2.5 
Summary of Maximum CAB Drug-Related Injection Site 
Reaction Adverse Event Grade by Needle Length (Common 
ISRs) – Maintenance Phase 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W48, W96 
3.51. 
Safety 
Shell TS2.2 
Summary of RPV Drug-Related Injection Site Reaction 
Adverse Events (Event-Level Summary) – Maintenance Phase  
W48, W96 
3.52. 
Safety 
Shell TS2.3 
Summary of RPV Drug-Related Subject-Level Characteristics 
of Injection Site Reaction Adverse Events (Overall and 
Common) – Maintenance Phase  
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W48, W96 
3.53. 
Safety 
Shell TS2.4 
Summary of RPV Drug-Related Injection Site Reaction 
Adverse Events by Visit and Maximum Severity (Overall and 
Common) – Maintenance Phase 
 
W48, W96 
3.54. 
Safety 
Shell TS2.5 
Summary of Maximum RPV Drug-Related Injection Site 
Reaction Adverse Event Grade by Needle Length (Common 
ISRs) – Maintenance Phase   
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for Q4W 
arm only) 
W48, W96 
Laboratory: Chemistry, Hematology and Renal Markers 
3.55. 
Safety 
LB1 
Summary of Chemistry Changes from Maintenance Baseline 
(Day 1) by Visit – Maintenance Phase 
CS Core (include lipids and 
glucose in Conventional Units, 
renal markers of Retinol Binding 
Protein, Cystatin C, and CKD-EP1 
GFR using Creatinine, and CKD-
EP1 using Cystatin C et al 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
248 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.56. 
Safety 
LB1 
Summary of Chemistry Changes from Maintenance Baseline 
(Day 1) by Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core (include lipids and 
glucose in Conventional Units, 
renal markers of Retinol Binding 
Protein, Cystatin C, and CKD-EP1 
GFR using Creatinine, and CKD-
EP1 using Cystatin C et al) 
 
Randomized Q4W arm only 
EOS 
3.57. 
ES 
LB1 
Summary of Chemistry Changes from Extension Baseline 
(Week 100) by Visit – Extension Phase (Extension Switch 
Population)  
CS Core (include lipids and 
glucose in Conventional Units, 
renal markers of Retinol Binding 
Protein, Cystatin C, and CKD-EP1 
GFR using Creatinine, and CKD-
EP1 using Cystatin C et al) 
 
Switch Q4W IM group only 
EOS 
3.58. 
Safety 
LB1 
Summary of Chemistry Values by Visit – Maintenance Phase 
(include lipids and glucose in 
Conventional Units, renal markers 
of Retinol Binding Protein, Beta-2 
Microglobulin, Cystatin C, et al) 
W48, W96, 
EOS 
3.59. 
Safety 
LB1 
Summary of Chemistry Values by Visit – Maintenance and 
Extension Phase (Randomized Q4W) 
(include lipids and glucose in 
Conventional Units, renal markers 
of Retinol Binding Protein, Beta-2 
Microglobulin, Cystatin C, et al) 
 
Randomized Q4W arm only 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
249 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.60. 
ES 
LB1 
Summary of Chemistry Values by Visit – Extension Phase 
(Extension Switch Population) 
(include lipids and glucose in 
Conventional Units, renal markers 
of Retinol Binding Protein, Beta-2 
Microglobulin, Cystatin C, et al) 
 
Switch Q4W IM group only 
EOS 
3.61. 
Safety 
LB1 
Summary of Hematology Changes from Maintenance Baseline 
(Day 1) by Visit – Maintenance Phase 
CS Core  
W48, 96, EOS 
3.62. 
Safety 
LB1 
Summary of Hematology Changes from Maintenance Baseline 
(Day 1) by Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
 
EOS 
3.63. 
ES 
LB1 
Summary of Hematology Changes from Maintenance Baseline 
(Day 1) by Visit – Extension Phase (Extension Switch 
Population) 
CS Core  
EOS 
3.64. 
Safety 
LB1 
Summary of Hematology Values by Visit – Maintenance 
Phase 
CS Core  
W48, W96, 
EOS 
3.65. 
Safety 
LB1 
Summary of Hematology Values by Visit – Maintenance and 
Extension Phase (Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
 
EOS 
3.66. 
ES 
LB1 
Summary of Hematology Values by Visit – Extension Phase 
(Extension Switch Population) 
CS Core  
 EOS 
3.67. 
Safety 
Shell TS9.1 
Summary of Maximum Maintenance Phase Emergent 
Chemistry Toxicities  
CS Core 
W48, W96 
3.68. 
Safety 
Shell TS9.2 
Summary of Maximum Maintenance and Extension Phase 
Emergent Chemistry Toxicities (Randomized Q4W) 
CS Core 
Randomized Q4W arm only 
 
 W96, EOS 
3.69. 
ES 
Shell TS9.3  
Summary of Maximum Extension Phase Emergent Chemistry 
Toxicities – Extension Switch Population 
CS Core  
Switch Q4W IM group only 
 W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
250 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.70. 
Safety 
(Q4W IM 
only) 
Shell TS9.2 
Summary of Maximum Maintenance Phase Emergent 
Chemistry Toxicities – Maintenance Phase Oral Lead-in 
Period 
CS Core  
Randomized Q4W arm only 
 
W48 
3.71. 
Safety 
Shell TS9.1  
Summary of Maximum Maintenance Phase Emergent 
Hematology Toxicities   
CS Core 
W48, W96 
3.72. 
Safety 
Shell TS9.2 
Summary of Maximum Maintenance and Extension Phase 
Emergent Hematology Toxicities (Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
 
 W96, EOS 
3.73. 
ES 
Shell TS9.3  
Summary of Maximum Extension Phase Emergent 
Hematology Toxicities – Extension Switch Population 
CS Core (for ABC/DTG/3TC arm 
only 
 W96, EOS 
3.74. 
Safety 
(Q4W IM 
only) 
Shell TS9.2 
Summary of Maximum Maintenance Phase Emergent 
Hematology Toxicities – Maintenance Phase Oral Lead-in 
Period 
CS Core  
Randomized Q4W arm only 
 
W48 
3.75. 
Safety 
Shell TS16 
Summary of Fasting Lipids Percentage Changes from 
Maintenance Baseline (Day 1) by Visit (Lipid LOCF) – 
Maintenance Phase 
 
W48, W96 
Laboratory: Urinalysis 
3.76. 
Safety 
UR3 or SHELL 
TS3 
Summary of Urinalysis Dipstick Results by Visit – Maintenance 
Phase (Randomized Q4W) 
 
W48, W96, 
EOS 
3.77. 
Safety 
UR3 or SHELL 
TS3 
Summary of Urinalysis Dipstick Results by Visit – Maintenance 
and Extension Phase (Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
 
EOS 
3.78. 
ES 
UR3 or SHELL 
TS3 
Summary of Urinalysis Dipstick Results by Visit – Extension 
Phase (Extension Switch Population) 
CS Core  
Switch Q4W IM group only 
EOS 
3.79. 
Safety 
LB1 
Summary of Urine Concentrations Changes from Maintenance 
Baseline (Day 1) by Visit – Maintenance Phase 
CS Core  
W48, W96, 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
251 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.80. 
Safety 
LB1 
Summary of Urine Concentrations Changes from Maintenance 
Baseline (Day 1) by Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core  
Randomized Q4W arm only 
 
EOS 
3.81. 
ES 
LB1 
Summary of Urine Concentrations Changes from Maintenance 
Baseline (Day 1) by Visit – Extension Phase (Extension Switch 
Population) 
CS Core  
 EOS 
3.82. 
Safety 
Shell TS4 
Summary of Changes in Proteinuria Maintenance Baseline 
(Day 1) Laboratory Result to Maximum Maintenance Phase 
Laboratory Result – Maintenance Phase 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
252 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Laboratory: NCEP Lipid and Markers 
3.83. 
Safety 
Shell TS5 
Summary of Changes in Maintenance Baseline (Day 1) NCEP 
Fasting Lipid Category to Maximum Maintenance Phase 
Category – Triglycerides 
 
W48, W96 
3.84. 
Safety 
Shell TS5 
Summary of Changes in Maintenance Baseline (Day 1) NCEP 
Fasting Lipid Category to Maximum Maintenance Phase 
Category – Total Cholesterol  
 
W48, W96 
3.85. 
Safety 
Shell TS5 
Summary of Changes in Maintenance Baseline (Day 1) NCEP 
Fasting Lipid Category to Minimum Maintenance Phase 
Category – HDL Cholesterol   
 
W48, W96 
3.86. 
Safety 
Shell TS5 
Summary of Changes in Maintenance Baseline (Day 1) NCEP 
Fasting Lipid Category to Maximum Maintenance Phase 
Category – LDL Cholesterol  
 
W48, W96 
3.87. 
Safety 
Shell TS6 
Summary of Fasting TC/HDL Ratio Changes from 
Maintenance Baseline (Day 1) (Maintenance Phase) – Lipids 
LOCF 
 
W48, W96 
3.88. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Maximum Extension Phase 
Category – Triglycerides (Extension Switch Population) 
Switch Q4W IM (Oral Lead-In) 
group only 
EOS 
3.89. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Maximum Extension Phase 
Category – Total Cholesterol (Extension Switch Population) 
Switch Q4W IM (Oral Lead-In) 
group only 
EOS 
3.90. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Minimum Extension Phase 
Category – HDL Cholesterol (Extension Switch Population) 
Switch Q4W IM (Oral Lead-In) 
group only 
EOS 
3.91. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Maximum Extension Phase 
Category – LDL Cholesterol (Extension Switch Population) 
Switch Q4W IM (Oral Lead-In) 
group only 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
253 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.92. 
ES 
Shell TS6 
Summary of Fasting TC/HDL Ratio Changes from Extension 
Baseline (Week 100) (Extension Phase) – Lipids LOCF 
(Extension Switch Population) 
Switch Q4W IM (Oral Lead-In) 
group only 
EOS 
3.93. 
Safety 
Shell TS7 
Summary of Bone Markers Changes from Maintenance 
Baseline (Day 1) – Maintenance Phase  
 
W48, W96 
3.94. 
Safety 
Shell TS7 
Summary of Bone Markers Values – Maintenance Phase 
 
W48, W96 
3.95. 
Safety 
Shell TS8 
Statistical Analysis of Log-Transformed Ratio to Maintenance 
Baseline (Day 1) in Bone Markers at Week 48 – Observed 
Case 
For W96, replace Week 48 with 
W96. 
W48, W96 
Laboratory: Hepatobiliary (Liver) 
3.96. 
Safety 
Liver1 /Shell 
TS11 
Summary of Liver Monitoring/Stopping Event Reporting - 
Maintenance Phase 
 
W48, W96 
3.97. 
Safety 
liver10/Shell 
TS12 
Summary of Subjects Meeting Hepatobiliary Abnormality 
Criteria - Maintenance Phase 
 
W48, W96 
3.98. 
Safety 
liver10/Shell 
TS12 
Summary of Subjects Meeting Hepatobiliary Abnormality 
Criteria - Maintenance and Extension Phase (Randomized 
Q4W) 
Randomized Q4W arm only 
 
W96, EOS 
3.99. 
ES 
liver10/Shell 
TS12 
Summary of Subjects Meeting Hepatobiliary Abnormality – 
Extension Phase (Extension Switch Population) 
CS Core  
Switch Q4W IM group only 
W96, EOS 
3.100. 
Safety 
(Q4W arm 
only) 
liver10/Shell 
TS12 
Summary of Subjects Meeting Hepatobiliary Abnormality 
Criteria – Maintenance Phase Oral Lead-in Period  
Randomized Q4W arm only 
 
WK48 
ECG 
3.101. Safety 
EG1 
Summary of ECG Findings – Maintenance Phase 
 
W48, W96 
3.102. ES 
EG1 
Summary of ECG Findings – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
254 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.103. Safety 
EG2 
Summary of Change from Maintenance Baseline (Day 1) in 
ECG Values by Visit -Maintenance Phase  
 
WK48, W96, 
EOS 
3.104. ES 
EG2 
Summary of Change from Extension Baseline (Week 100) in 
ECG Values by Visit – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM (Oral Lead-In) 
group only 
EOS 
3.105. Safety 
EG10 
Summary of QTc Values by Category – Maintenance Phase 
Mid200056/wk48idsl/Table 8.1043 
W48, W96 
3.106. ES 
EG10 
Summary of QTc Values by Category – Extension Phase 
(Extension Switch Population) 
Mid200056/wk48idsl/Table 8.1043  
Switch Q4W IM (Oral Lead-In) 
group only 
 
EOS 
3.107. Safety 
EG10 
Summary of Change from Maintenance Baseline (Day 1) QTc 
Values by Category – Maintenance Phase 
Mid200056/wk48idsl/Table 8.1044 
W48, W96 
3.108. ES 
EG10 
Summary of Change from Extension Baseline (Week 100) 
QTc Values by Category – Extension Phase (Extension Switch 
Population) 
Mid200056/wk48idsl/Table 8.1044 
 
Switch Q4W IM (Oral Lead-in) 
group only 
EOS 
eC-SSR and Others 
3.109. Safety 
VS1 
Summary of Change from Maintenance Baseline (Day 1) in 
Vital Signs by Visit – Maintenance Phase 
CS Core 
W48, W96 
3.110. ES 
VS1 
Summary of Change from Extension Baseline (Week 100) in 
Vital Signs by Visit – Extension Phase (Extension Switch 
Population) 
CS Core 
Switch Q4W IM (Oral Lead-in) 
group only 
 
EOS 
3.111. Safety 
Shell TS14 
Summary of Subjects with eC-SSRS Suicidal Ideation or 
Behaviour During the Maintenance Phase 
 
W48, W96 
3.112. Safety 
VS1 
Summary of Change from Induction Baseline (Week -20) in 
Weight and BMI by Visit – Maintenance Phase 
CS Core 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
255 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.113. Safety 
See Safety 
Table 1.16 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Shift in BMI Categories at Week 96 
 
W96 
3.114. Safety 
See Safety 
Table 1.17 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Shift in BMI from Induction Baseline (Week -20) 
to Maximum Post-baseline Category – Maintenance Phase 
 
W96 
3.115. ES 
VS1 
Summary of Change from Extension Baseline (Week 100) in 
Weight and BMI by Visit – Extension Phase (Extension Switch 
Population) 
CS Core 
 
Switch Q4W IM (Oral Lead-in) 
group only 
EOS 
3.116. Safety 
AE5B 
Summary of All Adverse Events Excluding Injection Site 
Reactions by System Organ Class and Maximum Toxicity – 
Maintenance Phase 
CS Core 
HL, W48, W96 
3.117. Safety 
AE5B 
Summary of All Adverse Events Excluding Injection Site 
Reactions by System Organ Class and Maximum Toxicity – 
Maintenance and Extension Phase (Randomized Q4W) 
CS Core 
 
Randomized Q4W arm only 
EOS 
3.118. ES 
AE5B 
Summary of All Adverse Events Excluding Injection Site 
Reactions by System Organ Class and Maximum Toxicity –
Extension Phase (Extension Switch Population) 
CS Core 
 
Switch Q4W IM group only 
EOS 
3.119. Safety 
AE5B 
Summary of All Drug-Related Adverse Events Excluding 
Injection Site Reactions by System Organ Class and 
Maximum Toxicity – Maintenance Phase 
CS Core 
HL, W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
256 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.120. Safety 
AE5B 
Summary of All Drug-Related Adverse Events Excluding 
Injection Site Reactions by System Organ Class and 
Maximum Toxicity – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
EOS 
3.121. ES 
AE5B 
Summary of All Drug-Related Adverse Events Excluding 
Injection Site Reactions by System Organ Class and 
Maximum Toxicity – Extension Phase (Extension Switch 
Population) 
CS Core 
 
Switch Q4W IM group only 
EOS 
Adverse Events of Special Interest 
3.122. Safety 
See Safety 
Table 3.44 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Depression Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.123. Safety 
See Safety 
Table 3.44 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Depression Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.124. ES 
See Safety 
Table 3.44 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Depression Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
257 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.125. Safety 
See Safety 
Table 3.48 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Anxiety Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.126. Safety 
See Safety 
Table 3.48 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Anxiety Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.127. ES 
See Safety 
Table 3.48 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Anxiety Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 
3.128. Safety 
See Safety 
Table 3.43 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Suicidal Ideation/Behaviour Adverse Events of 
Special Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.129. Safety 
See Safety 
Table 3.43 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Suicidal Ideation/Behaviour Adverse Events of 
Special Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) – Maintenance and 
Extension Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
258 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.130. ES 
See Safety 
Table 3.43 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Suicidal Ideation/Behaviour Adverse Events of 
Special Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) – Extension Phase 
(Extension Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.131. Safety 
Shell TS14.1 
Summary of Depression, Anxiety and Suicidal 
Ideation/Behaviour Adverse Events by System Organ Class, 
Maximum DAIDS Toxicity Grade, and History of Depression, 
Anxiety and Suicidal Ideation/Behaviour at Screening – 
Maintenance Phase 
For W96 and EOS: include 
additional stratification by ‘any 
history’ vs. ‘no history’. 
W48, W96, 
EOS 
3.132. Safety 
Shell TS14.1 
Summary of Depression, Anxiety and Suicidal 
Ideation/Behaviour Adverse Events by System Organ Class, 
Maximum DAIDS Toxicity Grade, and History of Depression, 
Anxiety and Suicidal Ideation/Behaviour at Screening – 
Maintenance and Extension Phase (Randomized Q4W) 
Randomized Q4W arm only 
 
For W96 and EOS: include 
additional stratification by ‘any 
history’ vs. ‘no history’ 
W96, EOS 
3.133. ES 
Shell TS14.1 
Summary of Depression, Anxiety and Suicidal and Self-Injury 
Adverse Events by System Organ Class, Maximum DAIDS 
Toxicity Grade, and History of Depression, Anxiety and 
Suicidal Ideation/Behaviour at Screening – Extension Phase 
(Extension Switch Population) 
Switch Q4W IM group only 
 
For W96 and EOS: include 
additional stratification by ‘any 
history’ vs. ‘no history’ 
W96, EOS 
3.134. Safety 
See Safety 
Table 3.38 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Seizure Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance Phase 
 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
259 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.135. Safety 
See Safety 
Table 3.38 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Seizure Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.136. ES 
See Safety 
Table 3.38 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Seizure Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 
3.137. Safety 
See Safety 
Table 3.39 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hepatic Safety Profile: Assessment of Risk of 
Hepatoxicity Adverse Events of Special Interest by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences) – Maintenance Phase 
 
W96, EOS 
3.138. Safety 
See Safety 
Table 3.39 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hepatic Safety Profile: Assessment of Risk of 
Hepatoxicity Adverse Events of Special Interest by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.139. ES 
See Safety 
Table 3.39 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hepatic Safety Profile: Assessment of Risk of 
Hepatoxicity Adverse Events of Special Interest by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences) – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
260 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.140. Safety 
See Safety 
Table 3.40 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hypersensitivity Reaction (HSR) Adverse Events 
of Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences) – Maintenance 
Phase 
 
W96, EOS 
3.141. Safety 
See Safety 
Table 3.40 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hypersensitivity Reaction (HSR) Adverse Events 
of Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences) – Maintenance 
and Extension Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.142. ES 
See Safety 
Table 3.40 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hypersensitivity Reaction (HSR) Adverse Events 
of Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences) – Extension 
Phase (Extension Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.143. Safety 
See Safety 
Table 3.41 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rash Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.144. Safety 
See Safety 
Table 3.41 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rash Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
261 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.145. ES 
See Safety 
Table 3.41 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rash Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 
3.146. Safety 
See Safety 
Table 3.42 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Prolongation of the Corrected QT Interval of the 
ECG in Supra Therapeutic Doses Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.147. Safety 
See Safety 
Table 3.42 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Prolongation of the Corrected QT Interval of the 
ECG in Supra Therapeutic Doses Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.148. ES 
See Safety 
Table 3.42 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Prolongation of the Corrected QT Interval of the 
ECG in Supra Therapeutic Doses Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.149. Safety 
See Safety 
Table 3.45 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Bipolar Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
262 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.150. Safety 
See Safety 
Table 3.45 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Bipolar Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.151. ES 
See Safety 
Table 3.45 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Bipolar Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.152. Safety 
See Safety 
Table 3.46 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Psychosis Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.153. Safety 
See Safety 
Table 3.46 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Psychosis Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.154. ES 
See Safety 
Table 3.46 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Psychosis Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
Switch Q4W IM group only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
263 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.155. Safety 
See Safety 
Table 3.47 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Mood Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.156. Safety 
See Safety 
Table 3.47 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Mood Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.157. ES 
See Safety 
Table 3.47 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Mood Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.158. Safety 
See Safety 
Table 3.49 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Sleep Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.159. Safety 
See Safety 
Table 3.49 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Sleep Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
264 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.160. ES 
See Safety 
Table 3.49 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Sleep Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.161. Safety 
See Safety 
Table 3.51 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Weight Gain Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.162. Safety 
See Safety 
Table 3.51 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Weight Gain Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.163. ES 
See Safety 
Table 3.51 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Weight Gain Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.164. Safety 
See Safety 
Table 3.52 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rhabdomyolysis Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
265 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.165. Safety 
See Safety 
Table 3.52 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rhabdomyolysis Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.166. ES 
See Safety 
Table 3.52 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rhabdomyolysis Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.167. Safety 
See Safety 
Table 3.53 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Pancreatitis Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.168. Safety 
See Safety 
Table 3.53 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Pancreatitis Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.169. ES 
See Safety 
Table 3.53 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Pancreatitis Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
266 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.170. Safety 
See Safety 
Table 3.54 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Impact on Creatinine Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.171. Safety 
See Safety 
Table 3.54 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Impact on Creatinine Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 
3.172. ES 
See Safety 
Table 3.54 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Impact on Creatinine Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 
3.173. Safety 
See Safety 
Table 3.55 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Safety in Pregnancy Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance Phase 
 
W96, EOS 
3.174. Safety 
See Safety 
Table 3.55 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Safety in Pregnancy Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
Randomized Q4W arm only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
267 
 
Safety Tables (Displays will be for both treatment arms, unless specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.175. ES 
See Safety 
Table 3.55 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Safety in Pregnancy Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
Switch Q4W IM group only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
268 
 
14.14.8. 
Safety Figures 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Adverse Events  
3.1.  
Safety 
AE10 
Plot of Common Maintenance Phase Adverse Events and 
Relative Risk (Excluding ISRs) – Q4W vs ABC/DTG/3TC  
CS CORE 
 
HL, W48, W96 
3.2.  
Safety 
LIVER9 
Scatter Plot of Maximum vs. Maintenance Baseline (Day 1) for 
ALT – Maintenance Phase 
CS CORE 
HL, W48, W96 
3.3.  
Safety 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
Maintenance Phase 
CS CORE 
HL, W48, W96 
3.4.  
Safety 
Shell FS2 
Matrix Plot of Maximum Liver Chemistries – Maintenance 
Phase 
CS CORE 
HL, W48, W96 
3.5.  
Safety 
LIVER9 
Scatter Plot of Maximum vs. Maintenance Baseline (Day 1) for 
ALT – Maintenance and Extension Phase 
CS CORE 
Randomized Q4W arm only 
EOS 
3.6.  
Safety 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
Maintenance and Extension Phase 
CS CORE 
Randomized Q4W arm only 
EOS 
3.7.  
Safety 
Shell FS2 
Matrix Plot of Maximum Liver Chemistries – Maintenance and 
Extension Phase 
CS CORE 
Randomized Q4W arm only 
EOS 
3.8.  
ES 
LIVER9 
Scatter Plot of Maximum vs. Extension Baseline (Week 100) for 
ALT – Extension Phase (Extension Switch Population) 
CS CORE 
Switch Q4W IM group only 
W96, EOS 
3.9.  
ES 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
Extension Phase (Extension Switch Population) 
CS CORE 
Switch Q4W IM group only 
W96, EOS 
3.10. 
ES 
Shell FS2 
Matrix Plot of Maximum Liver Chemistries – Extension Phase 
(Extension Switch Population) 
CS CORE 
Switch Q4W IM group only 
W96, EOS 
3.11. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance Phase Injection Site Reaction AEs by Maximum 
Grade — CAB and/or RPV  
Randomized Q4W arm only 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
269 
 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.12. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance Phase Drug-Related Injection Site Reaction AEs 
by Maximum Grade – CAB  
Randomized Q4W arm only 
W48, W96 
3.13. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance Phase Drug-Related Injection Site Reaction AEs 
by Maximum Grade – RPV  
Randomized Q4W arm only 
W48, W96 
3.14. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance Phase Injection Site Reaction 
Adverse Events by Visit (Overall and Common) – CAB and/or 
RPV 
Randomized Q4W arm only 
W48, W96 
3.15. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance Phase Drug-Related Injection 
Site Reaction Adverse Events by Visit (Overall and Common) – 
CAB  
Randomized Q4W arm only 
W48, W96 
3.16. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance Phase Drug-Related Injection 
Site Reaction Adverse Events by Visit (Overall and Common) – 
RPV 
Randomized Q4W arm only 
W48, W96 
3.17. 
Safety 
Shell FS4/  
Plot of Incidence of Grade 3-5 Maintenance Phase Injection 
Site Reaction Adverse Events by Visit (Overall and Common) 
— CAB and/or RPV 
Randomized Q4W arm only 
W48, W96 
3.18. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance and Extension Phase Injection Site Reaction AEs 
by Maximum Grade – CAB and/or RPV (Randomized Q4W) 
Randomized Q4W arm only 
EOS 
3.19. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance and Extension Phase Drug-Related Injection Site 
Reaction AEs by Maximum Grade – CAB (Randomized Q4W) 
Randomized Q4W arm only 
EOS 
3.20. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance and Extension Phase Drug-Related Injection Site 
Reaction AEs by Maximum Grade – RPV (Randomized Q4W) 
Randomized Q4W arm only 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
270 
 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.21. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance and Extension Phase 
Injection Site Reaction Adverse Events by Visit (Overall and 
Common) – CAB and/or RPV (Randomized Q4W) 
Randomized Q4W arm only 
EOS 
3.22. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance and Extension Phase Drug-
Related Injection Site Reaction Adverse Events by Visit 
(Overall and Common) – CAB (Randomized Q4W) 
Randomized Q4W arm only 
EOS 
3.23. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance and Extension Phase Drug-
Related Injection Site Reaction Adverse Events by Visit 
(Overall and Common) – RPV (Randomized Q4W) 
Randomized Q4W arm only 
EOS 
3.24. 
Safety 
Shell FS4  
Plot of Incidence of Grade 3-5 Maintenance and Extension 
Phase Injection Site Reaction Adverse Events by Visit (Overall 
and Common) — CAB and/or RPV (Randomized Q4W) 
Randomized Q4W arm only 
EOS 
3.25. 
ES 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Extension Phase Drug-Related Injection Site Reaction AEs by 
Maximum Grade – CAB (Extension Switch Population) 
Switch Q4W IM group only 
EOS 
3.26. 
ES 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Extension Phase Drug-Related Injection Site Reaction AEs by 
Maximum Grade – RPV (Extension Switch Population) 
Switch Q4W IM group only 
EOS 
3.27. 
ES 
Shell FS4  
Plot of Incidence of Extension Phase Injection Site Reaction 
Adverse Events by Visit (Overall and Common) – CAB and/or 
RPV (Extension Switch Population) 
Switch Q4W IM group only 
EOS 
3.28. 
ES 
Shell FS4  
Plot of Incidence of Extension Phase Drug-Related Injection 
Site Reaction Adverse Events by Visit (Overall and Common) – 
CAB (Extension Switch Population) 
Switch Q4W IM group only 
EOS 
3.29. 
ES 
Shell FS4  
Plot of Incidence of Extension Phase Drug-Related Injection 
Site Reaction Adverse Events by Visit (Overall and Common) – 
RPV (Extension Switch Population) 
Switch Q4W IM group only 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
271 
 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.30. 
ES 
Shell FS4/  
Plot of Incidence of Grade 3-5 Extension Phase Injection Site 
Reaction Adverse Events by Visit (Overall and Common) — 
CAB and/or RPV (Extension Switch Population) 
Switch Q4W IM group only 
EOS 
3.31. 
Safety 
Shell FS1 
Bar Chart of Fasting Lipid NCEP Categories at Week 48 vs. 
Maintenance Baseline (Day 1) – Triglycerides, Total 
Cholesterol, LDL Cholesterol 
For W96, replace W48 with W96 
Example: 
arenv/arprod/gsk3365791/mid_dori
_ph3/week48/outputs/Figure 3.062  
W48, W96 
3.32. 
Safety 
Shell FS1 
Bar Chart of Fasting Lipid NCEP Categories at Week 48 vs. 
Maintenance Baseline (Day 1) - HDL Cholesterol 
For W96, replace W48 with W96 
Example: 
arenv/arprod/gsk3365791/mid_dori
_ph3/week48/outputs/Figure 3.062  
W48, W96 
14.14.9. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title    
Programming Notes 
The similar outputs below from study 
200056 (week48idsl), unless 
otherwise specified 
Deliverable 
[Priority] 
PK  
14.1. 
PK  
PKCT1 
Summary of Plasma CAB PK Concentration (ug/mL) -Time 
Data by Treatment and Visit (Maintenance Phase) – Included 
Log-transformed Statistics 
Table 10.1010 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.2. 
PK  
PKCT1 
Summary of Plasma RPV PK Concentration (ng/mL) -Time 
Data by Treatment and Visit (Maintenance Phase) – Included 
Log-transformed Statistics 
Table 10.1011 
Visits up to W48 for the W48 
deliverable. 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
272 
 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title    
Programming Notes 
The similar outputs below from study 
200056 (week48idsl), unless 
otherwise specified 
Deliverable 
[Priority] 
14.3. 
PK  
PKCT1 
Summary of Evaluable Plasma CAB PK Concentration 
(ug/mL)-Time Data by Treatment and Visit (Maintenance 
Phase) – Included Log-transformed Statistics 
Table 10.1012 
Visits up to W48 for the W48 
deliverable. 
W48, W96 
14.4. 
PK  
PKCT1 
Summary of Evaluable Plasma RPV PK Concentration (ng/mL) 
-Time Data by Treatment and Visit (Maintenance Phase) – 
Included Log-transformed Statistics 
Table 10.1013 
Visits up to W48 for the W48 
deliverable. 
W48, W96 
14.5. 
PK 
Shell TPK01 
Summary of Results of Steady State Assessment 
(Maintenance Phase) 
Table 10.1005 
Visits up to W48 for the W48 
deliverable. 
W48 
14.6. 
PK 
Shell TPK01 
Summary of Results of Steady State Assessment 
(Maintenance Phase) - Evaluable concentration 
Table 10.1009 
Visits up to W48 for the W48 
deliverable. 
W48 
14.7. 
PK 
PKCT1 
Summary of Plasma CAB PK Concentration (ug/mL) -Time 
Data by Treatment and Visit (Maintenance Phase) – Included 
Log-transformed Statistics by Hepatitis C Status at Induction 
Baseline 
 
