Clinical trial NCT04542070
Conditions: HIV Infections
Keywords: HIV Cabotegravir Rilpivirine BIKTARVY Antiretroviral therapy
Sponsor: ViiV Healthcare
Start date: 2020-11-09; Completion date: 2023-04-17
Enrollment: 687 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is designed to assess the antiviral activity and safety of a two-drug regimen of CAB LA + RPV LA compared with maintenance of BIK. BIKTARVY is a registered trademark of Gilead Sciences.

Detailed description:

Arms: arm 1: Participants with HIV-1 received BIK tablet orally until month 12. BIK was a fixed dose combination of 50 mg Bictegravir (BIC) + 200 mg Emtricitabine (FTC) + 25 mg Tenofovir alafenamide (TAF). arm 2: Participants with human immunodeficiency viruses (HIV)-1 who chose oral lead in (OLI) received oral 30 milligram (mg) Cabotegravir (CAB) tablet + 25 mg Rilpivirine (RPV) tablet once daily (QD) for one month. At the month 1 visit, the last dose of oral CAB + RPV was given, followed by the first 600 mg CAB long-acting (LA) + 900 mg RPV LA intramuscular injection (IM), and second injection of CAB LA 600 mg + RPV LA 900 mg at month 2, and then subsequent injections once every 2 months (Q2M) until Month 12 (Maintenance Phase). The participants had the option to continue the regimen in the Extension Phase arm 3: Participants with HIV-1 who chose direct to injections (D2I) received the first injections of 600 mg CAB LA + 900 mg RPV LA, IM as initial loading doses at Day 1 one month, followed by second and third subsequent injections (CAB LA 600 mg + RPV LA 900 mg) at month 1 and month 3 followed by Q2M until Month 11. The participants had the option to continue the regimen in the Extension Phase. arm 4: Eligible participants with HIV-1 who received BIK tablet orally switched treatment after month 12 (Extension Phase) to CAB LA 600 mg + RPV LA 900 mg regimen, administered once every 2 months.
Interventions: intervention 1: Cabotegravir Tablets intervention 2: Cabotegravir Injectable Suspension (CAB LA) intervention 3: Rilpivirine Tablets intervention 4: Rilpivirine Injectable Suspension (RPV LA) intervention 5: BIKTARVY Tablets (BIK)
Intervention descriptions: intervention 1: CAB tablets were available as film coated tablets for oral administration. intervention 2: CAB LA was available as sterile suspension for injection in GSK1265744 for administration as IM injection. intervention 3: RPV was administered as tablets for oral administration. intervention 4: RPV LA was available as a sterile suspension of RPV to be administered as an IM injection. intervention 5: BIK was a three-drug fixed dose combination product BIC, FTC, and TAF for oral administration.

Protocol documents:
Prot_000.pdf: 
TMF-14364917 
CONFIDENTIAL 
 
ViiV Healthcare group of companies 
 
213500 
 
1 
 
TITLE PAGE 
Protocol Title: A Phase IIIb, Randomized, Multicenter, Active-controlled, Parallel-
group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and 
Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine 
administered every two months from a Bictegravir/emtricitabine/tenofovir alafenamide 
Single Tablet Regimen in HIV-1 Infected Adults who are Virologically Suppressed 
Protocol Number: 213500/ 03 
Compound Number 
or Name: 
GSK1265744/Cabotegravir 
Study Phase: IIIB  
Short Title: PH3b, CAB LA + RPV LA vs BIK, IM Every 2 Months, Non-inferiority, 
Efficacy and Safety Study in Participants with HIV-1 Who are Virologically Suppressed 
SOLAR (Switch Onto Long Acting Regimen) 
Sponsor Name and Legal Registered Address:  
This study is sponsored by ViiV Healthcare. GlaxoSmithKline is supporting ViiV 
Healthcare in the conduct of this study. 
Sponsor Name and 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 
Five Moore Drive 
P.O. 13398 
Research Triangle Park, NC 27709-3398, USA 
Telephone:  +1 919 438 2100 
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. 
Copyright 2022 ViiV Healthcare group of companies. All rights reserved. Unauthorised 
copying or use of this information is prohibited. 


TMF-14364917 
CONFIDENTIAL 
 
ViiV Healthcare group of companies 
 
213500 
 
2 
 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual  
Regulatory Agency Identifying Number(s):  
IND No. 109,678 
EudraCT No. 2020-002623-11 
Approval Date: 10-FEB-2022 
 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
3 
 
SPONSOR SIGNATORY: 
Protocol Title: A Phase IIIb, Randomized, Multicenter, Active-controlled, Parallel-
group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and 
Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine 
administered every two months from a Bictegravir/emtricitabine/tenofovir alafenamide 
Single Tablet Regimen in HIV-1 Infected Adults who are Virologically Suppressed 
Protocol Number: 213500/ 03 
Compound Number 
or Name: 
GSK1265744/Cabotegravir 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sherene Min  
VP and Head, Clinical Development 
ViiV Healthcare 
 
Date 
 
 
 
 
 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
4 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Amendment 3 
10-FEB-2022 
Amendment 2 
8-SEP-2021 
DEU Amendment 1 
12-JAN-2021 
GBR Amendment 1 
20-NOV-2020 
FR Amendment 1 
16-NOV-2020 
Amendment 1  
30-JUN-2020  
Original Protocol 
27-MAY-2020 
 
Amendment 03: 10-FEB-2022 
This amendment is considered to be non-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 Amendment 03:  
The primary reason for protocol amendment 03 is to address and clarify comments raised 
during the course of the study  
Section # and Name 
Description of Change 
Brief Rationale 
Headers 
Change to protocol reference 
number 
Due to sponsor protocol writing 
procedures 
Section 1.1. Synopsis and 
Section 3 Objectives 
Removed endpoint “Change 
from Baseline in incident 
metabolic syndrome at 
Months 6 and 12 (OLI and 
BIK)/Month 5 and Month 11 
(D2I) in Metabolic Syndrome 
Objective  
 
Not required 
Section 1.1. Synopsis and 
Section 3 Objectives 
Removed reference to BIK in 
the endpoint addressing 
Preference objective 
Not required 
Section 1.3 Schedule of 
Assessments 
Removal of height, weight, 
(BMI), waist and hip 
circumference assessments 
in “BIK to Direct to Injection” 
arm at Month 14 
Assessments not required 
Section 1.3 Schedule of 
Footnote aa. Addition of text 
BIK Participant who withdraw at or 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
5 
 
Section # and Name 
Description of Change 
Brief Rationale 
Assessments 
at the end: “Participants who 
do not enter Extension Phase 
or do not wish to transition to 
the commercial supply will not 
receive 1-month supply at 
M12.” 
after M12 will no longer be eligible 
for study BIK 
Section 4.1.3 Extension 
Phase 
Additional text provided on 
participants who transition to 
commercial product that the 
transition plan to marketed 
product should be done in 
consultation with the Central 
Study Team and study 
Medical Monitor 
To provide adequate patient 
management during transition 
Section 4.1.3.2 
Participants Entering from 
BIK arm 
Added text to remind 
Investigators to refer to list of 
prohibited medications  
To ensure there is not risk of drug-
drug interaction  
Section 4.5 End of Study 
Definitions 
Clarification on phone versus 
in-clinic safety Follow-up visits 
For clarification purposes 
Section 5.5.2 Cosmetic 
Surgery  
Paragraph expanded 
For clarification purposes 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
6 
 
TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY: ............................................................................................... 3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 4 
TABLE OF CONTENTS .................................................................................................. 6 
1. 
PROTOCOL SUMMARY ........................................................................................ 11 
1.1. 
Synopsis ..................................................................................................... 11 
1.2. 
Schema ...................................................................................................... 15 
1.3. 
Schedule of Activities (SoA) ........................................................................ 16 
2. 
INTRODUCTION .................................................................................................... 28 
2.1. 
Study Rationale .......................................................................................... 28 
2.1.1. 
Optional Oral Lead In ................................................................... 29 
2.1.2. 
Weight Gain ................................................................................. 29 
2.2. 
Background ................................................................................................ 31 
2.3. 
Benefit/Risk Assessment ............................................................................ 33 
2.3.1. 
Risk Assessment ......................................................................... 33 
2.3.2. 
Benefit Assessment ..................................................................... 52 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 52 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 52 
4. 
STUDY DESIGN .................................................................................................... 56 
4.1. 
Overall Design ............................................................................................ 56 
4.1.1. 
Screening Phase (up to 35 days) ................................................. 57 
4.1.2. 
Maintenance Phase ..................................................................... 58 
4.1.3. 
Extension Phase .......................................................................... 60 
4.1.4. 
LTFU Phase – IM Regimen Only ................................................. 62 
4.1.5. 
Independent Data Monitoring Committee ..................................... 63 
4.2. 
Type and Number of Participants ................................................................ 63 
4.3. 
Scientific Rationale for Study Design .......................................................... 64 
4.3.1. 
Participant Input into Design ........................................................ 66 
4.4. 
Justification for Dose .................................................................................. 66 
4.4.1. 
CAB + RPV .................................................................................. 66 
4.4.2. 
BIC/FTC/TAF (BIK) ...................................................................... 70 
4.5. 
End of Study Definition ............................................................................... 70 
5. 
STUDY POPULATION ........................................................................................... 71 
5.1. 
Inclusion Criteria ......................................................................................... 71 
5.2. 
Exclusion Criteria ........................................................................................ 74 
5.3. 
Additional Eligibility Criteria ......................................................................... 78 
5.3.1. 
HIV/HCV Treatment Considerations for Co-infected 
Participants .................................................................................. 79 
5.4. 
Screening/Baseline/Run-in Failures ............................................................ 79 
5.5. 
Lifestyle Considerations .............................................................................. 79 
5.5.1. 
Meals and Dietary Restrictions .................................................... 79 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
7 
 
5.5.2. 
Cosmetic Surgery ........................................................................ 79 
6. 
STUDY INTERVENTION ........................................................................................ 80 
6.1. 
Study Intervention(s) Administered ............................................................. 80 
6.1.1. 
Formulations of CAB + RPV ........................................................ 80 
6.1.2. 
Biktarvy Tablets (BIK) .................................................................. 81 
6.1.3. 
Medical Devices ........................................................................... 81 
6.2. 
Treatment Assignment ................................................................................ 82 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 82 
6.3.1. 
Randomization ............................................................................. 82 
6.3.2. 
Blinding ........................................................................................ 82 
6.4. 
Dosage and Administration ......................................................................... 83 
6.5. 
Packaging and Labelling ............................................................................. 86 
6.6. 
Preparation/Handling/Storage/Accountability .............................................. 86 
6.6.1. 
Dosing Considerations for CAB LA + RPV LA .............................. 87 
6.6.2. 
Dosing Considerations for BIK ..................................................... 87 
6.7. 
Study Intervention Compliance ................................................................... 88 
6.8. 
Protocol Permitted Substitutions ................................................................. 88 
6.8.1. 
Oral Bridging ................................................................................ 88 
6.9. 
Interruption of Study Intervention and Visit/Dosing Windows ...................... 88 
6.9.1. 
IM Dosing .................................................................................... 89 
6.9.2. 
Oral Dosing .................................................................................. 91 
6.10. 
Treatment after the End of the Study .......................................................... 91 
6.11. 
Concomitant Therapy.................................................................................. 91 
6.11.1. 
Prohibited Medications and Non-Drug Therapies ......................... 93 
6.12. 
Dose Modification ....................................................................................... 95 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 96 
7.1. 
Participant Discontinuation/Withdrawal from the Study ............................... 96 
7.1.1. 
Liver monitoring event – Increased monitoring ........................... 100 
7.1.2. 
Liver chemistry stopping criteria ................................................. 100 
7.1.3. 
General Guidance on Restart .................................................... 103 
7.1.4. 
QTc Stopping Criteria ................................................................ 105 
7.1.5. 
Virologic Failure ......................................................................... 105 
7.1.6. 
Definition of Protocol-Defined Confirmed Virologic Failure ......... 105 
7.1.7. 
Managing Virologic Failure ........................................................ 105 
7.2. 
Lost to Follow Up ...................................................................................... 107 
8. 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 108 
8.1. 
Efficacy Assessments ............................................................................... 109 
8.1.1. 
Plasma HIV-1 RNA .................................................................... 109 
8.1.2. 
Lymphocyte Subsets, CD4+ and CD8+ ..................................... 109 
8.1.3. 
CDC HIV-1 Classification and HIV Associated Conditions ......... 109 
8.2. 
Safety Assessments ................................................................................. 109 
8.2.1. 
Clinical Evaluations .................................................................... 109 
8.2.2. 
Laboratory Assessments ........................................................... 111 
8.2.3. 
Physical Examinations ............................................................... 113 
8.2.4. 
Vital Signs .................................................................................. 113 
8.2.5. 
Electrocardiograms .................................................................... 113 
8.2.6. 
Suicidal Ideation and Behaviour Risk Monitoring ....................... 114 
8.3. 
Adverse Events and Serious Adverse Events ........................................... 114 


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
8  
 
8. 3. 1.  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n ................................................................................. 1 1 5  
8. 3. 2.  
M et h o d of D et e cti n g A E s a n d S A E s  ........................................... 1 1 5  
8. 3. 3.  
F oll o w -u p of A E s a n d S A E s  ....................................................... 1 1 6  
8. 3. 4.  
Pr o m pt R e p orti n g of S eri o u s A d v er s e E v e nt s a n d Ot h er 
E v e nt s  ....................................................................................... 1 1 6  
8. 3. 5.  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s  ........................... 1 1 8  
8. 3. 6.  
Pr e g n a n c y  ................................................................................. 1 1 8  
8. 3. 7.  
Di s e a s e -R el at e d E v e nt s a n d/ or Di s e a s e -R el at e d 
O ut c o m e s N ot Q u alif yi n g a s S A E s ............................................. 1 2 0  
8. 3. 8.  
M e di c al D e vi c e D efi ci e n ci e s  ...................................................... 1 2 1  
8. 3. 9.  
C ar di o v a s c ul ar a n d D e at h E v e nt s  .............................................. 1 2 2  
8. 3. 1 0.  
T o xi cit y M a n a g e m e nt  ................................................................. 1 2 2  
8. 3. 1 1.  
S p e cifi c T o xi citi e s/ A d v er s e E v e nt M a n a g e m e nt  ......................... 1 2 5  
8. 4.  
Tr e at m e nt of O v er d o s e  ............................................................................. 1 3 1  
8. 5.  
P h ar m a c o ki n eti c s  ..................................................................................... 1 3 2  
8. 5. 1.  
R ati o n al e of P K S a m pli n g Str at e g y  ............................................ 1 3 2  
8. 5. 2.  
P K S a m pl e C oll e cti o n  ................................................................ 1 3 3  
8. 5. 3.  
S a m pl e A n al y si s  ........................................................................ 1 3 4  
8. 7.  
G e n eti c s  ................................................................................................... 1 3 4  
8. 8.  
Vir al G e n ot y p i n g a n d P h e n ot y pi n g ............................................................ 1 3 4  
8. 8. 1.  
HI V -1 P ol y m er a s e Vir al G e n ot y pi n g a n d P h e n ot y pi n g  ............... 1 3 5  
8. 9.  
I m m u n o g e ni cit y A s s e s s m e nt s ................................................................... 1 3 5  
8. 1 0.  M e di c al R e s o ur c e Utili z ati o n a n d H e alt h E c o n o mi c s  ................................ 1 3 5  
8. 1 1.  V al u e E vi d e n c e a n d O ut c o m e s  ................................................................. 1 3 5  
8. 1 1. 1.  
V al u e E vi d e n c e a n d O ut c o m e s E n d p oi nt s ( S e c o n d ar y)  ............. 1 3 7  
8. 1 2.  Bi o m ar k er s  ............................................................................................... 1 3 7  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ...................................................................... 1 3 8  
9. 1.  
St ati sti c al H y p ot h e s e s ............................................................................... 1 3 8  
9. 2.  
S a m pl e Si z e C o n si d er ati o n s  ..................................................................... 1 3 9  
9. 2. 1.  
S a m pl e Si z e D et er mi n ati o n  ....................................................... 1 3 9  
9. 2. 2.  
S a m pl e Si z e A s s u m pti o n s  ......................................................... 1 3 9  
9. 2. 3.  
S a m pl e Si z e S e n siti vit y  .............................................................. 1 4 0  
9. 3.  
P o p ul ati o n s f or A n al y s e s  .......................................................................... 1 4 0  
9. 3. 1.  
I nt e nt-t o-Tr e at E x p o s e d (I T T -E) P o p ul ati o n  ............................... 1 4 0  
9. 3. 2.  
P er -Pr ot o c ol P o p ul ati o n ( P P)  ..................................................... 1 4 1  
9. 3. 3.  
S af et y P o p ul ati o n  ....................................................................... 1 4 1  
9. 3. 4.  
P K P o p ul ati o n  ............................................................................ 1 4 1  
9. 4.  
St ati sti c al A n al y s e s  ................................................................................... 1 4 1  
9. 4. 1.  
Pri m ar y A n al y s e s  ....................................................................... 1 4 1  
9. 4. 2.  
S af et y a n d S e c o n d ar y A n al y s e s  ................................................ 1 4 2  
9. 4. 3.  
H e alt h O ut c o m e A n al y s e s  ......................................................... 1 4 3  
9. 4. 4.  
Vir al G e n ot y pi n g/ P h e n ot y pi n g A n al y s e s  .................................... 1 4 3  
9. 4. 5.  
P h ar m a c o ki n eti c A n al y si s  .......................................................... 1 4 3  
9. 5.  
I nt eri m A n al y s e s ....................................................................................... 1 4 3  
1 0.  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L  
C O N SI D E R A TI O N S  ............................................................................................. 1 4 5  
C CI
C CI
C CI


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
9 
 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations .......................................................................................... 145 
10.1.1. 
Regulatory and Ethical Considerations ...................................... 145 
10.1.2. 
Financial Disclosure ................................................................... 145 
10.1.3. 
Informed Consent Process ........................................................ 146 
10.1.4. 
Data Protection .......................................................................... 146 
10.1.5. 
Quality Control (Study Monitoring) ............................................. 147 
10.1.6. 
Dissemination of Clinical Study Data ......................................... 147 
10.1.7. 
Data Quality Assurance ............................................................. 148 
10.1.8. 
Source Documents .................................................................... 149 
10.1.9. 
Study and Site Start and Closure ............................................... 149 
10.1.10. Records Retention ..................................................................... 150 
10.1.11. Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication .......................................................................... 150 
10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 152 
10.2.1. 
Definition of AE .......................................................................... 152 
10.2.2. 
Definition of SAE ........................................................................ 153 
10.2.3. 
Definition of Cardiovascular Events ........................................... 154 
10.2.4. 
Recording and Follow-Up of AE and SAE .................................. 155 
10.2.5. 
Reporting of SAE to GSK ........................................................... 157 
10.3. 
Appendix 3:  CDC Classification for HIV-1 Infection (2014) ....................... 158 
10.4. 
Appendix 4: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Version 2.1, March 2017 ............................ 160 
10.4.1. 
Estimating Severity Grade for Parameters Not Identified in 
the Grading Table ...................................................................... 160 
10.5. 
Appendix 5: Contraceptive Guidance ........................................................ 184 
10.5.1. 
Definitions: ................................................................................. 184 
10.5.2. 
Contraception Guidance ............................................................ 185 
10.6. 
Appendix 6:  Information and Guidance for Managing Pregnant 
Participants ............................................................................................... 186 
10.6.1. 
Collection of Pregnancy Information: ......................................... 186 
10.6.2. 
Introduction ................................................................................ 186 
10.6.3. 
Background ............................................................................... 187 
10.6.4. 
Benefit/Risk Assessment ........................................................... 188 
10.6.5. 
Clinical Considerations .............................................................. 190 
10.6.6. 
Study Assessments and Procedures: specific 
assessments for pregnant participants ....................................... 193 
10.7. 
Appendix 7: Genetics ................................................................................ 195 
10.8. 
Appendix 8: Liver Safety: Required Actions, Follow-up Assessments 
and Study Intervention Guidelines ............................................................ 198 
10.8.1. 
VSLC Guidelines for Drug Restart after stop for Liver 
criteria ........................................................................................ 198 
10.8.2. 
VSLC Decision Process for Drug Restart Approval or 
Disapproval ................................................................................ 198 
10.8.3. 
Medical monitor, GCSP Physician and PI actions for 
Restart following VSLC decision ................................................ 200 
10.9. 
Appendix 9: AEs, ADEs, SAEs, SADEs, USADEs and Device 
Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting in Medical Device Studies ................................ 202 
10.9.1. 
Definition of Medical Device AE and ADE .................................. 203 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
10 
 
10.9.2. 
Definition of Medical Device SAE, SADE and USADE ............... 203 
10.9.3. 
Definition of Device Deficiency ................................................... 204 
10.9.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies ............................................................................... 204 
10.9.5. 
Reporting of SADEs ................................................................... 206 
10.10. Appendix 10: Recommendation for Assessment of Waist 
Circumference, Hip Circumference and Weight (Adapted from WHO 
STEPS Surveillance Manual, 2017) and for Resting Blood Pressure ........ 207 
10.10.1. Waist Circumference ................................................................. 207 
10.10.2. Hip Circumference ..................................................................... 209 
10.10.3. Weight ....................................................................................... 210 
10.10.4. Resting Blood Pressure ............................................................. 211 
10.11. Appendix 11:  COVID-19 Pandemic and Clinical Trial Continuity .............. 212 
10.11.1. Changes to Study Visits and Study Procedures ......................... 212 
10.11.2. Changes to Informed Consent ................................................... 213 
10.11.3. Permissible Use of Antiretroviral Therapy .................................. 213 
10.11.4. Direct-To-Patient (DTP) Shipment of Oral Study IP ................... 215 
10.11.5. COVID-19 Experimental Agents ................................................ 216 
10.11.6. COVID-19 Specific Data Capture ............................................... 216 
10.12. Appendix 12: Country-specific requirements ............................................. 219 
10.12.1. United Kingdom (UK) ................................................................. 219 
10.12.2. Ireland ....................................................................................... 219 
10.12.3. France (FRA) ............................................................................. 220 
10.12.4. Germany (DEU) ......................................................................... 220 
10.13. Appendix 13:  Protocol Amendment History .............................................. 221 
10.14. Appendix 14: Abbreviations and Trademarks ............................................ 230 
11. REFERENCES ..................................................................................................... 234 
 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
11 
 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase IIIb, Randomized, Multicenter, Active-controlled, Parallel-
group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and 
Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine 
administered every two months from a Bictegravir/emtricitabine/tenofovir alafenamide 
Single Tablet Regimen in HIV-1 Infected Adults who are Virologically Suppressed 
Short Title: PH3b, CAB LA + RPV LA vs BIK, IM Every 2 Months, Non-inferiority, 
Efficacy and Safety Study in Participants with HIV-1 Who are Virologically Suppressed  
Rationale:  Study 213500 (SOLAR:  Switch Onto Long Acting Regimen) is designed to 
demonstrate the non-inferior antiviral activity of CAB LA 600 mg + RPV LA 900 mg 
administered every 2 months (Q2M) compared to Biktarvy (BIK) administered orally 
once daily for 12 months.  The study will provide important comparative antiviral 
activity, safety and tolerability data of these regimens through Month 12 of the 
Maintenance Phase of the study as well as provide important comparative data on the 
optional oral lead in and anthropometric measures.  
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
To demonstrate the non-inferior antiviral 
activity of CAB LA + RPV LA every two 
months compared to a BIK single tablet 
regimen administered once daily over 12 
months in suppressed HIV-1 infected 
antiretroviral therapy (ART)-experienced 
participants 
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 Month 12 (OLI and BIK)/Month 11 
(D2I) (Intent-to-Treat Exposed [ITT-E] 
population) 
Secondary 
To demonstrate the antiviral and 
immunologic response with the use of 
CAB LA + RPV LA every 2 months 
compared to a BIK single tablet regimen 
administered once daily 
Proportion of participants with plasma 
HIV-1 RNA <50 c/mL (c/mL) at Month 6 
and Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I) using the FDA Snapshot 
algorithm (Intent-to-Treat Exposed [ITT-E] 
population) 
Proportion of participants with protocol-
defined confirmed virologic failure (CVF) 
through Month 6 and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I). 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
12 
 
Objectives 
Endpoints 
Proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL as per 
FDA Snapshot algorithm at Month 6, and 
Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I) 
Absolute values and changes from Baseline 
in viral load and CD4+ cell count over time 
including Month 6 and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I) 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure  
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV, 
BIC, FTC, and TAF through Month 6 and 
Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I). 
To evaluate renal (in urine and blood) and 
bone (in blood) biomarkers in participants 
treated with CAB LA + RPV LA compared 
to BIK 
Change from Baseline (Day 1) in renal and 
bone biomarkers at Months 6 and 12 (OLI 
and BIK)/Month 5 and Month 11 (D2I). 
To evaluate Metabolic Syndrome for 
participants treated with CAB + RPV and 
BIK 
Change from Baseline in proportions of 
participants with Metabolic syndrome at 
Months 6 and 12 (OLI and BIK)/Month 5 
and Month 11 (D2I) 
 
To evaluate insulin resistance in 
participants treated with CAB LA + RPV 
LA compared to BIK 
Change from Baseline (Day 1) in 
homeostasis model of assessment-insulin 
resistance (HOMA-IR) at Months 6 and 12 
(OLI and BIK)/Month 5 and Month 11 
(D2I). 
To assess preference for CAB LA + RPV 
LA administered every 2 months compared 
to a BIK single tablet regimen administered 
once daily  
 
Preference for CAB LA + RPV LA every 2 
months compared to a BIK single tablet 
regimen will be assessed using a preference 
questionnaire at Month 12 (OLI)/Month 11 
(D2I) (or Withdrawal). 
To assess patient reported treatment 
satisfaction, and injection tolerability. 
Change from baseline (Day 1) in total 
“treatment satisfaction” score, and 
individual item scores of the HIV 
Treatment Satisfaction Status 
Questionnaire (HIVTSQs) at Month 6 and 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
13 
 
Objectives 
Endpoints 
Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I), (or Withdrawal) 
Change in treatment satisfaction over time 
using the HIV Treatment Satisfaction 
Change Questionnaire HIVTSQc total 
score and individual item scores at Month 
12 (OLI and BIK)/Month 11 (D2I) (or 
Withdrawal). 
Change from Month 2 in Dimension scores 
(“Acceptance of ISRs”, “Bother of ISRs”, 
“Leg movement”, “Sleep”) 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) will be assessed 
using the Perception of injection 
questionnaire (PIN) at Months 2, 6, and 12 
(OLI)/Months 1, 5, 11 (D2I) (or 
Withdrawal)  
Safety 
To evaluate the safety and tolerability of 
CAB LA + RPV LA every 2 months 
compared to a BIK single tablet regimen 
administered once daily 
Incidence and severity of AEs and 
laboratory abnormalities over time 
including Month 6 and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I). 
Proportion of participants who discontinue 
treatment due to AEs over time including 
Month 6 and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I). 
Change from Baseline in laboratory 
parameters over time including Month 6 
and Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I). 
 
Overall Design:  This study is a Phase IIIb, randomized, open-label, active-controlled, 
multicenter, parallel-group, non-inferiority study designed to assess the antiviral activity 
and safety of a two-drug regimen of CAB LA + RPV LA administered every 2 months 
compared with maintenance of BIK.  Approximately 654 adult HIV-1 infected patients 
who are on the stable ARV regimen BIK will be randomized 2:1 to either be switched to 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
14 
 
the CAB LA + RPV LA regimen or continue BIK through 12 months. The study will 
continue with an Extension Phase after Month 12 (OLI and BIK)/Month 11 (D2I). 
Disclosure Statement: This is an Intervention Model (Parallel) Primary Purpose 
(Treatment) study with Number Arms (2) that is masking (No Masking).  
Number of Participants:  A total of 654 participants with a 2:1 randomization ratio to 
either CAB LA+RPV LA or BIK is such that the study has approximately 85% power to 
demonstrate non-inferiority in the proportion of participants with snapshot virologic 
failure at Month 12 using a 4% margin, assuming a true 2% failure rate for CAB LA + 
RPV LA and a 1% failure rate for the BIK arm using a 2.5% one-sided alpha level.  The 
randomized portion of the study will continue for 12 months with an Extension Phase. 
Intervention Groups and Duration:   
IM Injections every 2 months (Oral Lead In): 
Day 1 – CAB 30 mg + RPV 25 mg oral, administered once daily for 1 month 
Month 1 – CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 2 - CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 4 and Q2M thereafter - CAB LA 600 mg + RPV LA 900 mg IM, every 2 months 
until Month 12, each given as 1 X 3 mL IM injection 
IM Injections every 2 months (Direct to Injections): 
Day 1- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 1 and Q2M thereafter- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 
X 3 mL IM injection 
BIC/FTC/TAF (BIK) 
Day 1 – BIC 50 mg + FTC 200 mg + TAF 25 mg oral, administered once daily until 
Month 12. 
Data Monitoring or Other Committee: No 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
15 
 
1.2. 
Schema 
 
 


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 6  
 
1. 3.  
S c h e d ul e of A cti viti e s ( S o A)  
Ti m e a n d E v e nt s T a bl e f or C A B L A + R P V L A Or al L e a d I n ( O LI) P arti ci p a nt s:  
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p  z 
D a y 1 b  
M o nt h  
1 c 
2  
4  
6  
8  
1 0  
1 2  
Q 2 M aft er 
M o nt h 1 2  
Writt en I nf or m e d C o ns e nt  
X  
 
 
 
 
 
 
 
 
 
 
 
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X  
X d  
 
 
 
 
 
 
 
 
 
 
Ra n d o miz ati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
De mo gra p hy  
X  
 
 
 
 
 
 
 
 
 
 
 
M e dic al Hist ory e 
X  
 
 
 
 
 
 
 
 
 
 
 
Cardi ov asc ul ar risk ass ess m e nt e 
X  
X  
 
 
 
 
 
 
X  
 
X  
 
M e dic ati o n Hist ory/ Pri or A R T hist ory  
X  
 
 
 
 
 
 
 
 
 
 
 
Sy p hilis s erol o gy + refl ex Ra pi d Pl as m a R e a gi n 
( R P R) 
X  
X  
 
 
 
 
 
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d M e dic al 
Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
X  
 
X  
X  
X  
 
 
X  
 
X  
 
W aist Circ u mf er e nc e  
 
X  
 
X  
X  
X  
 
 
X  
 
X  
 
Hi p Circ u mf ere nc e  
 
X  
 
X  
X  
X  
 
 
X  
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h  
X  
X  
 
X  
X  
X  
 
 
X  
 
X  
 
 
1 2 -l e a d E C Gi  
(tri plicat e at Day 1 pre-dose)  
X  
X  
X  
 
 
 
 
 
X  
 
X  
 
C D C HI V -1 st a g e ff 
X  
X  
 
 
 
 
 
 
 
 
 
 
HI V Ass oci at e d Co n diti o ns  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
A Es, S A Es, Co nc o mit a nt M e dic ati o ns  
X j 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C CI


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 7  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p  z 
D a y 1 b  
M o nt h  
1 c 
2  
4  
6  
8  
1 0  
1 2  
Q 2 M aft er 
M o nt h 1 2  
Col u m bi a S uici d e S ev erity R ati n g Sc al e (e C-
S S R S)  k 
X  
X  
 
X  
 
X  
 
 
X  
 
X  
 
Cli nic al c h e mistry a n d He mat ol o gy  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Pre gn a ncy T esti n g l 
S  
U  
U  
U  
U  
U  
U  
U  
U  
U  
S  
U  
HI V -1 R N A  a nd s a m pl e f or st ora g e ( S) m  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
HI V -1 R N A l o w c o py s a m pl e  
 
X  
 
 
 
 
 
 
X  
 
 
 
C D4 + c ell c o u nt  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C D8 + c ell c o u nt  
 
X  
 
 
 
X  
 
 
X  
 
X  
 
Uri n alysis n 
 
X  
X  
 
 
X  
 
 
X  
 
X  
 
F asti n g L a bs  
Gl uc os e, Ch ol est erol ( T ot al, H D L a n d L D L) a n d 
Tri glyc eri d es o 
 
X  
 
 
 
X  
 
 
X  
 
X p 
 
He patitis B ( H Bs A g), A nti -H Bc, a n d A nti -
H Bs A G, He p atitis C  
(a nti-H C V A b)  
X  
 
 
 
 
 
 
 
 
 
 
 
P T/ P T T/I N R  
X  
X  
 
 
 
 
 
 
 
 
 
 
W h ol e Bl o o d ( Vir ol o gy)  
 
X  
 
 
 
X  
 
 
X  
 
X  
 
 
P B M Cs q  
 
X  
 
 
 
X  
 
 
X  
 
X  
 
I ns uli n, Hb A 1c a n d re n al, a n d b o n e bi o mark er 
a nalyt es (bl o o d uri n e) r 
 
X  
 
 
 
X  
 
 
X  
 
X x 
 
 
G e n etics s a m pl e t 
 
X  
 
 
 
 
 
 
 
 
 
 
P K s a m pli n g u 
( S) = St ora g e o nly 
 
 
S  
S  
S  
S  
S  
S  
S  
 
X  
S  
Or al C A B an d Oral R P V Dis p e ns ati o n v 
 
X  
 
 
 
 
 
 
 
 
 
 
C CI
C CI


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 8  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p  z 
D a y 1 b  
M o nt h  
1 c 
2  
4  
6  
8  
1 0  
1 2  
Q 2 M aft er 
M o nt h 1 2  
I P acc o unt a bility ( Pill Co u nts) 
 
 
X  
 
 
 
 
 
 
 
 
 
I M tre at m e nt a d mi nistrati o n w  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
 
 
HI V T S Qs cc 
 
X  
 
 
 
X  
 
 
X  
 
X d d  
 
HI V T S Qc cc 
 
 
 
 
 
 
 
 
X  
 
X d d  
 
 
Pref er e nc e cc  
 
 
 
 
 
 
 
 
X  
 
X d d  
 
PI N cc 
 
 
 
X  
 
X  
 
 
X  
 
X d d  
 
 
Hist ory of C os m etic pr oc e d ur es g g 
 
 
 
 
 
 
 
 
X  
 
X  
 
 
 
Ti m e a n d E v e nt s T a bl e f or C A B L A + R P V L A Dir e ct t o I nj e cti o n  ( D 2I) P arti ci p a nt s:  
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
3  
5  
7  
9  
1 1  
Q 2 M aft er 
M o nt h 1 1  
Writt en I nf or m e d C o ns e nt  
X  
 
 
 
 
 
 
 
 
 
 
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X  
X d  
 
 
 
 
 
 
 
 
 
Ra nd o miz ati o n  
 
X  
 
 
 
 
 
 
 
 
 
C CI
C CI


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 9  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
3  
5  
7  
9  
1 1  
Q 2 M aft er 
M o nt h 1 1  
De mo gra p hy  
X  
 
 
 
 
 
 
 
 
 
 
M e dic al Hist ory e 
X  
 
 
 
 
 
 
 
 
 
 
Cardi ov asc ul ar risk ass ess m e nt e 
X  
X  
 
 
 
 
 
X  
 
 
 
M e dic ati o n Hist ory/ Pri or A R T hist ory  
X  
 
 
 
 
 
 
 
 
 
 
Sy p hilis s erol o gy + refl ex Ra pi d Pl as m a 
Re agi n ( R P R)  
X  
X  
 
 
 
 
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d 
M e dic al Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
W ei g ht, Hei g ht a n d B MI g  
 
X  
X  
X  
X  
 
 
X  
 
X  
 
W aist Circ u mf er e nc e  
 
X  
X  
X  
X  
 
 
X  
 
X  
 
Hi p Circ u mf ere nc e  
 
X  
X  
X  
X  
 
 
X  
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h  
X  
X  
X  
X  
X  
 
 
X  
 
X  
 
 
1 2 -l e a d E C Gi  
(tri plicat e at Day 1 pre-dose)  
X  
X  
 
 
 
 
 
X  
 
X  
 
C D C HI V -1 st a g e ff 
X  
X  
 
 
 
 
 
 
 
 
 
HI V Ass oci at e d Co n diti o ns  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
A Es, S A Es, Co nc o mit a nt M e dic ati o ns  
X j 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Col u m bi a S uici d e S ev erity R ati n g Sc al e  
(e C-S S R S)  k 
X  
X  
X  
 
X  
 
 
X  
 
X  
 
Cli nic al c h e mistry a n d H e mat ol o gy  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Pre gn a ncy T esti n g l 
S  
U  
U  
U  
U  
U  
U  
U  
U  
S  
U  
HI V -1 R N A  a nd s a m pl e f or st ora g e ( S) m  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
HI V -1 R N A l o w c o py s a m pl e  
 
X  
 
 
 
 
 
X  
 
 
 
C D4 + c ell c o u nt  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C D8 + c ell c o u nt  
 
X  
 
 
X  
 
 
X  
 
X  
 
C CI


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 0  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
3  
5  
7  
9  
1 1  
Q 2 M aft er 
M o nt h 1 1  
Uri n alysis n 
 
X  
X  
 
X  
 
 
X  
 
X  
 
F asti n g L a bs: Gl uc os e, C h ol est erol ( T ot al, 
H DL a n d L D L) a n d Tri glyc eri d es o 
 
X  
 
 
X  
 
 
X  
 
X p 
 
He patitis B ( H Bs A g), A nti -H Bc, a n d A nti -
H Bs A G, He patitis C (a nti -H C V A b)  
X  
 
 
 
 
 
 
 
 
 
 
P T/ P T T/I N R  
X  
X  
 
 
 
 
 
 
 
 
 
W h ol e Bl o o d ( Vir ol o gy)  
 
X  
 
 
X  
 
 
X  
 
X  
 
 
P B M Cs q  
 
X  
 
 
X  
 
 
X  
 
X  
 
I ns uli n, Hb A 1c a n d re n al, a n d b o n e 
bi o m ark er a n alyt es (bl o o d uri n e) r 
 
X  
 
 
X  
 
 
X  
 
X x 
 
 
G e n etics s a m pl e t 
 
X  
 
 
 
 
 
 
 
 
 
P K s a m pli n g u ( S) = St ora g e o nly 
 
 
S  
S  
S  
S  
S  
S  
 
X  
S  
I M tre at m e nt a d mi nistrati o n  
 
X  
X  
X  
X  
X  
X  
X  
X  
 
 
HI V T S Qs cc 
 
X  
 
 
X  
 
 
X  
 
X d d  
 
HI V T S Qc cc 
 
 
 
 
 
 
 
X  
 
X d d  
 
 
Pref er e nc e cc  
 
 
 
 
 
 
 
X  
 
X d d  
 
PI N cc 
 
 
X  
 
X  
 
 
X  
 
X d d  
 
 
Hist ory of C os m etic pr oc e d ur e s g g 
 
 
 
 
 
 
 
X  
 
X  
 
 
 
C CI
C CI
C CI
C CI


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 1  
 
 
Ti m e a n d E v e nt s T a bl e f or BI K P arti ci p a nt s : 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
D a y 1 b  
M o nt h  
2  
4  
6  
8  
1 0  
1 2 b b  
Writt e n I nf or m e d C o ns e nt  
X  
 
 
 
 
 
 
 
 
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X  
X d  
 
 
 
 
 
 
 
R a n d o miz ati o n  
 
X  
 
 
 
 
 
 
 
D e mo gra p hy  
X  
 
 
 
 
 
 
 
 
M e dic al Hist ory e 
X  
 
 
 
 
 
 
 
 
Cardi ov asc ul ar risk ass ess m e nt e 
X  
X  
 
 
 
 
 
X  
 
M e dic ati o n Hist ory/ Pri or A R T hist ory  
X  
 
 
 
 
 
 
 
 
Sy p hilis s erol o gy + refl ex Ra pi d Pl as m a R e a gi n ( R P R)  
X  
X  
 
 
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d M e dic al Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
X  
X  
X  
X  
 
 
X  
X  
W aist Circ u mf er e nc e  
 
X  
X  
X  
X  
 
 
X  
X  
Hi p  Circ u mf ere nc e  
 
X  
X  
X  
X  
 
 
X  
X  
Vit al Si g ns ( B P, H R, T e m p er at ur e) h  
X  
X  
X  
X  
X  
 
 
X  
X  
1 2 -l e a d E C Gi  
(tri plicat e at Day 1 pre-dose)  
X  
X  
 
 
 
 
 
X  
X  
C D C HI V -1 st a g e ff 
X  
X  
 
 
 
 
 
 
 
HI V Ass oci at e d Co n diti o ns  
 
X  
X  
X  
X  
X  
X  
X  
X  
A Es, S A Es, C o nc o mit a nt M e dic ati o ns  
X j 
X  
X  
X  
X  
X  
X  
X  
X  
Col u m bi a S uici d e S ev erity R ati n g Sc al e (e C -S S R S)  k 
X  
X  
X  
 
X  
 
 
X  
X  
Cli nic al c h e mistry a n d He mat ol o gy  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Pre g n a ncy T esti n g l 
S  
U  
U  
U  
U  
U  
U  
U  
S  
HI V -1 R N A  a n d s a m pl e f or st ora g e ( S) m  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C CI


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 2  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
D a y 1 b  
M o nt h  
2  
4  
6  
8  
1 0  
1 2 b b  
HI V -1 R N A l o w c o py s a m pl e  
 
X  
 
 
 
 
 
X  
 
C D 4 + c ell c o u nt  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
X  
 
 
X  
 
 
X  
X  
Uri n alysis n 
 
X  
 
 
X  
 
 
X  
X  
F asti n g L a bs  
Gl uc os e, Ch ol est erol ( T ot al, H D L a n d L D L) a n d Tri glyc eri d es o 
 
X  
 
 
X  
 
 
X  
X p 
He patitis B ( H Bs A g), A nti -H Bc, a n d A nti -H Bs A G, He p atitis C  
(a nti-H C V A b)  
X  
 
 
 
 
 
 
 
 
P T/ P T T/I N R  
X  
X  
 
 
 
 
 
 
 
W h ol e Bl o o d ( Vir ol o gy)  
 
X  
 
 
X  
 
 
X  
X  
P B M Cs q  
 
X  
 
 
X  
 
 
X  
X  
I ns uli n, Hb A 1c a n d re n al, a n d b o n e bi o mark er a n alyt es (bl o o d 
uri n e) r 
 
X  
 
 
X  
 
 
X  
X x 
G e n etics s a m pl e t 
 
X  
 
 
 
 
 
 
 
BI K Dis p e ns ati o n  
 
X  
X  
X  
X  
X  
X  
X a a 
 
I P acc o u nt a bility ( Pill Co u nts) 
 
 
X  
X  
X  
X  
X  
X  
 
HI V T S Qs cc 
 
X  
 
 
X  
 
 
X  
X d d  
HI V T S Qc cc 
 
 
 
 
 
 
 
X  
X d d  
Hist ory of C os m etic pr oc e d ur e s g g 
 
 
 
 
 
 
 
X  
X  
 
C CI
C CI
C CI
C CI


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 3  
 
Ti m e a n d E v e nt s T a bl e f or BI K t o Or al L e a d I n –  E xt e n si o n P h a s e:  
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
M o nt h  
1 3  
1 4  
1 5  
Q 2 M After M o nt h 
1 5  
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X d  
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d M e dic al 
Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
 
 
 
X  
 
W aist Circ u mf er e nc e  
 
 
 
 
X  
 
Hi p Circ u mf ere nc e  
 
 
 
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h  
 
 
 
 
X  
 
1 2 -l e a d E C Gi  
 
 
 
 
 
X  
 
HI V Ass oci at e d Co n diti o ns  
X  
X  
X  
X  
X  
X  
A Es, S A Es, Co nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
 
X  
X  
X  
X  
X  
Cli nic al c h e mistry a n d He mat ol o gy 
X  
X  
X  
X  
X  
X  
Pre g n a ncy T esti n g l 
S  
U  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st ora g e ( S) m  
X  
X  
X  
X  
X  
X  
C D 4 + c ell c o u nt  
 
X  
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
 
 
 
X  
 
Uri n alysis n 
 
X  
 
 
X  
 
F asti n g L a bs  
Gl uc os e, Ch ol est erol ( T ot al, H D L a n d L D L) a n d 
Tri glyc eri d es o 
 
X  
 
 
X  
 
W h ol e Bl o o d ( Vir ol o gy)  
 
 
 
 
X  
 
P B M Cs q  
 
 
 
 
X  
 
C CI


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
24 
 
Procedure 
Extension Phase 
Withdrawal 
Assessmentsy 
Long-Term 
Follow-up z 
Month 
13 
14 
15 
Q2M After Month 
15 
PK sampling u 
(S)=Storage only 
 
S 
S 
 
X 
S 
Oral CAB and Oral RPV Dispensation v 
X 
 
 
 
 
 
IP accountability (Pill Counts) 
X 
X 
 
 
 
 
IM treatment administration w 
 
X 
X 
X 
 
 
Reason for Switchcc,ee 
X 
 
 
 
 
 
 
 
Time and Events Table for BIK to Direct to Injection – Extension Phase: 
Procedure 
Extension Phase 
Withdrawal 
Assessmentsy 
Long-Term 
Follow-up z 
Month 
13 
14 
Q2M After Month 14 
Eligibility Verification (Inclusion/ 
Exclusion Criteria) 
Xd 
 
 
 
 
Symptom Directed Physical Exam and Medical Assessmentf 
X 
X 
X 
X 
X 
Weight, Height and BMIg 
 
 
 
X 
 
Waist Circumference 
 
 
 
X 
 
Hip Circumference 
 
 
 
X 
 
Vital Signs (BP, HR, Temperature)h 
 
 
 
X 
 


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 5  
 
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
M o nt h  
1 3  
1 4  
Q 2 M After M o nt h 1 4  
1 2 -l e a d E C Gi  
 
 
 
 
X  
 
HI V Ass oci at e d Co n diti o ns  
X  
X  
X  
X  
X  
A Es, S A Es, Co nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
X  
X  
X  
X  
X  
Cli nic al c h e mistry a n d He mat ol o gy  
X  
X  
X  
X  
X  
Pre g n a ncy T esti n g l 
S  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st ora g e ( S) m  
X  
X  
X  
X  
X  
C D 4 + c ell c o u nt  
 
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
 
 
X  
 
Uri n alysis n 
 
X  
 
X  
 
F asti n g L a bs  
Gl uc os e, Ch ol est erol ( T ot al, H D L a n d L D L) a n d Tri glyc eri d es o 
 
X  
 
X  
 
W h ol e Bl o o d ( Vir ol o gy)  
 
 
 
X  
 
P B M Cs q  
 
 
 
X  
 
P K s a m pli n g u 
( S) = St ora g e o nly 
 
S  
 
X  
S  
I P acc o u nt a bility ( Pill Co u nts) 
X  
 
 
 
 
I M tre at m e nt a d mi nistrati o n w  
X  
X  
X  
 
 
R e as o n f or S witc h cc,e e 
X  
 
 
 
 
 
S af ety F oll o w U p Visit:  C o n d uct a p pr oxi m at ely 4 w e eks aft er t h e l ast d os e of I P.  R e q uir e d o nly if t h e p artici p a nt h as o n g oi n g A Es or l a b a b n or m aliti es at t h e l ast o n -st u dy visit.  T his 
visit m ay b e c o n d uct e d by t el e p h o n e. 
N ot e: B P –  Bl o o d pr ess ur e, H R –  H e art R at e, B MI –  Bo dy M ass I n d ex, H D L –  Hi g h D e nsity Li p o pr ot ei n, L D L –  L o w D e nsity Li p o pr ot ei n, P T - P r ot hr o m bi n Ti m e, P T T - P arti al 
T hr o m b o pl asti n Ti m e, I N R - I nt er n ati o n al n or m aliz e d r ati o, P B M C –  p eri p h er al bl o o d m o n o n ucl e ar c ell, R N A –  Ri b o n ucl eic aci d, H b A 1c = Glyc at e d h e m o gl o bi n, H Bs A g = h e p atitis B 
s urf ac e a nti g e n, H C V = h e p atitis C vir us, HI V-1 = h u m a n i m m u n o d efici e ncy vir us ty p e 1.  
C CI


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
26 
 
a. 
Complete all Screening assessments within 35 days.  Participants may begin the Maintenance Phase as soon as all Screening assessments are complete.  Participants may be 
rescreened once and will be assigned a new participant number.  
b. 
For participants who elect to participate in the oral lead in period, oral CAB 30 mg + RPV 25 mg will be administered and the oral lead will start on Day 1.  For participants who 
choose to go directly into injections, the first loading dose will be administered on Day 1. Visits for participants on the BIK arm are expected to occur every 56 days as projected 
according to the Day 1 visit.  There is a 3 day visit window, from the projected visit date (Maintenance Phase of the study). 
c. 
For participants who elect to participate in the oral lead in period, the first loading dose will be administered and the oral lead in will end.  For participants who choose to go directly 
into injections, the second loading dose will be administered.   
d. 
Confirmation of eligibility to continue the Maintenance Phase, and eligibility to enter the Extension Phase.  
e. 
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, bone, and 
neurologic disorders.  At Month 11 (D2I)/12 (OLI and BIK), assessments inclusive of smoking status, alcohol use and illicit drug use since the start of the study will be 
administered. 
f. 
Physical exams should be conducted as part of normal routine clinical care.  Medical assessments include any decisions the study staff must make for participants management 
and/or care of participant.   
g. 
Height collected at Baseline Day 1 only.  Recommended procedures to measure weight, waist and hip circumference can be found in Section 10.10.  Weight related 
measurements to be collected are weight, body fat %, total body water %, muscle mass, and bone mineral mass. 
h. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
i. 
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. ECG pre-dose will be performed in triplicate at 
Day 1.  A 2-hour post-dose ECG will also be performed at Day 1 (D2I), Month 1 (OLI) and Month 12 (OLI)/Month 11 (D2I) for participants receiving CAB LA + RPV LA with an 
allowable window of  30 minutes.  
j. 
Only SAEs related to study participation or to a concomitantly administered ViiV/GSK product will be collected between obtaining informed consent and administration of study 
drug at Day 1. 
k. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  The eC-SSRS will be completed at the beginning of the visit following administration of other PROs required 
prior to injections.  The eC-SSRS is not required during the Withdrawal visit if withdrawal occurs during the Extension Phase. 
l. 
Women of childbearing potential only.  S=serum, U=urine.  Pregnancy events will be captured starting at Day 1 following initial exposure to study drug.  Serum pregnancy test can 
substitute for urine pregnancy test if locally required but must be appropriately timed to confirm pregnancy status prior to randomization and first IM administration.  If the urine test 
is positive, perform a serum test and do not administer injection.  The frequency of pregnancy tests should be performed according to local legal requirements. 
m. Month 12 (OLI and BIK) and Month 11 (D2I) HIV-1 RNA retest (within 4 weeks) for results > 50 c/mL will be captured as unscheduled visit.  Plasma for storage samples will be 
used for possible future analyses. 
n. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; urine phosphate; beta-2-microglobulin; and retinol binding 
protein.   
o. 
An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
p. 
Only collect if the Withdrawal visit occurs at Month 6 or Month 12 (OLI and BIK); Month 5 or Month 11 (D2I). 
q. 
Whole blood/PBMC collection samples may be used for virologic analyses.  PBMCs will be collected at baseline Day 1, Month 6, Month 12, or Withdrawal if prior to Month 12 (OLI 
and BIK). PBMCs will be collected at baseline Day 1, Month 5, Month 11, or Withdrawal if prior to Month 11 (D2I) 
r. 
Blood sample for insulin, HbA1c, and renal and bone biomarker assessments:  Renal: CystatinC; Beta-2-Microglobulin; 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. 