W96 
14.8. 
PK 
PKCT1 
Summary of Plasma RPV PK Concentration (ng/mL) -Time 
Data by Treatment and Visit (Maintenance Phase) – Included 
Log-transformed Statistics by Hepatitis C Status at Induction 
Baseline 
 
W96 
14.9. 
ES  
PKCT1 
Summary of Plasma CAB PK Concentration (ug/mL) -Time 
Data by Treatment and Visit (Included Log-transformed 
Statistics) – Extension Phase (Extension Switch Population)  
 
EOS 
14.10. 
ES 
PKCT1 
Summary of Plasma RPV PK Concentration (ng/mL) -Time 
Data by Treatment and Visit (Included Log-transformed 
Statistics) – Extension Phase (Extension Switch Population) 
 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
273 
 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title    
Programming Notes 
The similar outputs below from study 
200056 (week48idsl), unless 
otherwise specified 
Deliverable 
[Priority] 
14.11. 
ES  
PKCT1 
Summary of Evaluable Plasma CAB PK Concentration 
(ug/mL)-Time Data by Treatment and Visit (Included Log-
transformed Statistics) – Extension Phase (Extension Switch 
Population) 
 
EOS 
14.12. 
ES  
PKCT1 
Summary of Evaluable Plasma RPV PK Concentration (ng/mL) 
-Time Data by Treatment and Visit (Included Log-transformed 
Statistics) – Extension Phase (Extension Switch Population) 
 
EOS 
14.13. 
LTFU 
PKCT1 
Summary of Long-Term Follow-up Phase Plasma CAB PK 
Concentration (ug/mL) -Time Data by Treatment and Visit - 
Included Log-transformed Statistics 
Table 10.1001 (WK96CDISC); 
For ‘Total’ treatment group (combining 
Q4W and Switch Q4W groups) 
W96, EOS 
14.14. 
LTFU 
PKCT1 
Summary of Long-Term Follow-up Phase Plasma RPV PK 
Concentration (ng/mL) -Time Data by Treatment and Visit - 
Included Log-transformed Statistics 
Table 10.1002 (WK96CDISC) 
For ‘Total’ treatment group (combining 
Q4W and Switch Q4W groups) 
W96, EOS 
14.14.10. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
The mock-up below from study 
200056 (week48idsl) 
Deliverable 
[Priority] 
PK  
14.1. 
PK  
PKCF1 
Individual Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) – Maintenance Phase  
Figure 10.1001 
Visits up to W52 for the W48 
deliverable. 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
274 
 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
The mock-up below from study 
200056 (week48idsl) 
Deliverable 
[Priority] 
14.2. 
PK  
PKCF1 
Individual Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) – Maintenance Phase 
Figure 10.1002 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.3. 
PK  
PKCF2 
Mean (SD) Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) – Maintenance Phase 
Figure 10.1003 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.4. 
PK  
PKCF3 
Median (5th and 95th percentile) Plasma CAB Concentration-
Time Plots (Linear and Semi-Log) – Maintenance Phase 
Figure 10.1004 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.5. 
PK  
PKCF2 
Mean (SD) Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) – Maintenance Phase 
Figure 10.1005 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.6. 
PK  
PKCF3 
Median (5th and 95th percentile) Plasma RPV Concentration-
Time Plots (Linear and Semi-Log) – Maintenance Phase 
Figure 10.1006 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.7. 
PK  
PKCF2 
Mean (SD) Evaluable Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) – Maintenance Phase 
Figure 10.1007 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.8. 
PK  
PKCF3 
Median (5th and 95th percentile) Evaluable Plasma CAB 
Concentration-Time Plots (Linear and Semi-Log) – 
Maintenance Phase 
Figure 10.1008 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.9. 
PK  
PKCF2 
Mean (SD) Evaluable Plasma RPV Concentration-Time 
Plots (Linear and Semi-Log) – Maintenance Phase 
Figure 10.1009 
Visits up to W52 for the W48 
deliverable. 
W48, W96 
14.10. 
PK  
PKCF3 
Median (5th and 95th percentile) Evaluable Plasma RPV 
Concentration-Time Plots (Linear and Semi-Log) – 
Maintenance Phase 
Figure 10.1010 
Visits up to W52 for the W48 
deliverable 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
275 
 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
The mock-up below from study 
200056 (week48idsl) 
Deliverable 
[Priority] 
14.11. 
PK  
PKCF2 
Mean (SD) Evaluable Plasma CAB Concentration-Time 
Plots (Semi-Log) – Maintenance Phase 
Figure 10.1011 
Visits up to W52 for the W48 
deliverable 
W48, W96 
14.12. 
PK  
PKCF2 
Mean (SD) Evaluable Plasma RPV Concentration-Time 
Plots (Semi-Log) – Maintenance Phase 
Figure 10.1012 
Visits up to W52 for the W48 
deliverable 
W48, W96 
14.13. 
LTFU 
PKCF6 
Individual Plasma CAB and RPV Concentration-Time Plots 
(Semi-Log) -- Post Last Injection for Subjects in LTFU 
Overlay all subjects, across arms; 
use actual relative time since last 
injection as the x-variable, labelled 
as “Time post last injection 
(Weeks)”; one graph each for CAB 
and RPV, respectively, on the 
same page.  Mark subjects who are 
receiving oral RPV during LTFU. 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
276 
 
14.14.11. Pharmacokinetic / Pharmacodynamic Tables 
Pharmacokinetic / Pharmacodynamic: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
Last Trough/ Nominal Week 8 Trough CAB/RPV Concentration and efficacy measures  
5.1.  
PK  
Shell 
TPK03/Table 
11.1007 (see 
applicable 
subgroups in 
Section 5.4.2) 
Logistic Regression Analysis of Snapshot ‘HIV-1 RNA≥50 
c/mL’ at Week 48 by Trough PK Concentration and 
subgroup –univariable analysis  
Last Trough Concentration and 
Nominal Week-8 trough PK 
concentration will be treated both 
as continuous variable and as a 
categorical subgroup. 
 
For W96 delivery, replace Week 48 
with Week 96. 
 
For W96: This analysis will not be 
performed if no CVF cases have 
occurred since Week 48 (for the 
Q4W arm). 
 
W48, W96 
5.2.  
PK 
Shell 
TPK03/Table 
11.1008 
Multivariable Logistic Regression Analysis of Predictors of 
Snapshot ‘HIV-1 RNA≥50 c/mL’ at Week 48 
For W96 delivery, replace Week 48 
with Week 96; 
 
For W96: This analysis will not be 
performed if no CVF cases have 
occurred since Week 48 (for the 
Q4W arm). 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
277 
 
Pharmacokinetic / Pharmacodynamic: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
5.3.  
PK 
Shell TPK02 
Summary of Last trough CAB PK concentration by 
Snapshot Virologic Response at Week 48– Included Log-
transformed Statistics 
The Virologic Response include:  
WK48 Snapshot HIV-1 RNA>=50 
(Yes/No) 
 
For W96 delivery, replace Week 48 
with Week 96 
W48 
5.4.  
PK 
Shell TPK02 
Summary of Last trough RPV PK concentration by 
Snapshot Virologic Response at Week 48 – Included Log-
transformed Statistics 
Same as above 
W48 
5.5.  
PK 
Shell TPK02 
Summary of Week 8 trough CAB PK concentration by 
Virologic Response at Maintenance– Included Log-
transformed Statistics 
The Virologic Response include:  
WK48 Snapshot HIV-1 RNA>=50 
(Yes/No) 
 
For W96 delivery, replace Week 48 
with Week 96; 
 
For W96: this summary will not be 
produced if no CVF cases have 
occurred since Week 48 (for the 
Q4W arm).  
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
278 
 
Pharmacokinetic / Pharmacodynamic: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
5.6.  
PK 
Shell TPK02 
Summary of Week 8 trough RPV PK concentration by 
Virologic Response at Maintenance– Included Log-
transformed Statistics 
Same as above 
 
For W96: this summary will not be 
performed if no CVF cases have 
occurred since Week 48 (for the 
Q4W arm). 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
279 
 
14.14.12. Pharmacokinetic / Pharmacodynamic Figures 
Pharmacokinetic / Pharmacodynamic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
Last trough/Nominal Week 8 trough CAB/RPV concentration/parameters and efficacy measures  
5.1.  
PK  
Shell 
FPK01/Figure 
11.1004 
Scatter Plot of Last Trough CAB PK Concentration by 
Snapshot HIV-1 RNA ≥50c/mL (yes vs. no) at Week 48  
 
W48 
5.2.  
PK  
Shell 
FPK01/Figure 
11.1005 
Scatter Plot of Last Trough RPV PK Concentration by 
Snapshot HIV-1 RNA≥50 c/mL (yes vs. no) at Week 48  
 
W48 
5.3.  
PK  
Shell 
FPK01/Figure 
11.1004 
Scatter Plot of Week 8 Trough CAB PK Concentration by 
Snapshot ‘HIV-1 RNA≥50 c/mL’ (yes vs. no) at Week 48  
 
W48 
5.4.  
PK  
Shell 
FPK01/Figure 
11.1005 
Scatter Plot of Week 8 Trough RPV PK Concentration by 
Snapshot HIV-1 RNA≥50 c/mL (yes vs. no) at Week 48  
 
W48 
5.5.  
PK  
Figure 11.1006 
Scatter Plot of Delay in last IP injection by Last Trough CAB 
Concentration at Week 48 at Maintenance Phase 
Different symbols for Snapshot 
Non- ‘HIV-1 RNA≥50’ and ‘HIV-1 
RNA≥50’.  X axis represents last 
trough CAB concentration, Y axis 
indicates Delay in last IP injection 
(Days) 
 
 
W48 


 
CONFIDENTIAL 
 
 
201584 
 
280 
 
Pharmacokinetic / Pharmacodynamic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
5.6.  
PK  
Figure 11.1006 
Scatter Plot of Delay in last IP injection by Last Trough RPV 
Concentration at Week 48 at Maintenance Phase 
Different symbols for Snapshot 
Non- ‘HIV-1 RNA≥50’ and ‘HIV-1 
RNA≥50’ . X axis represents last 
trough RPV concentration, Y axis 
indicates Delay in last IP injection 
(Days) 
W48 
5.7.  
PK 
Figure 11.1002 
Individual CAB trough concentration-time Profiles for 
subjects with Snapshot HIV-1 RNA≥50 c/mL at Week 48 
with Median, 5th & 95th percentile of CAB Conc-Time 
Profiles for other subjects (Semi-Log) 
For W96 delivery, replace Week 48 
with Week 96 
W48, W96 
5.8.  
PK 
Figure 11.1003 
Individual RPV trough concentration-time Profiles for 
subjects with Snapshot HIV-1 RNA≥50 c/mL at Week 48 
with Median, 5th & 95th CAB Conc-Time Profiles for other 
subjects (Semi-Log) 
For W96 delivery, replace Week 48 
with Week 96 
W48, W96 
5.9.  
PK 
Shell FPK02 
Scatter plot of Last Trough Concentration of CAB and RPV 
in relation to occurrence of Snapshot ‘HIV-1 RNA≥50 c/mL’ 
at Week 48  
Quartiles of CAB and RPV last 
trough concentration will be 
marked with vertical and horizontal 
lines. Induction Baseline BMI 
category will also be marked 
 
For W96 delivery, replace Week 48 
with Week 96 
W48 


 
CONFIDENTIAL 
 
 
201584 
 
281 
 
Pharmacokinetic / Pharmacodynamic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
5.10. 
PK 
Shell FPK02 
Scatter plot of Week 8 Trough Concentration of CAB and 
RPV in relation to occurrence of Snapshot ‘HIV-1 RNA≥50 
c/mL’ at Week 48  
Same as above. 
 
For W96: this figure will not be 
produced if no CVF cases have 
occurred since Week 48 (for the 
Q4W arm). 
W48, W96 
PK Concentration and safety measures   
5.11. 
PK  
shell FPK03  
Scatter Plot of Change from Maintenance Baseline (Day 1) 
in 2-Hr QTc versus CAB 2-Hr Post-dose PK Concentrations 
at Week X [Week 4b and Week 48 for Week 48 delivery, 
Week 96 for W96 delivery]  
For each visit (i.e. wk4b, 48, 96), 
produce separate plots of 2-Hr PK 
concentration vs QTcF and 
‘overall’. Missing QTcB/QTcF will 
be derived using RR, if RR is 
available.  For ‘overall’ plot, if QTcF 
remains missing with derivation 
from RR, then other QTc 
parameters will be used in the 
order of QTcB, QTc-unspecified, 
with different colours to 
differentiate each parameter.    
 (2hr post dose PK concentration at 
WK4b, week 48 vs CFB in QTc at 
these two visits) 
 
For W96 delivery, produce plot for 
Week 96 only 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
282 
 
Pharmacokinetic / Pharmacodynamic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
5.12. 
PK  
Shell FPK03 
Scatter Plot of Change from Maintenance Baseline (Day 1) 
in 2-Hr QTc versus RPV 2-Hr Post-dose PK Concentrations 
at Week X [Week4b and Week 48 for W48 delivery, Week 
96 for W96 delivery]   
 Similar to the above for CAB 
W48, W96 
5.13. 
PK  
shell FPK04  
Scatter Plot of Maximum Change from Maintenance 
Baseline (Day 1) in ALT versus Last Trough CAB PK 
Concentrations during the Maintenance Phase 
  
Last Trough CAB/RPV PK 
concentration is defined as the 
most recent trough PK 
concentration prior or equal to the 
date of ALT assessment with 
maximum CFB, at Maintenance 
Phase 
W48 
5.14. 
PK  
shell FPK04 
Scatter Plot of Maximum Change from Maintenance 
Baseline (Day 1) in ALT versus Last Trough RPV PK 
Concentrations during the Maintenance Phase 
 Same as above for CAB 
W48 
5.15. 
PK  
shell FPK04 
Scatter Plot of Maximum Change from Maintenance 
Baseline (Day 1) in Total Bilirubin versus Last Trough CAB 
PK Concentrations during the Maintenance Phase 
  
Last Trough CAB/RPV PK 
concentration is defined as the 
most recent trough PK 
concentration prior or equal to the 
date of Total Bili assessment with 
maximum CFB, at Maintenance 
Phase 
W48 
5.16. 
PK  
shell FPK04 
Scatter Plot of Maximum Change from Maintenance 
Baseline (Day 1) in Total Bilirubin versus Last Trough RPV 
PK Concentrations during the Maintenance Phase 
 Same as above for CAB 
W48 


 
CONFIDENTIAL 
 
 
201584 
 
283 
 
Pharmacokinetic / Pharmacodynamic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
The similar 
outputs below 
from study 
200056 
(week48idsl) 
Title  
Programming Notes 
 
Deliverable 
[Priority] 
5.17. 
PK 
shell FPK05 
Box Plot of Maximum Toxicity Grades of Most Frequently 
Reported non-ISR AEs (e.g. Headache, Fever, Fatigue, 
Nausea, Dizziness) versus Last Trough CAB PK 
Concentrations during the Maintenance Phase  
 
The AEs for this analysis should be 
the top 5 in incidence of non-ISR 
AEs within the Q4W arm during the 
Maintenance Phase.    
Last Trough CAB/RPV PK 
concentration is defined as the 
most recent trough PK 
concentration prior or equal to the 
onset date of the most frequently 
reported AE with maximum toxicity 
grade during the Maintenance 
Phase.  If a subject has no AE 
most commonly reported, then the 
last trough value at Maintenance 
Phase will be used for the plot 
W48 
5.18. 
PK 
shell FPK05 
Box Plot of Maximum Toxicity Grades of Most Frequently 
Reported AEs (e.g. Headache, Fever, Fatigue, Nausea, 
Dizziness) versus Last Trough RPV PK Concentrations 
during the Maintenance Phase  
The same as above 
W48 


 
CONFIDENTIAL 
 
 
201584 
 
284 
 
14.14.13. Health Outcomes Tables 
Health Outcomes: Tables 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title   
Programming Notes 
Deliverable  
Perception of Injection Questionnaire (PIN)  
6.1.  
ITT-E 
THO2 
Proportion of Subjects with each individual item score in PIN by 
Visit – LOCF (Maintenance Phase) 
 
W48, W96 
6.2.  
ITT-E 
THO1 
Summary of PIN in Domain Scores (Bother of ISRs, Leg 
movement, Sleep, and Acceptance) and Individual Items 
Scores (Anxiety before, Pain, Satisfaction, Anxiety After, 
Willingness) by Visit (Maintenance Phase) 
 
W48, W96 
6.3.  
ITT-E 
THO10 
Summary and Statistical Analysis of PIN in Domain Scores 
(Bother of ISRs, Leg movement, Sleep, and Acceptance) and 
Individual Items Scores (Anxiety before, Pain, Satisfaction, 
Anxiety After, Willingness) by Visit - LOCF (Maintenance 
Phase) 
Wilcoxon Signed -rank test for 
analysis (acceptance score 
only) 
W48, W96 
6.4.  
ITT-E 
THO1 
Summary of PIN Change from Week 5 in Domain Scores 
(Bother of ISRs, Leg movement, Sleep, and Acceptance) and 
Individual Items Scores (Anxiety before, Pain, Satisfaction, 
Anxiety After, Willingness) by Visit (Maintenance Phase) 
 
W48, W96 
6.5.  
ITT-E 
THO1 
Summary of PIN Change from Week 5 in Domain Scores 
(Bother of ISRs, Leg movement, Sleep, and Acceptance) and 
Individual Items Scores (Anxiety before, Pain, Satisfaction, 
Anxiety After, Willingness) by Visit – LOCF (Maintenance 
Phase) 
 
W48, W96 
Health-related quality of Life (HATQoL)  
6.6.  
ITT-E 
THO2 
Proportion of Subjects with each Individual Questionnaire Item 
Score in HATQoL by Visit - LOCF (Maintenance Phase) 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
285 
 
Health Outcomes: Tables 
6.7.  
ITT-E 
THO1 
Summary of Quality of Life (HATQoL) Score in Life 
Satisfaction, HIV Medication, and Disclosure worries by Visit 
(Maintenance Phase) 
 
W48, W96 
6.8.  
ITT-E 
THO1 
Summary of Quality of Life (HATQoL) Score in Life 
Satisfaction, HIV medication, and Disclosure worries by Visit - 
LOCF (Maintenance Phase) 
 
W48, W96 
6.9.  
ITT-E 
THO1 
Summary of Quality of Life Score (HATQoL) – Change from 
Maintenance Baseline (Day 1) in Life Satisfaction, HIV 
Medication, and Disclosure Worries by Visit (Maintenance 
Phase) 
 
W48, W96 
6.10. 
ITT-E 
THO1 
Summary of Quality of Life Score (HATQoL) – Change from 
Maintenance Baseline (Day 1) in Life Satisfaction, HIV 
Medication, and Disclosure Worries by Visit - LOCF 
(Maintenance Phase) 
 
W48, W96 
6.11. 
ITT-E 
Shell THO3 
Statistical Analysis of Quality of Life Score (HATQoL) – 
Change from Maintenance Baseline (Day 1) in Life 
Satisfaction, HIV medication, and Disclosure Worries by Visit – 
LOCF (Maintenance Phase) 
ANCOVA for analysis 
W48, W96 
Health Status:12-item short form survey (SF-12) 
6.12. 
ITT-E 
THO2 
Proportion of Subjects with SF-12 Individual Item Scores by 
Visit - LOCF (Maintenance Phase) 
 
W48, W96 
6.13. 
ITT-E 
THO1 
Summary of SF-12 (MCS and PCS Scores) by Visit 
(Maintenance Phase)  
 
W48, W96 
6.14. 
ITT-E 
THO1 
Summary of SF-12 (MCS and PCS Scores) by Visit - LOCF 
(Maintenance Phase) 
 
W48, W96 
6.15. 
ITT-E 
THO1 
Summary of Change from Maintenance Baseline (Day 1) in SF-
12 (MCS and PCS Scores) by Visit (Maintenance Phase) 
 
W48, W96 
6.16. 
ITT-E 
THO1 
Summary of Change from Maintenance Baseline (Day 1) in SF-
12 (MCS and PCS Scores) by Visit - LOCF (Maintenance 
Phase) 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
286 
 
Health Outcomes: Tables 
6.17. 
ITT-E 
Shell THO3 
Statistical Analysis of SF-12 Change from Maintenance 
Baseline (Day 1) in MCS, and PCS Score by Visit – LOCF 
(Maintenance Phase) 
ANCOVA for analysis 
 W48, W96 
Treatment Satisfaction (HIVTSQs) 
6.18. 
ITT-E 
Shell THO2 
Proportion of Subjects with HIVTSQs – Treatment Satisfaction 
Individual Item Scores by Visit - LOCF) (Maintenance Phase) 
 
W48, W96 
6.19. 
ITT-E 
Shell THO2 
Proportion of Subjects with HIVTSQs – Treatment Satisfaction 
Individual Item Scores by Visit and Subgroup - LOCF) 
(Maintenance Phase) 
Subgroups: Induction 
Baseline (Week -20) HIV-1 
RNA (<100,000, ≥100,000 
c/mL), gender at birth, age 
(<35; 35-<50; ≥50), 
Maintenance Baseline (Day 1) 
CD4+ cell count (<200; 200 to 
<350; 350 to <500; ≥ 500 
cells/mm3), and race (i.e. 
white, non-white).  
W48, W96 
6.20. 
ITT-E 
Shell THO1 
Summary of HIVTSQs - Total Treatment Satisfaction Score by 
Visit) (Maintenance Phase) 
 
W48, W96 
6.21. 
ITT-E 
Shell THO1 
Summary of HIVTSQs - Total Treatment Satisfaction Score by 
Visit - LOCF) (Maintenance Phase) 
 
W48, W96 
6.22. 
ITT-E 
Shell THO1 
Summary of HIVTSQs - Change from Maintenance Baseline 
(Day 1) in Total Treatment Satisfaction Score by Visit 
(Maintenance Phase) 
 
W48, W96 
6.23. 
ITT-E 
Shell THO1 
Summary of HIVTSQs - Change from Maintenance Baseline 
(Day 1) in Total Treatment Satisfaction Score by Visit – LOCF 
(Maintenance Phase) 
W48, W96 
6.24. 
ITT-E 
Shell THO3 
Statistical Analysis of HIVTSQs - Change from Maintenance 
Baseline (Day 1) in Total Treatment Satisfaction Score by Visit 
– LOCF) (Maintenance Phase) 
ANCOVA for analysis 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
287 
 
Health Outcomes: Tables 
6.25. 
ITT-E 
See Table 
6.40 in 
reporting 
effort: 
gsk1265744/2
01584/primary
_02 
Summary of HIVTSQs - Change from Maintenance Baseline 
(Day 1) in Individual Item Score by Visit - LOCF (Maintenance 
Phase) 
 
W96 
Treatment Satisfaction (HIVTSQc) 
6.26. 
ITT-E 
Shell THO2 
Proportion of Subjects with HIV-Treatment Satisfaction 
Questionnaire Individual Item Scores change) (Maintenance 
Phase)  
 