T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 7  
 
s. 
 
t. 
I nf or m e d c o ns e nt f or g e n etic r es e arc h m ust b e o bt ai n e d b ef or e s a m pl e c oll ecti o n.  Sa m pl e m ay b e c oll ect e d at a ny visit aft er si g ni n g i nf or m e d c o ns e nt, b ut pr ef er a bly at t h e D ay 1 
visit. 
u.  
O n e bl o o d s a m pl e f or C A B a n d R P V e a c h t o b e c oll e ct e d at e ac h P K ti m e p oi nt .  At M o nt h 1, f or p artici p a nts w h o el ect e d t o p artici p at e i n t h e Or al L e a d i n, a n d M o nt h 1 4 f or 
p artici p a nts w h o w er e r a n d o miz e d t o BI K a n d s witc h e d t o C A B L A + R P V L A i n t h e Ext e nsi o n Ph as e a n d will p artici p at e i n t h e Or al L e a d i n, Pr e d os e P K s a m p l es ar e t o b e 
c oll ect e d: P RI O R t o t h e fi n al or al d os e of C A B + R P V.  F or pre g n a nt p arti ci p a nt s  ( o n C A B + R P V ar m): t w o bl o o d s a m pl es f or C A B a n d o n e R P V s a m pl e at e ac h P K ti m e p oi nt. 
R ef er t o S ecti o n 1 0. 6. 6. 3 . 
v. 
P artici p a nts w h o el ect e d t o p artici p at e i n t h e Or al L e a d i n b ef or e s witc hi n g t o C A B L A + R P V L A i nj ecti o ns, will t ak e fi n al d os e of or al l e a d -i n r e gi m e n i n t h e cli nic at t h e M o nt h 
1/ M o nt h 1 4 visit a n d b e gi n i nj ecti o ns.   
w.  If p ossi bl e, i nj ecti o ns s h o ul d b e s p ac e d a p pr oxi m at ely 2 c m fr o m o n e a n ot h er a n d fr o m t h e sit e of a ny pr evi o us i nj ecti o n a n d or a ny i nj ecti o n sit e r e acti o n.  Bri n g R P V L A t o 
a p pr oxi m at ely r o o m t e m p er at ur e pri or t o i nj ecti n g.  Ti m e a n d l oc ati o n of i nj ecti o n (ri g ht or l eft) as w ell as n e e dl e l e n gt h us e d will b e c oll ect e d i n t h e e C R F.  T h e first i nj ect i o n c a n 
b e p erf or m e d b ef or e c e ntr al l a b res ults b ec o m e av ail a bl e a n d s af ety p ar a m et ers ar e r evi e w e d .  
x. 
C oll ect s a m pl e f or t h es e ass e ss m e nts O N L Y if t h e Wit h dr a w al visit occ urs at M o nt hs 6 a n d 1 2 ( O LI a n d BI K); M o nt h 5 a n d 1 1 ( D 2I).  
y. 
R ef er t o S ecti o n 7. 1  of t h e pr ot oc ol f or a d diti o n al i nf or m ati o n o n p erf or mi n g wit h dr a w al ass ess m e nts  
z. 
P artici p a nts r ec eivi n g o n e or m or e i nj ecti o ns wit h C A B L A a n d/ or R P V L A will b e ass ess e d wit h cli nic visits at M o nt hs 3, 6, 9  a n d 1 2 d uri n g t h e L o n g -T er m F oll o w -U p P h as e  
a a.  BI K dis p e ns ati o n ( 1 -m o nt h s u p ply) f or p artici p a nts w h o pl a n o n e nt eri n g i nt o t h e Ext e nsi o n Ph as e.  P artici p a nts w h o d o n ot e nt er  t h e E xt e nsi o n P h as e or d o n ot wis h t o tr a nsiti o n 
t o t h e c o m m erci al s u p ply will n o t r ec eiv e 1-m o nt h s u p ply at M 1 2 . 
b b.  D at a fr o m visit will b e us e d t o d et er mi n e p artici p a nt’s eli gi bility t o e nt er t h e Ext e nsi o n Ph as e of st u dy.  If p artici p a nt el ects t o e nt er t h e Ext e nsi o n P h as e, d et er mi n e if t h e p artici p a nt 
will el ect t o st art i nj ecti o ns i m m e di at ely or st art wit h or al l e a d i n.  
cc. All P R Os ar e r ec o m m e n d e d t o b e a d mi n ist er e d b ef or e ot h er ass ess m e nts a n d i nj ecti o ns t ak e pl ac e at e ac h d esi g n at e d visit. 
d d.  O nly c oll ect e d if Wit h dr a w al visit occ urs d uri n g t h e M ai nt e n a nc e P h as e.  
e e.  Will b e a d mi nist er e d o nly t o p artici p a nts r a n d o miz e d t o BI K, s ucc essf ully c o m pl eti n g t h e M ai nt e n a nc e P h as e a n d d eci di n g t o e nt er Ext e nsi o n P h as e a n d s witc hi n g t o C A B L A + 
R P V L A.  
ff. 
W h e n ass essi n g C D C st a g e at Scr e e ni n g/ B as eli n e, c o nsi d er o nly t h e l at est av ail a bl e C D 4 T -c ell c o u nt, exc e pt w h e n t h e p artici p a nt h a d a n activ e St a g e 3 ev e nt 6 m o nt hs pri or t o 
S cr e e ni n g. 
g g.  At M o nt h 1 1 ( D 2I) / M o nt h 1 2 ( O LI or BI K) or wit h dr a w al , (d e p e n di n g w hic h is s o o n er) p artici p a nts will b e ask e d if a ny c os m etic pr oc e d ur es w er e p erf or m e d d uri n g t h e c o n d uct of 
t h e st u dy. 
 
C CI


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
28 
 
2. 
INTRODUCTION 
The current paradigm in the treatment of Human Immunodeficiency Virus (HIV) 
involves life-long therapy with multiple antiretrovirals.  This dependency on medical 
therapy requires additional improvements on the durability, safety and tolerability, and 
convenience of all antiretroviral classes.  Fixed-dose combinations (FDCs) have greatly 
advanced HIV treatment by allowing simplification of dosing and reducing pill burden.  
However, adherence to therapy is essential to achieve viral suppression and prevent 
emergence of resistance mutations.  Among regimens of comparable efficacy, physicians 
and HIV-1-infected patients who receive ART rate total pill burden, dosing frequency, 
and safety concerns among the greatest obstacles to achieving adherence.  Drug resistant 
virus eventually emerges in most patients who struggle with consistent adherence.  
Different HIV treatment modalities are being developed to help improve adherence and 
patient outcomes and prevent resistance and transmission of the virus.  
There is also an increasing desire to develop nucleoside reverse transcriptase inhibitor 
(NRTI)-sparing regimens for long-term treatment of HIV infection as an approach to 
avoid known NRTI-associated adverse drug reactions and long-term toxicities.  In 
addition, simplifying treatment has long been a goal to increase treatment compliance and 
improve the quality of life for patients 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) is a 
diarylpyrimidine derivative and a potent non-nucleoside reverse transcriptase inhibitor 
(NNRTI) with in vitro activity against wild type HIV-1 and select NNRTI-resistant 
mutants.  RPV is a globally marketed product available as oral 25 mg tablets [Edurant 
Product Information, 2019], and is also formulated as a LA product.  Intramuscular 
administration of 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 patients. 
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 treatment convenience, compliance and improved 
quality of life for individuals with HIV compared to current standard of care.  Week 160 
efficacy (GSK data from study 200056 (LATTE-2)) [GlaxoSmithKline Document 
Number 2018N380094_00, 2019] demonstrated that 90% of patients randomized to the 
CAB LA + RPV LA Q8W dosing arm and 83% of patients randomized to the Q4W 
dosing arm maintained virologic suppression (HIV-1 RNA <50 c/mL), with both 
regimens being well tolerated.  In study 207966 (ATLAS-2M), 1.7% of participants in 
the CAB + RPV Q8W group and 1.0% of participants in the CAB + RPV Q4W group 
met the primary efficacy endpoint of plasma HIV-1 RNA 50◦c/mL at Week◦48. In both 
studies, both regimens were well tolerated, and the results justify further evaluation of 
both CAB LA + RPV LA dosing regimens.   


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
29 
 
The current study, 213500 (SOLAR – Switch Onto Long Acting Regimen) is designed 
to demonstrate the non-inferior antiviral activity of CAB LA 600 mg + RPV LA 900 mg 
administered every 2 months (Q2M) compared to Biktarvy (BIK) administered orally 
once daily for 12 months.  The study will also provide important comparative antiviral 
activity, safety, tolerability of these regimens through Month 12 of the Maintenance 
Phase of the study. Additionally, eligible participants (HIV-1 RNA <50 c/mL at Month 
12) will be given an option to continue their randomized CAB LA + RPV LA regimen 
(Q2M) or start CAB LA + RPV LA Q2M after 12 months of oral therapy in the 
Extension Phase of the study. 
2.1.1. 
Optional Oral Lead In 
Throughout the course of the clinical development program for CAB and RPV LA 
including the large P3 trials of FLAIR, ATLAS and ATLAS 2M, an oral lead-in phase of 
cabotegravir (30 mg) along with rilpivirine (25mg), administered  daily for 30 days, was 
an integral component of these trials and allowed for a safety assessment before study 
participants were allowed to advance to the LA phase of these studies. As a result, all 
study participants underwent a one-month period of oral dosing with CAB/RPV followed 
by an evaluation of safety labs, and if labs were within normal limits, participants were 
allowed to transition into LA dosing.  
An assessment of the safety data specific to four weeks of oral lead-in for participants on 
FLAIR and ATLAS (ViiV’s two registrational clinical trials) was recently undertaken 
and as a result of the accumulated safety data which has been generated, the safety of oral 
CAB and RPV during these four weeks of oral lead-in was not significantly different than 
at any other time during the FLAIR/ATLAS studies. The SOLAR study will also allow 
an optional oral lead in for participants randomized to the LA arm of SOLAR. This 
decision to dose with or without an oral-lead-in will be determined by the study 
participant following informed consent discussions with the investigator. 
2.1.2. 
Weight Gain 
Weight gain in people living with HIV is multifactorial with both traditional (diet, 
exercise, concomitant medications such as selective serotonin reuptake inhibitor and 
others) and HIV specific modifiable risks likely contributing factors. Which factor or 
factors are most significant in the pathogenesis of weight gain in HIV disease has not 
been fully elucidated. 
Whereas lipodystrophy involved accumulation of central abdominal or visceral fat, and 
loss of subcutaneous fat, weight gain in HIV-infected individuals receiving newer, more 
recently approved antiretroviral treatment consists of general fat gain – both 
subcutaneous and central fat – with an increase in waist circumference. Weight gain 
among HIV-infected individuals often occurs after the initiation of antiretroviral therapy 
with certain antiretrovirals linked more closely to weight gain than others.  Teasing out 
what is considered appropriate weight gain for individuals returning back to health versus 
what is consider more pathogenic weight gain has been challenging. Recent studies have 
demonstrated increase weight gain with integrase strand transfer inhibitor (INSTI)-based 
regimens compared to other classes of antiretroviral therapy [Bourgi, 2019; Kerchberger, 
2019; McComsey, 2019]. Moreover, additional components of the antiretroviral regimen, 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
30 
 
specifically the nucleoside reverse transcriptase inhibitor TAF has also been associated 
with excess weight gain [McCann, 2019]. Women and non-whites appear to be most at 
risk.  
Lipohypertrophy, an abnormal accumulation of visceral fat and/or ectopic fat depots, 
continues to be a problem for individuals with HIV infection, but the role that INSTIs 
plays in this metabolic alteration has not been fully elucidated. Moreover, weight gain 
and anthropometric changes in body composition in HIV disease is poorly understood but 
may lead to or exacerbate pre-existing comorbidities including cardiovascular disease and 
diabetes [Debroy, 2019; Hill, 2020]. Given the evolving nature of this issue, it is 
important to determine the impact that INSTI has on weight gain in the SOLAR study; if 
there are differences in weight gain between different types of integrase inhibitors and the 
role that TAF, in particular, plays on accentuating weight gain. The SOLAR study will 
allow an assessment of weight changes between participants continuing on an orally 
administered bictegravir based regimen (Biktarvy) compared to participants switching to 
an IM administered, integrase inhibitor, cabotegravir. Finally, the impact of TAF on 
weight changes will also be assessed in this study. 
Another important outcome that will be measured as an assessment in the SOLAR study 
is the impact between Biktarvy versus LA CAB/RPV on contributing to the metabolic 
alterations that have been associated with ARV therapy and that leads to the metabolic 
syndrome. Classically, metabolic syndrome is a cluster of conditions that occurs together 
increasing one’s risk of heart disease, stroke and type 2 DM. These conditions include 
increased BP, elevated blood glucose levels, excess body fat around the waist and 
abnormal fasting cholesterol and TG levels.  The defining levels for each characteristic of 
metabolic syndrome are listed below (Table 1) (Grundy, 2004). 
Table 1 
ATP III Clinical Identification of Metabolic Syndrome  
Risk Factor 
Defining Level 
Abdominal obesity, given as waist 
circumferencea, b 
 
Men 
102 cm (40 in) 
Women 
88 cm (35 in) 
Triglycerides 
150 mg/dL 
HDL cholesterol 
 
Men 
<40 mg/dL 
Women 
<50 mg/dL 
Blood pressure 
130/85 mmHg 
Fasting glucose 
110 mg/dLc 
a. 
Overweight and obesity are associated with insulin resistance and the metabolic syndrome. However, the 
presence of abdominal obesity is more highly correlated with the metabolic risk factors than is an elevated BMI. 
Therefore, the simple measure of waist circumference is recommended to identify the body weight component of 
the metabolic syndrome.  
b. 
Some male patients can develop multiple metabolic risk factors when the waist circumference is only marginally 
increased, eg, 94 to 102 cm (37 to 39 inch). Such patients may have a strong genetic contribution to insulin 
resistance. They should benefit from changes in life habits, similarly to men with categorical increases in waist 
circumference. 
c. 
The American Diabetes Association has recently established a cutpoint of 100 mg/dL, above which persons have 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
31 
 
either prediabetes (impaired fasting glucose) or diabetes. This new cutpoint should be applicable for identifying the 
lower boundary to define an elevated glucose as one criterion for metabolic syndrome. 
 
Additionally, non-alcoholic fatty liver disease (steatosis) is increasingly associated with 
chronic liver disease and diabetes and is an important contributor to insulin resistance and 
metabolic syndrome. Features of steatosis include hepatocellular injury, inflammation 
and fibrosis. The fibrosis-4 score (FIB-4) is a simple, non-invasive test to determine the 
degree of hepatic fibrosis. The FIB-4 score combines standard biochemical values (ALT, 
AST, platelets), and age into a simple formula that estimates the amount of scarring in the 
liver.    
Fibrosis 4 Score Formula: 
(Age x AST) / (Platelets x (√ALT)) 
In a previous study, A FIB-4 index < 1.45 had a negative predictive value of 94.7% to 
exclude severe fibrosis with a sensitivity of 74.3%. A FIB-4 index > 3.25 had a positive 
predictive value to confirm the existence of significant fibrosis (F3-4) of 82.1% with a 
specificity of 98.2% [Vallet-Pichar, 2007] 
Therefore, this study will explore whether there is a meaningful difference between these 
two regimens with respect to alterations in BP, blood glucose and cholesterol (and TG) 
levels, and whether there are changes in hip and waist circumferences in participants 
randomized to continue with Biktarvy versus those who are randomized to switch to LA 
CAB/RPV.  
2.2. 
Background 
It is estimated that 37.9 million people are currently living with HIV/Acquired 
Immunodeficiency Syndrome (AIDS) and that the worldwide epidemic continues to grow 
at a rate of 1.7 million new infections and cause 770, 000 deaths per year [UNAIDS, 
2019].  Chronic HIV infection in adults continues to be characterized by increased 
development of resistant virus, increasing transmission of resistant virus and issues 
associated with long term toxicity of ART.  The current paradigm in the treatment of HIV 
involves life-long therapy with multiple antiretrovirals.  This dependency on medical 
therapy requires a need for continuous improvement on the durability, tolerability and 
convenience of all antiretroviral classes. 
A study by the Antiretroviral Therapy Cohort Collaboration [ART-CC, 2013] found that 
of more than 21,000 patients in a European and North American cohort on their first 
combination antiretroviral therapy (cART) regimen (either PI or NNRTI-based), 51% 
modified or interrupted their first cART regimen during a median of 28 months of 
follow-up with one third of interruptions occurring within the first 6 months of starting 
therapy.  Forty percent of all treatment interruptions were due to the secondary side 
effects or toxicities of cART, 17% were due to the desire for simplification of the 
regimen and 14% were due to patient choice. These observations have led to numerous 
“switch” ART studies, designed to understand the efficacy, safety, and tolerability of 
switching patients from one regimen to another. 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
32 
 
Previous studies have evaluated switches to ritonavir-boosted PI monotherapy in 
virologically suppressed patients [Bierman, 2009 and Arribas, 2012].  These studies 
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 viral suppression.  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.  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]. 
CAB LA + RPV LA is indicated as a complete regimen for the treatment of human 
immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current 
antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 
50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure 
and with no known or suspected resistance to either CAB or RPV. 
Three Phase IIb studies (LAI116482 [LATTE], 200056 [LATTE-2], and 209035 
[POLAR]) have been conducted with oral CAB and/or IM CAB LA, evaluating an 
induction/maintenance simplification approach. Three Phase III studies (201584 
[FLAIR], 201585 [ATLAS], and 207966 [ATLAS-2M]) conducted with CAB LA + RPV 
LA are ongoing.  Details of these studies can be found in the CAB IB [GlaxoSmithKline 
Document Number  RPS-CLIN-004375, 2021]. 
Biktarvy (BIK) is a three-drug combination of bictegravir (BIC), a human 
immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and 
emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog 
reverse transcriptase inhibitors (NRTIs), and is indicated as a complete regimen for the 
treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to 
replace the current antiretroviral regimen in those who are virologically suppressed (HIV-
1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of 
treatment failure and no known substitutions associated with resistance to the individual 
components of BIK.  Clinical trial results of studies with BIK can be found in Biktarvy 
Prescribing Information, 2019. 
Long-acting 2-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 2-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 living with HIV. 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
33 
 
2.3. 
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’s Brochures [GlaxoSmithKline 
Document Number RPS-CLIN-004375, 2021; RPV IB, 2021]. 
The following section outlines the risk assessment and mitigation strategy for this 
protocol:   
2.3.1. 
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 from 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 [GlaxoSmithKline Document Number  
RPS-CLIN-004375, 2021]. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
3 4  
 
 
P ote nti al Ris k of Cli nic al 
Si g nific a nce  
S u m m ar y of D at a/ R ati o n ale f or Ris k  
Miti g ati o n Str ate g y  
Dr u g I n d uce d Li ver 
I nj ur y ( DI LI) 
 
A s mall pr o p orti o n of partici pa nts i n t he C A B 
pr o gra m t o date ha ve de v el o pe d tra nsa mi nitis 
(ele vate d li ver tra nsa mi n ases c haract erise d b y 
pre d o mi na nt ala ni ne a mi n otra nsferase ( A L T) 
ele vati o n).  I n m ost parti ci pa nts, tra nsie nt 
tra nsa mi nitis was e x plai ne d b y ac ute viral 
he patitis i nfecti o n ( maj orit y).  I n a s mall n u m ber 
of partici pa nts, t here was n ot a n alter nati ve 
e x pla nati o n, s u g gesti n g a mil d f or m of dr u g 
i n d uce d li ver i nj ur y ( DI LI) wit h o ut he patic 
d ysf u n cti o n, w hic h res ol ve d u p o n wit h dra wal of 
treat me nt wit h C A B.  
 
 
A n o pti o nal 4 -wee k oral lea d - i n is bei n g 
i m ple me nte d i n t his st u d y, w here p artici pa nts ca n 
c h o ose t o recei ve oral C A B pri or t o t he 
a d mi nistrati o n of I M C A B t o assess i n di vi d ual 
t olera bilit y  
 
•  E x cl usi o n criteria as descri be d i n Secti o n 5. 2  
will pr o hi bit partici pa nts wit h si g nifica nt li ver 
i m pair me nt base d o n scree ni n g li ver c h e mistr y 
i ncl u di n g tra ns a mi nases ( A L T a n d As partate 
a mi n otra nsferase [ A S T]) as well o n pri or 
me dical hist or y. Partici pa nts wit h a hist or y of 
c hr o nic li ver disease wit h o n g oi n g 
i nfla m mati o n a n d/ or fi br osis will ha ve 
a d diti o nal c o nfir mat or y assess me nts t o c o nfir m 
s uita bilit y f or e ntr y i nt o t he st u d y.  
 
•  Li ver tra nsa mi nas es ( A L T a n d A S T) will be 
m o nit ore d t hr o u g h o ut t his st u d y (refer t o S o A, 
Secti o n 1. 3 ) a n d t he li ver c he mistr y st o p pi n g 
criteria will be a d o pte d as descri be d i n Secti o n 
7. 1. 2. 1  of t his pr ot oc ol. Partici pa nts will be 
wit h dra w n fr o m C A B treat me nt w here n o 
c o m pelli n g alter nati ve ca use is i de ntifie d, a n d 
DI LI is s us pecte d.  
 
I njecti o n Site Re acti o ns 
(I S Rs) 
 
Cli nical, e x perie nce t o date has de m o nstrate d 
I S Rs occ ur i n t he maj orit y of e x p ose d 
partici pa nts treat e d wit h C A B L A b ut are 
ge n erall y  
( Gra de 1) or  
 ( Gra de 2) 
•  A d mi nistrati o n a d vice will be gi ve n t o 
mi ni mize ris k of p o or a d mi nistrati o n tec h ni q ue 
gi vi n g rise t o i njecti o n site reacti o ns.  A d vice 
o n care, m o nit ori n g, nat ural c o urse, a n d 
C CI
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
35 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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 withdrawing.  
 
treatment of ISRs is 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  
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 to date, there is a 
theoretical risk of systemic or severe 
hypersensitivity reactions with or without hepatic 
• The potential risk of developing a 
hypersensitivity reaction post administration of 
IM CAB may be minimized by the use of a 4-
week oral lead-in of oral CAB to determine 
individual safety and tolerability prior to the 
introduction of IM CAB if the participant is 
randomized to CAB LA administration and 
chooses to participate in the oral lead in.  
 
• Clinical assessments, laboratory tests (including 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
36 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
symptoms associated with use of IM CAB.  The 
long exposures anticipated after IM CAB 
injection may complicate the management of a 
drug hypersensitivity reaction, were it to occur. 
 
liver transaminases) and vital signs will be 
performed throughout this study (refer to 
Schedule of Activities, Section 1.3). Results 
from these assessments may aid early detection 
of HSR.  
 
• Oral CAB will be withdrawn immediately for 
participants with suspected HSR during the oral 
CAB lead-in phase and they would not proceed 
to the injection phase.  Participants in the 
injection phase would not receive further 
injections.  During oral and IM CAB treatment, 
any HSR reactions that occur would be 
managed supportively. 
Effects in late stage 
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 (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 
• 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 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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
37 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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 6 for additional data regarding 
CAB and 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 informed consent 
form (ICF) addendum is signed by the 
participant. Details regarding management of 
pregnant participants are found in Appendix 6 
 
 
Potential effects in women 
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 (NTDs) 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 
woman who started DTG during pregnancy had a 
NTD, out of 2,824 women. A causal relationship 
of these events to the use of DTG has not been 
established. The incidence of NTDs in the 
general population ranges from 0.5-1 cases per 
1,000 live births. As NTDs occur within the first 
• Pregnant females are excluded from enrolment 
in clinical trials of CAB at this time 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 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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
38 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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 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 
NTDs 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.  
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. Details regarding 
management of pregnant participants is found 
in Appendix 6.  
 
Development of 
Resistance following 
discontinuation of CAB 
LA 
 
Residual concentrations of CAB would remain in 
the systemic circulation for prolonged periods 
(more than 1 year in some cases) in participants 
who stop CAB LA treatment, (e.g., for 
tolerability issues or treatment failure). 
Participants discontinuing CAB LA regimen may 
therefore be at risk for developing HIV-1 
resistance to CAB after discontinuing injectable 
therapy.  
• After participants stop CAB LA, Oral HAART 
regimens will be prescribed within 8 weeks 
after the last Q2M dose, and following 
consultation with the medical monitor.  This 
would be anticipated to result in continued 
suppression or rapid resuppression of HIV-1 
RNA thus minimizing the risk of emergent 
resistance 
 
• The participants in this study who discontinue 
IM CAB for any reason will be monitored for a 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
39 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
minimum of 52 weeks from the time of the last 
IM CAB injection. 
Drug-Drug Interactions 
(DDIs) 
For a complete listing of permitted and prohibited 
concurrent medications for CAB and CAB LA, 
refer to Section 6.11 
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 
- the antimycobacterials rifampicin, 
rifapentine, rifabutin 
- St John’s wort (Hypericum perforatum) 
Oral CAB administration only:  Antacid products 
containing divalent cations (e.g., aluminum, 
calcium, and magnesium) must be taken at least 2 
hours before or at least 4 hours after CAB.  
Participants discontinuing a LA regimen may be 
at risk for developing DDIs many weeks after 
• All participants will be informed of prohibited 
medications throughout the study and updates 
provided as needed via the informed consent. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
40 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
discontinuing injectable therapy.   