W48 
6.27. 
ITT-E 
Shell THO1 
Summary of HIV-Treatment Satisfaction Questionnaire in 
Treatment Satisfaction Score Change) (Maintenance Phase) 
 
W48 
6.28. 
ITT-E 
Shell THO5 
Statistical Analysis of HIV-Treatment Satisfaction 
Questionnaire in Treatment Satisfaction Score Change at 
Week 48 (Maintenance Phase) 
ANOVA for analysis 
 
W48 
Treatment Acceptance (ACCEPT) 
6.29. 
ITT-E 
Shell THO2 
Proportion of Subjects with Treatment Acceptance 
Questionnaire (ACCEPT) Individual Item Scores by Visit - 
LOCF) (Maintenance Phase) 
 
W48, W96 
6.30. 
ITT-E 
Shell THO1 
Summary of Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit (Maintenance Phase) 
 
W48, W96 
6.31. 
ITT-E 
Shell THO1 
Summary of Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit – LOCF (Maintenance Phase) 
 
W48, W96 
6.32. 
ITT-E 
Shell THO1 
Summary of Change from Maintenance Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit (Maintenance Phase) 
 
W48, W96 
6.33. 
ITT-E 
Shell THO1 
Summary of Change from Maintenance Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit – LOCF (Maintenance Phase) 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
288 
 
Health Outcomes: Tables 
6.34. 
ITT-E 
Shell THO3 
Statistical Analysis of Change from Maintenance Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit – LOCF (Maintenance Phase) 
ANCOVA for analysis 
W48, W96 
Tolerability of Injection, NRS (for Q4W IM) 
6.35. 
ITT-E 
Shell THO2 
Proportion of Subjects with Tolerability of Injection (NRS) 
Individual item scores by Visit – LOCF (Maintenance Phase) 
 
W48, W96 
6.36. 
ITT-E 
Shell THO9 
Summary of Tolerability of Injection (NRS) scores by Visit 
(Maintenance Phase) 
 
W48, W96 
6.37. 
ITT-E 
Shell THO9 
Summary of Tolerability of Injection (NRS) scores by Visit –
LOCF (Maintenance Phase) 
 
W48, W96 
6.38. 
ITT-E 
Shell THO9 
Summary of Tolerability of Injection (NRS) by Visit – Change 
from Week 4b Scores (Maintenance Phase) 
 
W48, W96 
6.39. 
ITT-E 
Shell THO9 
Summary of Tolerability of Injection (NRS) by Visit – Change 
from Week 4b Scores - LOCF (Maintenance Phase) 
 
W48, W96 
Preferences (Dichotomous preference question) (for Q4W IM) 
6.40. 
ITT-E 
Shell THO8 
Treatment Preference at Week 48 (Maintenance Phase) 
 
W48 


 
CONFIDENTIAL 
 
 
201584 
 
289 
 
14.14.14. Health Outcomes Figures 
Health Outcomes: Figures 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title  
Programming Notes 
Deliverable  
6.1.  
ITT-E 
Shell FHO1 
Line Plot of Adjusted Mean (95% CI) Change from 
Maintenance Baseline (Day 1) in HIVTSQs Total Treatment 
Satisfaction Score over Time (ANCOVA) – LOCF 
 
W48, W96 
6.2.  
ITT-E 
Shell FHO2 
Line Plot of Difference (95% CI) in Adjusted Mean Change 
from Maintenance Baseline (Day 1) in HIVTSQs Total 
Treatment Satisfaction Score over Time (ANCOVA) – LOCF 
 
W48, W96 
6.3.  
ITT-E 
Shell FHO1 
Line Plot of Adjusted Mean (95% CI) Change from 
Maintenance Baseline (Day 1) in SF-12 (MCS and PCS 
subscale) Score over Time (ANCOVA) – LOCF 
 
W48, W96 
6.4.  
ITT-E 
Shell FHO2 
Line Plot of Difference (95% CI) in Adjusted Mean Change 
from Maintenance Baseline (Day 1) in SF-12 (MCS and PCS 
subscale) Score over Time (ANCOVA) – LOCF 
 
W48, W96 
6.5.  
ITT-E 
Shell FHO1 
Line Plot of Adjusted Mean (95% CI) Change from 
Maintenance Baseline (Day 1) in HATQoL (Life Satisfaction, 
HIV medication, and Disclosure Worries) by Visit (ANCOVA) –
LOCF 
 
W48, W96 
6.6.  
ITT-E 
Shell FHO2 
Line Plot of Difference in Adjusted Mean (95% CI) Change 
from Maintenance Baseline (Day 1) in HATQoL (Life 
Satisfaction, HIV Medication, and Disclosure Worries) by Visit 
(ANCOVA) – LOCF 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
290 
 
14.14.15. Virology Tables 
Virology: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
(mock up 
below from 
study 
200056\wk48id
sl) 
Title  
Programming Notes 
 
Deliverable  
Genotype  
7.1.  
CVF 
Table 9.1001 
Summary of the Prevalence of Known INI Resistance 
Mutations at time of CVF (Maintenance Phase) – Plasma 
Sample 
Known INI resistance mutation per  
Section 14.6.6. Need to add small 
‘n’ for actual no. of subjects 
included in the analysis. The % will 
be based on ‘n’ rather than ‘N’ 
W48, W96 
7.2.  
CVF 
Table 9.1002 
Summary of the Prevalence of Treatment Emergent Known INI 
Resistance Mutations at time of CVF (Maintenance Phase) – 
Plasma Sample 
Known INI resistance mutation per 
Section 14.6.6. Need to add small 
‘n’ for actual no. of subjects 
included in the analysis. The % will 
be based on ‘n’ rather than ‘N’ 
W48, W96 
7.3.  
CVF 
Table 9.1003 
(modify region 
to class) 
Summary of the Prevalence of Major Resistance Mutations of 
NRTI, NNRTI and PI Class at time of CVF (Maintenance 
Phase) - - Plasma Sample 
Major Mutation of NRTI, NNRTI, PI 
class per Section 14.6.6.  Need to 
add small ‘n’ for actual no. of 
subjects included in the analysis. 
The % will be based on ‘n’ rather 
than ‘N’ (programming for defining 
class: can refer to 
arenv/arprod/gsk1349572/mid2003
04/week24/drivers/t_adpf_4001.sas 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
291 
 
Virology: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
(mock up 
below from 
study 
200056\wk48id
sl) 
Title  
Programming Notes 
 
Deliverable  
7.4.  
CVF 
 
Summary of the Prevalence of Treatment-Emergent Major 
Resistance Mutations of NRTI, NNRTI and PI Class at time of 
CVF (Maintenance Phase) - - Plasma Sample 
Major Mutation of NRTI, NNRTI, PI 
class per Section 14.6.6. Need to 
add small ‘n’ for actual no. of 
subjects included in the analysis. 
The % will be based on ‘n’ rather 
than ‘N’ (programming for defining 
class: can refer to 
arenv/arprod/gsk1349572/mid2003
04/week24/drivers/t_adpf_4001.sas 
W48, W96 
7.5.  
ITT-E 
 
Summary of the Prevalence of Major Resistance Mutations of 
NRTI, NNRTI and PI Class at Induction Baseline (Week -20) -- 
Plasma Sample 
Major Mutation of NRTI, NNRTI, PI 
class per Section 14.6.6. Need to 
add small ‘n’ for actual no. of 
subjects included in the analysis. 
The % will be based on ‘n’ rather 
than ‘N’ (programming for defining 
class: can refer to 
arenv/arprod/gsk1349572/mid2003
04/week24/drivers/t_adpf_4001.sas 
W48, W96 
Phenotype  
7.6.  
CVF 
Table 9.1005 
Summary of Phenotype by Phenotypic Cutoff at time of CVF 
(Maintenance Phase) - - Plasma Sample 
 
W48, W96 
7.7.  
CVF 
Table 9.1005 
Summary of Genotypic Susceptibility at time of CVF 
(Maintenance Phase) - - Plasma Sample 
 
W48, W96 


 
CONFIDENTIAL 
 
 
201584 
 
292 
 
Virology: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
(mock up 
below from 
study 
200056\wk48id
sl) 
Title  
Programming Notes 
 
Deliverable  
7.8.  
CVF 
Table 9.1005 
Summary of Net Assessment at time of CVF (Maintenance 
Phase) - Plasma Sample 
 
W48, W96 
7.9.  
CVF 
Table 9.1006  
Summary of Phenotype: Number of Drugs to Which Subject are 
Resistant at Time of CVF (Maintenance Phase) - Plasma 
Sample 
 
W48, W96 
7.10. 
CVF 
Table 9.1007 
Summary of Fold Change to CAB, RPV and DTG at Induction 
Baseline (Week -20) and Time of CVF (Maintenance Phase) - 
Plasma Sample 
 
W48, W96 
7.11. 
CVF 
Table 9.1008 
Summary of Change from Induction Baseline (Week -20) in 
Fold Change to CAB, RPV, and DTG (Maintenance Period) 
 
W48, W96 
7.12. 
CVF 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Subjects Who Met Confirmed Virologic Failure Criteria During 
the Maintenance Phase – Induction Baseline (Week -20) and 
Time of CVF 
 
HL, W48, W96 
7.13. 
CVF 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Subjects Who Met Confirmed Virologic Failure During the 
Maintenance and Extension Phase – Induction Baseline (Week 
-20) and Time of CVF (Randomized Q4W arm) 
Randomized Q4W arm only 
W96, EOS 
7.14. 
CVF 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Subjects Who Met Confirmed Virologic Failure Criteria During 
the Extension Phase – Induction Baseline (Week -20) and Time 
of CVF (Switch Q4W IM)  
Switch Q4W IM group only 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
293 
 
Virology: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
(mock up 
below from 
study 
200056\wk48id
sl) 
Title  
Programming Notes 
 
Deliverable  
7.15. 
ITT-E 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Non-CVF Subjects  
May include genotypic and 
phenotypic data on the last on-
treatment isolates for participants 
with HIV-1 RNA ≥200 c/mL 
 
Include columns for phase, phase 
treatment, phase day. 
W48, W96, 
EOS 
 
14.14.16. ICH Listings 
ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases). 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Study Population  
1.  
Randomised 
Shell LSP1 
Listing of Subjects Randomised But Not Treated 
CS CORE (related to ‘Listing for 
exclusion from any population) 
W48, W96, EOS 
2.  
Randomised 
TA1 
Listing of Randomised and Actual Strata and Treatment 
Assignment 
CS CORE 
W48, W96, EOS 
3.  
All Subjects 
Screened 
ES7 
Listing of Reasons for Screen Failure 
CS CORE 
W48, W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
294 
 
ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases). 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
4.  
ITT-E 
ES2 
Listing of Reasons for Study Withdrawal 
CS CORE 
HL, W48, W96, 
EOS 
5.  
ITT-E 
ES2 
Listing of Reasons for Study Drug Discontinuation 
CS CORE 
W48, W96, EOS 
6.  
All Enrolled 
DV2 
Listing of Important Protocol Deviations  
CS CORE 
W48, W96, EOS 
7.  
ITT-E 
DV2 
Listing of Protocol Deviations Leading to Exclusion from the 
Per-Protocol Population 
CS CORE 
HL, W48, W96, 
EOS 
8.  
All Enrolled 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
CS CORE 
W48, W96, EOS 
9.  
ITT-E 
DM2 
Listing of Demographic Characteristics 
CS CORE 
W48, W96, EOS 
10.  
ITT-E 
DM9 
Listing of Race 
CS CORE 
W48, W96, EOS 
Primary Efficacy  
11.  
All Enrolled 
Study 201584 
(primary_02): 
Listing 33  
Listing of All Plasma HIV-1 RNA Data 
 
W96, EOS 
12.  
ITT-E 
Shell LPEF1 
Listing of Study Outcome (50 c/mL) at Week 48 – Snapshot 
Analysis 
 
HL, W48, W96, 
EOS 
Exposure 
13.  
Safety 
HIV_IP5 
Listing of Investigational Product Exposure Data 
CS CORE 
W48, W96, EOS 
Adverse Events  
14.  
All Enrolled 
AE8 
Listing of All Adverse Events 
CS CORE, 
Include LTFU AEs. 
W96, EOS 
15.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events  
CS CORE 
W48, W96, EOS 
16.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event  CS CORE 
 
W48, W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
295 
 
ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases). 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
17.  
Safety 
AE8 
Listing of Fatal Adverse Events  
CS CORE 
W48, W96, EOS 
18.  
All Enrolled 
AE8 
Listing of Non-Fatal Serious Adverse Events (Induction Phase) 
CS CORE 
W48, W96, EOS 
19.  
Safety 
AE8 
Listing of Non-Fatal Serious Adverse Events  
CS CORE 
W48, W96, EOS 
20.  
All Enrolled 
AE8 
Listing of Adverse Events Leading to Withdrawal/Permanent 
Discontinuation of Investigational Product (Induction Phase) 
CS CORE 
W48, W96, EOS 
21.  
Safety 
AE8 
Listing of Adverse Events Leading to Withdrawal/Permanent 
Discontinuation of Investigational Product  
CS CORE 
HL, W48, W96, 
EOS 
22.  
Safety 
AE8 
Listing of Changes in Intensity/Grades of Injection Site Related 
AE  
Based on AE details inform page 
for changes in intensity of the 
same event. 
W48, W96, EOS 
23.  
Safety  
PREG1a 
Listing of Subjects Who Became Pregnant During the Study 
(Maintenance +Extension Phase) 
 
W48, W96, EOS 
Laboratory 
Hepatobiliary (Liver) 
24.  
Safety 
MH2 
Listing of Medical Conditions for Subjects with Liver stopping 
Events 
 
W48, W96, EOS 
25.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events 
 
W48, W96, EOS 
ECG & Vital Signs 
26.  
Safety 
EG3 
Listing of ECG Values for subjects with a value of potential 
clinical importance 
 
W48, W96, EOS 
27.  
Safety 
EG5 
Listing of ECG Findings 
 
W48, W96, EOS 
eC-SSRS 
28.  
Safety 
PSRAE1 
Listing of Possible Suicidality-Related Adverse Event Data: 
Event and Description (Section 1-Section 2) 
 
W48, W96, EOS 
29.  
Safety 
PSRAE3 
Listing of Possible Suicidality-Related Adverse Event Data: 
Possible Cause(s) (Section 3) 
 
W48, W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
296 
 
ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases). 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
30.  
Safety 
PSRAE4 
Listing of Possible Suicidality-Related Adverse Event Data 
(Section 4) 
 
W48, W96, EOS 
31.  
Safety 
PSRAE5 
Listing of Possible Suicidality-Related Adverse Event Data 
(Section 5-Section 8) 
 
W48, W96, EOS 
PK 
32.  
PK  
Study 200056 
Listing 
10.1001(wk48i
dsl) 
Listing of Plasma CAB PK Concentration-Time Data 
Add a variable of ‘evaluable’ 
(Y/N) 
W48, W96, EOS 
33.  
PK  
Study 200056 
Listing 
10.1002(wk48i
dsl) 
Listing of Plasma RPV PK Concentration-Time Data 
Add a variable of ‘evaluable’ 
(Y/N) 
W48, W96, EOS 
34.  
LTFU 
Study 200056 
Listing 
10.1001(wk48i
dsl) 
Listing of Plasma CAB PK Concentration-Time Data (LTFU 
Phase) 
Add a variable of ‘evaluable’ 
(Y/N) 
W96, EOS 
35.  
LTFU 
Study 200056 
Listing 
10.1002(wk48i
dsl) 
Listing of Plasma RPV PK Concentration-Time Data (LTFU 
Phase) 
Add a variable of ‘evaluable’ 
(Y/N) 
W96, EOS 
Other 
36.  
All Enrolled 
CM2 
Listing of Concomitant Medications for Subjects with Confirmed 
Virologic Failure 
 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
297 
 
14.14.17. Non-ICH Listings 
Non-ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Study Population  
37.  
All Enrolled 
ES2 
Listing of Reasons for Induction Phase Withdrawal 
 
W48, W96, EOS 
38.  
ITT-E 
ES2 
Listing of Reasons for Maintenance Phase Withdrawal 
 
W48, W96, EOS 
39.  
ITT-E 
ES2 
Listing of Reasons for Maintenance Phase Oral Lead-in Period 
Withdrawal 
 
W48, W96, EOS 
40.  
ITT-E 
ES2 
Listing of Reasons for Extension Phase Withdrawal 
 
W96, EOS 
41.  
LTFU 
ES2 
Listing of Reasons for Long-term Follow Up Withdrawal 
 
W48, W96, EOS 
42.  
All Enrolled 
CA3 
Listing of Prior ART Medications  
 
W48, W96, EOS 
43.  
All Enrolled 
CA3 
Listing of Concomitant ART Medications Received during 
Induction Phase 
 
WK48, W96, EOS 
44.  
ITT-E 
CA3 
Listing of Concomitant ART Medications Received during 
Maintenance Phase 
 
W48, W96, EOS 
45.  
ITT-E 
CA3 
Listing of ART Medications Received during LTFU Phase 
 
W48, W96, EOS 
46.  
ITT-E 
CA3 
Listing of subjects with changes in Concomitant ARTs during 
Maintenance Phase 
 
W48, W96, EOS 
47.  
ITT-E 
Shell LSP11 
Listing of Investigational Product Accountability - Oral 
Regimens 
 
W48, W96, EOS 
48.  
ITT-E 
MHSZE 
Listing of Medical History of Seizure 
 
W48, W96, EOS 
49.  
All Enrolled 
 
Listing of Subjects with Hepatitis C at Induction Baseline (Week 
-20) 
 
W96 
Secondary Efficacy  
50.  
All Enrolled 
Shell LSEF3 
Listing of All Plasma HIV-1 RNA data for subjects with 
Confirmed Virologic Failure (Induction Phase) 
 
W48, W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
298 
 
Non-ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
51.  
CVF 
Shell LSEF3 
Listing of All Plasma HIV-1 RNA data for subjects with 
Confirmed Virologic Failure 
 
W48, W96, EOS 
52.  
ITT-E 
Shell LSEF1 
Listing of All Plasma HIV-1 RNA data for subjects with viral 
load >=50 c/mL at any time during the Maintenance Phase  
 
HL, W48, W96, 
EOS 
53.  
ITT-E 
Shell LSEF1 
Listing of Plasma All HIV-1 RNA data for subjects with viral 
load >=50 c/mL during the Maintenance Oral lead-in Period 
 
W48 
54.  
ITT-E 
Shell LSEF5 
Listing of HIV-1 Associated Conditions  
 
W48, W96, EOS 
Safety  
55.  
Safety 
ABC_HSR 
_EXPO2 
Listing of Abacavir Hypersensitivity Reaction Record - 
Exposure to Abacavir 
 
W48, W96, EOS 
56.  
Safety 
ABC_HSR 
_DRUG2 
Listing of Abacavir Hypersensitivity Reaction Record - Subject 
History of Drug Allergies 
 
W48, W96, EOS 
57.  
Safety 
ABC_HSR 
COND2 
Listing of Abacavir Hypersensitivity Reaction Record - Subject 
and Family Conditions 
 
W48, W96, EOS 
58.  
Safety 
ABC_HSR 
_RASH2 
Listing of Abacavir Hypersensitivity Reaction Record - Skin 
Rash Details 
 
W48, W96, EOS 
59.  
Safety 
ABC_HSR 
_SYMP4 
Listing of Abacavir Hypersensitivity Reaction Record - 
Symptoms 
 
W48, W96, EOS 
60.  
Safety 
VS4 
Listing of Abacavir Hypersensitivity Reaction Record - Vital 
Signs 
 
W48, W96, EOS 
61.  
Safety 
ABC_HSR 
_SYMP6 
Listing of Abacavir Hypersensitivity Reaction Record - 
Individual Symptoms and Diagnostic Category Assignments 
(Excluding Other Symptoms) 
 
W48, W96, EOS 
62.  
Safety 
ABC_HSR 
_SYMP7 
Listing of Abacavir Hypersensitivity Reaction Record - 
Individual Symptoms and Diagnostic Category Assignments 
(Other Symptoms) 
 
W48, W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
299 
 
Non-ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
63.  
Safety 
See Listing 3 in 
reporting effort: 
gsk1265744/mi
d209522/iss_0
1 
Listing of all Subjects Meeting Liver Stopping Criteria 
 
W96, EOS 
64.  
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting 
 
W48, W96, EOS 
65.  
Safety 
LIVER6 
Listing of Liver Event Information for RUCAM Score 
 
W48, W96, EOS 
66.  
Safety 
LIVER7 
Listing of Liver Biopsy Details 
 
W48, W96, EOS 
67.  
Safety 
LIVER8 
Listing of Liver Imaging Details 
 
W48, W96, EOS 
68.  
Safety 
Liver13 
Listing Subjects Meeting Hepatobiliary Lab Criteria  
Please also add those 
additional items shown in the 
summary of subjects meeting 
hepatobiliary lab criteria post-
baseline (i.e. AST >3xULN and 
ALP <2xULN and BIL 
>=2xULN]; ALT+AST>=xx) 
W48, W96, EOS 
69.  
Safety  
AE8 
Listing of Adverse Events Related to Prolongation of the 
Corrected QT Interval of the ECG in Supra Therapeutic Doses 
 
W48, W96, EOS 
70.  
Safety 
EG3 
Listing of ECG Values for Subjects with Adverse Events 
Related to Prolongation of the Corrected QT Interval of the 
ECG in Supra Therapeutic Doses 
 
W48, W96, EOS 
71.  
Safety 
Latte2 
WK96CDISC 
report 
Listing of Each Subjects ALT, AST, Bilirubin (including total and 
direct Bilirubin), INR, and ALP for subject meeting Hepatobiliary 
Lab abnormality criteria 
8.1037 (add AST, ALP, INR, 
and direct Bilirubin to the listing 
and only for subject meeting 
Hepatobiliary Lab abnormality 
criteria) 
HL, W48, W96, 
EOS 


 
CONFIDENTIAL 
 
 
201584 
 
300 
 
Non-ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
72.  
Safety 
Latte2 
WK96CDISC 
report 
Listing of Investigational Product Exposure Data for Subject 
Receiving Oral Bridging 
8.1038 
W48, W96, EOS 
73.  
Safety 
DEV1 
Listing of Dosing Errors and IP Device Malfunctions 
 
 
W48, W96, EOS 
Virology (mock up below from study 200056\wk96cdisc), ‘Study Phase’ will be added as a column to the listing.  
74.  
CVF 
Listing 9.1005 
Listing of Replication Capacity in IN and PR/RT Region 
 
W48, W96, EOS 
75.  
All Enrolled 
Table 9.1009 
Listing of Genotypic Mutation Data at All Timepoints 
 
W96, EOS 


 
CONFIDENTIAL 
 
 
201584 
 
301 
 
14.15. 
Appendix 15: List of Data Displays for Week 124 
All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects 
CDISC and GSK Data Display Standards terminology. 
Unless stated otherwise, all Extension Switch population tables and figures will include 
treatment groups for direct to inject, oral lead-in and total. 
14.15.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.01 to 1.n 
1.01 to 1.n 
Efficacy 
2.01 to 2.n 
2.01 to 2.n 
Safety 
3.01 to 3.n 
3.01 to 3.n 
Pharmacokinetic 
4.01 to 4.n 
4.01 to 4.n 
Virology 
7.01 to 7.n 
7.01 to 7.n 
Section 
Listings 
ICH Listings 
1 to x 
Other Listings 
y to z 
 
14.15.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided a separate document. 
14.15.3. 
Deliverables 
Delivery  
Description 
HL 
Headline for Week 124 
Week 124 
Week 124 
 
 


 
CONFIDENTIAL 
 
 
201584 
302 
 
14.15.4. 
Study Population Tables 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
Subject Disposition 
1.1.  
All Subjects 
Screened  
SA1 
Summary of Study Populations 
 
HL, W124 
1.2.  
All Subjects 
Screened 
Shell TSP1 
Summary of Subjects by Country and Investigator 
 
W124 
1.3.  
ITT-E 
ES1 
Summary of Subject Accountability: Study Conclusion 
Record  
 
W124 
1.4.  
ITT-E 
ES1 
Summary of Study Drug Discontinuation 
 
W124 
1.5.  
LTFU 
ES1 
Summary of Subject Accountability: Long-term follow 
up Phase Conclusion Record  
 
W124 
1.6.  
ITT-E 
ES1 
Summary of Subject Accountability: Maintenance and 
Extension Phase Conclusion Record (Randomized 
Q4W) 
For Randomized Q4W arm only 
Add the following subcategories 
under subject status:  a) 
Completed Maintenance and did 
not enter Extension b) Completed 
Extension c) Withdrawn from 
Maintenance d) Withdrawn from 
Extension. 
W124 
1.7.  
ITT-E 
HIV_ES1 
Summary of Subject Accountability: Withdrawals by 
Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
1.8.  
ES 
ES1 
Summary of Subject Accountability: Extension Phase 
Conclusion Record (Extension Switch Population) 
 
HL, W124 


 
CONFIDENTIAL 
 
 
201584 
303 
 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
1.9.  
ES 
HIV_ES1 
Summary of Subject Accountability: Withdrawals by 
Visit – Extension Phase (Extension Switch 
Population) 
 
W124 
1.10. 
All 
Participants 
Enrolled 
ES4 
Summary of Subject Disposition at Each Study Epoch 
 
W124 
1.11. 
All 
Participants 
Enrolled 
ES5 
Summary of Reasons for Withdrawal at Each Epoch 
 
W124 
1.12. 
ITT-E 
DV1a 
Summary of Important Protocol Deviations - 
Maintenance and Extension Phase (Randomized 
Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
304 
 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
1.13. 
ES 
DV1a 
Summary of Important Protocol Deviations – 
Extension Phase (Extension Switch Population) 
 
W124 
Demography and Baseline 
1.14. 
ES 
Shell TSP2 
Summary of Demographic Characteristics (Extension 
Switch Population) 
See also DM1 in IDSL 
Age categorization will include:  
<=18, 19-64, >=65 (FDAAA 
requirement) 
18-64, 65-84, >=85 (EMA 
requirement) 
 
HL, W124 
1.15. 
ES 
DM5 
Summary of Race and Racial Combinations 
(Extension Switch Population) 
CS CORE 
W124 
1.16. 
ES 
DM6 
Summary of Race and Racial Combinations Details 
(Extension Switch Population) 
CS CORE 
W124 
1.17. 
ES 
Shell TSP3 
Summary of Hepatitis Status at Induction Baseline 
(Week -20)  – Extension Switch Population 
 
W124 
1.18. 
ES 
CDC1 
Summary of Derived CDC Stages of HIV Infection at 
Extension Baseline (Week 100) 
 
W124 
1.19. 
ES 
Shell TSP5 
Distribution of CD4+ Cell Count Results at Extension 
Baseline (Week 100) - Extension Switch Population 
Same presentation as shown in 
the mock shell for induction 
baseline. 
W124 
Medical Conditions, Concomitant Medications & Antiretroviral Therapy 
1.20. 
ES 
MH4 
Summary of Current Cardiac, Gastrointestinal, 
Metabolism and Nutrition, Psychiatric, Renal and 
Urinary, Nervous System Conditions, and 
Hepatobiliary disorders (Extension Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
305 
 
Study Population Tables  
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
1.21. 
ES 
MH4 
Summary of Past Cardiac, Gastrointestinal, 
Metabolism and Nutrition, Psychiatric, Renal and 
Urinary, Nervous System Conditions, and 
Hepatobiliary disorders (Extension Switch Population) 
 
W124 
1.22. 
ITT-E 
CM8 
Summary of Concomitant Medication Ingredient 
Combinations - Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
1.23. 
ES 
CM8 
Summary of Concomitant Medication Ingredient 
Combinations – Extension Phase (Extension Switch 
Population) 
 
W124 
1.24. 
ES 
Shell TSP11 
Summary of Alternate Background NRTI Therapy at 
End of Maintenance Phase (Extension Switch 
Population) 
 
W124 
1.25. 
ES 
Shell TSP9 
Summary of Lipid Modifying Agent Use at Extension 
Baseline (Week 100) – Extension Switch Population 
 
W124 
1.26. 
ES 
Shell CLAD1 
Summary of the Prevalence of HIV-1 Subtype at 
Induction Baseline (Week -20) - Extension Switch 
Population 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
306 
 
14.15.5. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
Efficacy Analyses  
2.1.  
ES 
Shell TPEF2 
Summary of Study Outcomes (50 c/mL cut-off) at Week 124 – 
Snapshot Analysis (Extension Switch Population) 
Oral Lead-In, Direct to Inject, Total 
HL, W124 
2.2.  
ES 
Shell TSEF2 
Proportion of Subjects with Plasma HIV-1 RNA ≥50 c/mL by Visit 
(Extension Phase) – Snapshot Analysis (Extension Switch 
Population) 
Oral Lead-In, Direct to Inject, Total 
 
95% confidence intervals (CIs), for 
the proportion of participants with 
HIV-1 RNA ≥50c/mL by treatment 
group at each visit. The 95% CIs will 
be calculated using Exact (Clopper-
Pearson) confidence interval if the 
proportion is 0%; otherwise, they are 
derived using the normal 
approximation. 
 
HL, W124 


 
CONFIDENTIAL 
 
 
201584 
307 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.3.  
ES 
Shell TSEF2.1 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL by Visit 
(Extension Phase) – Snapshot Analysis (Extension Switch 
Population) 
Oral Lead-In, Direct to Inject, Total 
 
95% confidence intervals (CIs), for 
the proportion of participants with 
HIV-1 RNA ≥50c/mL by treatment 
group at each visit. The 95% CIs will 
be calculated using Exact (Clopper-
Pearson) confidence interval if the 
proportion is 0%; otherwise, they are 
derived using the normal 
approximation. 
 
HL, W124 
2.4.  
ES 
Shell TSEF2 
Proportion of Subjects with Plasma HIV-1 RNA <200 c/mL by Visit 
(Extension Phase) – Snapshot Analysis (Extension Switch 
Population) 
Oral Lead-In, Direct to Inject, Total 
 
95% confidence intervals (CIs), for 
the proportion of participants with 
HIV-1 RNA ≥50c/mL by treatment 
group at each visit. The 95% CIs will 
be calculated using Exact (Clopper-
Pearson) confidence interval if the 
proportion is 0%; otherwise, they are 
derived using the normal 
approximation. 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
308 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.5.  
ES 
Shell TSEF3 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria by Visit During the Extension Phase (Up to Week 
124) — Extension Switch Population 
Oral Lead-In, Direct to Inject, Total 
 
show all planned extension phase 
visits up to Week 124. 
HL, W124 
2.6.  
ES 
Shell TSEF3.1 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria During the Extension Phase (Extension Switch 
Population) 
 
Oral Lead-In, Direct to Inject, Total 
HL, W124 
2.7.  
ES 
Shell TSEF5 
Summary of CD4+ Cell Count (cells/mm^3) by Visit – Extension 
Phase (Extension Switch Population) 
Oral Lead-In, Direct to Inject, Total 
W124 
2.8.  
ES 
Shell TSEF5 
Summary of Change from Extension Baseline (Week 100) in 
CD4+ Cell Count (cells/mm^3) by Visit – Extension Phase 
(Extension Switch Population) 
Oral Lead-In, Direct to Inject, Total 
W124 
2.9.  
ES 
Shell TSEF5 
Summary of CD8+ Cell Count (cells/mm^3) by Visit– Extension 
Phase (Extension Switch Population) 
Oral Lead-In  
W124 
2.10. 
ES 
Shell TSEF5 
Summary of Change from Extension Baseline (Week 100) in 
CD8+ Cell Count (cells/mm^3) by Visit – Extension Phase 
(Extension Switch Population) 
Oral Lead-In 
W124 
2.11. 
ES 
Shell TSEF5 
Summary of CD4+/CD8+ Ratio Cell Count (cells/mm^3) by Visit – 
Extension Phase (Extension Switch Population) 
Oral Lead-In 
W124 
2.12. 
ES 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Including Recurrences 
– Extension Phase (Extension Switch Population) 
Oral Lead-In, Direct to Inject, Total 
W124 
2.13. 
ES 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Excluding Recurrences 
– Extension Phase (Extension Switch Population) 
Oral Lead-In, Direct to Inject, Total 
W124 
2.14. 
ES 
HIV2/Shell 
TSEF6.1 
Summary of HIV-1 Disease Progressions and/or Deaths – 
Extension Phase (Extension Switch Population) 
Oral Lead-In, Direct to Inject, Total 
W124 
2.15. 
ES 
Shell TPEF2 
Summary of Study Outcomes (200 c/mL) at Week 124 – 
Snapshot Analysis (Extension Switch Population) 
Oral Lead-In, Direct to Inject, Total 
W124 
2.16. 
ES 
Shell TSEF11 
Summary of Subjects per Viral Load Category by Visit (Extension 
Phase) — Extension Switch Population 
Oral Lead-In, Direct to Inject, Total 
W124 


 
CONFIDENTIAL 
 
 
201584 
309 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.17. 
ITT-E 
Shell TPEF2 
Summary of Study Outcomes (50 c/mL cut-off) at Week 124 – 
Snapshot Analysis (Randomized Q4W) 
 
HL, W124 
2.18. 
ITT-E 
Shell TSEF2 
Proportion of Subjects with Plasma HIV-1 RNA ≥50 c/mL by Visit 
(Maintenance and Extension Phase) – Snapshot Analysis 
(Randomized Q4W) 
 
W124 
2.19. 
ITT-E 
Shell TSEF2.1 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL by Visit 
(Maintenance and Extension Phase) – Snapshot Analysis 
(Randomized Q4W) 
 
W124 
2.20. 
ITT-E 
Shell TSEF2 
Proportion of Subjects with Plasma HIV-1 RNA <200 c/mL by Visit 
(Maintenance and Extension Phase) – Snapshot Analysis 
(Randomized Q4W) 
 
W124 
2.21. 
ITT-E 
Shell TSEF3 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria by Visit During the Maintenance and Extension 
Phase (Up to Week 124) — Randomized Q4W 
show all visits up to Week 124 
W124 
2.22. 
ITT-E 
Shell TSEF3.1 
Cumulative Proportion of Subjects Meeting Confirmed Virologic 
Failure Criteria During the Maintenance and Extension Phase 
(Randomized Q4W) 
 
HL, W124 
2.23. 
ITT-E 
Shell TSEF5 
Summary of Change from Maintenance Baseline (Day 1) in CD4+ 
Cell Count (cells/mm^3) by Visit - Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
2.24. 
ITT-E 
Shell TSEF5 
Summary of CD4+ Cell Count (cells/mm^3) by Visit – 
Maintenance and Extension Phase (Randomized Q4W) 
 
W124 
2.25. 
ITT-E 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Including Recurrences - 
Maintenance and Extension Phase (Randomized Q4W) 
 
W124 
2.26. 
ITT-E 
HIV1/Shell 
TSEF 6.0 
Summary of HIV-1 Associated Conditions Excluding Recurrences 
- Maintenance and Extension Phase (Randomized Q4W)  
 
W124 
2.27. 
ITT-E 
HIV2/Shell 
TSEF6.1 
Summary of HIV-1 Disease Progressions and/or Deaths -
Maintenance and Extension Phase (Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
310 
 
Efficacy: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell Title  
Programming Notes 
Deliverable  
2.28. 
ITT-E 
Shell TPEF2 
Summary of Study Outcomes (200 c/mL) at Week 124 
(Maintenance and Extension Phase) – Snapshot Analysis 
(Randomized Q4W) 
 
W124 
2.29. 
ITT-E 
Shell TSEF11 
Summary of Subjects per Viral Load Category by Visit 
(Maintenance and Extension Phase) — Randomized Q4W 
 
W124 
14.15.6. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.1.  
ES 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA ≥50 c/mL by 
Visit (Extension Phase) – Snapshot Analysis (Extension Switch 
Population) 
Oral Lead-In, Direct to Inject, Total 
 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA ≥50c/mL 
by treatment group at each visit. The 
95% CIs will be calculated using 
Exact (Clopper-Pearson) confidence 
interval if the proportion is 0%; 
otherwise, they are derived using the 
normal approximation. 
 
HL, W124 


 
CONFIDENTIAL 
 
 
201584 
311 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.2.  
ES 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA <50 c/mL by 
Visit (Extension Phase) – Snapshot Analysis (Extension Switch 
Population) 
Oral Lead-In, Direct to Inject, Total 
 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA <50c/mL 
by treatment group at each visit. The 
95% CIs will be calculated using 
Exact (Clopper-Pearson) confidence 
interval if the proportion is 0%; 
otherwise, they are derived using the 
normal approximation. 
 
HL, W124 
2.3.  
ES 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA <200 c/mL by 
Visit (Extension Phase) – Snapshot Analysis (Extension Switch 
Population) 
Oral Lead-In, Direct to Inject, Total 
 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA <200 
c/mL by treatment group at each 
visit. The 95% CIs will be calculated 
using Exact (Clopper-Pearson) 
confidence interval if the proportion is 
0%; otherwise, they are derived 
using the normal approximation. 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
312 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.4.  
ES 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA >=200 c/mL 
by Visit (Extension Phase) – Snapshot Analysis (Extension 
Switch Population) 
Oral Lead-In, Direct to Inject, Total 
 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA ≥200 
c/mL by treatment group at each 
visit. The 95% CIs will be calculated 
using Exact (Clopper-Pearson) 
confidence interval if the proportion is 
0%; otherwise, they are derived 
using the normal approximation. 
 
W124 
2.5.  
ES 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA (log10 copies/mL) Profiles by 
Visit for CVF subjects (Extension Switch Population – Direct to 
Inject Group) 
The first vertical line indicates 
extension phase day of first 
CAB/RPV injection.  The second 
vertical reference line indicates last 
on-treatment extension phase day, 
i.e. min (max(day of last IP injection 
dose+35 days, day of last oral 
CAB/RPV+1), day of LTFU HAART 
start date).  This line is only for 
participants who discontinue from the 
Extension phase. 
W124 


 
CONFIDENTIAL 
 
 
201584 
313 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.6.  
ES 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA (log10 copies/mL) Profiles by 
Visit for CVF subjects (Extension Switch Population – Oral 
Lead-in Group) 
The first vertical line indicates 
extension phase day for start of oral 
lead-in with oral CAB/RPV.  The 
second vertical reference line 
indicates last on-treatment extension 
phase day, i.e. min (max(day of last 
IP injection dose+35 days, day of last 
oral CAB/RPV+1), day of LTFU 
HAART start date).  This line is only 
for participants who discontinue from 
the Extension phase. 
W124 
2.7.  
ES 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA Profiles by Visit for subjects who 
are in the category of ‘viral load ≥50 c/mL’ at Week 124 per 
Snapshot algorithm (Extension Switch Population – Direct to 
Inject Group) 
The first vertical line indicates 
extension phase day of first 
CAB/RPV injection.  The second 
vertical reference line indicates last 
on-treatment extension phase day, 
i.e. min (max(day of last IP injection 
dose+35 days, day of last oral 
CAB/RPV+1), day of LTFU HAART 
start date).  This line is only for 
participants who discontinue from the 
Extension phase. 
HL, W124 


 
CONFIDENTIAL 
 
 
201584 
314 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.8.  
ES 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA Profiles by Visit for subjects who 
are in the category of ‘viral load ≥50 c/mL’ at Week 124 per 
Snapshot algorithm (Extension Switch Population – Oral Lead-
in Group) 
The first vertical line indicates 
extension phase day for start of oral 
lead-in with oral CAB/RPV.  The 
second vertical reference line 
indicates last on-treatment extension 
phase day, i.e. min (max(day of last 
IP injection dose+35 days, day of last 
oral CAB/RPV+1), day of LTFU 
HAART start date).  This line is only 
for participants who discontinue from 
the Extension phase. 
HL, W124 
2.9.  
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA ≥50 c/mL by 
Visit (Maintenance and Extension Phase) – Snapshot Analysis 
(Randomized Q4W) 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA ≥50c/mL 
by treatment group at each visit. The 
95% CIs will be calculated using 
Exact (Clopper-Pearson) confidence 
interval if the proportion is 0%; 
otherwise, they are derived using the 
normal approximation. 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
315 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.10. 
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA <50 c/mL by 
Visit (Maintenance and Extension Phase) – Snapshot Analysis 
(Randomized Q4W) 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA < 
50c/mL by treatment group at each 
visit. The 95% CIs will be calculated 
using Exact (Clopper-Pearson) 
confidence interval if the proportion is 
0%; otherwise, they are derived 
using the normal approximation. 
 
W124 
2.11. 
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA <200 c/mL by 
Visit (Maintenance and Extension Phase) – Snapshot Analysis 
(Randomized Q4W) 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA <200 
c/mL by treatment group at each 
visit. The 95% CIs will be calculated 
using Exact (Clopper-Pearson) 
confidence interval if the proportion is 
0%; otherwise, they are derived 
using the normal approximation. 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
316 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.12. 
ITT - E 
Shell FPEF1 
Proportion (95% CI) of Subjects with HIV-1 RNA >=200 c/mL 
by Visit (Maintenance and Extension Phase) – Snapshot 
Analysis (Randomized Q4W) 
Line plots, with 95% confidence 
intervals (CIs), for the proportion of 
participants with HIV-1 RNA ≥200 
c/mL by treatment group at each 
visit. The 95% CIs will be calculated 
using Exact (Clopper-Pearson) 
confidence interval if the proportion is 
0%; otherwise, they are derived 
using the normal approximation. 
 
W124 
2.13. 
ITT-E 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA (log10 copies/mL) Profiles by 
Visit) – for CVF subjects (Randomized Q4W)  
The first vertical line indicates start of 
Induction phase investigational 
product (ABC/DTG/3TC or DTG). 
The second vertical line indicates 
start of Maintenance phase 
investigational product (oral CAB + 
oral RPV). The third vertical 
reference line indicates last on-
treatment study day, i.e. min 
(max(day of last IP injection dose+35 
days, day of last oral CAB+RPV+1), 
day of LTFU HAART start 
date).  This line is only for 
participants who withdraw from the 
Maintenance/Extension phase. 
W124 


 
CONFIDENTIAL 
 
 
201584 
317 
 
Efficacy: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
2.14. 
ITT - E 
Mid200056//wk
96cdisc/Figure 
7.1007 
Individual Plasma HIV-1 RNA Profiles by Visit for subjects who 
are in the category of ‘HIV-1 RNA ≥50 c/mL’ at Week 124 per 
Snapshot algorithm (Randomized Q4W arm) 
The first vertical line indicates start of 
Induction phase investigational 
product (ABC/DTG/3TC or DTG). 
The second vertical line indicates 
start of Maintenance phase 
investigational product (oral CAB + 
oral RPV). The third vertical 
reference line indicates last on-
treatment study day, i.e. min 
(max(day of last IP injection dose+35 
days, day of last oral CAB+RPV+1), 
day of LTFU HAART start 
date).  This line is only for 
participants who withdraw from the 
Maintenance/Extension phase. 
HL, W124 
 
14.15.7. 
Safety Tables – Extension Switch Population 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Exposure  
3.1.  
ES 
Shell TS1.1 
Summary of Extent of Exposure to Investigational Product –
Extension Phase (Extension Switch Population) 
 
HL, W124 
3.2.  
ES 
Study 201584 
(primary_02): 
Table 3.114 
Summary of Categorized Needle Length and Gauge for CAB 
Injection - Extension Phase (Extension Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
318 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.3.  
ES 
Study 201584 
(primary_02): 
Table 3.115 
Summary of Categorized Needle Length and Gauge for RPV 
Injection - Extension Phase (Extension Switch Population) 
 
W124 
3.4.  
ES 
Shell TS1.3 
Summary of Adherence to Q4W IM Dosing Schedule - 
Extension Phase (Extension Switch Population) 
Please refer to Section 14.6.2-- 
Adherence to CAB/RPV Injection 
Schedule 
W124 
Adverse Events  
3.5.  
ES 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Extension Phase (Extension Switch 
Population) 
 
HL, W124 
3.6.  
ES 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Extension Phase Oral Lead-in Period 
(Extension Switch Population)  
Switch Q4W Oral Lead-in Group 
Only 
W124 
3.7.  
ES 
AE3 
Summary of Common Adverse Events (>=5%) by Overall 
Frequency – Extension Phase (Extension Switch Population) 
 
W124 
3.8.  
ES 
AE3 
Summary of Common Grade 2-5 Adverse Events (>=1%) by 
Overall Frequency – Extension Phase (Extension Switch 
Population) 
 
W124 
3.9.  
ES 
AE5B 
Summary of All Drug-Related Adverse Events by System 
Organ Class and Maximum Toxicity – Extension Phase 
(Extension Switch Population) 
 
HL, W124 
3.10. 
ES 
AE3 
Summary of All Drug-Related Grade 2-5 Adverse Events by 
Overall Frequency – Extension Phase (Extension Switch 
Population) 
 
W124 
Serious and Other Significant Adverse Events  
3.11. 
ES 
AE1 
Summary of Serious Adverse Events by System Organ Class 
– Extension Phase (Extension Switch Population) 
 
HL, W124 


 
CONFIDENTIAL 
 
 
201584 
319 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.12. 
ES 
AE1 
Summary of Serious Adverse Events by System Organ Class 
–– Extension Phase Oral Lead-in Period (Extension Switch 
Population) 
Switch Q4W Oral Lead-in Group 
Only 
W124  
3.13. 
ES 
AE1 
Summary of Drug-Related Serious Adverse Events by System 
Organ Class – Extension Phase (Extension Switch Population)  
W124 
3.14. 
ES 
AE3 
Summary of Non-Fatal Serious Adverse Events by Overall 
Frequency – Extension Phase (Extension Switch Population) 
 
W124 
3.15. 
ES 
AE3 
Summary of Drug-Related Non-Fatal Serious Adverse Events 
by Overall Frequency – Extension Phase (Extension Switch 
Population) 
 
W124 
3.16. 
ES 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by SOC – Extension Phase (Extension Switch 
Population) 
 
HL, W124 
3.17. 
ES 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by SOC – Extension Phase Oral Lead-in Period 
(Extension Switch Population) 
Switch Q4W Oral Lead-in Group 
Only 
W124 
3.18. 
ES 
AE3 
Summary of Common (>=5%) Non-Serious Adverse Events by 
Overall Frequency – Extension Phase (Extension Switch 
Population) 
 
W124 
3.19. 
ES 
EudraCT Non-
serious AE 
AE15 
Summary of Subjects and Number of Occurrences of 
Common (>=5%) Non-Serious Adverse Events by System 
Organ Class – Extension Phase (Extension Switch Population) 
CS Core for FDAAA and EMA 
disclosure requirements. EudraCT 
Use macro TD_AE4VCTR for New 
Data Disclosure HARP Reporting 
Tools 
W124 
3.20. 
ES 
EudraCT SAE 
AE16 
Summary of Subjects and Number of Occurrences of SAEs, 
Fatal SAEs, and Drug-related SAEs – Extension Phase 
(Extension Switch Population) 
CS Core for FDAAA and EMA 
disclosure requirements.  EudraCT  W124 


 
CONFIDENTIAL 
 
 
201584 
320 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.21. 
ES 
AE5B 
Summary of All Adverse Events Excluding Injection Site 
Reactions by System Organ Class and Maximum Toxicity –
Extension Phase (Extension Switch Population) 
 
W124 
3.22. 
ES 
AE5B 
Summary of All Drug-Related Adverse Events Excluding 
Injection Site Reactions by System Organ Class and 
Maximum Toxicity – Extension Phase (Extension Switch 
Population) 
 
 
W124 
Injection Site Reaction Adverse Events 
3.23. 
ES 
Shell TS2.2 
Summary of Injection Site Reaction Adverse Events (Event-
Level Summary) – Extension Phase (Extension Switch 
Population) 
 
HL, W124 
3.24. 
ES 
Shell TS2.3 
Summary of Subject-Level Characteristics of Injection Site 
Reaction Adverse Events (Overall and Common) – Extension 
Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects  
W124 
3.25. 
ES 
Shell TS2.4 
Summary of Injection Site Reaction Adverse Events by Visit 
and Maximum Severity (Overall and Common) – Extension 
Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects  
W124 
3.26. 
ES 
Shell TS2.2 
Summary of CAB Drug-Related Injection Site Reaction 
Adverse Events (Event-Level Summary) – Extension Phase 
(Extension Switch Population) 
 
W124 
3.27. 
ES 
Shell TS2.3 
Summary of CAB Drug-Related Subject-Level Characteristics 
of Injection Site Reaction Adverse Events (Overall and 
Common) – Extension Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects 
W124 
3.28. 
ES 
Shell TS2.4 
Summary of CAB Drug-Related Injection Site Reaction 
Adverse Events by Visit and Maximum Severity (Overall and 
Common) – Extension Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects 
W124 


 
CONFIDENTIAL 
 
 
201584 
321 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.29. 
ES 
Shell TS2.5 
Summary of Maximum CAB Drug-Related Injection Site 
Reaction Adverse Event Grade by Needle Length (Common 
ISRs) – Extension Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects 
W124 
3.30. 
ES 
Shell TS2.2 
Summary of RPV Drug-Related Injection Site Reaction 
Adverse Events (Event-Level Summary) – Extension Phase 
(Extension Switch Population) 
 
W124 
3.31. 
ES 
Shell TS2.3 
Summary of RPV Drug-Related Subject-Level Characteristics 
of Injection Site Reaction Adverse Events (Overall and 
Common) – Extension Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects 
W124 
3.32. 
ES 
Shell TS2.4 
Summary of RPV Drug-Related Injection Site Reaction 
Adverse Events by Visit and Maximum Severity (Overall and 
Common) – Extension Phase (Extension Switch Population) 
 
W124 
3.33. 
ES 
Shell TS2.5 
Summary of Maximum RPV Drug-Related Injection Site 
Reaction Adverse Event Grade by Needle Length (Common 
ISRs) – Extension Phase (Extension Switch Population) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects 
W124 
Laboratory: Chemistry, Hematology and Renal Markers 
3.34. 
ES 
LB1 
Summary of Chemistry Values by Visit – Extension Phase 
(Extension Switch Population) 
(include lipids and glucose in 
Conventional Units, renal markers 
of Retinol Binding Protein, Beta-2 
Microglobulin, Cystatin C, et al) 
W124 
3.35. 
ES 
LB1 
Summary of Chemistry Changes from Extension Baseline 
(Week 100) by Visit – Extension Phase (Extension Switch 
Population)  
CS Core (include lipids and 
glucose in Conventional Units, 
renal markers of Retinol Binding 
Protein, Cystatin C, and CKD-EP1 
GFR using Creatinine, and CKD-
EP1 using Cystatin C et al) 
W124 


 
CONFIDENTIAL 
 
 
201584 
322 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.36. 
ES 
Shell TS9.3  
Summary of Maximum Extension Phase Emergent Chemistry 
Toxicities (Extension Switch Population) 
 
W124 
3.37. 
ES 
Shell TS9.2 
Summary of Maximum Emergent Chemistry Toxicities – 
Extension Phase Oral Lead-in Period (Extension Switch 
Population) 
Switch Q4W Oral Lead-in Group 
Only 
W124 
3.38. 
ES 
LB1 
Summary of Hematology Values by Visit – Extension Phase 
(Extension Switch Population) 
 
W124 
3.39. 
ES 
LB1 
Summary of Hematology Changes from Extension Baseline 
(Week 100) by Visit – Extension Phase (Extension Switch 
Population) 
 
W124 
3.40. 
ES 
Shell TS9.3  
Summary of Maximum Extension Phase Emergent 
Hematology Toxicities (Extension Switch Population) 
 
W124 
3.41. 
ES 
Shell TS9.2 
Summary of Maximum Emergent Hematology Toxicities – 
Extension Phase Oral Lead-in Period (Extension Switch 
Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.42. 
ES 
Shell TS16 
Summary of Fasting Lipids Percentage Changes from 
Extension Baseline (Week 100) by Visit (Lipid LOCF) – 
Extension Phase (Extension Switch Population) 
 
W124 
Laboratory: Urinalysis 
3.43. 
ES 
UR3 or SHELL 
TS3 
Summary of Urinalysis Dipstick Results by Visit – Extension 
Phase (Extension Switch Population) 
 
W124 
3.44. 
ES 
LB1 
Summary of Urine Concentrations Changes from Extension 
Baseline (Week 100) by Visit – Extension Phase (Extension 
Switch Population) 
 
W124 
3.45. 
ES 
Shell TS4 
Summary of Changes in Proteinuria Extension Baseline 
(Week 100) Laboratory Result to Maximum Extension Phase 
Laboratory Result – Extension Phase (Extension Switch 
Population) 
 
W124 
Laboratory: NCEP Lipid and Markers 


 
CONFIDENTIAL 
 
 
201584 
323 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.46. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Maximum Extension Phase 
Category – Triglycerides (Extension Switch Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.47. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Maximum Extension Phase 
Category – Total Cholesterol (Extension Switch Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.48. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Minimum Extension Phase 
Category – HDL Cholesterol (Extension Switch Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.49. 
ES 
Shell TS5 
Summary of Changes in Extension Baseline (Week 100) 
NCEP Fasting Lipid Category to Maximum Extension Phase 
Category – LDL Cholesterol (Extension Switch Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.50. 
ES 
Shell TS6 
Summary of Extension Phase Fasting TC/HDL Ratio Changes 
from Extension Baseline (Week 100) – Lipids LOCF 
(Extension Switch Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
Laboratory: Hepatobiliary (Liver) 
3.51. 
ES 
Liver1 /Shell 
TS11 
Summary of Liver Monitoring/Stopping Event Reporting – 
Extension Phase (Extension Switch Population) 
 
W124 
3.52. 
ES 
liver10/Shell 
TS12 
Summary of Subjects Meeting Hepatobiliary Abnormality 
Criteria – Extension Phase (Extension Switch Population) 
 