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
41 
 
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 possibly 
resulting in higher than expected concentrations 
of CAB shortly after injection and lower 
concentrations thereafter.  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 
LA 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 post dose 
electrocardiogram (ECG), vital signs, or any 
other supportive testing may be obtained at the 
discretion of the investigator, and the medical 
monitor will be notified.   
 
• Laboratory samples for safety parameters and 
HIV-1 RNA will be closely monitored in all 
participants. Additionally, an unscheduled PK 
sample may be drawn approximately 2 hours 
post dosing for future evaluation of CAB 
concentrations. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
42 
 
ORAL RPV 
For safety and risk mitigation for oral RPV refer to the RPV local prescribing information [Edurant Product Information, 2021].   
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 [RPV IB, 2021].  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, some participants have required supportive care.  Where 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. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
4 3  
 
P ote nti al Ris k of 
Cli nic al Si g nific a nce  
S u m m a r y of D at a/ R ati o n ale f or Ris k  
Miti g ati o n Str ate g y  
I njecti o n Site Re acti o ns 
Cli nical, e x perie nce t o date has de m o nstrate d I S Rs 
occ ur i n t he maj orit y of e x p ose d partici pa nts 
treate d wit h R P V L A b ut are ge n erall y  
 
( Gra d e 1) or  
 ( Gra de 2) a n d i nclu de 
e ve nts of pai n, te n d er ness, er yt h e ma, or n o d ule 
f or mati o n of se veral da ys’  d urati o n ( me dia n 
d urati o n f or i n di vi d ual e ve nts < 1 wee k).  I S Rs 
ma y o cc ur m ore t ha n o nce i n a n i n di vi d ual 
partici pa nt recei vi n g m ulti ple i njecti o ns.  Alt h o u g h 
s o me Gra de 3 I S Rs were re p orte d, o v erall I S Rs 
ha ve bee n well t olerat e d a n d ha ve n ot t o date bee n 
ass ociate d wit h a n e x cess of partici pa nts’ 
wit h dra wal d ue t o I S Rs.  
N o ne of t he I S Rs was seri o us a n d n o cli nicall y 
si g nifica nt c o m plicati o ns were re p orte d 
 
•  A d mi nistrati o n a d vice t o mi ni mize ris k of p o or 
a d mi nistrati o n tec h ni q ue gi vi n g rise t o i njecti o n 
site reacti o ns.  A d vice o n care, m o nit ori n g, 
nat ural c o urs e, a n d tr eat me nt of I S Rs gi ve n i n 
st u d y d oc u me ntati o n. 
•  A d vice t o partici pa nts o n care of i njecti o n site o n 
da y/ d a ys i m me dia t el y p ost a d mi nistrati o n, use of 
a nal gesia, c o m presses w here a p pr o priate.  
•  Partici pa nts will be cl osel y m o nit ore d f or I S Rs 
partic ularl y f or si g ns of pai n, te n der ness, 
i nfecti o ns, er yt he ma, s welli n g, i n d urati o n, or 
n o d ules ( gra n ul o mas or c ysts) t hr o u g h o ut t h e 
st u d y. 
•  C o m plicati o ns of I S Rs s uc h as i nfecti o ns 
(a bscess, cell ulitis) a n d c ollecti o ns of fl ui d 
re q uiri n g drai na ge will be m o nit ore d  
•  Si g nifica nt I S Rs ma y be p h ot o gra p he d a n d 
referre d t o a der mat ol o gist f or s pecialist a d vice. 
R as h  
 
S o me o bser vati o ns of r as h wit h oral R P V ha ve 
bee n re p orte d i n cli nical st u dies e x ec ute d t o date 
(t he maj orit y are Gra d e 1 or 2).  
Se vere s ki n a n d h y p erse nsiti vit y reacti o ns ha v e 
bee n re p orte d d uri n g t he p ost mar keti n g 
e x perie nce, i ncl u di n g cas es of Dr u g Reacti o n wit h 
•  I n t his st u d y, f or p artici p a nts w h o are 
ra n d o mize d f or R P V L A a d mi nistrati o n a n d 
c h o ose t o partici pat e i n t he o pti o nal oral lea d i n 
will be prece d e d b y a n oral R P V lea d i n t o 
e val uate safet y a n d t olera bilit y i n i n di vi d ual 
partici pa nts.  
•  Partici pa nts wit h a Gra d e 1 or 2 ras h will be 
C CI
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
44 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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. 
allowed to continue treatment, depending on the 
clinical judgment of the investigator. 
 
• All participants experiencing a Grade 3 or 4 rash 
should discontinue their ARV medication (study 
medication) and 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.  
See Section 8.3.11.9 for additional guidance on 
management of rash events. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
45 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Development of 
Resistance 
 
Residual concentrations of RPV LA can remain in 
the systemic circulation of participants who 
stopped treatment (e.g., for tolerability issues or 
treatment failure) for prolonged periods (months to 
more than a year, in some participants, McGowan, 
2016).   
 
Participants discontinuing a LA regimen may be at 
risk for developing resistance to RPV many weeks 
after discontinuing injectable therapy. 
• After participants stop RPV LA, Oral HAART 
regimens will be prescribed within 8 weeks after 
the last Q2M dose and following consultation 
with the medical monitor.  This would be 
anticipated to result in rapid resuppression of 
HIV-1 RNA thus minimizing 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. 
Drug-Drug Interactions 
(DDIs) 
For a complete listing of permitted and prohibited 
concurrent medications for RPV and RPV LA, 
refer to Section 6.11 
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, 
• All participants will be informed of prohibited 
medications throughout the study and updates 
provided as needed via informed consent. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
46 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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.  
Oral RPV administration only:   
- Antacid products containing divalent cations 
(e.g., aluminum, calcium, and magnesium) 
must be taken at least 2 hours before or at least 
4 hours after RPV. 
- 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; 
Participants discontinuing a LA regimen may be at 
risk for developing DDIs many weeks after 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
47 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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 possibly 
resulting in higher than expected concentrations of 
RPV shortly after injection and lower 
concentrations thereafter.  This could be due to 
administrator error, improper injection technique 
and / or improper needle length used based on 
body type.   
In addition, HIV-1 viral suppression may not be 
effective following accidental intravenous 
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), 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, an unscheduled PK 
sample may be drawn approximately 2 hours 
post dosing for future evaluation of RPV 
concentrations. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
48 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Other Study Related Risks  
Venipuncture 
Participants will be required to have blood samples 
taken.  Risk of bruising, and rarely, infection 
• Trained personnel will perform 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 minimize contact 
time for application of the pads. 
Risk of Treatment 
Failure 
This study employs a novel 2 drug LA ART 
maintenance regimen for the treatment of HIV-1 
infection that remains experimental.  Both IM 
CAB and RPV have demonstrated antiviral 
activity in large clinical studies and the two-drug 
combination has demonstrated sustained antiviral 
activity in studies, LAI116482, 200056, 201584, 
201585 and 207966.    
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 and LA formulations. 
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 
• Viral loads and CD4+ cell counts will be closely 
monitored throughout the study (maintenance 
and extension phases), allowing for early 
detection of failing treatment.  Where confirmed 
virological failure occurs, participants would be 
discontinued from study drugs and transferred to 
an oral HAART regimen. 
• Plasma samples will be collected and stored 
throughout the Maintenance Phase for potential 
determination of CAB and RPV concentrations 
and possible pharmacokinetic correlation with 
virologic response. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
49 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
could lead to virologic failure and possibly the 
development of viral resistance.   
 
Biktarvy (BIK)  
For safety and risk mitigation for BIK, refer to the BIK product information [Biktarvy Product Information, 2019].   
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Severe Acute 
Exacerbation of 
Hepatitis B in Patients 
Coinfected with HIV-1 
and HBV 
Severe acute exacerbations of hepatitis B (e.g., liver 
decompensation and liver failure) have been reported 
in patients who are coinfected with HIV-1 and HBV 
and have discontinued products containing FTC 
and/or tenofovir disoproxil fumarate (TDF) and may 
occur with discontinuation of BIK.  
• All chronic HBV infected patients (HBsAg+ are 
excluded from study as are those who are 
negative for anti-HBs but positive for anti-HBc 
(negative HBsAg status) AND positive for HBV 
DNA are also excluded from study. 
• Patients coinfected with HIV-1 and HBV who 
discontinue BIK should be closely monitored 
with both clinical and laboratory follow-up for 
at least several months after stopping treatment. 
If appropriate, anti-hepatitis B therapy may be 
warranted, especially in patients with advanced 
liver disease or cirrhosis, since post-treatment 
exacerbation of hepatitis may lead to hepatic 
decompensation and liver failure. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
50 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Risk of Adverse 
Reactions or Loss of 
Virologic Response 
Due to Drug 
Interactions 
 
The concomitant use of BIK with certain other drugs 
may result in known or potentially significant drug 
interactions, some of which may lead to (See Section 
6.11.1):  
• Loss of therapeutic effect of BIK and possible 
development of resistance.  
• Possible clinically significant adverse reactions 
from greater exposures of concomitant drugs.  
 
Consider the potential for drug interactions prior to 
and during BIK therapy;  
• See BIK product information for steps to 
prevent or manage these possible and known 
significant drug interactions, including dosing 
recommendations. 
• Monitor for the adverse reactions associated 
with the concomitant drugs. 
New Onset or 
Worsening Renal 
Impairment 
Renal impairment, including cases of acute renal 
failure and Fanconi syndrome (renal tubular injury 
with severe hypophosphatemia), has been reported 
with the use of tenofovir prodrugs in both animal 
toxicology studies and human trials. In clinical trials 
of BIK, there have been no cases of Fanconi 
syndrome or Proximal Renal Tubulopathy (PRT). In 
clinical trials of BIK in participants with no 
antiretroviral treatment history with eGFRs greater 
than 30 mL per minute, and in virologically 
suppressed participants switched to BIK with eGFRs 
greater than 50 mL per minute, renal serious adverse 
events were encountered in less than 1% of 
participants treated with BIK through Week 48 (see 
Biktarvy Product Information, 2019).  
 
Patients taking tenofovir prodrugs who have 
• During treatment with BIK, assess serum 
creatinine, estimated creatinine clearance, urine 
glucose and urine protein in all patients as 
clinically appropriate.  
• In patients with chronic kidney disease assess 
serum phosphorus.  
• Discontinue BIK in patients who develop 
clinically significant decreases in renal function 
or evidence of Fanconi syndrome. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
51 
 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
impaired renal function and those taking nephrotoxic 
agents including non-steroidal anti-inflammatory 
drugs are at increased risk of developing renal-
related adverse reactions.  
 
Prior to or when initiating BIK, and during treatment 
with BIK, assess serum creatinine, estimated 
creatinine clearance, urine glucose and urine protein 
in all patients as clinically appropriate. In patients 
with chronic kidney disease, also assess serum 
phosphorus. Discontinue BIK in patients who 
develop clinically significant decreases in renal 
function or evidence of Fanconi syndrome.   
Lactic Acidosis/Severe 
Hepatomegaly with 
Steatosis 
Lactic acidosis and severe hepatomegaly with 
steatosis, including fatal cases, have been reported 
with the use of nucleoside analogs, including 
emtricitabine, a component of BIK, and tenofovir 
DF, another prodrug of tenofovir, alone or in 
combination with other antiretrovirals.  
• Treatment with BIK should be suspended in any 
patient who develops clinical or laboratory 
findings suggestive of lactic acidosis or 
pronounced hepatotoxicity (which may include 
hepatomegaly and steatosis even in the absence 
of marked transaminase elevations). 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
52 
 
2.3.2. 
Benefit Assessment 
The antiviral activity against HIV-1 of CAB has been well established through Phase 2a, 
Phase 2b and Phase 3 studies. RPV, both oral (marketed as EDURANT) and LA, is an 
established antiviral agent against HIV-1 in treatment naive patients, with long term 
durability (>96 weeks in Phase 3 and >240 weeks in Phase IIb). 
Participants receiving CAB LA + RPV LA are anticipated to benefit from maintenance of 
virological suppression using LA agents. The regimen provides an alternative to daily 
oral treatment with an extended dosing option, avoiding drug-drug and drug-food 
interactions within the GI tract with IM dosing. Participants randomized to receive CAB 
LA+ RPV LA Q2M dosing will not need to take concomitant daily oral therapy.  
Adherence in these participants is expected to be improved and will be directly observed 
during IM injections. Efficacy of the two-drug regimen, as oral agents, has been 
demonstrated through Week 312 of the LAI116482 study, and as IM agents, has been 
demonstrated through Week 160 of the ongoing 200056 study and Week 48 of the 
ongoing ATLAS 2M study. The reduction in ART, and the discontinuation of NRTIs, 
may offer long term safety and tolerability benefits in these participants. 
2.3.3. 
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 CAB LA and RPV LA Q2M 
and BIK regimens, and the study as a whole are justified by the anticipated benefits that 
may be afforded to treatment-experienced patients with HIV-1 infection. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To demonstrate the non-inferior antiviral 
activity of CAB LA + RPV LA every two 
months compared to a BIK single tablet 
regimen administered once daily over 12 
months in suppressed HIV-1 infected 
antiretroviral therapy (ART)-experienced 
participants 
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 Month 12 (OLI and BIK)/Month 11 
(D2I) (Intent-to-Treat Exposed [ITT-E] 
population) 
Secondary 
To demonstrate the antiviral and 
immunologic response with the use of 
CAB LA + RPV LA every 2 months 
compared to a BIK single tablet regimen 
administered once daily 
Proportion of participants with plasma 
HIV-1 RNA <50 c/mL (c/mL) at Month 6 
and Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I) using the FDA Snapshot 
algorithm (Intent-to-Treat Exposed [ITT-E] 
population) 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
53 
 
Objectives 
Endpoints 
Proportion of participants with protocol-
defined confirmed virologic failure (CVF) 
through Month 6 and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I). 
Proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL as per 
FDA Snapshot algorithm at Month 6, and 
Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I) 
Absolute values and changes from Baseline 
in viral load and CD4+ cell count over time 
including Month 6 and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I) 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure  
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV, 
BIC, FTC, and TAF through Month 6 and 
Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I). 
To evaluate renal (in urine and blood) and 
bone (in blood) biomarkers in participants 
treated with CAB LA + RPV LA compared 
to BIK 
Change from Baseline (Day 1) in renal and 
bone biomarkers at Months 6 and 12 (OLI 
and BIK)/Month 5 and Month 11 (D2I). 
To evaluate Metabolic Syndrome for 
participants treated with CAB + RPV and 
BIK 
Change from Baseline in proportions of 
participants with Metabolic syndrome at 
Months 6 and 12 (OLI and BIK)/Month 5 
and Month 11 (D2I) 
 
To evaluate insulin resistance in 
participants treated with CAB LA + RPV 
LA compared to BIK 
Change from Baseline (Day 1) in 
homeostasis model of assessment-insulin 
resistance (HOMA-IR) at Months 6 and 12 
(OLI and BIK)/Month 5 and Month 11 
(D2I). 
To assess preference for CAB LA + RPV 
LA administered every 2 months compared 
to a BIK single tablet regimen administered 
once daily  
 
Preference for CAB LA + RPV LA every 2 
months compared to a BIK single tablet 
regimen will be assessed using a preference 
questionnaire at Month 12 (OLI)/Month 11 
(D2I) (or Withdrawal). 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5 4  
 
O bjecti ves  
E n d p oi nts  
T o assess patie nt re p orte d treat me nt 
satisfacti o n, a n d i njecti o n t olera bilit y. 
C ha n ge fr o m bas eli ne ( Da y 1) i n t otal 
“treat me nt satisfacti o n” s c ore, a n d 
i n di vi d ual ite m sc ores of t he HI V 
Treat me nt Satisfacti o n Stat us 
Q uesti o n naire ( HI V T S Qs) at M o nt h 6 a n d 
M o nt h 1 2  ( O LI a n d BI K)/ M o nt h 5 a n d 
M o nt h 1 1 ( D 2I) , ( or Wit h dra wal) 
C ha n ge i n treat me nt satisfacti o n o ver ti me 
usi n g t he HI V Treat me nt Satis facti o n 
C ha n ge Q uesti o n naire HI V T S Qc t otal 
sc ore a n d i n di vi d ual ite m sc ores at M o nt h 
1 2  ( O LI a n d BI K)/ M o nt h 1 1 ( D 2I) ( or 
Wit h dra wal).  
C ha n ge fr o m M o nt h 2 i n Di me nsi o n sc ores 
(“ Acce pta nce of I S Rs”, “ B ot her of I S Rs”, 
“ Le g m o ve me nt”, “ Slee p ”) a n d i n di vi d ual 
ite m sc ores (ass essi n g p ai n d uri n g 
i njecti o n, a n xiet y b ef ore a n d after i njecti o n, 
willi n g ness t o be i njecte d i n t he f ut ure a n d 
o verall satisfacti o n wit h m o de of 
a d mi nistrati o n o ver ti me ) will be assesse d 
usi n g t he Perce pti o n of i njecti o n 
q u esti o n naire ( PI N) at M o nt hs 2, 6, a n d 1 2  
( O LI)/ M o nt hs 1, 5, 1 1 ( D 2I) ( or 
Wit h dra wal)  
S afet y  
T o e val uate t he s afet y a n d t olera bilit y of 
C A B L A + R P V L A e ver y 2 m o nt hs 
c o m pare d t o a BI K si n gl e ta blet re gi me n 
a d mi nistere d o nce d ail y  
I n ci de nce a n d se v erit y of A Es a n d 
la b orat or y a b n or malities o ver ti me 
i ncl u di n g M o nt h 6 a n d M o nt h 1 2 ( O LI a n d 
BI K)/ M o nt h 5 a n d M o nt h 1 1 ( D 2I) . 
Pr o p orti o n of partici pa nts w h o disc o nti n ue 
treat me nt d ue t o A Es o ver ti me i ncl u di n g 
M o nt h 6 a n d M o nt h 1 2  ( O LI a n d 
BI K)/ M o nt h 5 a n d M o nt h 1 1 ( D 2I) . 
C ha n ge fr o m Baseli ne i n la b orat or y 
para meters o ver ti me i ncl u di n g M o nt h 6 
a n d M o nt h 1 2  ( O LI a n d BI K)/ M o nt h 5 a n d 
M o nt h 1 1 ( D 2I) . 
C CI


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5 5  
 
C CI


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5 6  
 
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
2 1 3 5 0 0 ( S O L A R  –  S witc h O nt o L o n g A cti n g R e gi me n) is a P has e III b, ra n d o mize d, 
o pe n -la bel, a cti ve-c o ntr olle d, m ultice nter, parallel -gr o u p, n o n -i nferi orit y st u d y desi g n e d 
t o assess t he a nti viral acti vit y a n d safet y of a t w o-dr u g re gi me n of C A B L A + R P V L A 
a d mi nistere d e ver y 2 m o nt hs c o m pare d wit h mai nte n a nce of BI K.  A p pr o xi matel y 6 5 4 
a d ult HI V-1 i nf ecte d pati e nts w h o are o n t h e sta ble A R V re gi me n BI K will be 
ra n d o mize d 2: 1 t o eit her be s witc he d t o t he C A B L A + R P V L A re gi me n or c o nti n ue 
c urre nt A R T t hr o u g h 1 2 m o nt hs. T he st u d y will c o nti n ue wit h a n E xte n si o n P hase after 
M o nt h 1 2  ( O LI a n d BI K)/ M o nt h 1 1 ( D 2I). 
Partici pa nts will be ra n d o mize d ( 2: 1) at Da y 1 t o eit her disc o nti n ue BI K  a n d eit her 
c h o ose t o be gi n oral t hera p y wit h C A B 3 0 m g + R P V 2 5 m g o nce d ail y t o deter mi ne 
i n di vi d ual t olera bilit y, pri or t o a dmi nistrati o n of C A B L A + R P V L A, or tra nsiti o n 
directl y t o i nje cti o ns , or c o nti n ue o n BI K.  C urre nt A R T d osi n g o n Da y 1 is n ot 
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
57 
 
recommended to 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 BIK prior to coming into the clinic, randomization and initiation of 
oral CAB and RPV or injections should continue as planned for Day 1.  
For those randomized to receive CAB + RPV and choose to begin the oral lead in, at the 
Month 1 visit, safety assessments (including e.g., clinical chemistries) will be performed 
as per the SoA (Section 1.3).  At visit Month 1, 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 first 
injection visit (Month 1) can be performed before central lab results are available and 
safety parameters are reviewed.  If a retest is required based on Month 1 labs, the retest 
should be performed as soon as possible (and preferably no later than 7 days following 
Month 1).  Those participants who choose to start injections immediately will receive the 
first CAB LA (600 mg) + RPV LA (900 mg) injections on Day 1. 
Randomization will be stratified by gender at birth and BMI.  The primary endpoint for 
the study is the proportion of participants with plasma HIV-1 RNA 50 c/mL who meet 
the  50 c/mL criteria at Month 12.  The proportion of participants with plasma HIV-1 
RNA <50 c/mL at Month 12 using the FDA Snapshot algorithm (Missing, Switch or 
Discontinuation = Failure, Intent-to-Treat Exposed [ITT-E] population) is a key 
secondary endpoint. 
A total of 654 participants with a 2:1 randomization ratio to either CAB LA+RPV LA or 
BIK is such that the study has approximately 85% power to demonstrate non-inferiority 
in the proportion of participants with snapshot virologic failure at Month 12 using a 4% 
margin, assuming a true 2% failure rate for CAB LA + RPV LA and a 1% failure rate for 
the BIK arm using a 2.5% one-sided alpha level.  The randomized portion of the study 
will continue for 12 months with an Extension Phase. 
No dose reductions, modifications, or changes in the frequency of any components of 
each regimen will be allowed during this study, except those allowed and defined in the 
protocol.  Protocol waivers or exemptions are not allowed.  Therefore, adherence to the 
study design requirements, including those specified in the SoA (Section 1.3), are 
essential and required for study conduct.  If deviations are required for the management 
of immediate safety concerns, these should be communicated promptly to the study 
medical monitor. 
4.1.1. 
Screening Phase (up to 35 days) 
Informed consent must be obtained prior to any study procedures, including any 
Screening assessment. 
Participants will complete a screening period of up to 35 days.  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. Participants may be re-screened once which 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
58 
 
requires a new participant number.  Participants who are randomized into the trial and 
subsequently withdrawn from the study, for any reason, may not be re-screened.  
Participants may be randomized as soon as all eligibility requirements have been 
confirmed at the site. 
4.1.2. 
Maintenance Phase 
At Day 1, eligible participants will be randomized 2:1 to either the CAB LA + RPV LA 
Q2M arm or the BIK arm. For participants who are randomized to the CAB LA + RPV 
LA arm, they will be able to choose to 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 or transition directly to injections: 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
59 
 
Oral Lead In 
Participants will remain on oral BIK until the Day 1 visit, and until any required 
Screening visit retest results are available for review.  On Day 1, participants who choose 
to participate in the oral lead in will be administered oral CAB 30 mg + RPV 25 mg once 
daily for one month (participants will be assessed for tolerability after one month).  At 
Month 1, participants will have the assessments completed as per the SoA (Section 1.3.), 
including clinical chemistries.  The participant will take the last dose of oral CAB + RPV, 
and to receive the first CAB LA + RPV LA injections (within 2 hours of the final oral 
dose).  The first injection visit with IM CAB LA 600 mg and RPV LA 900 mg can be 
performed before central lab results are available and safety parameters are reviewed.  
The second IM injection with CAB LA 600 mg and RPV LA 900 mg will be performed 
at Month 2 with a visit window of -7 days allowed.  Receiving LA dosing up to +7 days 
is not recommended and the Medical Monitor must be contacted.  Subsequent 
injections with CAB LA 600 mg and RPV LA 900 mg will occur every 2 months 
thereafter, from the projected visit date, with a dosing window of 7 days allowed If the 
injection is expected to fall outside of the dosing window, the Medical Monitor must be 
contacted to discuss individual participant case management. 
Direct to Inject (no oral lead-in) 
Central lab results (or local lab results if a central lab is not available) and safety 
parameters from the Screening visit must be available and reviewed for participants who 
choose to transition directly to injections without an oral lead-in.  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 Maintenance Phase. If a 
clinical chemistry retest is required based on Screening visit labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following the 
Screening visit).  Participants will remain on BIK until the Day 1 injection visit, and until 
any required Screening visit retest results are available for review. 
At Day 1, eligible participants will take the last dose of BIK and receive the first 
injections of CAB LA (600 mg) + RPV LA (900 mg) as initial loading doses.  Clinical 
chemistries will also be obtained at Day 1.  The second and third injections (CAB LA 
600 mg + RPV LA 900 mg) will be administered at Month 1 and Month 3.  The second 
IM injection with CAB LA 600 mg and RPV LA 900 mg will be performed at Month 1 
with a visit window of -7-days .  For the second IM injection, a visit window for LA 
dosing from +1 to +7 days is not recommended and the Medical Monitor must be 
contacted before  the second IM injection is given. Subsequent injections (CAB LA 
600 mg + RPV LA 900 mg) will occur every 2 months thereafter, from the projected visit 
date, with a 7-day dosing window being allowed.   If the injection is expected to fall 
outside of the dosing window, the Medical Monitor must be contacted to discuss 
individual participant case management. 
Note:  Study participants with Grade 1 ALT at screening and or Day 1 must be 
discussed with the Medical Monitor prior to initiation of LA dosing; continuation in 
the study or progression onto LA dosing may require additional evaluations, including 
labs drawn after a period of oral dosing with CAB + RPV. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
60 
 
BIK 
Continue on current ART (BIK) regimen for 12 months.  Participants who successfully 
complete Month 12 (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 (with or without an OLI) or to successfully complete and 
withdraw from the study (no withdrawal visit needed). 
4.1.3. 
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 2 months.  
Participants not eligible to enter the Extension Phase will end their study participation.  
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. 
NOTE: the transition plan to marketed product (either CAB+RPV LA or alternative 
HAART) should be done in consultation with the Central Study Team and the Medical 
Monitor. 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 to commercial supply.  
 