W124 
3.53. 
ES 
liver10/Shell 
TS12 
Summary of Subjects Meeting Hepatobiliary Abnormality 
Criteria – Extension Phase Oral Lead-in Period (Extension 
Switch Population)  
Switch Q4W Oral Lead-in Group 
Only 
W124 
ECG 
3.54. 
ES 
EG1 
Summary of ECG Findings – Extension Phase (Extension 
Switch Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.55. 
ES 
EG2 
Summary of Change from Extension Baseline (Week 100) in 
ECG Values by Visit – Extension Phase (Extension Switch 
Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 


 
CONFIDENTIAL 
 
 
201584 
324 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.56. 
ES 
EG10 
Summary of QTc Values by Category – Extension Phase 
(Extension Switch Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.57. 
ES 
EG10 
Summary of Change from Extension Baseline (Week 100) in 
QTc Values by Category – Extension Phase (Extension Switch 
Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
Others 
3.58. 
ES 
VS1 
Summary of Change from Extension Baseline (Week 100) in 
Vital Signs by Visit – Extension Phase (Extension Switch 
Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.59. 
ES 
VS1 
Summary of Change from Extension Baseline (Week 100) in 
Weight and BMI by Visit – Extension Phase (Extension Switch 
Population) 
Switch Q4W Oral Lead-in Group 
Only  
W124 
3.60. 
ES 
 
Summary of Shift in BMI Categories at Week 104b 
Switch Q4W Oral Lead-in Group 
Only  
W124 
Adverse Events of Special Interest 
3.61. 
ES 
See Safety 
Table 3.44 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Depression Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
 
W124 
3.62. 
ES 
See Safety 
Table 3.48 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Anxiety Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
325 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.63. 
ES 
See Safety 
Table 3.43 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Suicidal Ideation/Behaviour Adverse Events of 
Special Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) – Extension Phase 
(Extension Switch Population) 
 
W124 
3.64. 
ES 
Shell TS14.1 
Summary of Depression, Anxiety and Suicidal and Self-Injury 
Adverse Events by System Organ Class, Maximum DAIDS 
Toxicity Grade, and History of Depression, Anxiety and 
Suicidal Ideation/Behaviour at Screening – Extension Phase 
(Extension Switch Population) 
 
include additional stratification by 
‘any history’ vs. ‘no history’ 
W124 
3.65. 
ES 
See Safety 
Table 3.38 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Seizure Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
 
W124 
3.66. 
ES 
See Safety 
Table 3.39 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hepatic Safety Profile: Assessment of Risk of 
Hepatotoxicity Adverse Events of Special Interest by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences) – Extension Phase (Extension Switch 
Population) 
 
W124 
3.67. 
ES 
See Safety 
Table 3.40 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hypersensitivity Reaction (HSR) Adverse Events 
of Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences) – Extension 
Phase (Extension Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
326 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.68. 
ES 
See Safety 
Table 3.41 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rash Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
 
W124 
3.69. 
ES 
See Safety 
Table 3.42 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Prolongation of the Corrected QT Interval of the 
ECG in Supra Therapeutic Doses Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 
3.70. 
ES 
See Safety 
Table 3.45 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Bipolar Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 
3.71. 
ES 
See Safety 
Table 3.46 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Psychosis Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Extension Phase (Extension Switch 
Population) 
 
W124 
3.72. 
ES 
See Safety 
Table 3.47 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Mood Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
327 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.73. 
ES 
See Safety 
Table 3.49 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Sleep Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 
3.74. 
ES 
See Safety 
Table 3.51 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Weight Gain Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 
3.75. 
ES 
See Safety 
Table 3.52 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rhabdomyolysis Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 
3.76. 
ES 
See Safety 
Table 3.53 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Pancreatitis Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 
3.77. 
ES 
See Safety 
Table 3.54 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Impact on Creatinine Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
328 
 
All Tables will have treatment columns for Oral lead-in, Direct-to-Inject and Total, unless otherwise specified) 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.78. 
ES 
See Safety 
Table 3.55 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Safety in Pregnancy Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Extension Phase (Extension 
Switch Population) 
 
W124 
14.15.8. 
Safety Tables – Maintenance + Extension Phase (Randomized Q4W Only) 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Exposure  
3.79. 
Safety 
Shell TS1.1 
Summary of Extent of Exposure to Investigational Product – 
Maintenance and Extension Phase (Randomized Q4W) 
 
W124 
3.80. 
Safety 
Study 201584 
(primary_02): 
Table 3.114 
Summary of Categorized Needle Length and Gauge for CAB 
Injection – Maintenance and Extension Phase (Randomized 
Q4W) 
 
W124 
3.81. 
Safety 
Study 201584 
(primary_02): 
Table 3.115 
Summary of Categorized Needle Length and Gauge for RPV 
Injection – Maintenance and Extension Phase (Randomized 
Q4W) 
 
W124 
3.82. 
Safety 
Shell TS1.3 
Summary of Adherence to Q4W IM Dosing Schedule – 
Maintenance and Extension Phase (Randomized Q4W) 
please refer to Section 14.6.2-- 
Adherence to CAB/RPV Injection 
Schedule 
W124 
Adverse Events  
3.83. 
Safety 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
329 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.84. 
LTFU 
AE5B 
Summary of All Adverse Events by System Organ Class and 
Maximum Toxicity – Long-term Follow-up Phase 
 
W124 
3.85. 
Safety 
AE3 
Summary of Common Adverse Events (>=5%) by Overall 
Frequency – Maintenance and Extension Phase (Randomized 
Q4W) 
 
W124 
3.86. 
Safety 
AE3 
Summary of Common Grade 2-5 Adverse Events (>=1%) by 
Overall Frequency – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.87. 
Safety 
AE5B 
Summary of All Drug-Related Adverse Events by System 
Organ Class and Maximum Toxicity – Maintenance and 
Extension Phase (Randomized Q4W) 
 
W124 
3.88. 
Safety 
AE3 
Summary of All Drug-Related Grade 2-5 Adverse Events by 
Overall Frequency – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
Serious and Other Significant Adverse Events  
3.89. 
Safety 
AE1 
Summary of Serious Adverse Events by System Organ Class 
– Maintenance and Extension Phase (Randomized Q4W) 
 
W124 
3.90. 
Safety 
AE1 
Summary of Drug-Related Serious Adverse Events by System 
Organ Class – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.91. 
Safety 
AE3 
Summary of Non-Fatal Serious Adverse Events by Overall 
Frequency – Maintenance and Extension Phase (Randomized 
Q4W) 
 
W124 
3.92. 
Safety 
AE3 
Summary of Drug-Related Non-Fatal Serious Adverse Events 
by Overall Frequency – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
330 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.93. 
Safety 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by System Organ Class – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.94. 
Safety 
AE3 
Summary of Common (>=5%) Non-Serious Adverse Events 
by Overall Frequency – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.95. 
Safety 
EudraCT Non-
serious AE 
AE15 
Summary of Subjects and Number of Occurrences of 
Common (>=5%) Non-Serious Adverse Events by System 
Organ Class – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core for FDAAA and EMA 
disclosure requirements. EudraCT 
Use macro TD_AE4VCTR for New 
Data Disclosure HARP Reporting 
Tools 
W124 
3.96. 
Safety 
EudraCT SAE 
AE16 
Summary of Subjects and Number of Occurrences of SAEs, 
Fatal SAEs, and Drug-related SAEs – Maintenance and 
Extension Phase (Randomized Q4W) 
CS Core for FDAAA and EMA 
disclosure requirements.  EudraCT  W124 
Injection Site Reaction Adverse Events 
3.97. 
Safety 
Shell TS2.2 
Summary of Injection Site Reaction Adverse Events (Event-
Level Summary) – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.98. 
Safety 
Shell TS2.3 
Summary of Subject-Level Characteristics of Injection Site 
Reaction Adverse Events (Overall and Common) – 
Maintenance and Extension Phase (Randomized Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W124 
3.99. 
Safety 
Shell TS2.4 
Summary of Injection Site Reaction Adverse Events by Visit 
and Maximum Severity (Overall and Common) – Maintenance 
and Extension Phase (Randomized Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W124 


 
CONFIDENTIAL 
 
 
201584 
331 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.100. Safety 
Shell TS2.2 
Summary of CAB Drug-Related Injection Site Reaction 
Adverse Events (Event-Level Summary) – Maintenance and 
Extension Phase (Randomized Q4W) 
 
W124 
3.101. Safety 
Shell TS2.3 
Summary of CAB Drug-Related Subject-Level Characteristics 
of Injection Site Reaction Adverse Events (Overall and 
Common) – Maintenance and Extension Phase (Randomized 
Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for Q4W 
arm only) 
W124 
3.102. Safety 
Shell TS2.4 
Summary of CAB Drug-Related Injection Site Reaction 
Adverse Events by Visit and Maximum Severity (Overall and 
Common) – Maintenance and Extension Phase (Randomized 
Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for Q4W 
arm only) 
W124 
3.103. Safety 
Shell TS2.5 
Summary of Maximum CAB Drug-Related Injection Site 
Reaction Adverse Event Grade by Needle Length (Common 
ISRs) – Maintenance and Extension Phase (Randomized 
Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W124 
3.104. Safety 
Shell TS2.2 
Summary of RPV Drug-Related Injection Site Reaction 
Adverse Events (Event-Level Summary) – Maintenance and 
Extension Phase (Randomized Q4W) 
 
W124 
3.105. Safety 
Shell TS2.3 
Summary of RPV Drug-Related Subject-Level Characteristics 
of Injection Site Reaction Adverse Events (Overall and 
Common) – Maintenance and Extension Phase (Randomized 
Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for 
randomized Q4W arm only) 
W124 
3.106. Safety 
Shell TS2.4 
Summary of RPV Drug-Related Injection Site Reaction 
Adverse Events by Visit and Maximum Severity (Overall and 
Common) – Maintenance and Extension Phase (Randomized 
Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
332 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.107. Safety 
Shell TS2.5 
Summary of Maximum RPV Drug-Related Injection Site 
Reaction Adverse Event Grade by Needle Length (Common 
ISRs) – Maintenance and Extension Phase (Randomized 
Q4W) 
Common ISR includes pain, 
induration, nodules and any other 
ISR with ≥5% subjects (for Q4W 
arm only) 
W124 
3.108. Safety 
AE5B 
Summary of All Adverse Events Excluding Injection Site 
Reactions by System Organ Class and Maximum Toxicity – 
Maintenance and Extension Phase (Randomized Q4W) 
 
 
W124 
3.109. Safety 
AE5B 
Summary of All Drug-Related Adverse Events Excluding 
Injection Site Reactions by System Organ Class and 
Maximum Toxicity – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
Laboratory: Chemistry, Hematology and Renal Markers 
3.110. Safety 
LB1 
Summary of Chemistry Values by Visit – Maintenance and 
Extension Phase (Randomized Q4W) 
(include lipids and glucose in 
Conventional Units, renal markers 
of Retinol Binding Protein, Beta-2 
Microglobulin, Cystatin C, et al) 
W124 
3.111. Safety 
LB1 
Summary of Chemistry Changes from Maintenance Baseline 
(Day 1) by Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
CS Core (include lipids and 
glucose in Conventional Units, 
renal markers of Retinol Binding 
Protein, Cystatin C, and CKD-EP1 
GFR using Creatinine, and CKD-
EP1 using Cystatin C et al) 
W124 
3.112. Safety 
LB1 
Summary of Hematology Values by Visit – Maintenance and 
Extension Phase (Randomized Q4W) 
 
W124 
3.113. Safety 
LB1 
Summary of Hematology Changes from Maintenance Baseline 
(Day 1) by Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
333 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.114. Safety 
Shell TS9.2 
Summary of Maximum Maintenance and Extension Phase 
Emergent Chemistry Toxicities (Randomized Q4W) 
 
W124 
3.115. Safety 
Shell TS9.2 
Summary of Maximum Maintenance and Extension Phase 
Emergent Hematology Toxicities (Randomized Q4W) 
 
W124 
Laboratory: Hepatobiliary (Liver) 
3.116. Safety 
Liver1 /Shell 
TS11 
Summary of Liver Monitoring/Stopping Event Reporting – 
Maintenance and Extension Phase (Randomized Q4W) 
 
W124 
3.117. Safety 
liver10/Shell 
TS12 
Summary of Subjects Meeting Hepatobiliary Abnormality 
Criteria - Maintenance and Extension Phase (Randomized 
Q4W) 
 
W124 
Urinalysis 
3.118. Safety 
UR3 or SHELL 
TS3 
Summary of Urinalysis Dipstick Results by Visit – 
Maintenance and Extension Phase (Randomized Q4W) 
 
W124 
3.119. Safety 
LB1 
Summary of Urine Concentrations Changes from Maintenance 
Baseline (Day 1) by Visit – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.120. Safety 
Shell TS4 
Summary of Changes in Proteinuria Maintenance Baseline 
(Day 1) Laboratory Result to Maximum Maintenance Phase 
Laboratory Result – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
AEs of Special Interest 
3.121. Safety 
See Safety 
Table 3.44 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Depression Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
334 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.122. Safety 
See Safety 
Table 3.48 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Anxiety Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.123. Safety 
See Safety 
Table 3.43 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Suicidal Ideation/Behaviour Adverse Events of 
Special Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) – Maintenance and 
Extension Phase (Randomized Q4W) 
 
W124 
3.124. Safety 
Shell TS14.1 
Summary of Depression, Anxiety and Suicidal and Self-Injury 
Adverse Events by System Organ Class, Maximum DAIDS 
Toxicity Grade, and History of Depression, Anxiety and 
Suicidal Ideation/Behaviour at Screening – Maintenance and 
Extension Phase (Randomized Q4W) 
 
include additional stratification by 
‘any history’ vs. ‘no history’ 
W124 
3.125. Safety 
See Safety 
Table 3.38 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Seizure Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.126. Safety 
See Safety 
Table 3.39 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hepatic Safety Profile: Assessment of Risk of 
Hepatotoxicity Adverse Events of Special Interest by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
335 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.127. Safety 
See Safety 
Table 3.40 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Hypersensitivity Reaction (HSR) Adverse Events 
of Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences) – Maintenance 
and Extension Phase (Randomized Q4W) 
 
W124 
3.128. Safety 
See Safety 
Table 3.41 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rash Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 
3.129. Safety 
See Safety 
Table 3.42 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Prolongation of the Corrected QT Interval of the 
ECG in Supra Therapeutic Doses Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.130. Safety 
See Safety 
Table 3.45 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Bipolar Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.131. Safety 
See Safety 
Table 3.46 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Psychosis Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of Subjects 
and Occurrences) – Maintenance and Extension Phase 
(Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
336 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.132. Safety 
See Safety 
Table 3.47 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Mood Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.133. Safety 
See Safety 
Table 3.49 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Sleep Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.134. Safety 
See Safety 
Table 3.51 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Weight Gain Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.135. Safety 
See Safety 
Table 3.52 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Rhabdomyolysis Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.136. Safety 
See Safety 
Table 3.53 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Pancreatitis Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
337 
 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.137. Safety 
See Safety 
Table 3.54 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Impact on Creatinine Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
3.138. Safety 
See Safety 
Table 3.55 in 
reporting effort: 
gsk1265744/mid
209522/iss_01 
Summary of Safety in Pregnancy Adverse Events of Special 
Interest by System Organ Class and Preferred Term (Number 
of Subjects and Occurrences) – Maintenance and Extension 
Phase (Randomized Q4W) 
 
W124 
14.15.9. 
Safety Tables – Long Term Follow Up 
 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Exposure  
3.139. LTFU 
AE1 
Summary of Serious Adverse Events by System Organ Class 
– Long Term Follow Up Phase 
 
W124 
 


 
CONFIDENTIAL 
 
 
201584 
338 
 
14.15.10. Safety Figures – Extension Switch Population 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Adverse Events  
3.1.  
ES 
LIVER9 
Scatter Plot of Maximum vs. Extension Baseline (Week 100) for 
ALT – Extension Phase (Extension Switch Population) 
 
W124 
3.2.  
ES 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
Extension Phase (Extension Switch Population) 
 
W124 
3.3.  
ES 
Shell FS2 
Matrix Plot of Maximum Liver Chemistries – Extension Phase 
(Extension Switch Population) 
 
W124 
3.4.  
ES 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Extension Phase Injection Site Reaction AEs by Maximum 
Grade — CAB and/or RPV (Extension Switch Population) 
 
W124 
3.5.  
ES 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Extension Phase Drug-Related Injection Site Reaction AEs by 
Maximum Grade – CAB (Extension Switch Population) 
 
W124 
3.6.  
ES 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Extension Phase Drug-Related Injection Site Reaction AEs by 
Maximum Grade – RPV (Extension Switch Population) 
 
W124 
3.7.  
ES 
Shell FS4  
Plot of Incidence of Extension Phase Injection Site Reaction 
Adverse Events by Visit (Overall and Common) – CAB and/or 
RPV (Extension Switch Population) 
 
W124 
3.8.  
ES 
Shell FS4  
Plot of Incidence of Extension Phase Drug-Related Injection 
Site Reaction Adverse Events by Visit (Overall and Common) – 
CAB (Extension Switch Population) 
 
W124 
3.9.  
ES 
Shell FS4  
Plot of Incidence of Extension Phase Drug-Related Injection 
Site Reaction Adverse Events by Visit (Overall and Common) – 
RPV (Extension Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
339 
 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.10. 
ES 
Shell FS4/  
Plot of Incidence of Grade 3-5 Extension Phase Injection Site 
Reaction Adverse Events by Visit (Overall and Common) — 
CAB and/or RPV (Extension Switch Population) 
 
W124 
3.11. 
Safety 
Shell FS1 
Bar Chart of Fasting Lipid NCEP Categories at Week W104 vs. 
Extension Baseline (Week 100) – Triglycerides, Total 
Cholesterol, LDL Cholesterol 
Switch Q4W Oral Lead-in Group 
Only 
W124 
3.12. 
Safety 
Shell FS1 
Bar Chart of Fasting Lipid NCEP Categories at Week 104 vs. 
Extension Baseline (Week 100) - HDL Cholesterol 
Switch Q4W Oral Lead-in Group 
Only 
W124 
14.15.11. Safety Figures – Maintenance + Extension Phase (Randomized Q4W) 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Adverse Events  
3.13. 
Safety 
LIVER9 
Scatter Plot of Maximum vs. Maintenance Baseline (Day 1) for 
ALT – Maintenance and Extension Phase 
 
W124 
3.14. 
Safety 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
Maintenance and Extension Phase 
 
W124 
3.15. 
Safety 
Shell FS2 
Matrix Plot of Maximum Liver Chemistries – Maintenance and 
Extension Phase 
 
W124 
3.16. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance and Extension Phase Injection Site Reaction AEs 
by Maximum Grade – CAB and/or RPV (Randomized Q4W) 
 
W124 
3.17. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance and Extension Phase Drug-Related Injection Site 
Reaction AEs by Maximum Grade – CAB (Randomized Q4W) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
340 
 
Safety: Figures  
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
3.18. 
Safety 
Shell FS3  
Plot of Onset, Duration, and Severity of Overall and Common 
Maintenance and Extension Phase Drug-Related Injection Site 
Reaction AEs by Maximum Grade – RPV (Randomized Q4W) 
 
W124 
3.19. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance and Extension Phase 
Injection Site Reaction Adverse Events by Visit (Overall and 
Common) – CAB and/or RPV (Randomized Q4W) 
 
W124 
3.20. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance and Extension Phase Drug-
Related Injection Site Reaction Adverse Events by Visit 
(Overall and Common) – CAB (Randomized Q4W) 
 
W124 
3.21. 
Safety 
Shell FS4  
Plot of Incidence of Maintenance and Extension Phase Drug-
Related Injection Site Reaction Adverse Events by Visit 
(Overall and Common) – RPV (Randomized Q4W) 
 
W124 
3.22. 
Safety 
Shell FS4  
Plot of Incidence of Grade 3-5 Maintenance and Extension 
Phase Injection Site Reaction Adverse Events by Visit (Overall 
and Common) — CAB and/or RPV (Randomized Q4W) 
 
W124 
14.15.12. Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title    
Programming Notes 
The similar outputs below from study 
200056 (week48idsl), unless 
otherwise specified 
Deliverable 
[Priority] 
PK  
4.1.  
PK  
PKCT1 
Summary of Extension Phase Plasma CAB PK Concentration 
(ug/mL) -Time Data by Treatment and Visit – Including Log-
transformed Statistics (Extension Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
341 
 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title    
Programming Notes 
The similar outputs below from study 
200056 (week48idsl), unless 
otherwise specified 
Deliverable 
[Priority] 
4.2.  
PK  
PKCT1 
Summary of Extension Phase Plasma RPV PK Concentration 
(ng/mL) -Time Data by Treatment and Visit – Including Log-
transformed Statistics (Extension Switch Population) 
 
W124 
4.3.  
PK  
PKCT1 
Summary of Evaluable Extension Phase Plasma CAB PK 
Concentration (ug/mL) -Time Data by Treatment and Visit – 
Including Log-transformed Statistics (Extension Switch 
Population) 
 
W124 
4.4.  
PK  
PKCT1 
Summary of Evaluable Extension Phase Plasma RPV PK 
Concentration (ng/mL) -Time Data by Treatment and Visit – 
Including Log-transformed Statistics (Extension Switch 
Population) 
 
W124 
4.5.  
PK  
PKCT1 
Summary of Extension Phase Plasma CAB PK Concentration 
(ug/mL) -Time Data by Visit and Hepatitis C Status at Induction 
Baseline – Including Log-transformed Statistics (Extension 
Switch Population) 
 
W124 
4.6.  
PK  
PKCT1 
Summary of Extension Phase Plasma RPV PK Concentration 
(ng/mL) -Time Data by Visit and Hepatitis C Status at Induction 
Baseline – Including Log-transformed Statistics (Extension 
Switch Population) 
 
W124 
4.7.  
LTFU 
PKCT1 
Summary of Long-Term Follow-up Phase Plasma CAB PK 
Concentration (ug/mL) -Time Data by Treatment and Visit - 
Included Log-transformed Statistics 
Table 10.1001 (WK96CDISC); 
For ‘Total’ treatment group (combining 
Q4W and Switch Q4W groups) 
W124 
4.8.  
LTFU 
PKCT1 
Summary of Long-Term Follow-up Phase Plasma RPV PK 
Concentration (ng/mL) -Time Data by Visit (Excluding Subjects 
Receiving Oral RPV in the LTFU Phase) - Including Log-
transformed Statistics 
Table 10.1002 (WK96CDISC) 
For ‘Total’ treatment group (combining 
Q4W and Switch Q4W groups) 
W124 


 
CONFIDENTIAL 
 
 
201584 
342 
 
14.15.13. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
The mock-up below from study 
200056 (week48idsl) 
Deliverable 
[Priority] 
PK  
4.1.  
PK  
PKCF1 
Individual Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) – Extension Phase (Extension Switch 
Population) 
 
W124 
4.2.  
PK  
PKCF1 
Individual Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) – Extension Phase (Extension Switch 
Population) 
 
W124 
4.3.  
PK  
PKCF2 
Mean (SD) Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) – Extension Phase (Extension Switch 
Population) 
 
W124 
4.4.  
PK  
PKCF3 
Median (5th and 95th percentile) Plasma CAB Concentration-
Time Plots (Linear and Semi-Log) – Extension Phase 
(Extension Switch Population) 
 
W124 
4.5.  
PK  
PKCF2 
Mean (SD) Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) – Extension Phase (Extension Switch 
Population) 
 
W124 
4.6.  
PK  
PKCF3 
Median (5th and 95th percentile) Plasma RPV Concentration-
Time Plots (Linear and Semi-Log) – Extension Phase 
(Extension Switch Population) 
 
W124 
4.7.  
PK  
PKCF2 
Mean (SD) Evaluable Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) – Extension Phase (Extension 
Switch Population) 
 
W124 
4.8.  
PK  
PKCF3 
Median (5th and 95th percentile) Evaluable Plasma CAB 
Concentration-Time Plots (Linear and Semi-Log) – 
Extension Phase (Extension Switch Population) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
343 
 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
The mock-up below from study 
200056 (week48idsl) 
Deliverable 
[Priority] 
4.9.  
PK  
PKCF2 
Mean (SD) Evaluable Plasma RPV Concentration-Time 
Plots (Linear and Semi-Log) – Extension Phase (Extension 
Switch Population) 
 
W124 
4.10. 
PK  
PKCF3 
Median (5th and 95th percentile) Evaluable Plasma RPV 
Concentration-Time Plots (Linear and Semi-Log) – 
Extension Phase (Extension Switch Population) 
 
W124 
4.11. 
PK  
PKCF2 
Mean (SD) Evaluable Plasma CAB Concentration-Time 
Plots (Semi-Log) – Extension Phase (Extension Switch 
Population) 
 
W124 
4.12. 
PK  
PKCF2 
Mean (SD) Evaluable Plasma RPV Concentration-Time 
Plots (Semi-Log) – Extension Phase (Extension Switch 
Population) 
 
W124 
4.13. 
LTFU 
PKCF6 
Individual Plasma CAB and RPV Concentration-Time Plots 
(Semi-Log) -- Post Last Injection for Subjects in LTFU 
Overlay all subjects, across arms; 
use actual relative time since last 
injection as the x-variable, labelled 
as “Time post last injection 
(Weeks)”; one graph each for CAB 
and RPV, respectively, on the 
same page.  Mark subjects who are 
receiving oral RPV during LTFU. 
W124 


 
CONFIDENTIAL 
 
 
201584 
344 
 
14.15.14. Virology Tables 
Virology: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
(mock up 
below from 
study 
200056\wk48id
sl) 
Title  
Programming Notes 
 
Deliverable  
7.1.  
ES 
 
Summary of the Prevalence of Major Resistance Mutations of 
INI, NRTI, NNRTI and PI Class at Induction Baseline (Week -
20) -- Plasma Sample (Extension Switch Population) 
Major Mutation of NRTI, NNRTI, PI 
class, and known INI resistance 
mutations, per Section 14.6.6. 
Need to add small ‘n’ for actual no. 
of subjects included in the analysis. 
The % will be based on ‘n’ rather 
than ‘N’ (programming for defining 
class: can refer to 
arenv/arprod/gsk1349572/mid2003
04/week24/drivers/t_adpf_4001.sas 
W124 
7.2.  
CVF 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Subjects Who Met Confirmed Virologic Failure During the 
Maintenance and Extension Phase – Induction Baseline (Week 
-20) and Time of CVF (Randomized Q4W arm) 
Randomized Q4W arm only 
W124 
7.3.  
CVF 
(Extension 
Switch) 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Subjects Who Met Confirmed Virologic Failure Criteria During 
the Extension Phase – Induction Baseline (Week -20) and Time 
of CVF (Extension Switch Population)  
Switch Q4W IM group only 
HL, W124 


 
CONFIDENTIAL 
 
 
201584 
345 
 
Virology: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
(mock up 
below from 
study 
200056\wk48id
sl) 
Title  
Programming Notes 
 