4.1.3.1. 
Participants Entering from the CAB LA + RPV LA Arm 
All participants who successfully complete 12 months 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 SoA (Section 1.3) for more information. 
4.1.3.2. 
Participants Entering from the BIK Arm 
Participants randomized to continue BIK 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 Month 12 (no withdrawal visit needed).  The transition from 
BIK 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 Month 13 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 
BIK while eligibility is being confirmed.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
61 
 
All participants with an undetectable HIV-1 RNA (<50 c/mL) result from the Month 12 
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 Month 12 must be 
performed. The retest should be scheduled as soon as possible (but no later than 4 weeks 
from the Month 12 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 Month 
12 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 Month 12 
Action 
<50 c/mL 
Begin Extension Phase for participants 
randomized to BIK at Month 13  
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 for participants 
randomized to BIK at Month 13  
Single repeat 50 c/mL 
Cannot begin Extension Phase and must be 
withdrawn from study; Complete withdrawal visit 
400 c/mL 
Cannot begin Extension Phase and must be 
withdrawn from study; Complete withdrawal 
visit. 
 
Please refer to Section 6.11.1 for a list of prohibited medications concurrent with either 
formulation for CAB and/or RPV. 
Participants Transitioning Direct to Injection in the Extension Phase:   
Central lab results (or local lab results if a central lab is not available) and safety 
parameters from the Month 12 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 Month 12 labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following Month 
12).  Participants will remain on oral BIK until the Month 13 injection visit, and until any 
required Month 12 retest results are available for review. 
At Month 13, eligible participants will take the last dose of BIK and receive the first 
injections of CAB LA (600 mg) + RPV LA (900 mg) as initial loading doses.  Clinical 
chemistries and safety assessments will also be obtained at Month 13.  The second 
injection (CAB LA 600 mg + RPV LA 900 mg) will be administered at Month 14, with a 
visit window of -7-days . Receiving LA dosing from +1 to +7 days is not 
recommended and the Medical Monitor must be contacted before the next injection 
is given. Subsequent injections (CAB LA 600 mg + RPV LA 900 mg) will occur every 2 
months thereafter, from the projected visit date, with a 7-day dosing window being 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
62 
 
allowed. If the injection is expected to fall outside of the dosing window, the Medical 
Monitor must be contacted to discuss individual participant case management. 
Participants Receiving Optional Oral Lead-In in the Extension Phase: 
As participants approach the Month 13 visit, sites must ensure sufficient oral CAB and 
RPV are available for participants who choose to use the oral lead-in. 
At Month 13, 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 BIK on the day the participant begins 
the oral lead-in with CAB + RPV.  However, if the participant takes BIK prior to coming 
into the clinic, initiation of oral CAB and RPV should continue as planned.  Clinical 
chemistries will be assessed at Month 13.  At Month 14, following the 4-week CAB + 
RPV oral lead-in, participants will have additional safety assessments including clinical 
chemistries as per the SoA (Section 1.3).  At the Month 14 visit, participants will 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 first injections 
can be performed before central lab results become available and safety parameters are 
reviewed.  The second injection (CAB LA 600 mg + RPV LA 900 mg) will be 
administered at Month 15 with a - 7-day window being allowed. Receiving LA dosing 
up to +7 days is not recommended and the Medical Monitor must be contacted.  
Subsequent injections (CAB LA 600 mg + RPV LA 900 mg) will occur every 2 months 
(bi-monthly) thereafter, from the projected visit date, with a 7-day dosing window being 
allowed. If the injection is expected to fall outside of the dosing window, the Medical 
Monitor must be contacted to discuss individual participant case management. 
4.1.4. 
LTFU Phase – IM Regimen Only 
Any participant who receives at least one dose of CAB LA and/or RPV LA and 
discontinues the CAB LA + RPV LA regimen for any reason 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 participant.  HAART 
therapy should be initiated within 8 weeks ( 7 days) after the last Q2M injection.  
The LTFU will begin the day of the last CAB LA and/or RPV LA dose and continue for 
52 weeks, or until the assigned CAB LA + RPV LA regimen is locally approved and 
commercially available.  These participants will complete Withdrawal assessments and 
will then enter into the LTFU as per the Time and Events Schedule.  In addition, for 
participants who withdraw during the LTFU, the final visit will be considered the study 
withdrawal visit.  
After receiving at least one dose of LA CAB and LA RPV, participants who decide to no 
longer continue with LA dosing for whatever reason must transition to the 52 week long 
term follow up (LTFU) phase of SOLAR. These participants are considered on study but 
off IP and should return for follow up visits at 3, 6, 9 and 12 months after the last LA was 
administered.Female participants of child bearing potential must continue to use adequate 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
63 
 
contraception methods (see Study Procedures Manual for list of accepted forms of 
contraception) for the entire year of follow up.   
In order to assure that participants have access to HAART during the LTFU, ViiV may 
supply HAART regionally or reimbursement will be provided as needed during this 
phase.  The LTFU Phase may be shortened or terminated 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.  If the participant is administered an ABC-containing product, see 
Section 8.3.11.8. 
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 LTFU Phase.  The participants’ last on study visit will be considered as their 
withdrawal visit. 
Participants who are randomized to LA CAB and LA RPV and chose to perform the Oral 
Lead In and decide not to continue while performing the Oral Lead in are not required to 
enter the LTFU. 
4.1.5. 
Independent Data Monitoring Committee 
Given the well-established safety and efficacy data for CAB and RPV LA from multiple 
prior studies including LATTE-2, ATLAS, FLAIR, and ATLAS-2M, coupled with a well 
characterized safety profile of the comparator arm (BIK), the SOLAR study team in 
consultation with the ViiV Safety and Labeling Committee (VSLC) decided that no 
formal IDMC or iSRC is warranted for this study.   
Furthermore, accumulating study data from this study will be regularly reviewed in 
aggregate by the CAB Safety Review Team (SRT). Any new, emerging safety signals 
detected by the SRT will be acted upon by the study team. An interim analysis is planned 
to review primary and secondary efficacy data and key safety data when all participant 
complete Month 6 visit.  These actions will provide comprehensive data monitoring for 
the study in the absence of IDMC. 
4.2. 
Type and Number of Participants 
The target population to be enrolled is HIV-1 infected, virologically suppressed (HIV-1 
RNA <50 c/mL) participants on a BIK single tablet regimen.  
It is anticipated that approximately 654 participants will be enrolled into SOLAR.  A 
15% screen failure rate is anticipated.  Participants will be enrolled from multiple 
countries including (but not limited to) Canada, UK, Ireland, France, Germany, Spain, 
Italy, Switzerland, Austria, Netherlands, Belgium, Japan, Australia, and the United 
States. 
Randomization will be stratified by gender at birth and BMI.  A goal of this study is to 
enroll populations who are underrepresented in clinical studies, including approximately 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
64 
 
20% women.  Sites are expected to take into account gender in their screening strategies 
in order to achieve women enrolment. .  
4.3. 
Scientific Rationale for Study Design 
The design of this study (2:1 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 defined as virologic failures by the FDA 
Snapshot algorithm is recommended in the FDA’s 2015 guidance document [CDER, 
2015] for assessing efficacy in Switch Trials.  The key secondary endpoints, proportion 
with plasma HIV-1 RNA <50 c/mL at Month 6 and Month 12, is also a well-established 
surrogate endpoint for prognosis of HIV-1 infection and disease progression. The 
Extension Phase will allow for a collection of longer-term efficacy, safety and tolerability 
data for the CAB LA + RPV LA Q2M regimen. 
Various approaches to simplify a patient's antiretroviral therapy (ART) regimen, after 
achieving viral suppression, have been studied.  Previous studies have evaluated switches 
to ritonavir-boosted PI monotherapy therapy in virologically suppressed patients 
[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 viral suppression. 
The 200056 (LATTE-2) [GlaxoSmithKline Document Number 2013N168152_09, 2017] 
and the ATLAS-2M [GlaxoSmithKline Document Number 2017N326521_02, 2018] 
clinical trials evaluated a different simplification approach and served as proof of concept 
for this study.  In 200056, HIV-1 RNA suppression was induced with a three-drug 
antiretroviral regimen consisting of CAB + ABC/3TC FDC, and then participants 
switched to a two-drug two-class regimen consisting of CAB LA + RPV LA for the 
maintenance of HIV-1 RNA suppression.  Results demonstrate that through 96 weeks on 
two-drug maintenance therapy, 94% (Q8W IM arm) and 87% (Q4W IM) of participants 
maintained virologic suppression (HIV-1 RNA <50 c/mL) compared to 84% of 
participants continuing oral CAB + 2 NRTIs. CAB LA + RPV LA was well tolerated 
through Week 96 for both the Q8W and Q4W dosing regimens, as demonstrated by a low 
discontinuation rate due to AEs, including injection site reaction (ISR) related AEs in 
either dosing arm, with no significant dose-dependent trends in safety parameters.  On the 
basis of 200056 Week 48, and Week 96 data, Q4W and Q8W IM dosing are being 
progressed into Phase 3 for further clinical development, respectively.  In 207966, 1.7% 
of participants in the CAB + RPV Q8W group and 1.0% of participants in the CAB + 
RPV Q4W group met the primary efficacy endpoint of plasma HIV-1 RNA 50◦c/mL at 
Week◦48.  Based on a 4% non-inferiority margin, CAB◦+◦RPV Q8W is non-inferior to 
CAB + RPV Q4W at Week◦48 because the upper bound of the 95% CI for the adjusted 
treatment difference [0.8 (-0.6, 2.2)] is less than 4%.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
65 
 
The open-label design for 213500 (SOLAR) 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 participants who elect to receive 
this short-term regimen at the start of study before the initiation of CAB LA + RPV LA 
injections.  Blinding the oral lead-in would require additional placebo pills for 5 weeks in 
the ART continuation arm, that otherwise would not be required.  This study utilizes a 
2:1 randomization that provides advantages with respect to costs, gathering additional 
safety information, reduces the effect of any learning curves due to injection 
administration or metabolic testing and improves recruitment. 
In addition to study design challenges, the impact of blinding 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 
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, this study is planned as an open label study. 
To maintain the integrity of the trial, data aggregated by actual treatment group will not 
be made available to members of the Study Team and will not be shared with 
Investigators until the primary analysis at Month 12.  In addition, central stratified 
randomization will be used to ensure that selection bias is avoided (see Section 6.2).  The 
stratification factors gender and BMI will be considered based on historical studies.  
Lastly, ascertainment bias affecting the primary efficacy analysis is unlikely since the 
primary endpoint is inherently objective, being primarily determined by HIV-1 RNA 
laboratory assessment. The open label design should therefore have no impact on the 
analysis of study endpoints.   


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
66 
 
4.3.1. 
Participant Input into Design 
Participants were not involved in the design of the clinical trial. 
4.4. 
Justification for Dose 
4.4.1. 
CAB + RPV 
4.4.1.1. 
CAB and RPV Pharmacokinetics Following Q8W and Q4W Dosing 
In pivotal Phase 3 studies 201585 and 201584 (ATLAS and FLAIR, CAB LA 400 mg + 
RPV LA 600 mg Q4W demonstrated non-inferiority to oral standard of care.  In the 
Phase 3b Study 207966 (ATLAS 2M), CAB LA 600 mg + RPV LA 900 mg Q8W was 
non-inferior to the Q4W regimen while achieving lower overall trough concentrations.  
Participants naïve to CAB+RPV received CAB LA 600 mg + RPV LA 900 mg initiation 
injections at Week 4b (following a 4-week oral lead-in) and second (first continuation) 
injections at Week 8 regardless of regimen.  Select trough concentrations following Q8W 
and Q4W dosing in ATLAS 2M are summarized in Table 2.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
67 
 
Table 2 
Summary of Evaluable Plasma CAB and RPV Trough Concentrations 
by Regimen at Select Visits for Participants with No Prior Exposure 
to CAB + RPV (Study 207966, ATLAS 2M) 
Visit 
Plasma CAB (g/mL) 
Plasma RPV (ng/mL) 
n 
Q8W 
(n=326) 
n 
Q4W 
(n=326) 
n 
Q8W 
(n=326) 
n 
Q4W 
(n=326) 
Week 
4bb 
282 
5.18 
[4.93, 5.45] 
(45) 
292 
5.29 
[5.04, 5.55] 
(43) 
283 
77.2 
[72.8 ,81.9] 
(54) 
292 
78.3 
[73.6, 83.3] 
(58) 
Week 8c 
273 
1.57 
[1.46, 1.69] 
(67) 
267 
1.52 
[1.40, 1.64] 
(74) 
272 
48.2 
[45.3, 51.2] 
(54) 
267 
45.5 
[42.7, 48.4] 
(56) 
Week 16 
262 
1.41 
[1.32, 1.51] 
(58) 
253 
2.13 
[2.02, 2.25] 
(46) 
260 
46.2 
[44.0, 48.5] 
(41) 
252 
57.8 
[54.6, 61.2] 
(49) 
Week 24 
219 
1.44 
[1.34, 1.56] 
(62) 
228 
2.41 
[2.29, 2.54] 
(41) 
220 
49.5 
[46.8, 52.3] 
(44) 
228 
63.4 
[60.1, 67.0] 
(44) 
Week 48 
217 
1.58 
[1.49, 1.68] 
(47) 
236 
2.71 
[2.58, 2.84] 
(39) 
217 
65.4 
[61.9, 69.1] 
(43) 
235 
89.3 
[84.5, 94.2] 
(44) 
Data Source: 207966 CSR Table 4.5. GlaxoSmithKline Document Number 2019N406358_00, 2019] 
a. 
Geometric mean [95% CI] (CVb%). 
b. 
Represents trough at the end of 1-month oral lead-in prior to initiation injections.  
c. 
Represents trough 4-weeks following CAB 600 mg and RPV 900 mg initiation injections prior to first continuation injections.  
4.4.1.2. 
Q8W versus Every 2 Month Dosing 
Separate population PK models for CAB LA and RPV LA that included concentration 
data from Phase 3 studies were developed and validated [GlaxoSmithKline Document 
Number 2019N421460_00, 2019 and GlaxoSmithKline Document Number EDMS-ERI-
198151177, 2019].  Simulations (including oral lead in) were performed to compare the 
impact of changing from Q8W (7 doses/year 1) to every other month dosing (6.5 doses/ 
year 1).  Differences between predicted trough concentrations following Q8W and every 
2-month dosing are considered minimal (Figure 1,  Figure 2).  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
68 
 
Figure 1 
Comparison of CAB LA Q8W and Every 2 Months 
 
 Figure 2 
Comparison of RPV LA Q8W and Every 2 Months 
 
For 1-week delays in dosing median CAB and RPV troughs decrease ~10% with 99% of 
participants predicted to have troughs above respective PA-IC90 values. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
6 9  
 
4. 4. 1. 3.  
O pti o n al Or al l e a d -i n  
T he p ur p ose of t h e oral l ea d -i n is t o assess t he i n di vi d ual partici pa nt  t olera bilit y of C A B 
a n d R P V pri or t o  a d mi nistrati o n of t he pr ol o n ge d releas e s us pe nsi o n i njecti o ns. T he 
i m pact of t he oral lea d-i n o n t he C A B L A a n d R P V L A P K pr ofiles is li mite d a n d it is n ot 
re q uire d f or t he ac hie ve me nt of eit her t hera pe uti c or stea d y-st ate d ose le vels. I n a d diti o n, 
partici pa nt s are vir ol o gic all y s u p presse d u p o n i nitiati o n of C A B L A + R P V L A i njecti o ns 
a n d will recei v e c o nti n ui n g c o ntri b uti o n of t he pri or oral re gi me n t o t he o v erall a nti viral 
acti vit y if st o p pe d t he s a me da y as i nitiati o n i njecti o ns. Plas ma c o nce ntrat i o ns at t he e n d 
of t he first d osi n g i nter val ( 4 wee ks after i njecti o n) are si milar wit h or wit h o ut t he pri or 
oral lea d -i n (Fi g ure 3 , Fi g ure 4 ). 
 
   
Partici pa nt s o pti n g t o recei ve oral lea d -i n d osi n g will recei ve C A B 3 0 m g + R P V 2 5  m g 
o nce dail y wit h f o o d d uri n g t he first m o nt h of t he st u d y.  
Fi g ur e 3  
Si m ul at e d M e di a n ( 9 0 % PI) C A B C o n c e ntr ati o n -Ti m e Pr ofil e s f or 
C A B L A 6 0 0  m g I niti ati o n I nj e cti o n wit h a n d wit h o ut O LI  
 
R ef er e nc e li n es:  0. 1 6 6  g/ m L = P A -I C 9 0; 0. 6 5g/ m L = 5 th p erc e ntil e pre dict e d W 8 tro u g h f oll o wi n g i niti ati o n 
i nj ecti o ns i n F L AI R a n d A T L A S; 1 3. 1g/ m L = m e di a n C m ax f oll o wi n g C A B 6 0 m g P O Q D o bs erv e d i n L A T T E  
 
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
70 
 
Figure 4 
Simulated Median (90% PI) RPV Concentration-Time Profiles for RPV 
LA 900 mg Initiation Injection with and without OLI 
 
 
4.4.2. 
BIC/FTC/TAF (BIK) 
BIK will be administered as the marketed three-drug fixed dose combination product 
containing 50 mg of BIC, 200 mg of FTC, and 25 mg of TAF orally once daily with or 
without food in adults. 
4.5. 
End of Study Definition 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition.  
Study Completion 
Participants are considered to have completed the study if they remain on therapy (i.e., 
have not permanently discontinued IP) and satisfy one of the following: 
• Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including Month 11/12 (with or without Month 11/12 study 
treatment) and did not enter the Extension Phase; 
• Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including Month 11/12, and entered and completed the 
Extension Phase (defined as remaining on study until commercial supplies of the 
CAB LA + RPV LA Q8W regimen become locally available or development of 
CAB LA + RPV LA is terminated). 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
71 
 
An safety Follow-Up visit will be conducted approximately 4 weeks after the last dose of 
study medication for participants with ongoing AEs, and serious adverse events (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 safety Follow-up 
visit should reflect any ongoing complaints (e.g., blood draws to follow a laboratory 
abnormality).  Safety Follow-Up visits are not required for successful completion of the 
study and can be in clinic or conducted by phone. 
5. 
STUDY POPULATION 
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the investigational regimen or other study treatment 
that may impact participant eligibility is provided in the current  IBs for CAB 
[GlaxoSmithKline Document Number  RPS-CLIN-004375, 2021 and RPV IB, 2021], 
Edurant Prescribing Information, 2021 and Biktarvy prescribing information, 2019. 
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. 
5.1. 
Inclusion Criteria 
A participant will be eligible for inclusion in this study only if all of the following criteria 
apply: 
• 
Be able to understand and comply with protocol requirements, instructions, and 
restrictions; 
• 
Understand the long-term commitment to the study and be likely to complete the 
study as planned; 
• 
Be considered appropriate candidates for participation in an investigative clinical 
trial with oral and intramuscularly injectable medications (e.g., no active 
substance use disorder, acute major organ disease, or planned long-term work 
assignments out of the country, etc.).   
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 antiretroviral therapy in accordance with 
local treatment guidelines. 
Laboratory results from the central laboratory services provided by this trial will be used 
to assess eligibility.  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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
72 
 
Source documentation to verify entry criteria must be reviewed by the Principal 
Investigator or designee prior to randomization.  Source documents from other medical 
facilities must be located/received during the 14-day screening phase (or up to 35 days) 
and under no circumstances may the participant be randomized in the absence of source 
documentation.  
All Participants eligible for enrolment in the study must meet all of the following 
criteria: 
AGE 
1. Aged 18 years or older (or ≥19 where required by local regulatory agencies), at 
the time of signing the informed consent. 
SEX 
2. A female participant is eligible to participate if she is not pregnant (as confirmed 
by a negative serum human chorionic gonadotropin (hCG) test at screen and a 
negative urine hCG test at Randomization), 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) from 30 days prior to the first dose of study 
medication, throughout the study, 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.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
73 
 
The investigator is responsible for ensuring that participants understand how to properly 
use these methods of contraception.   
INFORMED CONSENT 
3. Capable of giving signed 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. 
OTHER 
4. Participants enrolled in France must be affiliated to, or a beneficiary of, a social 
security category.   
 
5. Must be on the uninterrupted current regimen of BIK for at least 6 months prior to 
Screening with an undetectable HIV-1 viral load for at least 6 months prior to 
Screening.  BIK must be the participant’s first or second regimen.  If BIK is the 
second regimen, the first regimen must be an INI regimen.  Any history of non-
INSTI regimens (ie. NNRTI, PI, C-C chemokine receptor type 5 [CCR5] and 
other entry inhibitors) are not permitted. Any prior change in regimen, defined as 
a change of a single drug or multiple drugs simultaneously, must have occurred 
due to tolerability/safety, access to medications, or convenience/simplification, 
and must NOT have been done for treatment failure (HIV-1 RNA ≥400 c/mL).  
 
The following are limited exceptions:  
 
• A change from TDF to TAF will not be considered a regimen change.   
 
• Historical perinatal use of an NRTI when given in addition to an ongoing 
HAART will not be considered a change in ART regimen. 
 
• The past use of ARVs in the context of PEP or PrEP while the patient was 
HIV negative will be allowed. Such cases will be evaluated on a case by 
case basis with the Medical Monitor, and may require documentation of 
HIV negative serology during time of PEP or PrEP 
 
• A change in dosing scheme of the same drug from twice daily to once 
daily will not be considered a change in ART regimen if data support 
similar exposures and efficacy. 
 
• A change in formulation from multiple class regimens to single treatment 
regimens (of the same medications) would not be considered a change in 
ART regimen. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
74 
 
6. Documented evidence of plasma HIV-1 RNA measurements <50 c/mL in the 6 
months prior to Screening . 
 
7. Plasma HIV-1 RNA <50 c/mL at Screening. 
All participants participating 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. 
5.2. 
Exclusion Criteria 
Deviations from 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.  A 
participant will not be eligible for inclusion in this study if any of the following criteria 
apply: 
Exclusionary Criteria prior to Screening or Day 1  
 
1. Within 6 months prior to Screening, any plasma HIV-1 RNA measurement 
50 c/mL 
2. Within the 6 to 12-month window prior to Screening, documented evidence of 
any plasma HIV-1 RNA measurement >200 c/mL, or 2 or more plasma HIV-1 
RNA measurements 50 c/mL.  NOTE: This statement does not apply to study 
participants who started treatment within the 6 to 12-month window prior to 
screening. 
3. History of prior treatment failure to any DHHS recommended ART regimen. 
4. History of drug holiday >1 month for any reason prior to Screening visit, except 
where all ART was stopped due to tolerability and/or safety concerns 
5. Any change to a second line regimen, defined as change of a single drug or 
multiple drugs simultaneously, due to virologic failure to therapy (defined as a 
confirmed plasma HIV-1 RNA measurement 200 c/mL after initial suppression 
to <50 c/mL while on first line HIV therapy regimen)  
6. Participants who are currently participating in or anticipate being selected for any 
other interventional study. 
Exclusionary medical conditions- for all participants 
7. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed 
during the study 
8. Any evidence of a current Center for Disease Control and Prevention (CDC) 
Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
75 
 
systemic therapy, and CD4+ counts <200 cells/L are not exclusionary. 
9. Participants with moderate to severe hepatic impairment 
10. Any pre-existing physical or mental condition (including substance use 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 
11. 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 
12. All participants will be screened for syphilis.  
• Participants with untreated secondary (late latent) or tertiary syphilis 
infection, defined as a positive RPR and a positive treponemal test without 
clear documentation of treatment, are excluded.  
• Participants with a false positive RPR (with negative treponemal test) or 
serofast RPR result (persistence of a reactive nontreponemal syphilis test 
despite history of adequate therapy and no evidence of re-exposure) may 
enroll after consultation with the Medical Monitor. 
• Participants with primary syphilis or early latent secondary syphilis 
(acquired within the preceding year) who have a positive RPR test and 
have not been treated may be treated during the screening period and if 
completion of antibiotic treatment occurs during the screening period, may 
be allowed entry after consultation with the Medical Monitor. If antibiotic 
treatment cannot be completed before the screening window ends, 
participants may be rescreened once following completion of antibiotic 
therapy for primary or early latent secondary syphilis.  
13. Participants who, in the investigator's judgment, pose a significant suicide risk.  
Participant’s recent history of suicidal behavior and/or suicidal ideation should be 
considered when evaluating for suicide risk 
14. The participant has a tattoo, gluteal implant/enhancements or other dermatological 
condition overlying the gluteus region which may interfere with interpretation of 
injection site reactions 
15. 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: 
a. Participants positive for HBsAg are excluded; 
b. Participants negative for anti-HBs but positive for anti-HBc (negative 
HBsAg status), whether negative or 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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
76 
 
16. 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 require or qualify for immediate 
HCV treatment are excluded (see Section 5.3.1 for those co-infected participants 
who post entry into SOLAR decide treatment for HCV infection is warranted or 
desired either by the participant or by the treating physician.   
Participants with HCV co-infection will be allowed entry into this study if:  
a. Liver enzymes meet entry criteria 
b. HCV Disease has undergone appropriate work-up, and is not advanced, 
and will not require treatment prior to the Month 14 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. 
c. In the event that recent biopsy or imaging data is not available or 
inconclusive, the Fib-4 score will be used to verify eligibility  
i. Fib-4 score >3.25 is exclusionary  
ii. Fib-4 scores 1.45 – 3.25 requires Medical Monitor consultation 
Fibrosis 4 Score Formula:  
(Age x AST) / (Platelets x (sqr [ALT]) 
17. Unstable liver disease (as defined by any of the following:  presence of ascites, 
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, 
or persistent jaundice or cirrhosis, or decompensated cirrhosis (eg. ascites, 
encephalopathy, or variceal bleeding)), known biliary abnormalities (with the 
exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable 
chronic liver disease per investigator assessment) 
18. History of liver cirrhosis with or without hepatitis viral co-infection. 
19. Ongoing or clinically relevant pancreatitis 
20. 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 
21. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell 
carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or 
cervical intraepithelial neoplasia; other localized malignancies require agreement 
between the investigator and the Study medical monitor for inclusion of the 
participant prior to randomization 
22. 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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
77 
 
23. 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 
24. Current or anticipated need for chronic anti-coagulation with the exception of the 
use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and 
platelet disorders such as haemophilia or Von Willebrand Disease. 
25. Corrected QT interval (QTc (Bazett)) >450 msec or QTc (Bazett) >480 msec for 
participants with bundle branch block. 
26. Known or suspected active COVID-19 infection OR has had contact with an 
individual with known COVID-19, within 14 days of study enrolment. 
 