Deliverable  
7.4.  
ITT-E 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Non-CVF Subjects (Randomized Q4W) 
May include genotypic and 
phenotypic data on the last on-
treatment isolates for participants 
with HIV-1 RNA ≥200 c/mL 
 
Include columns for phase, phase 
treatment, phase day. 
W124 
7.5.  
ES 
Shell TV1 
Summary of Viral load, Genotypic and Phenotypic data for 
Non-CVF Subjects (Extension Switch Population) 
May include genotypic and 
phenotypic data on the last on-
treatment isolates for participants 
with HIV-1 RNA ≥200 c/mL 
 
Include columns for phase, phase 
treatment, phase day. 
W124 
 


 
CONFIDENTIAL 
 
 
201584 
346 
 
14.15.15. ICH Listings 
ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases).  Listings will present 
data for the Randomized Q4W arm (data collected in any study phase, where applicable) and the Extension Switch Q4W arm (data collected in the Extension and 
LTFU phases, where applicable). 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Study Population  
1.  
ITT-E 
ES2 
Listing of Reasons for Study Withdrawal 
 
W124 
2.  
ITT-E 
ES2 
Listing of Reasons for Study Drug Discontinuation 
 
W124  
3.  
ITT-E 
DV2 
Listing of Important Protocol Deviations  
Remove column for “Deviation 
Requires Exclusion from the Per 
Protocol Population”. 
W124 
4.  
ITT-E 
DM2 
Listing of Demographic Characteristics 
 
W124 
5.  
ITT-E 
DM9 
Listing of Race 
 
W124 
Primary Efficacy  
6.  
ITT-E 
Study 201584 
(primary_02): 
Listing 33  
Listing of All Plasma HIV-1 RNA Data 
 
W124 
7.  
ITT-E 
Shell LPEF1 
Listing of Study Outcome (50 c/mL) at Week 124 – Snapshot 
Analysis 
 
HL, W124 
Exposure 
8.  
Safety 
HIV_IP5 
Listing of Investigational Product Exposure Data 
 
HL, W124 
Adverse Events  
9.  
Safety 
AE8 
Listing of All Adverse Events 
 
W124 
10.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events  
 
W124 
11.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event   
W124 


 
CONFIDENTIAL 
 
 
201584 
347 
 
ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases).  Listings will present 
data for the Randomized Q4W arm (data collected in any study phase, where applicable) and the Extension Switch Q4W arm (data collected in the Extension and 
LTFU phases, where applicable). 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
12.  
Safety 
AE8 
Listing of Fatal Adverse Events  
 
W124 
13.  
Safety 
AE8 
Listing of Non-Fatal Serious Adverse Events  
 
W124 
14.  
Safety 
AE8 
Listing of Adverse Events Leading to Withdrawal/Permanent 
Discontinuation of Investigational Product  
 
HL, W124 
15.  
Safety 
AE8 
Listing of Changes in Intensity/Grades of Injection Site Related 
AE  
Based on AE details inform page 
for changes in intensity of the 
same event. 
W124 
16.  
Safety  
PREG1a 
Listing of Subjects Who Became Pregnant During the Study 
 
W124 
Laboratory 
Hepatobiliary (Liver) 
17.  
Safety 
MH2 
Listing of Medical Conditions for Subjects with Liver stopping 
Events 
 
W124 
18.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver Stopping 
Events 
 
W124 
ECG & Vital Signs 
19.  
Safety 
EG3 
Listing of ECG Values for subjects with a value of potential 
clinical importance 
 
W124 
20.  
Safety 
EG5 
Listing of ECG Findings 
 
W124 
eC-SSRS 
21.  
Safety 
PSRAE1 
Listing of Possible Suicidality-Related Adverse Event Data: 
Event and Description (Section 1-Section 2) 
 
W124 
22.  
Safety 
PSRAE3 
Listing of Possible Suicidality-Related Adverse Event Data: 
Possible Cause(s) (Section 3) 
 
W124 
23.  
Safety 
PSRAE4 
Listing of Possible Suicidality-Related Adverse Event Data 
(Section 4) 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
348 
 
ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases).  Listings will present 
data for the Randomized Q4W arm (data collected in any study phase, where applicable) and the Extension Switch Q4W arm (data collected in the Extension and 
LTFU phases, where applicable). 
No. 
Population 
IDSL / TST ID 
/ Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
24.  
Safety 
PSRAE5 
Listing of Possible Suicidality-Related Adverse Event Data 
(Section 5-Section 8) 
 
W124 
PK 
25.  
PK  
Study 200056 
Listing 
10.1001(wk48i
dsl) 
Listing of Plasma CAB PK Concentration-Time Data 
Add a variable of ‘evaluable’ 
(Y/N) 
W124 
26.  
PK  
Study 200056 
Listing 
10.1002(wk48i
dsl) 
Listing of Plasma RPV PK Concentration-Time Data 
Add a variable of ‘evaluable’ 
(Y/N) 
W124 
27.  
LTFU 
Study 200056 
Listing 
10.1001(wk48i
dsl) 
Listing of Plasma CAB PK Concentration-Time Data (LTFU 
Phase) 
Add a variable of ‘evaluable’ 
(Y/N) 
W124 
28.  
LTFU 
Study 200056 
Listing 
10.1002(wk48i
dsl) 
Listing of Plasma RPV PK Concentration-Time Data (LTFU 
Phase) 
Add a variable of ‘evaluable’ 
(Y/N) 
W124 
Other 
29.  
ITT-E 
CM2 
Listing of Concomitant Medications for Subjects with Confirmed 
Virologic Failure 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
349 
 
14.15.16. Non-ICH Listings 
Non-ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases). Listings will 
present data for the Randomized Q4W arm (data collected in any study phase, where applicable) and the Extension Switch Q4W arm (data collected in the 
Extension and LTFU phases, where applicable), unless otherwise stated in the programming notes. 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Study Population  
30.  
ITT-E 
ES2 
Listing of Reasons for Maintenance Phase Withdrawal 
(Randomized Q4W)  
 
W124 
31.  
ITT-E 
ES2 
Listing of Reasons for Extension Phase Withdrawal 
(Randomized Q4W) 
 
HL, W124 
32.  
ES 
ES2 
Listing of Reasons for Extension Phase Withdrawal (Extension 
Switch Population) 
 
HL, W124 
33.  
LTFU 
ES2 
Listing of Reasons for Long-term Follow Up Withdrawal 
 
W124 
34.  
ITT-E 
CA3 
Listing of Concomitant ART Medications Received during the 
Maintenance and/or Extension Phase 
 
W124 
35.  
ITT-E 
CA3 
Listing of Subjects with Changes in Concomitant ARTs during 
the Maintenance Phase and/or Extension Phase (Randomized 
Q4W) 
 
W124 
36.  
ES 
CA3 
Listing of Subjects with Changes in Concomitant ARTs during 
the Extension Phase (Extension Switch Population) 
 
W124 
37.  
ITT-E 
CA3 
Listing of ART Medications Received during LTFU Phase 
 
W124 
38.  
ES 
Shell LSP11 
Listing of Investigational Product Accountability - Oral 
Regimens (Extension Switch Population) 
 
W124 
39.  
ITT-E 
 
Listing of Subjects with Hepatitis C at Induction Baseline (Week 
-20) 
 
W124 
Efficacy  
40.  
CVF 
Shell LSEF3 
Listing of All Plasma HIV-1 RNA Data for Subjects with 
Confirmed Virologic Failure 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
350 
 
Non-ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases). Listings will 
present data for the Randomized Q4W arm (data collected in any study phase, where applicable) and the Extension Switch Q4W arm (data collected in the 
Extension and LTFU phases, where applicable), unless otherwise stated in the programming notes. 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
41.  
ITT-E 
Shell LSEF1 
Listing of All Plasma HIV-1 RNA data for subjects with viral 
load >=50 c/mL at any time during the Maintenance and/or 
Extension Phase  
 
HL, W124 
42.  
ITT-E 
Shell LSEF5 
Listing of HIV-1 Associated Conditions  
 
W124 
Safety  
43.  
Safety 
See Listing 3 in 
reporting effort: 
gsk1265744/mi
d209522/iss_0
1 
Listing of all Subjects Meeting Liver Stopping Criteria 
 
W124 
44.  
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting 
 
W124 
45.  
Safety 
LIVER6 
Listing of Liver Event Information for RUCAM Score 
 
W124 
46.  
Safety 
LIVER7 
Listing of Liver Biopsy Details 
 
W124 
47.  
Safety 
LIVER8 
Listing of Liver Imaging Details 
 
W124 
48.  
Safety 
Liver13 
Listing Subjects Meeting Hepatobiliary Lab Criteria  
Please also add those 
additional items shown in the 
summary of subjects meeting 
hepatobiliary lab criteria post-
baseline (i.e. AST >3xULN and 
ALP <2xULN and BIL 
>=2xULN]; ALT+AST>=xx) 
W124 
49.  
Safety  
AE8 
Listing of Adverse Events Related to Prolongation of the 
Corrected QT Interval of the ECG in Supra Therapeutic Doses 
 
W124 


 
CONFIDENTIAL 
 
 
201584 
351 
 
Non-ICH: Listings (Global Programming Note: Include columns for phase, phase treatment, phase day, where data is collected in multiple phases). Listings will 
present data for the Randomized Q4W arm (data collected in any study phase, where applicable) and the Extension Switch Q4W arm (data collected in the 
Extension and LTFU phases, where applicable), unless otherwise stated in the programming notes. 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
50.  
Safety 
EG3 
Listing of ECG Values for Subjects with Adverse Events 
Related to Prolongation of the Corrected QT Interval of the 
ECG in Supra Therapeutic Doses 
 
W124 
51.  
Safety 
Latte2 
WK96CDISC 
report 
Listing of Each Subjects ALT, AST, Bilirubin (including total and 
direct Bilirubin), INR, and ALP for subject meeting Hepatobiliary 
Lab abnormality criteria 
8.1037 (add AST, ALP, INR, 
and direct Bilirubin to the listing 
and only for subject meeting 
Hepatobiliary Lab abnormality 
criteria) 
W124 
52.  
Safety 
Latte2 
WK96CDISC 
report 
Listing of Investigational Product Exposure Data for Subject 
Receiving Oral Bridging 
8.1038 
W124 
53.  
Safety 
DEV1 
Listing of Dosing Errors and IP Device Malfunctions 
 
 
W124 
Virology (mock up below from study 200056\wk96cdisc), ‘Study Phase’ will be added as a column to the listing.  
54.  
CVF 
Listing 9.1005 
Listing of Replication Capacity in IN and PR/RT Region 
Show data in all phases for 
randomized Q4W IM and 
extension switch IM 
participants. 
W124 
55.  
ITT-E 
Table 9.1009 
Listing of Genotypic Mutation Data at All Timepoints 
Show data in all phases for 
randomized Q4W IM and 
extension switch IM 
participants. 
W124 
 
 


 
CONFIDENTIAL 
 
 
201584 
352 
 
14.16. 
Appendix 16: IDMC 
An IDMC was instituted to perform a triggered periodic review of the accumulating data based on confirmed virologic failures to ensure 
that subjects are not being sub-optimally treated.  In addition, the IDMC will review a futility analysis when 50% of subjects will have 
reached their Week 24 visit.  See full details of the analysis and decision criteria in the IDMC charter. 
A list of outputs required for each IDMC analysis was provided in the IDMC Charter, Section 12.3, Appendix C.  
Data handing methods and derived data definitions were provided in a separate critical components RAP. 
14.16.1. 
 CVF Monitoring (Adhoc IDMC review)  
The number of subjects meeting Confirmed Virologic Failure (CVF) Criterion per the protocol is being monitored and may result in ad-
hoc IDMC data reviews. 
The Statistics Data Analysis Centre (SDAC) is notified by the study virologist in writing every time a CVF occurs in either study. The 
SDAC will track the number of subjects past Week 4. The rate of CVF will be monitored against the thresholds specified in IDMC 
Charter Table 1 (See IDMC Charter, Section 3.5.2).   


 
CONFIDENTIAL 
 
 
201584 
353 
 
14.17. 
Appendix 17: Variables Defined for Time to Event Analysis 
Programming Instructions for the Kaplan-Meier analysis of treatment-related discontinuation equals failure (TRDF) 
Condition 
Censor 
Status  
Event Description/AVAL 
1. Participant met CVF event criteria during the 
Maintenance Phase (based on derived CVF) 
CNSR=0 
EVNTDESC=CVF 
AVAL=Date of SVF*  
*immediately preceding CVF 
2. Participant with Maintenance Phase 
withdrawal due to ‘Lack of Efficacy’, 
‘Treatment related AE’, ‘intolerability due to 
injection’, or ‘protocol defined Safety stopping 
criteria’ during Maintenance Phase 
  
Note: primary reason for discontinuation based 
on Maintenance Conclusion form in the eCRF.  
‘Treatment related AE’ is defined as subjects 
that have primary reason for withdrawal =AE 
and that the participant has at least one AE 
considered drug related and leading to 
withdrawal/permanent discontinuation of 
investigational product. 
CNSR=0 
EVNTDESC= terms in italic, respectively. 
 
For ABC/DTG/3TC arm: 
AVAL= min [Study Day of Maintenance Phase Discontinuation, Study Day of 
Maintenance IP Stop Date + 1] 
 
For Q4W arm: 
AVAL= min [Study Day of Maintenance Phase Discontinuation, max(Study Day of 
Last Q4W IM Dose + 35, Study Day of Last Oral CAB/RPV Dose + 1)] 
 
Note: Last Q4W IM / last oral dose/ Maintenance IP Stop Date is only applied to 
subjects who permanently discontinue from study treatment. 
Note: Date of Maintenance Phase discontinuation is from the Maintenance Phase 
Conclusion form in the eCRF. 
If none of the above conditions met 
 
 
3.  Participant with Maintenance Phase 
withdrawal due to other reasons 
CNSR=1 
EVNTDESC=’Censored due to Study Discontinuation for Other Reasons’ 
 
AVAL will be defined as the same as above 2 
4. Participant did not have premature 
withdrawal from the Maintenance Phase 
CNSR=1 
EVNTDESC=’Censored due to data cutoff for analysis’ 
 


 
CONFIDENTIAL 
 
 
201584 
354 
 
Programming Instructions for the Kaplan-Meier analysis of treatment-related discontinuation equals failure (TRDF) 
Condition 
Censor 
Status  
Event Description/AVAL 
AVAL = Last on-treatment date during the Maintenance Phase,   
 
For ABC/DTG/3TC arm: 
min [Study Day of Week 100 Visit, Day of Last Contact at time of analysis, Study 
Day of Maintenance IP stop Date + 1] 
 
For Q4W arm 
min [Study Day of Week 100 Visit, Study Day of Starting LTFU HAART, Study 
Day of Last Contact Date at time of analysis, max(Study Day of Last Q4W IM 
Dose + 35, Study Day of Last oral CAB/RPV dose + 1)] 
Note: Last Q4W IM Dose & Last oral CAB/RPV dose is only applied to participants who permanently discontinue from study treatment. 
 
The same approach as will be used to define ‘ERDF’, Efficacy-related discontinuation equals failure, except that the reason of withdrawal 
in Condition 2 will be restricted to ‘Lack of Efficacy’. 


 
CONFIDENTIAL 
 
 
201584 
355 
 
14.18. 
Appendix 18: Japan-Specific Requirements 
The following data displays will be produced to support reporting requirements for an expected regulatory submission in Japan. 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
11.01 to 11.n 
11.01 to 11.n 
Efficacy 
12.01 to 12.n 
12.01 to 12.n 
Safety 
13.01 to 13.n 
13.01 to 13.n 
Pharmacokinetic 
14.01 to 14.n 
14.01 to 14.n 
Health Outcomes 
15.01 to 15.n 
15.01 to 15.n 
Section 
Listings 
ICH Listings 
100 to y 
Other Listings 
200 to z 
 
Non IDSL specifications will be referenced as indicated and if required an example mock-up displays provided a separate document. 


 
CONFIDENTIAL 
 
 
201584 
356 
 
14.18.1. 
Study Population Tables - Japan 
Study Population Japan: Tables 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title  
Programming Notes 
Deliverable  
Demography and Baseline 
11.1. 
Intent-to-Treat 
Exposed (Japan) 
Shell TSP2 
Summary of Demographic Characteristics 
See also DM1 in IDSL 
Age categorization will 
include:  
<=18, 19-64, >=65 (FDAAA 
requirement) 
18-64, 65-84, >=85 (EMA 
requirement) 
W48 Japan, 
W96 Japan 
14.18.2. 
Efficacy Tables - Japan 
Efficacy Japan: Tables 
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
12.1. 
 Intent-to-Treat 
Exposed (Japan) 
Shell TPEF1 
Summary of Analysis for Proportion of Subjects 
with Plasma HIV-1 RNA ≥50 c/mL at Week 48 
(Maintenance Phase) – Snapshot Analysis  
For W96 deliverable, replace 
‘Week 48’ with ‘Week 96’ 
W48 Japan, 
W96 Japan 
12.2. 
 Per-Protocol (Japan) Shell TPEF1 
Summary of Analysis for Proportion of Subjects 
with Plasma HIV-1 RNA ≥50 c/mL at Week 48 
(Maintenance Phase) – Snapshot Analysis (Per-
Protocol Population - Japan) 
For W96 deliverable, replace 
‘Week 48’ with ‘Week 96’ 
W48 Japan,  
W96 Japan 


 
CONFIDENTIAL 
 
 
201584 
357 
 
Efficacy Japan: Tables 
No. 
Population 
IDSL / TST 
ID / Example 
Shell 
Title  
Programming Notes 
Deliverable  
12.3. 
 Intent-to-Treat 
Exposed (Japan) 
Shell TPEF2 
Summary of Study Outcomes (50 c/mL cut-off) 
at Week 48 (Maintenance Phase) – Snapshot 
Analysis 
For W96 deliverable, replace 
‘Week 48’ with ‘Week 96’ 
W48 Japan, 
W96 Japan 
14.18.3. 
Safety Tables - Japan 
Safety Japan: Tables 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Adverse Events  
13.1. 
Safety (Japan) 
AE1 
Summary of All Adverse Events by System 
Organ Class – Maintenance Phase 
CS Core  
W48 Japan,  
W96 Japan 
13.2. 
Safety (Japan) 
AE5B 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity – 
Maintenance Phase 
CS Core 
W48 Japan,  
W96 Japan 
13.3. 
Safety (Japan) 
AE5B 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity – Oral 
Lead-in Period at Maintenance Phase 
CS Core (for Q4W arm only) 
W48 Japan,  
W96 Japan 
13.4. 
Safety (Japan) 
AE3 
Summary of All Grade 3 or Higher Adverse 
Events by Overall Frequency – Maintenance 
Phase  
 
W48 Japan,  
W96 Japan 
13.5. 
Safety  
AE3 
Summary of All Grade 3 or Higher Adverse 
Events by Overall Frequency – Maintenance 
Phase (Safety Population) 
New 
W48 Japan,  
W96 Japan 


 
CONFIDENTIAL 
 
 
201584 
358 
 
Safety Japan: Tables 
13.6. 
Safety (Japan) 
AE1 
Summary of All Drug-Related Adverse Events 
by System Organ Class– Maintenance Phase 
 
W48 Japan,  
W96 Japan 
13.7. 
Safety (Japan) 
AE5B 
Summary of All Drug-Related Adverse Events 
by System Organ Class and Maximum Toxicity 
– Maintenance Phase 
CS Core 
W48 Japan,  
W96 Japan 
Serious and Other Significant Adverse Events  
13.8. 
Safety (Japan) 
AE1 
Summary of Serious Adverse Events by 
System Organ Class – Maintenance Phase 
CS Core 
W48 Japan,  
W96 Japan 
13.9. 
Safety (Japan) 
AE1 
Summary of Drug-Related Serious Adverse 
Events by System Organ Class – Maintenance 
Phase 
CS Core 
W48 Japan,  
W96 Japan 
13.10. 
Safety (Japan) 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ 
Class– Maintenance Phase 
CS Core 
W48 Japan,  
W96 Japan 
Injection Site Reaction Adverse Events 
13.11. 
Safety (Japan) 
Shell TS2.2 
Summary of Injection Site Reaction Adverse 
Events (Event-Level Summary) –Maintenance 
Phase 
(for Q4W arm only) 
W48 Japan,  
W96 Japan 
13.12. 
Safety (Japan) 
Shell TS2.3 
Summary of Subject-Level Characteristics of 
Injection Site Reaction Adverse Events – 
Overall and Common (Maintenance Phase) 
Common ISR includes pain, 
induration, nodules and any 
other ISR with ≥5% subjects 
(for Q4W arm only) 
W48 Japan,  
W96 Japan 


 
CONFIDENTIAL 
 
 
201584 
359 
 
14.18.4. 
Pharmacokinetic Tables - Japan 
Pharmacokinetic Japan: Tables 
No. 
Population 
IDSL / 
TST ID / 
Example 
Shell 
Title    
Programming Notes 
The similar outputs below 
from study 200056 
(week48idsl), unless 
otherwise specified 
Deliverable 
[Priority] 
PK  
14.1. 
Japan PK  
PKCT1 
Summary of Plasma CAB PK Concentrations (ug/mL) 
-Time Data (Q4W arm) – Day 1 
Day 1 (following first oral CAB 
dose during lead-in phase): 
Pre-dose, 1, 2, 3, 4, 8, and 24 
hours post-dose 
W48 Japan 
14.2. 
Japan PK  
PKCT1 
Summary of Plasma CAB PK Concentration (ug/mL) -
Time Data by Visit (Q4W arm) – Week 4b to Week 48 
Table 10.1011 
 
Japan W48 
14.3. 
Japan PK  
PKCT1 
Summary of Evaluable Plasma CAB PK 
Concentration (ug/mL) -Time Data by Visit (Q4W 
arm) – Week 4b to Week 48 
Table 10.1011 
 
Japan W48 
14.4. 
Japan PK  
PKCT1 
Summary of Plasma RPV PK Concentration (ng/mL) -
Time Data by Visit (Q4W arm) – Week 4b to Week 48 
Table 10.1011 
 
Japan W48 
14.5. 
Japan PK  
PKCT1 
Summary of Evaluable Plasma RPV PK 
Concentration (ng/mL) -Time Data by Visit (Q4W 
arm) – Week 4b to Week 48 
Table 10.1011 
 
Japan W48 
14.6. 
Japan PK 
PKPT4 
Summary of Derived Plasma CAB PK Parameters at 
Day 1 
GSK1265744/LAI117010, 
Table 3.3 
 


 
CONFIDENTIAL 
 
 
201584 
360 
 
14.18.5. 
Pharmacokinetic Figures - Japan 
Pharmacokinetic Japan: Figures 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title 
Programming Notes 
 
Deliverable 
[Priority] 
PK  
14.1. 
Japan PK 
PKCF1P 
Individual Plasma CAB Concentration-Time Plots 
by Subject (Linear and Semi-Log) – Day 1  
One plot per subject; 
Day 1 (following first oral CAB 
dose during lead-in phase): Pre-
dose, 1, 2, 3, 4, 8, and 24 hours 
post-dose 
Japan W48 
14.2. 
Japan PK 
PKCF1P 
Individual Plasma CAB Concentration-Time Plots 
by Treatment (Linear and Semi-Log) – Day 1  
Overlay all subjects; 
Day 1 (following first oral CAB 
dose during lead-in phase): Pre-
dose, 1, 2, 3, 4, 8, and 24 hours 
post-dose 
Japan W48 
14.3. 
Japan PK 
PKCF1P 
Individual Plasma CAB Concentration-Time Plots 
by Subject (Linear and Semi-Log) – Week 4b to 
Week 48 
One plot per subject 
 
Japan W48 
14.4. 
Japan PK 
PKCF1P 
Individual Plasma CAB Concentration-Time Plots 
by Treatment (Linear and Semi-Log) – Week 4b 
to Week 48 
Overlay all subjects 
 
Japan W48, 
Japan W96 
14.5. 
Japan PK 
PKCF1 
Individual Plasma RPV Concentration-Time Plots 
by Subject (Linear and Semi-Log) – Week 4b to 
Week 48 
One plot per subject 
Japan W48, 
Japan W96 
14.6. 
Japan PK 
PKCF1 
Individual Plasma RPV Concentration-Time Plots 
by Treatment (Linear and Semi-Log) – Week 4b 
to Week 48 
Overlay all subjects 
 
Japan W48, 
Japan W96 


 
CONFIDENTIAL 
 
 
201584 
361 
 
Pharmacokinetic Japan: Figures 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title 
Programming Notes 
 
Deliverable 
[Priority] 
14.7. 
Japan PK 
PKCF2 
Mean (SD) Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) – Day 1 
Figure 10.1003; 
Day 1 (following first oral CAB 
dose during lead-in phase): Pre-
dose, 1, 2, 3, 4, 8, and 24 hours 
post-dose 
Japan W48, 
 
14.8. 
Japan PK  
PKCF3 
Median (5th and 95th percentile) Plasma CAB 
Concentration-Time Plots (Linear and Semi-Log) 
– Day 1 
Figure 10.1004; 
Day 1 (following first oral CAB 
dose during lead-in phase): Pre-
dose, 1, 2, 3, 4, 8, and 24 hours 
post-dose 
Japan W48 
14.9. 
Japan PK 
PKCF2 
Mean (SD) Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) – Week 4b to Week 
48 
Figure 10.1003 
Japan W48, 
Japan W96 
14.10. 
Japan PK 
PKCF3 
Median (5th and 95th percentile) Plasma CAB 
Concentration-Time Plots (Linear and Semi-Log) 
– Week 4b to Week 48 
Figure 10.1004 
Japan W48, 
Japan W96 
14.11. 
Japan PK 
PKCF2 
Mean (SD) Evaluable Plasma CAB 
Concentration-Time Plots (Linear and Semi-Log) 
– Week 4b to Week 48 
Figure 10.1003 
Japan W48, 
Japan W96 
14.12. 
Japan PK 
PKCF3 
Median (5th and 95th percentile) Evaluable 
Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) – Week 4b to Week 48 
Figure 10.1004 
Japan W48, 
Japan W96 
14.13. 
Japan PK 
PKCF2 
Mean (SD) Plasma RPV Concentration-Time 
Plots (Linear and Semi-Log) – Week 4b to Week 
48 
Figure 10.1005 
Japan W48, 
Japan W96 
14.14. 
Japan PK  
PKCF3 
Median (5th and 95th percentile) Plasma RPV 
Concentration-Time Plots (Linear and Semi-Log) 
– Week 4b to Week 48 
Figure 10.1006 
Japan W48, 
Japan W96 


 
CONFIDENTIAL 
 
 
201584 
362 
 
Pharmacokinetic Japan: Figures 
No. 
Population 
IDSL / TST 
ID / 
Example 
Shell 
Title 
Programming Notes 
 