Exclusionary Laboratory Values or Clinical Assessments at Screening (a single repeat to 
determine eligibility is allowed) 
27. Known or suspected presence of resistance mutations as defined by the IAS-USA 
resistance guidelines [IAS-USA, 2019] to the individual components of BIK 
(BIC, FTC, TAF), RPV, and CAB by any historical resistance test result. 
Note: Prior genotypic resistance testing (genotyping of plasma vRNA 
and/or PBMC vDNA) is not required but if available it must be provided 
to ViiV, after screening and before randomization according to guidance 
in the SPM, to provide direct evidence of no pre-existing exclusionary 
resistance mutations. You must wait for the study virologists to confirm 
the lack of exclusionary resistance mutations, which will be provided 
before the screening window closes. Details regarding baseline or prior 
resistance data must be noted in the source documentation 
28. Any verified Grade 4 laboratory abnormality. A single repeat test is allowed 
during the Screening phase to verify a result  
29. 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 
30. Participant has estimated creatine clearance <30mL/min per 1.73m2 via Chronic 
Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method 
31. Alanine aminotransferase (ALT) 3 × ULN 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
78 
 
Concomitant Medications 
32. Exposure to an experimental drug or experimental vaccine within either 30 days, 
5 half-lives of the test agent, or twice the duration of the biological effect of the 
test agent, whichever is longer, prior to Day 1 of this study; 
33. Treatment with any of the following agents within 28 days of Screening: 
•  radiation therapy;  
• cytotoxic chemotherapeutic agents;  
• tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH); 
• anti-coagulation agents; 
• Immunomodulators that alter immune responses such as chronic systemic 
corticosteroids, interleukins, or interferons. Note: Participants using short-term 
(e.g. ≤21 days) systemic corticosteroid treatment; topical, inhaled and intranasal 
corticosteroids are eligible for enrolment.  
34. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening 
35. Treatment with any agent, except recognized ART as allowed above, with 
documented activity against HIV-1 within 28 days of study Day 1. Treatment 
with acyclovir/valacyclovir is permitted.  
36. Use of medications which are associated with Torsade de Pointes.  (See SPM for 
a list of relevant medications) 
37. Participants receiving any prohibited medication and who are unwilling or unable 
to switch to an alternate medication.  Note: Any prohibited medications that 
decrease CAB, RPV, BIC, FTC or TAF 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 
  
5.3. 
Additional Eligibility Criteria 
To assess any potential impact on participant eligibility with regard to safety, the 
investigator must refer to the IB and supplements, approved product labels, and/or local 
prescribing information for detailed information regarding warnings, precautions, 
contraindications, AEs, drug interactions, and other significant data pertaining to the 
study drugs. 
Notwithstanding these minimum inclusion and exclusion criteria, investigators must also 
follow country specific guidelines where they exist when making decisions about 
participants who are eligible for study participation. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
7 9  
 
5. 3. 1.  
HI V/ H C V Tr e at m e nt C o n si d er ati o n s f or C o-i nf e ct e d P arti ci p a nt s 
F or partici pa nt s w h o deci de t o i nitiate H C V treat me nt at a n y p oi nt w hile o n st u d y, eit her 
sec o n dar y t o n e wl y ac q uire d ac ut e H C V i nfecti o n or, if a c h a n ge i n treat me nt strate g y f or 
t h ose w h o e ntere d t he st u d y HI V/ H C V c o-i nf ecte d, s uc h partici pa nt s ma y b e per mitte d 
d uri n g t he M ai nte na nce P hase bef ore t he pri mar y e n d p oi nt is reac h e d b ut w o ul d re q uire 
c o ns ultati o n wit h a n d a p pr o val b y t h e Me dical M o nit or t o c o m me nce H C V t hera p y. T h e 
c h oice of H C V direct a cti n g a nti viral a ge nts bei n g c o nsi dere d m ust be H C V re gi me ns 
e n d orse d b y D H H S g ui d eli nes wit h mi ni mal  dr u g -dr u g i nteracti o ns as detaile d i n t he 
m ost c urre nt D H H S HI V treat me nt g ui deli nes.  
5. 4.  
S cr e e ni n g/ B a s eli n e/ R u n -i n F ail ur e s 
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical trial 
b ut are ne v er s u bse q u e ntl y ra n d o mize d.   I n or der t o e ns ure tra ns p are nt re p orti n g of scree n 
fail ure partici pa nts, meet t he C o ns oli date d Sta n dar ds of Re p orti n g Trials ( C O N S O R T) 
p u blis hi n g re q uire m e nts, a n d res p o n d t o q ueries fr o m Re g ulat or y a ut h orities, a mi ni mal 
set of scree n fail ure i nf or mati o n is re q uire d i ncl u di n g De m o gra p h y, Scree n Fail ure 
details, Eli gi bilit y Criteri a, a n d Seri o us A d verse E ve nts.  
A si n gle re peat of a pr oce d ure / la b para meter is all o we d t o deter mi ne eli gi bilit y ( u nl ess 
ot her wise s pecifie d).  
Partici pa nts are all o we d t o re -scree n f or t his st u d y o ne ti me.  T his will re q uire a ne w 
partici pa nt n u m ber.  
5. 5.  
Lif e st yl e C o n si d er ati o n s  
5. 5. 1.  
M e al s a n d Di et ar y R e stri cti o n s  
Partici pa nts w h o are ra n d o mize d t o t he C A B + R P V ar m a n d c h o ose t o partici pate i n t he 
oral lea d i n s h o ul d ta ke t he rec o m me n d e d d osa ge of oral C A B 3 0 m g + R P V 2 5 m g o nce 
dail y wit h a meal.  C o -a d mi nistrati o n of a ntaci d s u p ple me nts has t he p ote ntial t o decrease 
oral ca b ote gra vir a bs or pti o n a n d has n ot bee n st u die d. A ntaci d pr o d ucts c o ntai ni n g 
p ol y vale nt cati o ns are rec o m me n de d t o be  a d mi nistere d at least 2 h o urs bef ore or 4 h o urs 
after oral C A B.  
If t he partici p a nt is ra n d o mize d t o BI K a n d calci u m -c o ntai ni n g s u p ple m e nts ca n be ta ke n 
t o get her, wit h o ut re gar d t o f o o d.  BI K s h o ul d be a d mi nistere d at least 2 h o urs bef ore ir o n 
s u p ple me nts or ta ke n t o get her wit h f o o d.  B I K s h o ul d be a d mi nistere d at least 2 h o urs 
bef ore, or wit h f o o d 2 h o urs after a ntaci ds c o nt ai ni n g ma g nesi u m a n d/ or al u mi ni u m.  
5. 5. 2.  
C o s m eti c S ur g er y  
Partici pa nts w h o are ra n d o mise d t o t he BI K or C A B + R P V ar m  will be q u esti o ne d at t he 
e n d of t he st u d y if t he y h a d a n y c os metic s ur ger y d uri n g t he c o urse of t he st u d y o nl y. 
C os metic  pr oce d ures s uc h as li p os ucti o n/li p osc ul pt ure/i m pla nts ( b ut n ot li mite d t o) ma y 
affect meta b olic e n d p oi nts  
T heref ore, s uc h p atie nts will be e x cl u de d fr o m t he fi nal a nal yses f or t hese 
C CI
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
80 
 
metabolic endpoints. Cosmetic procedures involving the face and neck are out of scope as 
such procedures are unlikely to have an impact on these metabolic endpoints. 
6. 
STUDY INTERVENTION 
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 is 
defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to 
the study protocol. 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 BIK single tablet regimen (or 
alternately BIK), oral CAB, and CAB LA, which will be supplied by GlaxoSmithKline 
and oral RPV and RPV LA which will be supplied by Janssen Pharmaceuticals. 
Participants entering the Long-Term Follow-Up Phase will not have their selected 
HAART provided as clinical trial material.  The selected HAART will be recorded on the 
Concomitant Antiretroviral Therapy (ConART) eCRF page. 
6.1. 
Study Intervention(s) Administered 
6.1.1. 
Formulations of CAB + RPV 
6.1.1.1. 
Cabotegravir Tablets (CAB) 
CAB is manufactured by GlaxoSmithKline 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. 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 labeling. 
CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline 
cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-
coating.  The white film-coating contains hypromellose, titanium dioxide and 
polyethylene glycol. 
6.1.1.2. 
Rilpivirine Tablets (RPV) 
RPV 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 a globally marketed product 
which includes approvals in the US and the European Union.  RPV will be overlabeled 
and packaged in bottles of 30 tablets.  RPV tablets should be stored according to the 
product labeling. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
81 
 
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. 
6.1.1.3. 
Cabotegravir Injectable Suspension (CAB LA) 
CAB LA (GSK1265744 LA) is manufactured by GlaxoSmithKline and is a sterile white 
to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for 
administration by intramuscular (IM) injection.  The product is packaged in a glass vial 
with a 13 mm gray stopper and aluminum seal.  Each vial is for single-dose use 
containing a withdrawable volume of 2.0 mL (400 mg) or 3 mL (600 mg) and does not 
require dilution prior to administration.  CAB LA injectable suspension is to be stored 
according to the product labeling.  
CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 
3350, mannitol, and water for injection. 
6.1.1.4. 
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 glass vial with a 13 mm grey stopper and aluminum 
seal. Each vial contains a nominal fill of 2.0 mL (600 mg) or 3.0 mL (900 mg) and does 
not require dilution prior to administration. RPV LA injectable suspension is to be stored 
according to product labeling. RPV LA should also 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. 
6.1.2. 
Biktarvy Tablets (BIK) 
BIK is a three-drug fixed dose combination product containing 50 mg of BIC, 200 mg of 
FTC, and 25 mg of TAF manufactured by Gilead Sciences.  The recommended dosage of 
BIK is one tablet taken orally once daily with or without food in adults and pediatric 
patients weighing at least 25 kg.  The tablets are purplish brown, capsule-shaped, film-
coated, and debossed with “GSI” on one side and “9883” on the other side.  Each bottle 
contains 30 tablets, a silica gel desiccant, polyester coil, and is closed with a child 
resistant closure.  BIK tablets are to be stored according to product labelling.  
6.1.3. 
Medical Devices 
• 
The medical devices to be used in this study are: syringe, vial adaptor and needle. 
• 
Instructions for medical device use are provided in the Study Reference Manual 
(SRM).  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
82 
 
• All device deficiencies, (including malfunction, use error and inadequate labelling) 
shall be documented, and reported by the investigator throughout the clinical 
investigation (see Section 8.3.8 and Section 10.9 and appropriately managed by the 
sponsor. 
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 2:1 treatment allocation 
within each block, which are shared across centers via central randomization.  
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1. 
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 participants does not 
predict which treatment group will be assigned to the next randomized participant.  
Randomization and study treatment assignment will be facilitated by the interactive 
response technology (IRT) through the central Randomization and Medication Ordering 
System Next Generation (RAMOS NG).  
Following confirmation of fulfillment of study entry criteria, 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.  On Day 1, A unique treatment number 
(randomization number) in ascending numerical order will be assigned for each 
participant participating in the study at each study site. Participants will be randomized in 
a 2:1 ratio to CAB LA + RPV LA Q2M or to continue BIK in accordance with the 
computer-generated randomization schedule.  Returned study intervention should not be 
re-dispensed to participants. 
Participants who successfully complete 12 months of treatment and have a viral load 
<50 c/ml at Month 11/12 (or upon retest 4 weeks later) will be given the opportunity to 
enter the Extension Phase in which they will continue to receive their CAB LA + RPV 
LA regimen or switch from BIK to CAB LA + RPV LA.  In addition, RAMOS NG will 
facilitate the initial supply and subsequent resupply of IP to study sites. 
6.3.2. 
Blinding 
This will be an open-label study and therefore no blinding is required.  No summaries of 
the study data according to actual randomized treatment groups will be available to 
sponsor staff prior to the planned Month 6 interim analysis. Public presentation of the 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
83 
 
Month 6 analysis will not be done prior to the last participant’s Month 12 (OLI and 
BIK)/Month 11 (D2I) visit. 
6.4. 
Dosage and Administration 
Participants will be randomly assigned to receive treatment with CAB LA + RPV LA 
Q2M or BIK taken orally once daily.  Participants who choose to participate in the oral 
lead in will initiate their randomized treatment regimen with Oral CAB 30 mg + RPV 25 
mg once daily for 4 weeks, followed by CAB LA + RPV LA IM injections initiating at 
Month 1.  Participants transitioning directly to CAB LA + RPV LA IM injections will 
initiate their randomized treatment regimen at Day 1.  If the participant is randomly 
assigned to continue the oral standard of care therapy, BIK will continue to be 
administered as was done prior to the study. Regardless of treatment arm assignment, the 
investigator should instruct all participants on the importance of treatment adherence.  
This study has an open-label design.  Dosing is outlined in the table below. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
84 
 
Maintenance Phase and Extension Phase (Day 1 to End of Study+) 
Q2M Arm – Optional Oral Lead In (OLI) 
Oral Lead-In   
 
• Receive last dose of BIK regimen during Day 1 visit 
• 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 Injections (Loading Dose) – Month 1 
Month 1 
(two 3mL injections once) 
• Receive last dose of oral CAB + RPV regimen during 
Month 1 visit 
• 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 2 months (Q2M) following Month 1 
Month 2 to End of Study+ 
(two 3 mL injections every 2 
months) 
• 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 
Q2M Arm- No Oral Lead In (D2I) 
First Injections (Loading Doses) – Day 1 
Day 1  
(two 3 mL injections once) 
• Receive last dose of BIK regimen during Day 1 visit 
• 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 2 months (Q2M) following Month 1 
Month 1 to End of Study+ 
(two 3 mL injections every 2 
months) 
• 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  
Continuing BIK  
Day 1 to Month 13+ 
• Take 1 tablet BIC 50 mg/FTC 200 mg/TAF 25 mg once 
daily with or without a meal 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
85 
 
(1 tablet dosed orally) 
Extension Phase (Month 13 through End of Study) 
BIK Arm (Transition to CAB LA + RPV LA) – Optional OLI 
Oral Lead-in 
Month 13 to Month 14 
(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) – Month 14 – Optional Oral Lead-in 
Month 14 
(two 3 mL injections once) 
• Receive last dose of oral CAB + RPV during Month 14 
visit 
• Receive CAB LA 600 mg given as 1 X 3mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3mL IM injection 
Maintenance Injections – every 2 months (Q2M) following Month 14 
Month 15 to End of Study+ 
(two 3 mL injections every 2 
months) 
• 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 
Direct to Inject Dosing – if Not Using Oral Lead-in 
First Injection (Loading Dose) – Month 13– Optional Oral Lead-in 
Month 13 
(two 3 mL injections once) 
• Receive last dose of oral BIK during Month 13 visit 
• Receive CAB LA 600 mg given as 1 X 3mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3mL IM injection 
Maintenance Injections – every 2 months (Q2M) following Month 13 – No Oral Lead-in 
Month 14 to End of Study+ 
(two 3 mL injections every 2 
months) 
• 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 
+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 
Participants will be given an option to continue their randomized Q2M CAB LA + RPV LA regimen, switch from BIK to 
Q2M CAB LA + RPV LA (or complete trial participation) at Month 12.  If the participant decides not to continue 
participation in the study, any arrangements for off-study ART should be made in advance of the Month 12 visit. 
NOTE: Refer to Section 6.6.1 and Section 6.6.2 for Dosing Considerations for CAB LA + RPV LA and BIK, 
respectively. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
86 
 
 
6.5. 
Packaging and Labelling 
The contents of the label will be in accordance with all applicable regulatory 
requirements. 
6.6. 
Preparation/Handling/Storage/Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study intervention 
are provided in the Study Reference Manual.  
Under normal conditions of handling and administration, study intervention 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. 
IP accountability will be evaluated using pill counts of unused IP for patients receiving 
oral treatment (oral CAB, oral RPV, BIK).  This assessment will be conducted, when the 
participant completes oral CAB and RPV lead-in treatment and BIK in the Maintenance 
Phase, or any withdrawal that occurs during an oral treatment 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. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
8 7  
 
6. 6. 1.  
D o si n g C o n si d er ati o n s f or C A B L A + R P V L A  
Vials of C A B L A a n d R P V L A are eac h s u p plie d as a s us pe nsi o n a n d nee d n o f urt her 
dil uti o n o r rec o nstit uti o n.  Si nce R P V L A re q uires refri gerati o n, sites s h o ul d all o w t he 
vial t o c o me t o a p pr o xi matel y r o o m te m perat ure pri or t o i njecti n g. T h e vials s h o ul d be 
ge ntl y i n vert e d a fe w ti mes t o re -s us pe n d s e di me nts a n d all o w b u b bles t o s u bsi de, a n d 
t he n use a s yri n ge t o wit h dra w t he re q uire d v ol u me of s us pe nsi o n f or I M i njecti o n.   
All i njecti o ns m ust be gi ve n i ntra m usc ularl y i n t h e gl ute us me di us.  Sites ma y use t h eir 
discreti o n as t o w here i n t he gl ute us m uscle eac h i njecti o n is gi ve n acc or di n g t o 
i n divi d ual partici pa nt cir c u msta nce.  If p ossi ble, i njecti o ns s h o ul d be s pace d 
a p pr o xi matel y 2 c m fr o m o ne a n ot her, fr o m t he site of a n y pre vi o us i njecti o n or a n y 
i njecti o n site reacti o n.  T he ti me a n d l ocati o n of i njecti o n will be ca pt ure d i n t he e C R F.   
I M inje cti o ns s h o ul d be a d mi nistere d at a 9 0 -de gree a n gle i nt o t he gl ute us me di us m uscle 
usi n g a n ee dle of a p pr o priate ga u ge a n d le n gt h (I n m ost partici pa nts, a 1. 5” 2 3 -ga u ge 
nee dle f or C A B L A a n d a 1. 5” 2 3 -ga u ge nee dle f or R P V L A is rec o m me n de d).  T he 
nee dle s h o ul d be l o n g e n o u g h t o r eac h t he m us cle mass a n d pre v e nt st u d y dr u g fr o m 
see pi n g i nt o s u bc ut a ne o us tiss ue, b ut n ot s o l o n g as t o i n v ol ve u n derl yi n g n er ves, bl o o d 
vessels, or b o ne.  V aria bl e nee dle l e n gt hs a n d/ or nee dles wit h differe nt ga u ge ( C A B L A: 
2 1 t o 2 5  ga u ge; R P V L A: 2 1 t o 2 3 ga u ge) are per mitte d if nee de d t o acc o m m o date 
i n di vi d ual b o d y t y p es.  L o n ger nee dl e le n gt hs ma y be re q uir e d is rec o m me n de d f or 
partici pa nts base d o n b o d y ha bit us a n d/ or wit h hi g her b o d y mass i n de xes ( B MIs, 
e x a m ple > 3 0), t o e ns ure t hat i njecti o ns are a d mi nistere d i ntra m usc ularl y as o p p ose d t o 
s u bc uta ne o usl y.  B MI, w aist circ u mfere nce, hi p circ u mfere nce, nee dl e ga u ge a n d le n gt h 
use d will be c ollecte d i n t he e C R F.  A d diti o nal details of t he i njecti o n de vice use d b y 
sites f or I M a dmi nistrati o n i ncl u di n g, b ut n ot li mite d t o f u ncti o nal perf or ma nce, ma y als o 
be c ollecte d wit hi n t he e C R F.  
At t he Da y 1 a n d M o nt h 1 visits, partici pa nts tra nsiti o ni n g fr o m BI K a n d t h e oral lea d i n 
of oral C A B + R P V s h o ul d be d ose d wit h t he I M re gi me n wit hi n  2 h o urs of ta ki n g t he 
last oral re gi me n d ose w here p ossi ble.  
S h o ul d I M mala d mi nistrati o n be s us pecte d at a n y ti me (e. g., s us p ecte d u n der or o ver d ose 
or i na d verte nt I V d osi n g),  t he i n vesti gat or m a y c o nsi der re q uesti n g t he partici pa nt sta y 
o nsite f or a p pr o xi matel y 2 -3 h o urs p ost d ose f or s afet y m o nit ori n g a n d n otif yi n g t he 
Me dical M o nit or.  A n E C G or a n y ot her s u p p orti ve testi n g ma y b e o btai ne d at t he 
discreti o n of t he i n vesti gat or.  
 
A d diti o nal d osi n g i nstr ucti o ns a n d c o nsi derati o ns ca n be f o u n d i n t he S P M.  
6. 6. 2.  
D o si n g C o n si d er ati o n s f or BI K  
BI K s h o ul d be t a ke n e x actl y as i nstr uct e d b y t he i n vesti gat or.  It s h o ul d n ot be ta ke n wit h 
ot her HI V -1 me dici nes.  BI K s h o ul d be a d mi nistere d o ne ti me eac h da y wit h or wit h o ut 
f o o d.  T he d ose s h o ul d n ot be c ha n ge d, or a d mi nistrati o n st o p pe d wit h o ut i nf or mi n g t he 
me dical m o nit or.     
C CI
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
88 
 
6.7. 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from 
the investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents.  The dose of study 
intervention 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 
intervention.  If oral study treatment is dosed at site, study site personnel will examine 
each participant’s mouth to ensure that the study intervention was ingested. 
When participants self-administer study intervention(s) at home, compliance with CAB, 
RPV and BIK dosed orally once daily will be assessed by counting returned 
tablets/capsules during the site visits and documented in the source documents and CRF.   
A record of the number of CAB, RPV and BIK tablets dispensed to and taken by each 
participant must be maintained and reconciled with study intervention and compliance 
records. Intervention start and stop dates, including dates for intervention delays and/or 
dose reductions will also be recorded in the CRF. 
6.8. 
Protocol Permitted Substitutions 
6.8.1. 
Oral Bridging 
In exceptional circumstances, to address pre-planned missed CAB LA + RPV LA dosing 
visits, in consultation with and approval by the medical monitor, Investigators may 
provide daily oral CAB 30 mg and RPV 25 mg as a short-term “bridging” strategy for 
participants who have begun CAB LA + RPV LA.  In certain circumstances (e.g., prior to 
steady state dosing and following a >8-week oral bridge) repeating the loading doses of 
CAB IM and RPV IM may be required.  Should a participant require “oral bridging”, 
sites must contact the study Medical Monitor for guidance with treatment and dosing 
strategies prior to a missed CAB LA + RPV LA dose.  
Please refer to Appendix 11in Section 10.11 for study management information during 
the COVID-19 pandemic. 
6.9. 
Interruption of Study Intervention and Visit/Dosing Windows 
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.   


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
89 
 
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/or RPV LA are anticipated to be at 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 
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 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 injection).  The first injections for participants 
who choose to start injections immediately will occur at Day 1.  The first injections for 
participants electing to participate in the oral lead are administered at Month 1 (can be 
performed before lab results become available), and the second injections are given at 
Month 2.   
The participant’s projected visit is determined by their first injection date and, ideally, is 
the same date for every injection. For example, if the1st dose (Month 1) is January 15th, 
then dose 2 (Month 2) will be February 15th, and dose 3 (Month 4) will be April 15th, etc. 
Since the first injection visit (Day 1 or Month 1) will determine the future injection visit 
schedule for participants, planning for the first injection visit date (within allowed visit 
windows) should take into consideration the availability of the participants to adhere to 
future visit windows (planned vacations, business trips, weekends, holidays, etc.). 
Dosing for participants randomized to CAB LA + RPV LA is as follows: 
All injections should be planned as single injections per drug. 
6.9.1.1. 
IM injections every 2 months (Oral Lead In): 
Month 1 – CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 2 - CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 4 and Q2M thereafter - CAB LA 600 mg + RPV LA 900 mg IM, every 2 months 
until Month 12, each given as 1 X 3 mL IM injection 
At Month 1, participants will return to the clinic, take the last dose of their oral (CAB 
30 mg + RPV 25 mg), 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 first injection visit 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
90 
 
with IM CAB LA + RPV LA at Month 1 can be performed before central lab results are 
available and safety parameters are reviewed from the Month 1 visit.   
The second loading injection will be administered at Month 2 (CAB LA 600 mg + RPV 
LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring 
every 2 months thereafter.  A -7-day dosing window for the second injection is allowed.  
Receiving LA dosing from +1 to +7 days is not recommended and the Medical 
Monitor must be contacted before  the second IM injection is given.  Starting at Month 
4 and at subsequent visits, a 7 day dosing window for injections is allowed. If the 
injection is expected to fall outside of the dosing window, the Medical Monitor must be 
contacted to discuss individual participant case management.  
6.9.1.2. 
IM injections every 2 months (Q2M) (Direct to injections): 
Participants electing not to receive the oral lead in and are receiving CAB LA + RPV LA 
Q2M will initiate dosing at the Day 1 visit: 
Day 1- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 1 and Q2M thereafter- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 
X 3 mL IM injection 
The second injection will be administered at Month 1 (CAB LA 600 mg + RPV LA 
900 mg, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) every 2 
months thereafter.  A -7-day dosing window for the second injection is allowed.  
Receiving LA dosing from +1 to +7 days is not recommended and the Medical 
Monitor must be contacted before  the second IM injection is given.  Starting at Month 
3 (third injection) and every 2 months thereafter, a 7-day dosing window for injections 
is allowed. If the injection is expected to fall outside of the dosing window, the Medical 
Monitor must be contacted to discuss individual participant case management. 
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 6.8.1. 
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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
91 
 
6.9.2. 
Oral Dosing 
The Month 1 Visit during the Oral Lead-in Phase for participants randomized to CAB + 
RPV but choosing to participate in the oral lead in is expected to occur 4 weeks (3 days) 
after the Day 1 visit.  Visits for participants on the BIK arm are expected to occur every 
56 days as projected according to the Day 1 visit.  There is a 3-day visit window, from 
the projected visit date (Maintenance Phase 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.  In general, four LTFU visits should occur from the last date of 
LA therapy until week 52 with clinic visits at months 3, 6, 9 and 12, although the timing 
of the actual visits are flexible, but not the frequency, in LTFU. 
6.10. 
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 ViiV/GSK is providing 
specific post-study treatment.  Participants randomized to CAB LA + RPV LA arm, who 
have successfully completed 12 months of treatment will continue to have access to both 
CAB LA and RPV LA in the Extension Phase until study treatment is 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.  Participants randomized to the BIK arm 
who have successfully completed 12 months of treatment will be given the option of 
continuing onto the Extension Phase to receive CAB LA + RPV LA.  If these participants 
choose not to continue, they will end participation in the study after Month 12 will be 
responsible for obtaining post-study treatment. 
6.11. 
Concomitant Therapy 
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 BIK, 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-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
92 
 
Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study (except prohibited medications described in 
Section 6.11.1).  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). 
Hepatitis C infection treatment is allowed throughout the entire study.  If HCV treatment 
occurs during the study, a DHHS approved HCV regimen should be used to limit any 
drug-drug interactions that may occur. Options for treatment of HCV should be discussed 
with the Medical Monitor prior to initiation of therapy. 
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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
93 
 
Drugs that cause Torsade de Pointes (TdP) should be used with caution when taking 
rilpivirine (see SPM for list of drugs associated with TdP). 
BIK:  BIK and calcium-containing supplements can be taken together, without regard to 
food. 
 
BIK should be administered at least 2 hours before iron supplements or taken together 
with food. 
 
BIK should not be taken simultaneously with supplements containing magnesium and/or 
aluminium due to the expected substantial decrease of BIC exposure. 
 
BIK should be administered at least 2 hours before, or with food 2 hours after antacids 
containing magnesium and/or aluminium.  
Metformin concentrations may be increased by BIK.  Refer to the prescribing 
information of metformin for assessing the benefit and risk of concomitant use of BIK 
and metformin.  
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 BIK. 
6.11.1. 
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-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
94 
 
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.   
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. BIK), please consult 
the current BIC 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). 
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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
95 
 
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 BIK 
The following medications or their equivalents may cause decreased concentrations of 
BIC.  Therefore, the following medications must not be administered concurrently with 
BIC: 
• Carbamazepine 
• Oxcarbazepine 
• Phenobarbital 
• Phenytoin 
• Rifampicin / Rifampin 
• Rifabutin 
• Rifapentine  
• St. John’s wort (Hypericum perforatum) 
• Dofetilide is prohibited as BIC may inhibit renal tubular secretion resulting in 
increased dofetilide/pilsicainide concentrations and potential for toxicity. 
Note:  Any prohibited medication that decrease BIC 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 local prescribing information for other drugs that should be 
used with caution, require dose adjustment, or increased clinical monitoring if taken with 
BIK. 
6.12. 
Dose Modification 
No dose reductions, modifications, or changes in the frequency of any components of 
each regimen will be allowed during the study beyond what is allowed within the 
protocol or directly approved by the study Medical Monitor.  Protocol waivers or 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
96 
 
exemptions are not allowed.  Therefore, adherence to the study design requirements is 
essential and required for study conduct. 
In exceptional circumstances, and in consultation with the Medical Monitor, Investigators 
may provide oral CAB and/or RPV as a short-term “bridging” strategy for participants 
who have begun CAB LA + RPV LA (see Section 6.8.1 for additional details).  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. 
Please refer to Appendix 11 in Section 10.11 for study management information during 
the COVID-19 pandemic. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM), which is available on 
the online Study Web Portal.  The SPM will provide the site personnel with 
administrative and detailed technical information. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Participant Discontinuation/Withdrawal from the Study 
Participants permanently discontinuing study treatments prior to the Month 12 visit are 
considered to be withdrawn from the study treatments.  Participants who enter the 
Extension Phase but permanently discontinue participation in the Extension Phase prior 
to commercially available CAB LA + RPV LA are considered to be withdrawn from the 
study treatments but are not considered to be withdrawn from the study because they will 
enter the follow Follow-up Phase. 
A participant may withdraw consent and discontinue participation in this study at any 
time at his/her own request. The investigator may also, at his or her discretion, 
discontinue the participant from participating in this study at any time (e.g., safety, 
behavioral or administrative reasons).  Participants may have a temporary interruption to 
their study treatment for management of toxicities. 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. Withdrawn participants 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.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
97 
 
An in-clinic withdrawal visit will also be used to assess 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.  The withdrawal visit will be distinct from visits conducted during the LTFU 
Phase. 
Following completion of withdrawal assessments, all participants who received one or 
more injections of CAB LA+ RPV LA will subsequently enter the LTFU Phase initiating 
with the Month 3 LTFU visit.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
98 
 
Withdrawal decision coincides with a planned clinic visit:  
• For any participant who withdraws prematurely from the Maintenance or 
Extension Phase during a planned in-clinic study visit, withdrawal assessments 
and procedures are to be performed (according to the SoA (Section 1.3) instead of 
the assessments for the active planned visit during which the withdrawal decision 
is made.   
Withdrawal decision occurs between planned clinic visits: 
• In the event that a decision to withdraw a participant occurs between clinic visits, 
participants will be instructed to return for an unscheduled withdrawal visit 
(within 8 weeks of the last Q2M LA injection received or within 4 weeks if 
participant is randomised to BIK or during the administration of the OLI (oral 
CAB and oral RPV)  if randomized to CAB LA + RPV LA and choosing to 
perform the OLI) during which withdrawal assessments according to the SoA 
(Section 1.3) will be completed.   For participants who received one or more 
injections of CAB LA+ RPV LA withdrawal assessments must occur prior to 
initiation of the next ART regimen.  
If withdrawal coincides with the active planned Month 13 visit, HIV-1 RNA will only be 
assessed if the last HIV-RNA measurement from Month 12 was 50 copies per mL (i.e. 
retest for viral load blip). This will ensure that only the Month 12 viral load assessment or 
required retest will be counted towards the primary and secondary efficacy endpoint 
windows.  
The in-clinic visit will be recorded as an unscheduled withdrawal visit with the following 
exception. A withdrawal visit and assessments coinciding with the planned Month 13 
visit will be recorded as the Month 13 visit such that the participant can be considered a 
completer, consistent with the definition of study completer in Section 4.5. 
Participants may be prematurely discontinued from the study treatment for any of 
the following reasons: 
• Adverse event / Serious adverse event 
• Protocol deviation 
• Intolerability of injections 
• Participant lost to follow-up 
• 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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
99 
 
Participants must be discontinued from study treatment 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. 
• 
Virologic withdrawal criteria as specified in Section 7.1.6 are met; 
• 
Participant requires substitution of ART;  
• 
Participant requires substitution or dose reduction of CAB LA or RPV LA (oral 
bridging supply and potential for a second loading dose may be permissible 
following discussion with the Medical Monitor). 
• 
Liver toxicity where stopping criteria are met and no compelling alternate cause 
is identified (see Section 7.1.2); 
• 
Renal toxicity is met and no compelling alternate cause is identified; 
• 
QT interval (QTc) interval >550 msec from three or more tracings separated by 
at least 5 minutes and considered causally related to IP.   
• 
Grade 4 clinical AE considered causally related to study drug;  
• 
Participant has a Grade 3 or higher rash or Grade 2 rash with evidence of 
systemic involvement and no compelling alternative cause is identified 
• 
Pregnancy (intrauterine), regardless of termination status of pregnancy (for 
participants on BIK only)Participant withdrew consent 
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. 
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. 
The following actions must be taken in relation to a participant who fails to attend the 
clinic for a required study visit: 
a. 
The site must attempt to contact the participant and re-schedule the missed visit 
as soon as possible.  
b. 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.  
c. 
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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
100 
 
last known mailing address or local equivalent methods). These contact attempts 
should be documented in the participant’s medical record.  
d. 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”.  
A participant may withdraw from study treatment at any time at his/her own request or 
may be withdrawn at any time at the discretion of the investigator for 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. 
7.1.1. 
Liver monitoring event – Increased monitoring  
A liver monitoring event is an occurrence of predefined liver chemistry changes that 
triggers increased monitoring of the participant’s liver chemistries, but no action is taken 
with study treatment unless liver chemistry stopping criteria are met. 
Liver monitoring event criteria:  
• Baseline ALT ≤1.5x ULN: ALT ≥5x ULN and <8xULN and bilirubin <2xULN 
without symptoms believed to be related to liver injury or hypersensitivity. 
• Baseline ALT >1.5x ULN: ALT ≥3x baseline and <5x baseline and bilirubin 
<2xULN without symptoms believed to be related to liver injury or 
hypersensitivity 
Actions: 
• Notify the VH medical monitor within 24 hours of learning of the abnormality to 
discuss participant safety.  
• Participant can continue study intervention   
• Participant must return every 2 weeks for repeat liver chemistries (ALT, AST, 
alkaline phosphatase, bilirubin) until resolution or stabilisation (ALT <5×ULN 
on 2 consecutive evaluations) 
• If at any time participant meets the liver chemistry stopping criteria, proceed as 
described below  
7.1.2. 
Liver chemistry stopping criteria 
Study treatment or Investigational Product must stop immediately when participant meets 
one of the criteria described in Table below: 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
101 
 
Table 3 
Liver Chemistry Stopping Criteria - Liver Stopping Event for phase 
III - IV studies 
Liver Chemistry Stopping Criteria - Liver Stopping Event 
If Baseline ALT ≤ 1.5x ULN 
ALT-absolute ALT  8xULN 
ALT Increase 
ALT  5xULN but <8xULN persists for 2 weeks (with bilirubin <2xULN and no 
signs or symptoms of acute hepatitis or hypersensitivity) 
Bilirubin1, 2 
ALT  3xULN and bilirubin  2xULN (>35% direct bilirubin)  
Cannot 
Monitor 
ALT  5xULN but <8xULN and cannot be monitored every 1 - 2 weeks 
Symptomatic3 ALT  3xULN with symptoms (new or worsening) believed to be related to liver 
injury or hypersensitivity 
If Baseline ALT > 1.5x ULN 
ALT-absolute 
ALT ≥ 5x baseline OR > 500 U/L (whichever occurs first) 
ALT Increase 
ALT ≥ 3x baseline but <5x baseline persists for ≥2 weeks (with bilirubin <2xULN 
and no signs or symptoms of acute hepatitis or hypersensitivity) 
Bilirubin1, 2 
ALT ≥ 3x baseline OR > 300 U/L (whichever occurs first) and bilirubin ≥ 2xULN 
Cannot 
Monitor 
ALT ≥ 3x baseline but <5x baseline and cannot be monitored every 1 - 2 weeks 
Symptomatic3 
ALT ≥ 3x baseline and symptoms (new or worsening) believed to be related to 
liver injury or hypersensitivity. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT 3xULN and bilirubin 
2xULN.Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable 
urinary bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
2. 
All events of ALT >3xULN and bilirubin >2xULN (>35% direct bilirubin) must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); INR measurement is not required, and the threshold value stated will 
not apply to participants receiving anticoagulants. 
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia). 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
102 
 
7.1.2.1. 
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 criteria is met, do the following: 
• Immediately hold IP.  If on 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. 
• Complete the liver event eCRF and SAE eCRF, where applicable. 
• 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: 
• 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 (N-acetyl-para-aminophenol [APAP] adduct test).  The 
site must contact GSK when this test is required.  Please refer to the central 
laboratory manual. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
103 
 
• Blood sample for pharmacokinetic (PK) analysis, obtained during follow up 
assessments.  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 CRF 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. 
7.1.3. 
General Guidance on Restart 
• The definition of 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 7.1.2), 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.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
104 
 
• 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. 
7.1.3.1. 
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 
Study drug must be held while labs and evaluation are completed to assess diagnosis. 
7.1.3.1.1. 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 
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 ULN).    
• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• If restart / redosing of drug 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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
105 
 
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. 
7.1.4. 
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. RPV and RPV LA should not be 
administered to patients who are receiving a drug known to be associated with TdP. 
When performing ECGs, 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.   
7.1.5. 
Virologic Failure 
Only plasma HIV-1 RNA values determined by the central laboratory will be used to 
assess virologic failure. 
7.1.6. 
Definition of Protocol-Defined Confirmed Virologic Failure 
For the purposes of clinical management in this study, CVF is defined as:  
Rebound as indicated by two consecutive plasma HIV-1 RNA levels 200 c/mL (Day 1 
values are not applicable) after prior suppression to <200 c/mL.  
7.1.7. 
Managing Virologic Failure 
Following study entry, no changes, or intensification of ART will be permitted prior to 
protocol-defined virologic failure, outside of the planned protocol regimens.  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 study 
Day 1.  The definition of confirmed virologic failure does not apply to participants in the 
LTFU Phase.  These participants will be followed for the emergence of viral resistance.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
106 
 
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). Upon notification that a participant’s HIV-1 
RNA plasma level qualifies him/her as a suspected virologic failure, the Investigator 
should query the participant regarding intercurrent illness, recent immunization, or 
interruption of oral therapy. 
7.1.7.1. 
HIV-1 RNA Blips 
HIV-1 RNA “blips” are not usually associated with subsequent virologic failure [DHHS, 
2019].  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 the key analysis 
timepoints (Month 6 and 12 [OLI and BIK] and Months 5 and 11 [D2]) must return to the 
clinic as soon as possible (but no later than 4 weeks after the date of the Months 6 or 12 
[OLI and BIK] and Months 5 or 11 [D2I] visits, respectively) 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 / 
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. 
7.1.7.2. 
Suspected Virologic Failure 
Upon notification that a participant’s HIV-1 RNA plasma level meets the definition of 
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 within 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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
107 
 
• 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. 
7.1.7.3. 
Confirmed Virologic Failure 
Participants with confirmed virologic failure (CVF) must be discontinued from study 
treatment.  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 LTFU Phase. 
A plasma sample from the suspected virologic failure visit as well as Day 1 (if baseline 
HIV-1 RNA level 200 c/mL) 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. 
For all participants who meet CVF, baseline and suspected virologic failure plasma 
samples with HIV-1 RNA level 200 c/mL will be analyzed in an attempt to obtain 
genotype/phenotype data on as many samples as possible.  Plasma samples for storage 
will also be obtained at unscheduled visits including confirmation of CVF.  Participants 
may continue to receive study drug at the discretion of the investigator until results of 
resistance testing are available at which time the participant must be discontinued from 
the study. Even if genotype/phenotype data cannot be generated, participant must also be 
discontinued from the study treatment. 
If a participant is prematurely discontinued from the study treatment, the investigator 
must make every effort to perform the Withdrawal Visit evaluations outlined in the Time 
and Events These data will be recorded as they comprise essential evaluations needed to 
be done before discharging any participant from the study. 
7.2. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
108 
 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and 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. 
• Before a 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, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
8. 
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 SoA, 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 SoA, Section 1.3 
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. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 0 9  
 
8. 1.  
Effi c a c y A s s e s s m e nt s  
8. 1. 1.  
Pl a s m a HI V -1 R N A  
Plas ma f or q ua ntitati ve HI V -1 R N A will be c ollecte d acc or di n g t o t he S o A  ( Secti o n 1. 3 ).  
Met h o ds t o be use d ma y i ncl u de b ut are n ot li mite d t o t he A b b ott Real Ti me HI V-1 Ass a y 
l o wer li mit of detecti o n ( L L O D) 4 0 c/ m L. 
8. 1. 2.  
L y m p h o c yt e S u b s et s, C D 4 + a n d C D 8 +  
L y m p h oc yte s u bs ets will be c ollecte d f or ass ess me nt b y fl o w c yt o metr y (t otal 
l y m p h oc yte c o u nts, perce nta ge a n d a bs ol ute C D 4 + a n d  C D 8 + l y m p h oc yte c o u nts, rati os) 
acc or di n g t o S o A  ( Secti o n 1. 3 ) a n d La b orat or y Assess me nts ( Secti o n 8. 2. 2 ). 
8. 1. 3.  
C D C HI V -1 Cl a s sifi c ati o n a n d HI V A s s o ci at e d C o n diti o n s  
HI V -ass o ciate d c o n diti o ns will be rec or de d as per t he S o A ( Secti o n 1. 3 ).  HI V-ass o ciate d 
c o n diti o ns will be assesse d acc or di n g t o t he 2 0 1 4 C D C Re vise d Classificati o n S yst e m f or 
HI V I nfecti o n (see Secti o n 1 0. 3 ).  W he n assessi n g C D C sta ge at Scree ni n g/ Baseli ne, 
c o nsi der o nl y t he latest a vaila ble C D 4 T -cell c o u nt, e xce pt w he n t he partici pa nt ha d a n 
acti ve Sta ge 3 e v e nt 6 m o nt hs pri or t o Scree ni n g. I n dicat ors of c li nical disease 
pr o gressi o n are defi n e d as:  
C D C Sta ge 1 at e nr ol me nt → Sta ge 3 e v e nt;  
C D C Sta ge 2 at e nr ol me nt → Sta ge 3 e v e nt;  
C D C Sta ge 3 at e nr ol me nt → Ne w Sta ge 3 E ve nt;  
C D C Sta ge 1, 2 or 3 at e nr ol me nt → Deat h.  
8. 2.  
S af et y A s s e s s m e nt s  
8. 2. 1.  
Cli ni c al E v al u ati o n s  
T he f oll o wi n g cli nical e v al uati o ns will be perf or m e d acc or di n g t o t he Ti me a n d E ve nts 
sc he d ule: 
•  M o nit ori n g a n d rec or di n g of all A Es a n d S A Es.  A d diti o nal i nf or mati o n o n t he 
Ti me Peri o d a n d Fre q ue n c y of Detecti n g A Es a n d S A Es is pr o vi de d i n Secti o n 
1. 3 . 
•  P h ysical e x a ms s h o ul d be c o n d ucte d as part of n or mal r o uti ne cli nical care.  
A b n or malities n ote d d uri n g a n y e x a m m ust be rec or de d i n t he e C R F (e. g., i n t he 
c urre nt me di cal c o n diti o ns or A E l o gs).  
•  Hei g ht, w ei g ht, waist a n d hi p circ u mfere nce assess me nts will be meas ure d per t he 
S o A , Secti o n 1. 3 .  Rec o m m e n de d pr oce d ures t o meas ure wei g ht, waist a n d hi p 
circ u mfere nce ca n be f o u n d i n Secti o n 1 0. 1 0 . A p pr o priate wei g ht r elate d 
meas ure me nts t o ca pt ure are wei g ht, b o d y fat %, t otal b o d y water %, m uscl e 
mass, a n d b o ne mi neral mass . 
C CI
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
110 
 
• Vital signs will include systolic and diastolic blood pressure and heart rate 
collected after resting for about 5 minutes.  Temperature will also be collected. 
• 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 5 minutes of rest.  On Day 1 (Baseline) of the Maintenance Phase, ECGs 
should be performed in triplicate prior to first dose.  An ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals is preferred (and RR if calculated manually), 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.  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. 
• Regular monitoring of hematology, blood chemistry, urinalysis and fasting 
glucose and lipids (parameters to be tested listed below).   
• Periodic assessment of glucose, insulin, and bone, cardiovascular, and renal 
markers; 
• Pregnancy testing.  A negative urine pregnancy test is required prior to initiation 
of IP, any 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 
SoA (Section 1.3). 
• Evaluation and documentation of all concomitant medications and blood products.  
• Injection Site Reactions (ISRs) will be assessed clinically during the Maintenance 
and Extension Phases 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 
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 
SoA (see Section 1.3 and Suicidal Risk Monitoring Section 8.2.6). 
Any appropriately qualified site personnel (e.g., Investigator, sub-Investigator, or study 
coordinator/nurse) can perform assessments. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
111 
 
8.2.2. 
Laboratory Assessments 
All protocol required laboratory assessments, as defined in the SoA (see Section 1.3), 
must be performed by the central laboratory.  Laboratory assessments must be conducted 
in accordance with the Central Laboratory Manual and Protocol SoA.  Laboratory 
requisition forms must be completed, and samples must be clearly labeled with the 
participant number, protocol number, site/center 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. 
• The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
Section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
• All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or medical monitor.  
• If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
• All protocol-required laboratory assessments must be conducted in accordance 
with the laboratory manual and the protocol Time and Events table.  
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 10.4 “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. 
Table 4 includes lab parameters to be assessed as per the SoA (see Section 1.3).  In 
addition to the protocol-specified laboratory assessments the study Medical Monitor, in 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 1 2  
 
c olla b orati o n wit h t he site i n vesti gat or, ma y re q u est a d diti o nal ce ntral la b orat or y 
assess me nts be perf or me d t o s u p p ort safet y pr ofili n g a n d case m a na ge m e nt of i n di vi d ual 
st u d y partici p a nts.  
 
T a bl e 4  
S af et y L a b or at or y A s s e s s m e nt s  
H e m at ol o g y  
Pl at el et c o u nt  
Aut o m at e d W B C diff er e nti al:  
R B C c o u nt  
N e utr o p hils  
W B C c o u nt ( a bs ol ut e)  
Ly m p h ocyt es  
H e m o gl o bi n  
M o n ocyt es  
H e m at ocrit  
Eosi n o p hils  
M C V  
Bas o p hils  
Cli ni c al C h e mi stry  
B U N  
P ot assi u m  
A S T  
T ot al bilir u bi n a 
Cr e ati ni n e  
C hl ori d e  
AL T  
Al b u mi n  
Gl uc os e c 
T ot al C O 2 
Alk ali n e p h os p h at as e  
Cr e ati n e p h os p h oki n as e  
S o di u m  
Li p as e  
Ph os p h at e  
Cr e ati ni n e cl e ar a nc e b 
F a sti n g Li pi d P a n el d 
T ot al c h ol est er ol  
H D L c h ol est er ol 
L D L c h ol est er ol  
Tri glyc eri d es  
Ot h er T e st s  
Pl as m a HI V -1 R N A e  
C D 4 + a n d C D 8 + c ell c o u nts [ C D 4/ C D 8 r ati o] f 
P eri p h er al Bl o o d M o n o n ucl e ar C ells ( P B M Cs):  D ay 1, M o nt h 1 2, Wit h dr a w al o nly  
H e p atitis B ( H Bs A g), a nti -H Bc, a nti -H Bs A g, a n d h e p atitis  C a nti b o dy ( Scr e e ni n g ) g 
Sy p hilis s er ol o gy + R efl ex R a pi d Pl as m a R e a gi n ( R P R) ( Scr e e ni n g a n d B as eli n e)  
Pr ot hr o m bi n Ti m e ( P T)/I nt er n ati o n al N or m aliz e d R ati o (I N R)/ P arti al T hr o m b o pl asti n Ti m e ( P T T)  
Pr e g n a ncy t est f or w o m e n of c hil d b e ari n g p ot e nti al h 
Uri n alysis, uri n e al b u mi n/cr e ati ni n e r ati o, a n d uri n e pr ot ei n/cr e ati ni n e r ati o, uri n e p h os p h at e  
G e n etics S a m pl e  
F ollicl e sti m ul ati n g h or m o n e ( F S H) a n d estr a di ol ( o nly f or i nst a nc es w h e n p ost m e n o p a us al st at us is q u esti o n a bl e)  
R e n al bi o m ark ers i ncl u di n g Cyst ati n -C ( bl o o d), R eti n ol Bi n di n g Pr ot ei n ( R B P, bl o o d/ uri n e); a n d B et a -2 -Micr o gl o b uli n 
( B 2 M, bl o o d/ uri n e)i 
B o n e bi o m ark ers i ncl u di n g: B o n e -s p ecific alk ali n e p h os p h at as e, pr oc oll a g e n ty p e 1 N -pr o p e pti d e, ty p e 1 c oll a g e n 
cr oss-li nk e d C-t el o p e pti d e, ost e ocalci n, 2 5 hy dr oxy -Vit a mi n D i 
 