Deliverable 
[Priority] 
14.15. 
Japan PK 
PKCF2 
Mean (SD) Evaluable Plasma RPV 
Concentration-Time Plots (Linear and Semi-Log) 
– Week 4b to Week 48 
Figure 10.1007 
Visits up to W52 for the W48 
deliverable. 
Japan W48, 
Japan W96 
14.16. 
Japan PK  
PKCF3 
Median (5th and 95th percentile) Evaluable 
Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) – Week 4b to Week 48 
Figure 10.1008 
Visits up to W52 for the W48 
deliverable. 
Japan W48, 
Japan W96 
14.18.6. 
Health Outcomes Tables - Japan 
Health Outcomes Japan: Tables 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title   
Programming Notes 
Deliverable  
Treatment Satisfaction (HIVTSQs) 
15.1. 
Intent-to-Treat 
Exposed (Japan) 
Shell THO2 
Proportion of Subjects with HIVTSQs – Treatment 
Satisfaction Individual Item Scores by Visit - LOCF) 
(Maintenance Phase) 
 
Japan W48,  
Japan W96 
15.2. 
Intent-to-Treat 
Exposed (Japan) 
Shell THO1 
Summary of HIVTSQs - Total Treatment Satisfaction 
Score by Visit - LOCF) (Maintenance Phase) 
Japan W48,  
Japan W96 
15.3. 
Intent-to-Treat 
Exposed (Japan) 
Shell THO1 
Summary of HIVTSQs - Change from Maintenance 
Baseline (Day 1) in Total Treatment Satisfaction 
Score by Visit (Maintenance Phase) 
Japan W48,  
Japan W96 
15.4. 
Intent-to-Treat 
Exposed (Japan) 
Shell THO1 
Summary of HIVTSQs - Change from Maintenance 
Baseline (Day 1) in Total Treatment Satisfaction 
Score by Visit - LOCF (Maintenance Phase) 
Japan W48,  
Japan W96 


 
CONFIDENTIAL 
 
 
201584 
363 
 
Health Outcomes Japan: Tables 
Treatment Satisfaction (HIVTSQc) 
15.5. 
Intent-to-Treat 
Exposed (Japan) 
Shell THO2 
 
Proportion of Subjects with HIVTSQc – Treatment 
Satisfaction Individual Item Scores at Week 48 
(Maintenance Phase) 
 
Japan W48 
15.6. 
Intent-to-Treat 
Exposed (Japan) 
Shell THO1 
Summary of HIVTSQc - Total Treatment Satisfaction 
Score at Week 48 (Maintenance Phase) 
 
Japan W48 
15.7. 
Intent-to-Treat 
Exposed (Japan) 
See Table 6.41 in 
reporting effort: 
gsk1265744/2015
84/primary_02 
Summary of HIVTSQc Individual Item Scores at Week 
48 (Maintenance Phase)  
 
Japan W48 
Preferences (Dichotomous preference question) (for Q4W IM) 
15.8. 
Intent-to-Treat 
Exposed (Japan) 
Shell THO8 
Treatment Preference at Week 48 (Maintenance 
Phase) 
 
Japan W48 
14.18.7. 
ICH Listings - Japan 
Non-ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming 
Notes 
Deliverable 
[Priority] 
Pharmacokinetic  
100. 
All Enrolled 
(Japan) 
AE8 
Listing of All Adverse Events (Induction + Maintenance Phase)  
 
Japan W48,  
Japan W96 
101. 
All Enrolled 
(Japan) 
Study 201584 
(primary_02): 
Listing 33  
Listing of All Plasma HIV-1 RNA Data 
 
Japan W48,  
Japan W96 


 
CONFIDENTIAL 
 
 
201584 
364 
 
14.18.8. 
Non-ICH Listings - Japan 
Non-ICH: Listings 
No. 
Population 
IDSL / TST ID / 
Example Shell 
Title 
Programming Notes 
Deliverable 
[Priority] 
Pharmacokinetic  
200. 
Japan PK 
PKPL1 
Listing of Derived Plasma CAB Pharmacokinetic Parameters – 
Day 1 
 
Japan W48 
201. 
Japan PK 
PKCL1 
Listing of Plasma CAB Pharmacokinetic Concentration Time 
Data  
 
Japan W48,  
Japan W96 
202. 
Japan PK 
PKCL1 
Listing of Plasma RPV Pharmacokinetic Concentration Time 
Data 
 
Japan W48,  
Japan W96 


 
CONFIDENTIAL 
 
 
201584 
365 
 
14.19. 
Appendix 19: List of Data Displays for Subcutaneous Sub-
study Analysis 
Unless otherwise specified, in sub-study analysis, age refers to the age at the sub-study 
screening, Baseline weight and Baseline BMI refer to the weight and BMI at the sub-
study baseline respectively, and the listings will not be presented by prior exposure to 
CAB + RPV as the shell.  
All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects 
CDISC and GSK Data Display Standards terminology. The RAPIDO Data Viewer will 
be utilized in this study at SAC and will take the place of many previously produced 
listings. 
14.19.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.18 
 
Efficacy 
2.1 to 2.20 
2.1 to 2.4 
Safety 
3.1 to 3.75 
3.1 to 3.13 
Pharmacokinetic 
4.1 to 4.12 
4.1 to 4.8 
Health Outcomes 
6.1 to 6.21 
 
Virology 
7.1 to 7.3 
 
Section 
Listings 
ICH Listings 
1 to 13 
Other Listings 
14 to 20 
 
14.19.2. 
Mock Example Shell Referencing 
For all displays referring to A2M (207966), remove treatment arm distinction from all 
shells (i.e. Q4W vs. Q8W) unless otherwise specified.  
14.19.3. 
Deliverables 
Delivery [1] 
Description 
SS-ISR 
Sub-study ISR Monitoring Interim 
SS-Interim 
Sub-study Week 9 Interim Analysis 
SS-HL 
Headline at Sub-study SAC 
SS-SAC 
Sub-study SAC  
 


 
CONFIDENTIAL 
 
 
201584 
366 
 
14.19.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Subject Disposition 
1.1 
Sub-study 
Enrolled 
201584/primary_01/T1.2 
Summary of Sub-study Subjects Enrolled 
by Country and Site ID 
Remove Induction Phase column. Do not 
include countries and sites without any 
subjects enrolled in the sub-study. 
SS-Interim 
SS-SAC 
1.2 
Sub-study 
Screened 
207966/primary_46/T1.2 
Summary of Screening Status and 
Reasons for Sub-study Screening Failures  
SS-SAC 
1.3 
Sub-study 
Screened 
201584/primary_01/T1.1 
Summary of Sub-study Populations 
Remove Induction Phase column. Only 
include analysis populations used in the 
sub-study analysis 
SS-SAC 
1.4 
Sub-study 
Safety 
207966/primary_46/T1.3 
Summary of Subject Accountability: Sub-
study Conclusion Record 
Include counts of those transitioned to 
marketed product 
SS-SAC 
1.5 
Sub-study 
Safety 
207966/primary_46/T1.4 
Summary of Subject Accountability: SC 
Injection Phase Conclusion Record 
 
SS-SAC 
1.6 
Sub-study 
Safety 
207966/primary_46/T1.5 
Summary of Subject Accountability: 
Return to Gluteal Injection Phase 
Conclusion Record 
 
SS-SAC 
1.7 
Sub-study 
Safety 
207966/primary_46/T1.6 
Summary of Subject Disposition at Each 
Study Phase 
Replace Thigh Injection Phase with SC 
Injection Phase 
SS-SAC 
1.8 
Sub-study 
Safety 
207966/primary_46/T1.9 
Summary of Important Sub-study Protocol 
Deviations 
 
SS-SAC 
1.9 
Sub-study 
Safety 
207966/primary_46/T1.10 Summary of Important Sub-study Protocol 
Deviations (SC Injection Phase) 
 
SS-SAC 
1.10 
Sub-study 
Safety 
207966/primary_46/T1.12 Summary of Important COVID-19 Related 
Sub-study Protocol Deviations  
 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
367 
 
Study Population Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
1.11 
Sub-study 
Safety 
207966/primary_46/T1.13 Summary of Important Non-COVID-19 
Related Sub-study Protocol Deviations 
 
SS-SAC 
Demographic and Baseline Characteristics 
1.12 
Sub-study 
Safety 
207966/primary_46/T1.14 Summary of Demographic Characteristics 
After the continuous BMI parameter, add a 
categorical BMI parameter (BMI < 30 
kg/m^2, >=30 kg/m^2) 
SS-HL 
SS-SAC 
1.13 
Sub-study 
Safety 
207966/primary_46/T1.15 Summary of Race and Racial 
Combinations 
 
SS-SAC 
1.14 
Sub-study 
Safety 
207966/primary_46/T1.16 Summary of Race and Racial 
Combinations Details 
 
SS-SAC 
Medications / Other 
1.15 
Sub-study 
Safety 
207966/primary_46/T1.17 
Summary of Extent of Exposure to Study 
Treatment including SOC Oral Bridging 
Prior to the First SC Injection 
Replace references to ATLAS/A2M with 
FLAIR. Include FLAIR Maintenance 
randomization assignments in the columns.  
SS-SAC 
1.16 
Sub-study 
Safety 
207966/primary_46/T1.18 
Summary of Concomitant Non-ART 
Medication Ingredient Combinations by 
Study Phase 
Include columns for SC Phase, Return to 
Gluteal Phase, and Overall  
SS-SAC 
1.17 
Sub-study 
Safety 
207966/primary_46/T1.19 Summary of Smoking Status at Sub-study 
Baseline 
 
SS-SAC 
1.18 
Sub-study 
Safety 
207966/primary_46/T1.20 Summary of COVID-19 Pandemic Visit 
Impacts in Sub-study 
Only include visits in sub-study 
SS-SAC 
 
 
 


 
CONFIDENTIAL 
 
 
201584 
368 
 
14.19.5. 
Efficacy Tables 
Note: The following subgroups will be included in subgroup summaries: Age (<35; 35-<50; >=50), Sex at Birth (Female vs Male), 
Race/Ethnicity (White: Non-Hispanic, White: Hispanic, Black, Asian, Other), Sub-study Baseline BMI (<30, >=30). 
Efficacy Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.1 
Sub-study Safety 
207966/primary_46/T2.1 
Summary of Study Outcomes (50 c/mL Threshold) at 
Sub-study Week 12 – Snapshot Analysis 
 
SS-HL 
SS-SAC 
2.2 
Sub-study Safety 
207966/primary_46/T2.2 
Summary of Study Outcomes (50 c/mL Threshold) at 
Sub-study Week 12 by Subgroup – Snapshot Analysis 
 
SS-SAC 
2.3 
Sub-study Safety 
207966/primary_46/T2.3 
Proportion of Subjects with Plasma HIV-1 RNA >=50 
c/mL by Visit (SC Injection Phase) – Snapshot Analysis 
Observed values to be 
displayed prior to Week 12 
SS-SAC 
2.4 
Sub-study Safety 
207966/primary_46/T2.4 
Proportion of Subjects with Plasma HIV-1 RNA >=50 
c/mL by Subgroup and Visit (SC Injection Phase) – 
Snapshot Analysis 
Observed values to be 
displayed prior to Week 12 
SS-SAC 
2.5 
Sub-study Safety 
207966/primary_46/T2.5 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL by Visit (SC Injection Phase) – Snapshot Analysis 
Observed values to be 
displayed prior to Week 12 
SS-SAC 
2.6 
Sub-study Safety 
207966/primary_46/T2.6 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL by Subgroup and Visit (SC Injection Phase) – 
Snapshot Analysis 
Observed values to be 
displayed prior to Week 12 
SS-SAC 
2.7 
Sub-study Safety 
207966/primary_46/T2.7 
Summary of Change from Sub-study Baseline in 
Plasma HIV-1 RNA (log10 c/mL) by Visit (SC Injection + 
Return to Gluteal Injection Phase) 
 
SS-SAC 
2.8 
Sub-study Safety 
207966/primary_46/T2.8 
Summary of Plasma HIV-1 RNA (log10 c/mL) by Visit 
(SC Injection + Return to Gluteal Injection Phase) 
 
SS-SAC 
2.9 
Sub-study Safety 
207966/primary_34/T2.25 
Cumulative Proportion of Subjects Meeting Confirmed 
Virology Failure Criteria by Visit (SC Injection + Return 
to Gluteal Injection Phase) 
 
SS-HL 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
369 
 
Efficacy Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.10 
Sub-study Safety 
207966/primary_34/T2.27 
Distribution of Quantitative Plasma HIV-1 RNA Results 
at Suspected and Confirmation of Confirmed Virologic 
Failure (SC Injection + Return to Gluteal Injection 
Phase) 
 
SS-SAC 
2.11 
Sub-study Safety 
207966/primary_46/T2.11 Summary of Subjects per Viral Load Category by Visit 
(SC Injection Phase) 
 
SS-SAC 
2.12 
Sub-study Safety 
207966/primary_46/T2.12 
Summary of Change from Sub-study Baseline in CD4+ 
Cell Count (cells/mm^3) by Visit (SC Injection + Return 
to Gluteal Injection Phase) 
 
SS-SAC 
2.13 
Sub-study Safety 
207966/primary_46/T2.13 
Summary of Change from Sub-study Baseline in CD4+ 
Cell Count (cells/mm^3) at Sub-study Week 12 by 
Subgroup 
 
SS-SAC 
2.14 
Sub-study Safety 
207966/primary_46/T2.14 Summary of CD4+ Cell Count (cells/mm^3) by Visit (SC 
Injection + Return to Gluteal Injection Phase) 
 
SS-SAC 
2.15 
Sub-study Safety 
207966/primary_46/T2.15 Summary of Change from Sub-study Baseline in CD8+ 
Cell Count (cells/mm^3) by Visit (SC Injection Phase) 
 
SS-SAC 
2.16 
Sub-study Safety 
207966/primary_46/T2.16 Summary of CD8+ Cell Count (cells/mm^3) by Visit (SC 
Injection Phase) 
 
SS-SAC 
2.17 
Sub-study Safety 
207966/primary_46/T2.17 Summary of CD4+/CD8+ Ratio Cell Count (cells/mm^3) 
by Visit (SC Injection Phase) 
 
SS-SAC 
2.18 
Sub-study Safety 
207966/primary_46/T2.18 
Summary of HIV-1 Associated Conditions Including 
Recurrences (SC Injection + Return to Gluteal Injection 
Phase) 
 
SS-SAC 
2.19 
Sub-study Safety 
207966/primary_46/T2.19 
Summary of HIV-1 Associated Conditions Excluding 
Recurrences (SC Injection + Return to Gluteal Injection 
Phase) 
 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
370 
 
Efficacy Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.20 
Sub-study Safety 
207966/primary_46/T2.20 
Summary of HIV-1 Disease Progression from Sub-study 
Baseline and/or Deaths (SC Injection + Return to 
Gluteal Injection Phase) 
 
SS-SAC 
 
 


 
CONFIDENTIAL 
 
 
201584 
371 
 
14.19.6. 
Efficacy Figures 
Efficacy Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.1 
Sub-study Safety 
201584/primary_01/F2.1 Proportion (95% CI) of Subjects with HIV-1 RNA ≥50 
c/mL by Visit (SC Injection Phase) – Snapshot Analysis 
 
SS-SAC 
2.2 
Sub-study Safety 
201584/primary_01/F2.3 Proportion (95% CI) of Subjects with HIV-1 RNA <50 
c/mL by Visit (SC Injection Phase) – Snapshot Analysis 
 
SS-SAC 
2.3 
Sub-study Safety 
201584/primary_01/F2.6 Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by 
Sub-study Visit – for CVF Subjects  
Replace the first 2 footnotes 
with "First vertical reference 
line corresponds to the date of 
first SC injection." 
SS-HL 
SS-SAC 
2.4 
Sub-study Safety 
201584/primary_01/F2.8 
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by 
Visit for Subjects Who are in the Category of ‘HIV-1 
RNA >=50 c/mL’ at Sub-study Week 12 per Snapshot 
Algorithm 
Replace the first 2 footnotes 
with "First vertical reference 
line corresponds to the date of 
first SC injection." 
SS-SAC 
 
 


 
CONFIDENTIAL 
 
 
201584 
372 
 
14.19.7. 
Safety Tables 
Note: The following subgroups will be included in subgroup summaries: Age (<35, 35-<50, >=50), Sex at Birth (Female vs Male), 
Race/Ethnicity (White: Non-Hispanic, White: Hispanic, Black, Asian, Other), Sub-study Baseline BMI (<30, >=30). 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Exposure 
3.1 
Sub-study 
Safety 
207966/primary_46/T3.1 
Summary of Extent of Exposure to Study 
Treatment (SC Injection + Return to Gluteal 
Injection Phase) 
Add footnote: “Note: Overall exposure 
includes 35 days since the last Q4W 
injection.”  
SS-HL 
SS-SAC 
3.2 
Sub-study 
Safety 
207966/primary_46/T3.2 
Summary of Needle Length and Gauge for 
CAB Injection (SC Injection Phase) 
 
SS-SAC 
3.3 
Sub-study 
Safety 
207966/primary_46/T3.3 
Summary of Needle Length and Gauge for 
RPV Injection (SC Injection Phase) 
 
SS-SAC 
3.4 
Sub-study 
Safety 
207966/primary_34/T3.4 
Summary of Adherence to CAB/RPV 
Injection Dosing Schedule (SC Injection 
Phase) 
 
SS-SAC 
3.5 
Sub-study 
Safety 
207966/primary_34/T3.5 
Summary of Adherence to CAB/RPV 
Injection Dosing Schedule (SC Injection + 
Return to Gluteal Injection Phase) 
 
SS-SAC 
3.6 
Sub-study 
Safety 
207966/primary_34/T3.4 
Summary of Adherence to CAB/RPV 
Injection Dosing Schedule by Subgroup 
(SC Injection Phase) 
Repeat Table 3.4 by subgroup 
SS-SAC 
Adverse Events 
3.7 
Sub-study 
Safety 
213199/final_01/T3.9 
Adverse Event Overview by Study Phase 
and Overall 
Do not include any LTFU information 
SS-Interim 
SS-HL 
 SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
373 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.8 
Sub-study 
Safety 
213199/final_01/T3.11 
Summary of All Adverse Events by Study 
Phase, System Organ Class, and 
Maximum Toxicity  
Repeat results for both study phases 
and overall. 
SS-Interim 
SS-HL 
 SS-SAC 
3.9 
Sub-study 
Safety 
213199/final_01/T3.12 
Summary of All Adverse Events by Study 
Phase, System Organ Class, and 
Maximum Toxicity – Excluding Injection 
Site Reactions 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.10 
Sub-study 
Safety 
213199/final_01/T3.11 
Summary of All Adverse Events by 
Subgroup, System Organ Class, and 
Maximum Toxicity 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.11 
Sub-study 
Safety 
213199/final_01/T3.15 
Summary of Common Adverse Events 
(>=5%) by Study Phase and Overall 
Frequency  
Repeat results for both study phases 
and overall. 
SS-SAC 
3.12 
Sub-study 
Safety 
213199/final_01/T3.16 
Summary of Common Grade 2-5 Adverse 
Events (>=1%) by Study Phase and Overall 
Frequency 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.13 
Sub-study 
Safety 
213199/final_01/T3.19 
Summary of Drug-related Adverse Events 
by Study Phase, System Organ Class, and 
Maximum Toxicity 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.14 
Sub-study 
Safety 
213199/final_01/T3.22 
Summary of Drug-related Adverse Events 
by Study Phase, System Organ Class, and 
Maximum Toxicity – Excluding Injection 
Site Reactions 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.15 
Sub-study 
Safety 
213199/final_01/T3.19 
Summary of Drug-related Adverse Events 
by Subgroup, System Organ Class, and 
Maximum Toxicity 
Repeat results for both study phases 
and overall. 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
374 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.16 
Sub-study 
Safety 
213199/final_01/T3.24 
Summary of Common Grade 2-5 Drug-
Related Adverse Events (>=1%) by Study 
Phase and Overall Frequency 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.17 
Sub-study 
Safety 
213199/final_01/T3.9 
Adverse Event Overview by Subgroup, 
Study Phase and Overall 
Repeat Table 3.7 by subgroup 
Do not include any LTFU information 
SS-SAC 
Serious and Other Significant Adverse Events 
3.18 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Serious Adverse Events by 
Study Phase, System Organ Class, and 
Maximum Grade  
Repeat results for both study phases 
and overall. 
SS-HL 
SS-Interim 
SS-SAC 
3.19 
Sub-study 
Safety 
213199/final_01/T3.30 
Summary of Serious Adverse Events by 
Study Phase, System Organ Class, and 
Preferred Term (Number of Subjects and 
Occurrences) 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.20 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Serious Adverse Events by 
Study Phase, System Organ Class, and 
Maximum Grade – Excluding Injection Site 
Reactions 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.21 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Serious Adverse Events by 
Subgroup, System Organ Class, and 
Maximum Grade  
Repeat results for both study phases 
and overall. 
SS-SAC 
3.22 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Drug-related Serious Adverse 
Events by Study Phase, System Organ 
Class, and Preferred Term 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.23 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by Study Phase, 
Repeat results for both study phases 
and overall. 
SS-HL 
SS-Interim 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
375 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
System Organ Class, and Maximum Grade 
3.24 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by Study Phase, 
System Organ Class, and Maximum Grade 
– Excluding Injection Site Reactions 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.25 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Drug-related Serious Adverse 
Events by Subgroup, System Organ Class, 
and Preferred Term 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.26 
Sub-study 
Safety 
213199/final_01/T3.27 
Summary of Serious Adverse Events 
Leading to Withdrawal/Permanent 
Discontinuation of Investigational Product 
by Study Phase, System Organ Class, and 
Maximum Grade 
Repeat results for both study phases 
and overall. 
SS-SAC 
3.27 
Sub-study 
Safety 
213199/final_01/T3.23 
Summary of Common (>=5%) Non-Serious 
Adverse Events by Study Phase, System 
Organ Class, and Preferred Term (Number 
of Subjects and Occurrences) 
Repeat results for both study phases 
and overall. 
SS-SAC 
Study Drug Injection Site Reaction Adverse Events 
3.28 
Sub-study 
Safety 
213199/final_01/T3.37 
Summary of Study Drug Injection Site 
Reaction Adverse Events (Event-level 
Summary) 
Report Study Phase in the columns 
Sort by CAB+RPV, CAB, RPV 
SS-Interim 
SS-HL 
SS-SAC 
3.29 
Sub-study 
Safety 
213199/final_01/T3.38 
Summary of Subject-level Characteristics 
of Study Drug Injection Site Reaction 
Adverse Events – Overall and Common 
Report Study Phase in the columns 
Sort by CAB+RPV, CAB, RPV 
>=5% is common threshold 
SS-Interim 
SS-HL 
SS-SAC 
3.30 
Sub-study 
213199/final_01/T3.39 
Summary of Study Drug Injection Site 
Report Study Phase in the columns 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
376 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Safety 
Reaction Adverse Events by Visit and 
Maximum Severity – Overall and Common 
in Sub-study 
Sort by CAB+RPV, CAB, RPV 
>=5% is common threshold 
3.31 
Sub-study 
Safety 
213199/final_01/T3.37 
Summary of Study Drug Injection Site 
Reaction Adverse Events by Subgroup 
(Event-level Summary) - Overall and 
Common 
Report Study Phase in the columns 
Report only for CAB+RPV 
>=5% is common threshold 
SS-SAC 
3.32 
Sub-study 
Safety 
213199/final_01/T3.38 
Summary of Subject-level Characteristics 
of Study Drug Injection Site Reaction 
Adverse Events by Subgroup – Overall and 
Common 
Report Study Phase in the columns 
Report only for CAB+RPV >=5% is 
common threshold 
SS-SAC 
3.33 
Sub-study 
Safety 
207966/primary_46/T3.27 
Summary of Maximum Study Drug Injection 
Site Reaction Adverse Event Grade by 
Needle Length & Categorical BMI (SC 
Injection Phase) – Common (CAB) 
Repeat results for each ISR, needle 
length, and BMI category within needle 
length (overall, >=30, <30) 
SS-SAC 
3.34 
Sub-study 
Safety 
207966/primary_46/T3.27 
Summary of Maximum Study Drug Injection 
Site Reaction Adverse Event Grade by 
Needle Length & Categorical BMI (SC 
Injection Phase) – Common (RPV) 
Repeat results for each ISR, needle 
length, and BMI category within needle 
length (overall, >=30, <30) 
SS-SAC 
3.35 
Sub-study 
Safety 
213199/final_01/T3.37 
Summary of High Impact Study Drug 
Injection Site Reaction Adverse Events 
(Event-level Summary) 
Report Study Phase in the columns 
Sort by CAB+RPV, CAB, RPV 
Add footnote “Note: High Impact ISRs 
include Grade 4 ISRs and Grade 3 
ISRs of ulceration, secondary 
infection, phlebitis, drainage, or sterile 
abscess and may potentially lead to 
pausing or stopping SC injections.” 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
377 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.36 
Sub-study 
Safety 
213199/final_01/T3.38 
Summary of Subject-level Characteristics 
of High Impact Study Drug Injection Site 
Reaction Adverse Events 
Report Study Phase in the columns 
Sort by CAB+RPV, CAB, RPV 
Add footnote “Note: High Impact ISRs 
include Grade 4 ISRs and Grade 3 
ISRs of ulceration, secondary 
infection, phlebitis, drainage, or sterile 
abscess and may potentially lead to 
pausing or stopping SC injections.” 
SS-SAC 
3.37 
Sub-study 
Safety 
213199/final_01/T1.15 
Summary of Dimensions of Select, 
Measurable SC Injection Site Reaction 
Adverse Events (Erythema, Redness, 
Induration, & Swelling) 
Report Study Phase in the columns 
Sort by CAB+RPV, CAB, RPV 
Report descriptive statistics of the 
diameter and width (mm) of the ISRs.  
SS-SAC 
3.38 
Sub-study 
Safety 
GSK3640254/208379/primary_01/T2.1 
Summary of the Posterior Probability that 
the True Rate of SC ISRs of Interest >0.05 
after 50% of Subjects Initiate SC Injections 
Keep the first and last statistical 
categories, use only one column for 
SC, update study info to align with 
FLAIR ISR monitoring criteria.  
SS-ISR 
Laboratory: Chemistry and Hematology 
3.39 
Sub-study 
Safety 
207966/primary_46/T3.32 
Summary of Chemistry Changes from Sub-
study Baseline by Visit (SC Injection + 
Return to Gluteal Injection Phase) 
Do not use lipid LOCF at interim, use 
actual values. 
 
Replace first footnote with “Note: 
Fasting data is shown for lipids and 
glucose. “ 
 
Use lipid LOCF at SS-SAC. 
SS-Interim 
SS-SAC 
3.40 
Sub-study 
Safety 
207966/primary_46/T3.33 
Summary of Chemistry Values by Visit (SC 
Injection + Return to Gluteal Injection 
Phase) 
Use Lipid LOCF at SS-SAC. 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
378 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.41 
Sub-study 
Safety 
207966/primary_46/T3.36 
Summary of Maximum Post Sub-study 
Baseline Emergent Chemistry Toxicities 
(SC Injection Phase) 
 
SS-SAC 
3.42 
Sub-study 
Safety 
207966/primary_46/T3.34 
Summary of Hematology Changes from 
Sub-study Baseline by Visit (SC Injection + 
Return to Gluteal Injection Phase) 
 
SS-Interim 
SS-SAC 
3.43 
Sub-study 
Safety 
207966/primary_46/T3.35 
Summary of Hematology Values by Visit 
(SC Injection + Return to Gluteal Injection 
Phase) 
 
SS-SAC 
3.44 
Sub-study 
Safety 
207966/primary_46/T3.37 
Summary of Maximum Post Sub-study 
Baseline Emergent Hematology Toxicities 
(SC Injection Phase) 
 
SS-SAC 
Laboratory: Urinalysis 
3.45 
Sub-study 
Safety 
207966/primary_46/T3.38 
Summary of Urinalysis Dipstick Results by 
Visit (SC Injection Phase) 
 
SS-SAC 
3.46 
Sub-study 
Safety 
207966/primary_46/T3.39 
Summary of Urine Concentrations 
Changes from Sub-study Baseline by Visit 
(SC Injection Phase) 
 
SS-SAC 
3.47 
Sub-study 
Safety 
207966/primary_46/T3.40 
Summary of Changes in Proteinuria 
Baseline Laboratory Result to Maximum 
Post Sub-study Baseline Laboratory Result 
(SC Injection Phase) 
 
SS-SAC 
Laboratory: Hepatobiliary (Liver) 
3.48 
Sub-study 
Safety 
213199/final_01/T3.46 
Summary of Liver Stopping Event 
Reporting (SC Injection Phase) 
 
SS-SAC 
3.49 
Sub-study 
207966/primary_46/T3.42 
Summary of Subjects Meeting 
 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
379 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Safety 
Hepatobiliary Abnormality Criteria (SC 
Injection Phase) 
ECG 
3.50 
Sub-study 
Safety 
207966/primary_46/T3.43 
Summary of ECG Findings (SC Injection 
Phase) 
 
SS-SAC 
3.51 
Sub-study 
Safety 
207966/primary_46/T3.44 
Summary of Change from Sub-study 
Baseline in ECG values by Visit (SC 
Injection Phase) 
 
SS-SAC 
Vital Signs 
3.52 
Sub-study 
Safety 
207966/primary_46/T3.47 
Summary of Change from Sub-study 
Baseline in Vital Signs by Visit (SC 
Injection Phase) 
Include weight and BMI 
SS-SAC 
Adverse Event of Special Interest (AESI) 
3.53 
Sub-study 
Safety 
207966/primary_46/T3.48 
Summary of Depression, Anxiety and 
Suicidal Ideation/Behaviour Adverse 
Events by System Organ Class, Maximum 
DAIDS Toxicity Grade, and Prior History of 
Depression, Anxiety and Suicidal Ideation 
at Screening (SC Injection Phase) 
 
SS-SAC 
3.54-
3.70 
Sub-study 
Safety 
207966/primary_46/T3.50-3.66 
Summary of XXX Adverse Events of 
Special Interest by System Organ Class 
and Preferred Term (Number of Subjects 
and Occurrence) – SC Injection Phase 
 
SS-SAC 
3.71 
Sub-study 
Safety 
207966/primary_46/T3.67 
Summary of Characteristics of Adverse 
Events of Special Interest – SC Injection 
Phase 
 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
380 
 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
COVID-19 Adverse Event 
3.72 
Sub-study 
Safety 
213199/final_01/T3.11 
Summary of COVID-19 Adverse Events by 
Study Phase, System Organ Class, and 
Maximum Toxicity  
Repeat results for both study phases 
and overall. 
SS-SAC 
3.73 
Sub-study 
Safety 
213199/final_01/T3.52 
Summary of COVID-19 Assessments for 
Subjects with COVID-19 Adverse Events 
 
SS-SAC 
3.74 
Sub-study 
Safety 
213199/final_01/T3.53 
Summary of COVID-19 Additional 
Assessments for Subjects with COVID-19 
Adverse Events 
 
SS-SAC 
3.75 
Sub-study 
Safety 
213199/final_01/T3.54 
Summary of COVID-19 Symptoms for 
Subjects with COVID-19 Adverse Events 
 
SS-SAC 
 
 
 


 
CONFIDENTIAL 
 
 
201584 
381 
 
14.19.8. 
Safety Figures 
Safety Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.1 
Sub-study 
Safety 
207966/primary_34/F3.1 
Plot of Common Adverse Events and Relative Risk – 
SC vs. IM, Excluding Study Drug ISRs (SC Sub-study) 
Only IM events occurring during 
the sub-study should be included. 
SS-SAC 
3.2 
Sub-study 
Safety 
207966/primary_34/F3.2 
Plot of Common Study Drug Injection Site Reaction 
Adverse Events and Relative Risk – SC vs. IM (SC 
Sub-study) 
Only IM events occurring during 
the sub-study should be included. 
SS-SAC 
3.3 
Sub-study 
Safety 
AE10 
Plot of Common Grade 1+ Injection Site Reaction 
Adverse Events and Relative Risk Overall & by 
Subgroup – SC vs. Pre-SC IM  
Include ISRs from all SC 
injections and the first 3 IM 
injections of the parent study for 
each participant 
Report incidence rate ratios 
instead of risk ratios as mentioned 
in Section 8.6 
SS-SAC 
3.4 
Sub-study 
Safety 
AE10 
Plot of Common Grade 1+ Injection Site Reaction 
Adverse Events and Relative Risk Overall & by 
Subgroup – SC vs. Post-SC IM 
Include ISRs from the first 2 SC 
injections and the 2 IM injections 
subsequent to SC dosing for each 
participant 
Report incidence rate ratios 
instead of risk ratios as mentioned 
in Section 8.6 
SS-SAC 
3.5 
Sub-study 
Safety 
AE10 
Plot of Common Grade 2+ Injection Site Reaction 
Adverse Events and Relative Risk Overall & by 
Subgroup – SC vs. Pre-SC IM  
Include ISRs from all SC 
injections and the first 3 IM 
injections of the parent study for 
each participant 
Report incidence rate ratios 
instead of risk ratios as mentioned 
in Section 8.6 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
382 
 
Safety Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.6 
Sub-study 
Safety 
AE10 
Plot of Common Grade 2+ Injection Site Reaction 
Adverse Events and Relative Risk Overall & by 
Subgroup – SC vs. Post-SC IM 
Include ISRs from the first 2 SC 
injections and the 2 IM injections 
subsequent to SC dosing for each 
participant 
Report incidence rate ratios 
instead of risk ratios as mentioned 
in Section 8.6 
SS-SAC 
3.7 
Sub-study 
Safety 
207966/primary_34/F3.3 
Plot of Incidence of Sub-study Study Drug Injection Site 
Reaction Adverse Events by Visit (Overall and 
Common) – CAB and/or RPV 
X-Axis timepoints to run from 
Screening to Week 20.  
Remove the second footnote. 
SS-SAC 
3.8 
Sub-study 
Safety 
207966/primary_34/F3.4 
Plot of Incidence of Sub-study Study Drug Injection Site 
Reaction Adverse Events by Visit (Overall and 
Common) – CAB 
X-Axis timepoints to run from 
Screening to Week 20.  
Remove the second footnote. 
SS-SAC 
3.9 
Sub-study 
Safety 
207966/primary_34/F3.5 
Plot of Incidence of Sub-study Study Drug Injection Site 
Reaction Adverse Events by Visit (Overall and 
Common) – RPV 
X-Axis timepoints to run from 
Screening to Week 20.  
Remove the second footnote. 
SS-SAC 
3.10 
Sub-study 
Safety 
207966/primary_34/F3.6 
Plot of Incidence of Sub-study Study Drug Injection Site 
Reaction Adverse Events by Subgroup and Visit – CAB 
and/or RPV 
X-Axis timepoints to run from 
Screening to Week 20.  
Remove the second and third 
footnotes. 
SS-SAC 
3.11 
Sub-study 
Safety 
207966/primary_46/F3.2 
Scatter Plot of Maximum vs. Sub-study Baseline for 
ALT (SC Injection Phase) 
 
SS-SAC 
3.12 
Sub-study 
Safety 
213199/final_01/F3.4 
Scatter Plot of Maximum Total Bilirubin vs. Maximum 
ALT – eDISH Plot (SC Injection Phase) 
 
SS-SAC 
3.13 
Sub-study 
Safety 
207966/primary_46/F3.4 
Histogram of Timeliness of Injections (SC Injection 
Phase) 
 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
383 
 
14.19.9. 
Pharmacokinetic Tables 
Note: The following subgroups will be included in subgroup summaries: Age (<35; 35-<50; >=50), Sex at Birth (Female vs Male), 
Race/Ethnicity (White: Non-Hispanic, White: Hispanic, Black, Asian, Other), Sub-study Baseline BMI (<30, >=30). 
Pharmacokinetic Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.1 
Sub-study PK 
Concentration  
208832/final_01/T4.3 
Summary of Sub-study Plasma Cabotegravir PK 
Concentration (ug/mL)-Time Data by Study Phase and 
Nominal Timepoint 
 
SS-Interim, 
SS-SAC 
4.2 
Sub-study PK 
Concentration 
208832/final_01/T4.4 
Summary of Sub-study Plasma Rilpivirine PK 
Concentration (ng/mL)-Time Data by Study Phase and 
Nominal Timepoint 
 
SS-Interim, 
SS-SAC 
4.3 
Sub-study PK 
Parameter 
207966/primary_46/T4.5 
Summary of Sub-study Derived Plasma CAB PK 
Parameters by Dosing Interval 
Parameters included are 
AUC(0-Tau), CMax, 
TMax, and CTau. 
Dosing intervals will 
include Screening Gluteal 
injection, 1st SC injection, 
2nd, SC injection, and last 
SC injection. 
CTau will be taken from 
concentration data at Day 
1 (gluteal), Week 4, and 
Week 12 (SC) 
SS-Interim, 
SS-SAC 
4.4 
Sub-study PK 
Parameter 
207966/primary_46/T4.6 
Summary of Sub-study Derived Plasma RPV PK 
Parameters by Dosing Interval 
Same notes as 4.3. 
SS-Interim, 
SS-SAC 
4.5 
Sub-study PK 
Concentration  
208832/final_01/T4.3 
Summary of Sub-study Plasma Cabotegravir PK 
Concentration (ug/mL)-Time Data by Study Phase, 
Subgroup, and Nominal Timepoint 
Repeat 4.1 with 
subgroups 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
384 
 
Pharmacokinetic Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.6 
Sub-study PK 
Concentration 
208832/final_01/T4.4 
Summary of Sub-study Plasma Rilpivirine PK 
Concentration (ng/mL)-Time Data by Study Phase, 
Subgroup, and Nominal Timepoint 
Repeat 4.2 with 
subgroups 
SS-SAC 
4.7 
Sub-study PK 
Parameter 
207966/primary_46/T4.5 
Summary of Sub-study Derived Plasma CAB PK 
Parameters by Subgroup & Dosing Interval 
Repeat 4.3 with 
subgroups 
SS-SAC 
4.8 
Sub-study PK 
Parameter 
207966/primary_46/T4.6 
Summary of Sub-study Derived Plasma RPV PK 
Parameters by Subgroup & Dosing Interval 
Repeat 4.4 with 
subgroups 
SS-SAC 
4.9 
Sub-study PK 
Parameter 
207966/primary_46/T4.7 
Statistical Analysis of Plasma CAB PK Parameters by 
Treatment in Sub-study 
GMR will be calculated for 
AUC(0-Tau), CMax, and 
CTau for SC Injection 1 / 
Gluteal Injection, SC 
Injection 2 / Gluteal 
Injection and SC Injection 
3 / Gluteal Injection 
Add footnote: “GMR taken 
from exponentiated log 
values output from an 
ANCOVA with fixed 
effects of Phase and Sub-
study Baseline BMI (<30, 
>=30) as a covariate and 
a random effect of 
subject.” 
SS-HL 
SS-SAC 
4.10 
Sub-study PK 
Parameter 
207966/primary_46/T4.8 
Statistical Analysis of Plasma RPV PK Parameters by 
Treatment in Sub-study 
Same notes as 4.5. 
SS-HL 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
385 
 
Pharmacokinetic Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.11 
Sub-study PK 
Concentration 
GSK3739937/212548/final_01/T4.6 Summary Results of SC Steady State CAB 
Concentration Assessment 
Model to begin with 
subcutaneous phase 
concentrations Day 1 – 
Week 12 
SS-SAC 
4.12 
Sub-study PK 
Concentration 
GSK3739937/212548/final_01/T4.6 Summary Results of SC Steady State RPV 
Concentration Assessment 
Same note as 4.7. 
SS-SAC 
 
 
 


 
CONFIDENTIAL 
 
 
201584 
386 
 
14.19.10. Pharmacokinetic Figures 
Pharmacokinetic Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.1 
Sub-study PK 
Concentration 
207966/primary_46/F4.1 
Individual Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) in Sub-study 
Add to footnote: “The LLQ has 
been imputed for non-quantifiable 
values” 
SS-SAC 
4.2 
Sub-study PK 
Concentration 
207966/primary_46/F4.2 
Individual Plasma RPV Concentration-Time 
Plots (Linear and Semi-Log) in Sub-study 
Add to footnote: “The LLQ has 
been imputed for non-quantifiable 
values” 
SS-SAC 
4.3 
Sub-study PK 
Concentration 
207966/primary_46/F4.3 
Mean (SD) Evaluable Plasma CAB 
Concentration-Time Plots (Linear and Semi-
Log) in Sub-study 
Add to footnote: “The LLQ has 
been imputed for non-quantifiable 
values” 
SS-Interim, 
SS-SAC 
4.4 
Sub-study PK 
Concentration 
207966/primary_46/F4.4 
Mean (SD) Evaluable Plasma RPV 
Concentration-Time Plots (Linear and Semi-
Log) in Sub-study 
Add to footnote: “The LLQ has 
been imputed for non-quantifiable 
values” 
SS-Interim, 
SS-SAC 
4.5 
Sub-study PK 
Concentration 
207966/primary_46/F4.5 
Median (5th and 95th Percentile) Evaluable 
Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) in Sub-study 
Add to footnote: “The LLQ has 
been imputed for non-quantifiable 
values” 
SS-Interim, 
SS-SAC 
4.6 
Sub-study PK 
Concentration 
207966/primary_46/F4.6 
Median (5th and 95th Percentile) Evaluable 
Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) in Sub-study 
Add to footnote: “The LLQ has 
been imputed for non-quantifiable 
values” 
SS-Interim, 
SS-SAC 
4.7 
Sub-study PK 
Parameter 
207966/primary_46/F4.7 
Geometric Mean Ratios and 90% CIs of 
Plasma CAB PK Parameters in Sub-study by 
Treatment and Comparison Type 
The comparisons include First SC 
vs Gluteal, Second SC vs Gluteal 
and Last SC vs Gluteal. 
SS-SAC 
4.8 
Sub-study PK 
Parameter 
207966/primary_46/F4.8 
Geometric Mean Ratios and 90% CIs of 
Plasma RPV PK Parameters in Sub-study by 
Treatment and Comparison Type 
Same notes as Figure 4.7. 
SS-SAC 
 
 


 
CONFIDENTIAL 
 
 
201584 
387 
 
14.19.11. Health Outcomes Tables 
Note: The following subgroups will be included in subgroup summaries: Age (<35; 35-<50; >=50), Sex at Birth (Female vs Male), 
Race/Ethnicity (White: Non-Hispanic, White: Hispanic, Black, Asian, Other), Sub-study Baseline BMI (<30, >=30). 
Note: LOCF should not be used for any Health Outcomes table. 
Health Outcomes Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
HIV Treatment Satisfaction Questionnaire Status or Change Version (HIVTSQs, HIVTSQc) 
6.1 
Sub-study 
Safety 
207966/primary_46/T6.1 
Proportion of Subjects with HIVTSQs - Individual 
Item Scores by Visit in Sub-study 
 
SS-SAC 
6.2 
Sub-study 
Safety 
207966/primary_46/T6.4 
Summary of HIVTSQs - Change in Individual Item 
Score in Sub-study 
Replace Weeks 16 and 24/20 with 9 
and 17 
SS-SAC 
6.3 
Sub-study 
Safety 
207966/primary_46/T6.2 
Summary of HIVTSQs - Total Treatment 
Satisfaction Score by Visit in Sub-study 
Replace Weeks 16 and 24/20 with 9 
and 17 
Add the footnote: “[1] Sub-study Week 
9 and Sub-study Week 17 are 
compared with the Sub-study Baseline 
using Wilcoxon signed-rank test.” 
SS-SAC 
6.4 
Sub-study 
Safety 
207966/primary_46/T6.3 
Summary of HIVTSQs - Change in Total Treatment 
Satisfaction Score in Sub-study 
Replace Weeks 16 and 24/20 with 9 
and 17. 
SS-SAC 
6.5 
Sub-study 
Safety 
207966/primary_46/T6.2 
Summary of HIVTSQs - Total Treatment 
Satisfaction Score by Visit & Subgroup in Sub-
study 
Repeat Table 6.3 by subgroup 
SS-SAC 
6.6 
Sub-study 
Safety 
207966/primary_46/T6.5 
Proportion of Subjects with HIVTSQc - Individual 
Item Change Score at Sub-study Week 9 (SC 
Injection Phase) 
 
SS-SAC 
6.7 
Sub-study 
Safety 
207966/primary_46/T6.6 
Summary of HIVTSQc - Individual Item Change 
Score at Sub-study Week 9 (SC Injection Phase) 
Replace Week 16 with 9. 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
388 
 
Health Outcomes Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.8 
Sub-study 
Safety 
207966/primary_46/T6.7 
Summary of HIVTSQc - Total Treatment 
Satisfaction Change Score at Sub-study Week 9 
(SC Injection Phase) 
Replace Week 16 with 9 
SS-SAC 
Tolerability of Injection (NRS) 
6.9 
Sub-study 
Safety 
208832/final_01/T6.3 
Proportion of Subjects with Tolerability of Injection 
(NRS) Individual Item Scores by Visit in Sub-study 
Replace Actual Relative Time values 
with Week -4, Week -3, Day 1, Week 
1, Week 8, Week 9, Week 12, and 
Week 13 
SS-SAC 
6.10 
Sub-study 
Safety 
208832/final_01/T6.4 
Summary of Tolerability of Injection (NRS) Scores 
by Visit in Sub-study 
Replace Actual Relative Time values 
with same visits as Table 6.9 
SS-Interim 
SS-SAC 
6.11 
Sub-study 
Safety 
208832/final_01/T6.6 
Summary of Tolerability of Injection (NRS) Change 
from Baseline Scores by Visit in Sub-study 
Replace Actual Relative Time values 
with same visits as Table 6.9 
SS-SAC 
6.12 
Sub-study 
Safety 
208832/final_01/T6.4 
Summary of Tolerability of Injection (NRS) Scores 
by Visit & Subgroup in Sub-study 
Repeat Table 6.10 by subgroup 
SS-SAC 
Perception of Injection (PIN) 
6.13 
Sub-study 
Safety 
208832/final_01/T6.2 
Proportion of Subjects with each individual item 
score in PIN by Visit and Item in Sub-study 
Replace Day 8 with Week -3, Week 1, 
Week 9, and Week 13 
SS-SAC 
6.14 
Sub-study 
Safety 
201584/primary_01/T6.2 
Summary of Perception of Injection (PIN) 
Questionnaire Results in Domain Scores and 
Individual Item Scores by Visit in Sub-study 
Replace current visits with Week -3, 
Week 1, Week 9, and Week 13 
Remove p-value column 
SS-SAC 
6.15 
Sub-study 
Safety 
201584/primary_01/T6.4 
Summary of PIN Change from Baseline (Week -3) 
Results in Domain Scores and Individual Item 
Scores by visit in Sub-study 
Replace current visits with Week -3, 
Week 1, Week 9, and Week 13 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
389 
 
Health Outcomes Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.16 
Sub-study 
Safety 
201584/primary_01/T6.2 
Summary of Perception of Injection (PIN) 
Questionnaire Results in Domain Scores and 
Individual Item Scores by Visit & Subgroup in Sub-
study 
Repeat Table 6.14 by subgroup 
SS-SAC 
6.17 
Sub-study 
Safety 
201584/primary_01/T6.3 
Summary and Statistical Analysis of PIN in Domain 
Scores and Individual Item Scores by Visit in Sub-
study 
Compare scores at Weeks 1, 9, and 
13 to Baseline using the Wilcoxon 
Signed Rank test 
SS-SAC 
Preference 
6.18 
Sub-study 
Safety 
207966/primary_46/T6.11 
Proportion of Subjects with Response to Each 
Individual Question in Preference SC Injection vs 
Gluteal Injection Questionnaire by Visit in Sub-
study 
Replace Weeks 8/12 and 24/20 with 9 
and 17. 
SS-Interim 
SS-HL 
 SS-SAC 
6.19 
Sub-study 
Safety 
207966/primary_46/T6.11 
Proportion of Subjects with Response to Each 
Individual Question in Preference SC Injection vs 
Gluteal Injection Questionnaire by Visit & Subgroup 
in Sub-study 
Repeat 6.18 by subgroup 
SS-SAC 
Reason for Switch 
6.20 
Sub-study 
Safety 
207966/primary_46/T6.11 
Proportion of Subjects with Response to Each 
Reason in the Reason for Switch to SC 
Questionnaire in Sub-study 
Map question and responses based on 
questionnaire 
SS-SAC 
Interest 
6.21 
Sub-study 
Safety 
207966/primary_46/T6.11 
Proportion of Subjects with Each Response to the 
Interest in Home Administration Questionnaire in 
Sub-study 
Map question and responses based on 
questionnaire 
SS-SAC 
 
 


 
CONFIDENTIAL 
 
 
201584 
390 
 
14.19.12. Virology Tables 
If no data are available, Virology Tables will be displayed with “No data to report.” 
Virology Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Genotype & Phenotype 
7.1 
Sub-study 
Safety 
213199/final_01/T2.9 
Summary of the Prevalence of Treatment-Emergent 
Major Resistance Mutations of INI, NRTI, NNRTI and PI 
Class at time of CVF (SC Injection + Return to Gluteal 
Injection Phase) – Plasma Sample 
 
SS-SAC 
7.2 
Sub-study 
Safety 
213199/final_01/T2.10 
Summary of Viral load, Genotypic and Phenotypic data 
for Subjects Who Met Confirmed Virologic Failure Criteria 
during the SC Injection or Return to Gluteal Injection 
Phase 
 
SS-SAC 
7.3 
Sub-study 
Safety 
213199/final_01/T2.11 
Summary of Viral load, Genotypic and Phenotypic data 
for Subjects Who Did Not Meet Confirmed Virologic 
Failure Criteria during the SC Injection or Return to 
Gluteal Injection Phase 
 
SS-SAC 
 
 
 


 
CONFIDENTIAL 
 
 
201584 
391 
 
14.19.13. ICH Listings 
ICH Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
1 
Sub-study 
Screened 
207966/primary_46/L1 
Listing of Reasons for Screen Failure 
in Sub-study 
 
SS-SAC 
2 
Sub-study 
Safety 
213199/final_01/L1 
Listing of Reasons for Sub-study 
Withdrawal 
 
SS-SAC 
3 
Sub-study 
Safety 
213199/final_01/L2 
Listing of Reasons for Study Drug 
Discontinuation 
 
SS-SAC 
4 
Sub-study 
Safety 
207966/primary_46/L4 
Listing of Important Protocol 
Deviations 
 
SS-SAC 
5 
Sub-study 
Safety 
213199/final_01/L8 
Listing of Demographic 
Characteristics 
 
SS-SAC 
Efficacy 
6 
Sub-study 
Safety 
213199/final_01/L11 
Listing of Study Outcome (50 c/mL 
Threshold) at Sub-study Week 12 – 
Snapshot Analysis 
 
SS-SAC 
Safety 
7 
Sub-study 
Safety 
207966/primary_46/L10 
Listing of Serious Adverse Events 
and Reasons for Considering as a 
Serious Adverse Event 
 
SS-SAC 
8 
Sub-study 
Safety 
213199/final_01/L14 
Listing of Adverse Events Leading to 
Withdrawal/Permanent 
Discontinuation of Investigational 
Product 
 
SS-SAC 
9 
Sub-study 
LB5A 
Listing of all Laboratory Data for 
 
SS-SAC 


 
CONFIDENTIAL 
 
 
201584 
392 
 
ICH Listings 
Safety 
Subjects with Any Value Outside 
Normal Range 
10 
Sub-study 
Safety 
207966/primary_46/L20 
Listing of ECG Values for Subjects 
with a Value of Potential Clinical 
Importance in Sub-study 
 
SS-SAC 
11 
Sub-study 
Safety 
213199/final_01/L46 
Listing of All Vital Signs Results 
Include Weight and BMI 
SS-SAC 
PK 
12 
Sub-study PK 
Concentration 
207966/primary_46/L21 Listing of Plasma CAB PK 
Concentration-Time Data 
 
SS-SAC 
13 
Sub-study PK 
Concentration 
207966/primary_46/L22 Listing of Plasma RPV PK 
Concentration-Time Data 
 
SS-SAC 
 
 
 


 
CONFIDENTIAL 
 
 
201584 
393 
 
14.19.14. Non-ICH Listings 
Non-ICH Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
14 
Sub-study 
Safety 
213199/final_01/L31 
Listing of Concomitant ART Medications During the 
Sub-study 
Only list ART medications that were 
concomitant at any time during the 
sub-study.  
SS-SAC 
15 
Sub-study 
Safety 
207966/primary_46/L30 Listing of Transition to CAB + RPV LA Marketed 
Product Status 
 
SS-SAC 
Efficacy 
16 
Sub-study 
Safety 
207966/primary_34/L35 Listing of All Plasma HIV-1 RNA Data for Subjects 
with Confirmed Virologic Failure 
 
SS-SAC 
Safety 
17 
Sub-study 
Safety 
207966/primary_34/L43 
Listing of Subjects Meeting Hepatobiliary Lab 
Criteria (SC Injection + Return to Gluteal Injection 
Phase) 
Drop Treatment, Display by Phase 
SS-SAC 
PK 
18 
Sub-study 
PK 
Parameter 
208832/final_01/L34 
Listing of Derived Plasma Cabotegravir PK 
Parameters by Sub-study Phase 
Replace Treatment column with 
Phase/Dosing Interval 
SS-SAC 
19 
Sub-study 
PK 
Parameter 
208832/final_01/L35 
Listing of Derived Plasma Rilpivirine PK Parameters 
by Sub-study Phase 
Replace Treatment column with 
Phase/Dosing Interval 
SS-SAC 
 


 
CONFIDENTIAL 
 
 
201584 
394 
 
14.20. 
Appendix 20: Example Mock Shells for Data Displays 
Data Display Specification will be made available on Request.