H b A 1c, I ns uli n, H O M A -I R 
M C V = m e a n c or p usc ul ar v ol u m e, R B C = r e d bl o o d c ells, W B C = w hit e bl o o d c ells, B U N = Bl o o d ur e a nitr o g e n, 
A S T = as p art at e a mi n o tr a nsf er as e, A L T = al a ni n e a mi n otr a nsf er as e, C O 2 = c ar b o n di oxi d e, H D L = hi g h d e nsity 
li p o pr ot ei n, L D L = l o w d e nsity li p o pr ot ei n, H Bs Ag = h e p atitis B vir us s urf ac e a nti g e n, P T/I N R = pr ot hr o m bi n 
ti m e/i nt er n ati o n al n or m aliz e d r ati o. 
a)  Dir ect bilir u bi n will b e r efl exiv ely p erf or m e d f or all t ot al bilir u bi n v al u es > 1. 5  ×  U L N.  
b)  Gl o m er ul ar filtr ati o n r at e ( G F R) will b e esti m at e d by t h e c e ntr al l a b or at ory usi n g t h e C hr o nic Ki d n ey Dis e as e 
E pi d e mi ol o gy C oll a b or ati o n ( C K D -E PI) [ L ev ey , 2 0 0 9]. 
c) 
F or f asti n g gl uc os e ass ess m e nts, a n ov er ni g ht f ast is pr ef err e d; h o w ev er, a mi ni m u m of a 6 -h o ur f ast is 
acc e pt a bl e f or p artici p a nts wit h aft er n o o n a p p oi nt m e nts.  
d)  F or f asti n g li pi ds ass ess m e nts, a n ov er ni g ht f ast is pr ef err e d; h o w ev er, a mi ni m u m of a 6 -h o ur f ast is acc e pt a bl e 
f or p artici p a nts wit h aft er n o o n a p p oi nt m e nts. 
e)  F or p artici p a nts m e eti n g vir ol o gic wit h dr a w al crit eri a, pl as m a s a m pl es will b e a n alyz e d i n att e m pt t o o bt ai n 
g e n oty p e/ p h e n oty p e d at a.  
f) 
C D 8 + c ells will o nly b e r e p ort e d at B as eli n e, D ay 1, M o nt hs 1, 6, a n d 1 2.  
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
113 
 
g) HBV DNA will only be performed for participants with a positive anti-HBc and negative HBsAg and negative anti-
HBs (past and/or current evidence). 
h) Urine pregnancy test/ serum pregnancy test will be performed according to the SoA (Section 1.3).   
i) 
The intention is to utilize these biomarker data for research purposes; the sponsor will not be reporting real-time 
results of these assessments to the investigator, except for Cystatin C (Day 1 only) and 25 hydroxy-Vitamin D. 
 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.3. 
Physical Examinations 
Physical exams should be conducted as part of normal routine clinical care.  
Abnormalities noted during any exam must be recorded in the eCRF (e.g., in the current 
medical conditions or AE logs). 
• 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 SoA in 
Section 1.3 above.  
• 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 8.3.11.6 for additional information. 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
8.2.4. 
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 pulse rate.  These will be recorded 
as per the SoA, in Section 1.3. 
8.2.5. 
Electrocardiograms 
A 12-lead ECG will be performed in a semi-supine position.  On Day 1, (Baseline), 
ECGs should be performed in triplicate prior to first dose.  At Day 1, Month 1 (OLI) and 
Month 12 (OLI)/Month 11 (D2I) of the Maintenance Phase, a 2-hour post dose ECG will 
be performed for participants receiving CAB LA + RPV LA with an allowable window 
of  30 minutes.  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.  Refer to the SoA for 
collection timepoints (Section 1.3).  Refer to Section 7.1.4  for [QTc] withdrawal criteria 
and additional [QTc] readings that may be necessary. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
114 
 
8.2.6. 
Suicidal Ideation and Behaviour 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 patients being treated with INIs.  
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. 
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 behavioural 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 patient completed questionnaire specified in the SoA (Section 1.3).  
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 possible risks for suicide 
related events. 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Section 10.2. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative). 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 1 5  
 
T he i n vesti gat or a n d a n y q ualifie d desi g nees  are res p o nsi ble f or detecti n g, d oc u me nti n g, 
a n d re p orti n g e v e nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble f or 
f oll o wi n g u p A Es t hat are seri o us, c o nsi dere d relate d t o t he st u d y i nter ve nti o n or t he 
st u d y, or t hat c a use d t he partici pant t o disc o nti n ue t he st u d y i nter ve nti o n a n d/ or st u d y 
(see Secti o n 7 ).  
Please refer t o A p p e n di x 1 1  i n Secti o n 1 0. 1 1  f or st u d y ma na ge me nt i nf or m ati o n d uri n g 
t he C O VI D-1 9 p a n de mic.  
8. 3. 1.  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n 
•  A n y S A Es ass esse d as relate d t o st u d y partici pati o n (e. g., pr ot oc ol -ma n date d 
pr oce d ures, i n vasi ve tests, or c ha n ge i n e xisti n g t hera p y) or rel ate d t o a G S K 
pr o d uct will be rec or de d fr o m t he ti me a partici p a nt c o nse nts t o partici pate i n t he 
st u d y u p t o a n d i ncl u di n g a n y f oll o w-u p c o ntact.  
•  All S A Es will be rec or de d a n d r e p ort e d t o t he s p o ns or or desi g nee i m me di atel y 
a n d u n der n o circ u msta n ce s h o ul d t his e x cee d 2 4 h o urs. T he i n vesti gat or will 
s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs of it bei n g a vaila ble.  
•  A Es will be c ollecte d fr o m t he start of St u d y Trea t me nt u ntil t he fi nal f oll o w-u p 
c o ntact, at t he ti me p oi nts s pecifie d i n t he S o A  ( Secti o n 1. 3 ). 
•  Me dical occ urre n ces t hat be gi n pri or t o t he start of s t u d y treat me nt b ut after 
o btai ni n g i nf or me d c o nse nt ma y be rec or de d o n t h e Me dical Hist or y/ C urre nt 
Me dical C o n diti o ns S ecti o n of t he e C R F.  
•  T he met h o d of rec or di n g, e val uati n g a n d ass essi n g ca usalit y of A Es a n d S A Es 
pl us pr oce d ures f or c o m pleti n g a n d tr a ns m itti n g S A E re p orts t o G S K are pr o vi de d 
i n Secti o n 1 0. 2 .  
•  I n v esti gat ors are n ot o bli gat e d t o acti vel y see k A Es or S A Es i n f or mer st u d y 
partici pa nts. H o we v er, if t he i n vesti gat or l ear ns of a n y S A E, i n cl u di n g a d eat h, at 
a n y ti me after a partici p a nt has bee n disc har ge d fr o m t he st u d y, a n d he/s h e 
c o nsi ders t he e v e nt reas o na bl y relate d t o t he st u d y treat me nt or st u d y 
partici pati o n, t he i n vesti gat or m ust pr o m ptl y n otif y G S K.  
8. 3. 2.  
M et h o d of D et e cti n g A E s a n d S A E s  
T he met h o d of rec or di n g, e val uati n g, a n d ass essi n g ca usalit y of A Es a n d S A Es a n d t he 
pr oce d ures f or c o m pleti n g a n d tr a ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 . 
Care will be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A E a n d/ or S A E. O pe n -e n de d a n d 
n o n -lea di n g ver bal q uesti o ni n g of t he p artici pa nt is t he preferre d m et h o d t o i n q uire a b o ut 
A E  occ urre nce. A p pr o pri ate q uesti o ns i ncl u de:  
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.


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
116 
 
8.3.3. 
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 will be followed until the event is resolved, stabilized, otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.2). Further information on follow-
up procedures is given in Section 10.2. 
8.3.4. 
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 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 5. 
Criteria for liver chemistry stopping and follow-up criteria are in Section 7.1.1. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
117 
 
Table 5 
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 reporteda  
“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 
reporteda 
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” and SAE if 
required 
Seizure or suspected 
seizure 
24 hours 
eCRF 
24 hours 
eCRF 
Suspected ABC HSR in 
participants receiving 
Oral SOC during the 
Long-Term Follow-Up 
Phaseb 
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 hoursc 
“SAE” data 
collection tool. 
“Liver Event eCRF” 
and “Liver Imaging” 
and/or “Liver 
Biopsy” eCRFs, if 
applicabled 
24 hours 
Updated “SAE” data 
collection tool/“Liver 
Event” documentsd 
ALT≥5×ULN that 
persists ≥2 weeks  
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
ALT ≥8×ULN  
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
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 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
a. 
Additional details and time frames for reporting supplementary information for cardiovascular and death events 
are provided in Section 8.3.9. 
b. 
ABC HSR eCRF only required if event meets one of the ICH E2A definitions of seriousness. 
c. 
GSK must be contacted at onset of liver chemistry elevations to discuss participant safety. 
d. 
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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
118 
 
8.3.5. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met.  
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, 
if appropriate according to local requirements. 
8.3.6. 
Pregnancy 
8.3.6.1. 
Pregnancy testing 
Women of childbearing potential must have a negative pregnancy test at Screening, and 
at Baseline (Day 1).  Pregnancy testing will also be conducted as per the SoA (Section 
1.3) and at any time during the trial when pregnancy is suspected. 
Additionally, the Medical Monitor may request that a urine pregnancy test be performed 
in the event of a treatment interruption greater than 7 days. 
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 6 for details. The above is applicable to participants randomised to CAB+RPV 
and not to participants on BIK. 
Pregnant participants who remain in the study do not need pregnancy testing during the 
study, for the duration of their pregnancy. 
8.3.6.2. 
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 6. 
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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
119 
 
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 
8.3.6.3. 
Time Period for Collecting Pregnancy Information 
Pregnancy information will be collected from Day 1 until the last follow-up assessment.  
This includes the entirety of the LTFU Phase. 
Pregnant study participants who consent to remain in the study during pregnant will 
continue to have all clinical assessments (with the exception of pregnancy tests) 
performed as per the Schedule of Activities  (Section 1.3), including the collection of 
additional PK samples for CAB and RPV. See Appendix 6 for details. 
 
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. 
8.3.6.4. 
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 6. 
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.  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
120 
 
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 6) and at the time of 
delivery.    
 
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/index.htm. 
8.3.7. 
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 10.3) can be serious/life threatening and will be recorded on 
the HIV-Associated Conditions eCRF page if they occur. 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. If any of the conditions below is met, then record the event on either the AE 
or SAE page (according to severity) in addition to the HIV Associated Conditions eCRF 
page.  If it is categorized as an SAE, report promptly (i.e., expedited reporting), see 
Section 8.3.4, to GSK   
• The investigator determines that the event or outcome qualifies as an SAE under 
part ‘other situations’ of the SAE definition (see Section 10.2.2), or 
• The event 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. 
. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
121 
 
8.3.8. 
Medical Device Deficiencies  
The vial adaptor, syringe, and needles used in the study are classed as medical devices by 
the 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 Section 10.9.  
Instructions for medical device use are provided in the Study Reference Manual. 
All device deficiencies, (including malfunction, use error and inadequate labelling) shall 
be documented, and reported by the investigator to the manufacturer of the device (if 
known) 
NOTE: The medical devices supplied for the trial will not be supplied or manufactured 
by GSK/ViiV, reports of medical device deficiencies should be reported to the device 
manufacturer (if known) through the manufacturers’ complaints process.  
8.3.8.1. 
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 manufacturer of the device (if known) within 24 hours. 
 
8.3.8.2. 
Follow-up of Medical Device Deficiencies 
• Follow-up applies to all participants including those participants who discontinue 
study intervention 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. 
8.3.8.3. 
Prompt Reporting of Medical Device Deficiencies to Manufacturer 
• Device deficiencies will be reported to the manufacturer of the device (if known) 
within 24 hours after the investigator determines that the event meets the protocol 
definition of a device deficiency. 
8.3.8.4. 
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, to the manufacturer of the device (if known). In order 
for the manufacturer to fulfil the legal responsibility to notify appropriate regulatory 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
122 
 
authorities and other entities about certain safety information relating to medical devices 
being used in clinical studies. 
8.3.9. 
Cardiovascular and Death Events 
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 
• 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. 
For any cardiovascular events detailed above, whether or not they are considered SAEs, 
and all deaths, specific Cardiovascular (CV) and Death Sections of the eCRF will be 
required to be completed.  These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death.  
The CV CRFs are presented as queries in response to reporting of certain CV MedDRA 
terms.  The CV information should be recorded in the specific cardiovascular section of 
the eCRF within one week of receipt of a CV Event data query prompting its completion. 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
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. 
8.3.10. 
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 10.4. 
“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 8.3 and Section 10.2. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
123 
 
8.3.10.1. 
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 ART medication is held due to toxicity or AEs, all ART 
medications should be held to reduce the risk of development of resistance taking into 
account the length of the planned interruptions and the PK half-life of each ART of the 
regimen, in order 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 first injection visit).  An additional (+ or -) 7-day window, from the 
projected visit date, is allowable 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 
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 during the Long-Term Follow-Up (LTFU) Phase, in the event of a 
discontinuation of ABC for any reason, re-initiation 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 but is not required to confirm study eligibility. 
8.3.10.2. 
Grade 1 or Grade 2 Toxicity/Adverse Event 
Participants who develop a Grade 1 or Grade 2 AE or toxicity may continue study drug at 
the discretion of the investigator.  Participants who choose to withdraw from the 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 + RPV LA 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
124 
 
8.3.10.3. 
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 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 LTFU 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 
evidence that the toxicity is not related to IP, with the exception of liver chemistry 
stopping criteria (See Section 8.3.11.1).  Isolated Grade 3 lipid abnormalities do 
not require withdrawal of IP. 
8.3.10.4. 
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 LTFU 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 8.3.11.1).  An in-clinic follow-up 
visit will be performed approximately 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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
125 
 
8.3.11. 
Specific Toxicities/Adverse Event Management 
General guidelines for the management of specific toxicities that are considered to be 
associated with treatment of HIV patients.  
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 8.3.3. 
8.3.11.1. 
Liver Chemistry Stopping and Follow-up Criteria 
Liver chemistry threshold stopping criteria have been designed to assure participant 
safety and to evaluate liver event etiology during administration of study drug and the 
follow-up phase.  
8.3.11.2. 
Seizures 
A small number of seizure cases have been reported following CAB administration (less 
than 1% of all those receiving CAB in clinical studies).   
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 confounders 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, 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 seizure page. 
8.3.11.3. 
Decline in Renal Function 
Participants who experience an increase in serum creatinine from Baseline of 
45 micromoles/liter (Mol/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 study medical 
monitor to discuss additional follow-up and medical management. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
126 
 
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 study 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.   


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
127 
 
8.3.11.3.1. Proximal Renal Tubule Dysfunctions (PRTD) 
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 Study 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. 
8.3.11.4. 
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 2-4 weeks. If confirmed, then consideration should be given to 
additional evaluation after consultation with the study medical monitor. Additional 
evaluation may include a 24-hour 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 study medical monitor should be contacted immediately. Agreement on 
further management should be agreed between the investigator and medical monitor. 
8.3.11.5. 
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., 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
128 
 
participant receiving drug known to cause prolonged QT or TdP), then IP may be 
restarted after consultation with, and agreement by, the Medical Monitor. 
8.3.11.6. 
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 persists 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. 
8.3.11.7. 
Allergic Reaction 
Participants may continue study drug 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 study drug should permanently discontinue the CAB LA + RPV 
LA regimen and the participant should be withdrawn from the study.  Participants should 
be treated as clinically appropriate and followed until resolution of the AE. 
8.3.11.8. 
Abacavir Hypersensitivity Reaction (ABC HSR) 
If a study participant discontinues study IP, enters into the LTFU period and are 
administered an ABC-containing product, please follow the information contained within 
this section.   
Background  
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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
129 
 
management are included in the Local Country Prescribing Information for EPZICOM.  
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 patients, 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., ZIAGEN, EPZICOM/KIVEXA, TRIZIVIR, or 
TRIUMEQ) if a HSR cannot be ruled out on clinical grounds, due to the potential for a 
severe or even fatal reaction. 
8.3.11.8.1. Essential Patient 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., ZIAGEN, 
EPZICOM, KIVEXA, TRIZIVIR, or TRIUMEQ) 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 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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
130 
 
before restarting 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 
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.  
8.3.11.8.2. Reporting of Hypersensitivity Reactions 
If a clinically suspected case of HSR to ABC meets one of the International Conference 
on Harmonization (ICH E2A), 1994 definitions of seriousness listed in Section 10.2.2 
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. 
8.3.11.9. 
Rash Without ABC HSR Symptoms 
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. 
CAB is an analogue of DTG and 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 
IB [GlaxoSmithKline Document Number  RPS-CLIN-004375, 2021]. 
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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
131 
 
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. 
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 10.4). 
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 Follow-Up Phase 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 
The Month 1b visit for participants in the Oral Lead-in Phase, 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 LTFU Phase for 52 
weeks of follow-up. 
8.4. 
Treatment of Overdose 
For participants receiving oral study intervention, any tablet intake exceeding the total 
daily dose 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 2-3 hours post 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
132 
 
dose for safety monitoring and an ECG will be performed at 2 hours post dose.  The 
Medical Monitor will be notified in the event of a suspected maladministration.  
In the event of suspected maladministration, additional PK samples will be drawn at 
2 hours post dosing for evaluation of CAB and RPV concentrations. 
For participants randomized to BIK, in the case of an overdose, the participant should go 
to the nearest hospital emergency room immediately. 
For the purposes of this study, an overdose is not an AE (refer to Section 10.2.1) 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 10.2.2). 
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 ViiV Healthcare 
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 the IP can no longer be detected 
systemically (at least 5 days for oral CAB, oral RPV and BIK, and 52 weeks for 
CAB LA and RPV LA 
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 CRF. 
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. 
8.5. 
Pharmacokinetics 
Plasma samples will be collected throughout the Maintenance, Extension and LTFU 
Phases of the study and stored for potential determination of CAB and RPV 
concentrations. Samples (blood and plasma) for potential determination of RPV 
concentrations will be protected from light at all times, from sampling collection through 
analysis. 
8.5.1. 
Rationale of PK Sampling Strategy 
Blood sampling for CAB and RPV concentrations will be performed during the 
Maintenance Phase of the study for potential evaluation of PK in HIV infected 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
133 
 
participants.  The PK visits and sampling scheme at each visit detailed in Section 1.3 is 
based on known PK profiles to support interim and final PK analyses planned in this 
study. 
8.5.2. 
PK Sample Collection 
Blood samples for storage of CAB (2 mL each) and RPV (2 mL each) plasma PK 
concentrations will be collected from all participants as described in Table 6. Assay 
results for stored samples may be requested on an ad hoc bases for various reasons 
including cases of suspected virologic failure or AEs.  Although expected to be minimal, 
any plasma concentrations that are generated will be listed by individual participant 
number. 
 
For participants transitioning from oral CAB + RPV at Month 1 and Month 14 (BIK to 
CAB LA+ RPV LA in Extension Phase), PK samples should be collected within the 
window of 20-28 hours after the last administered oral dose of CAB + RPV was taken the 
day prior to the clinic visit. Participants will take their final dose of oral CAB + RPV in 
the clinic after the pre-dose PK sample.    
For CAB + RPV participants, on the clinic day where PK is collected, the date and time 
of dosing administration and the actual date and time of the PK samples, must be 
recorded on the eCRF.   
Pregnant participants will have additional PK samples collected during the duration of the 
pregnancy. See Appendix 6 for details. 
 
Table 6 
CAB and RPV Plasma Pharmacokinetic Sample Schedule 
Group 
Analytes 
PK Sample Times Relative to Dose 
Participants receiving 
CAB LA + RPV LA 
Q2M injections 
CAB and RPV 
Maintenance Phase Pre-Dose: (OLI participants) 
Months 1, 2, 4, 6, 8, 10, and 12; (D2I participants) 
Months 1, 3, 5, 7, 9, and 11 
Extension Phase Pre-Dose: (BIK to OLI participants) 
Month 14, 15; (BIK to D2I) participants Month 14 
• A PK sample will be taken at Withdrawal. 
• PK samples for storage only. 
• Long-term follow-up Period (off-drug; 
storage sample): Months 3, 6, 9, and 12. 
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.  Pre-dose sample collection at Month 1 (for participants transitioning from oral 
therapy) should be collected 20 to 28 hours after the last oral dose of CAB and RPV was 
taken the day prior to the clinic visit. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 3 4  
 
If a partici pa nt wit h dra ws fr o m t he st u d y, a P K sa m ple s h o ul d be c ollecte d as earl y as 
practicall y p ossi ble  (i.e., at wit h dra wal visit or o n t he da y t he wit h dra wal d ecisi o n was 
ma de).   
A d diti o nal details c o ncer ni n g ha n dli n g of P K sa m ples, la beli n g a n d s hi p pi n g directi o ns 
will be s u p plie d i n t he S R M . 
Sa m ples f or deter mi nati o n of R P V will be pr otecte d fr o m li g ht t hr o u g h o ut ha n dli n g.  
8. 5. 3.  
S a m pl e A n al y si s  
8. 5. 3. 1.  
C A B S a m pl e A n al y si s  
If ele cte d or re q uire d, plas ma C A B bi o a nal ysis will be perf or m e d u n der t h e c o ntr ol of 
I V/I V T BI B, Gla x o S mit h Kli ne, t he details of w hi c h will be i ncl u de d i n t he St u d y 
Refere n ce M a n ual ( S R M).   C o nce ntrati o ns of C A B will be deter m i ne d i n plas ma sa m ples 
usi n g t he c urre ntl y a p pr o ve d bi oa nal ytical met h o d ol o g y.   Ra w data will be arc hi ve d at 
t he bi oa nal yti cal site ( det aile d i n t he S R M).  N o h u ma n D N A a n al ysis will be perf or me d 
o n t hese sa m ples.  
8. 5. 3. 2.  
R P V S a m pl e A n al y si s  
If ele cte d or re q uire d, p las ma R P V bi o a nal ysis will be perf or m e d u n der t h e c o ntr ol of 
J a nsse n R & D. C o nce ntrati o ns of R P V will be deter mi ne d i n plas ma sa m ples usi n g t he 
c urre ntl y a p pr o ve d bi oa n al ytical met h o d ol o g y.  R a w data will be arc hi ve d at t he 
bi oa nal ytical site .  N o h u ma n D N A a n al ysis will b e perf or me d o n t hese s a m ples.  
8. 7.  
G e n eti c s  
See  Secti o n 1 0. 7  f or I nf or mati o n re gar di n g ge neti c researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt a n d destr ucti o n of t hes e sa m ples ca n be f o u n d i n S P M . 
8. 8.  
Vir al G e n ot y pi n g a n d P h e n ot y pi n g  
W h ole ve n o us  bl o o d sa m ples will be o btai ne d fr o m eac h partici pa nt t o pr o vi de P B M Cs 
a n d plas ma f or st or a ge sa m ples acc or di n g t o t he S o A  (see Secti o n 1. 3 ) f or p ote ntial viral 
ge n ot y pic a n d p he n ot y pi c a nal yses.  
Details c o ncer ni n g t he ha n dli n g, la belli n g a n d s hi p pi n g of t hes e sa m ples will be s u p plie d 
se parat el y. Ge n ot y pic a n d p he n ot y pic a nal yses m a y b e carrie d o ut b y M o n o gra m 
Bi oscie nces usi n g, b ut n ot li mite d t o, t heir Sta n dar d P he n o Se nse a n d Ge n o S ure testi n g 
met h o ds f or pr oteas e ( P R O), re v erse tr a nscri p tas e ( R T), a n d i nte gras e assa ys. 
C CI


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 3 5  
 
8. 8. 1.  
HI V -1 P ol y m er a s e Vir al G e n ot y pi n g a n d P h e n ot y pi n g  
Partici pa nts meeti n g c o nfir me d vir ol o gic fail ure will ha ve plas ma sa m ples teste d f or 
HI V -1 P R O a n d R T ge n ot y pe a n d p he n ot y pe a n d HI V -1 i nte grase ge n ot y p e a n d 
p he n ot y p e fr o m sa m ples c ollecte d at t he ti me of m eeti n g s us p ecte d vir ol o gi c fail ure; 
t hese res ults will be re p orte d t o t he i n vesti gat or as s o o n as a vaila ble t o pr o vi de g ui da nce 
f or ele cti o n of a n alter nati ve re gi me n. 
8. 9.  
I m m u n o g e ni cit y A s s e s s m e nt s  
N ot a p plica ble f or t his st u d y.  
8. 1 0.  
M e di c al R e s o ur c e Utili z ati o n a n d H e alt h E c o n o mi c s  
N ot a p plica ble f or t his st u d y.  
8. 1 1.  
V al u e E vi d e n c e a n d O ut c o m e s  
Healt h o utc o mes assess m e nts will be c o n d ucte d acc or di n g t o t he S o A  ( Secti o n 1. 3 ).  
Assess me nts are rec o m m e n de d t o be a d mi nistere d wit h a pa per i nstr u me nt at t he 
be gi n ni n g of t he visit pri or t o c ollecti o n of bl o o d f or a nal ysis a n d ot her sc h e d ule d 
assess me nts.  
T he “ Prefere nce” q uesti o n naire will assess w het her patie nts prefer t h e C A B L A + R P V 
L A i nje cta ble treat me nt or t he dail y oral A R V re gi me n , als o e v al uati n g t he attri b utes 
s u p p orti n g t his prefere n ce.  T he “ Prefere nce” q u esti o n naire will i ncl u de 3 q uesti o ns 
e val uati n g prefere nce of HI V treat me nt a n d t he attri b utes s u p p orti n g t his pr efere nce.  
T he HI V Treat me nt Satisfacti o n Q uesti o n nair e ( HI V T S Q) [W o o dc oc k , 2 0 0 1,W o o dc oc k , 
2 0 0 6] was de vel o pe d t o e val uate treat me nts f or HI V a n d patie nt satisfacti o n.  T he ori gi nal 
HI V T S Q i ncl u de d 1 0 ite ms a n d u n der we nt t w o st a ges of ps yc h o m etric vali dati o n 
[W o o dc oc k , 2 0 0 1, W o o dc oc k , 2 0 0 6]. Rece ntl y, t he HI V T S Q was a da pt e d t o i ncl u de 
i njecta ble treat me nt f or HI V f oll o wi n g a q ualitati ve st u d y wit h HI V patie nts i n fi ve 
E ur o pea n c o u ntries.  T he a da ptati o n of t he HI V T S Q i ncl u de d t w o a d diti o nal ite ms 
relate d t o t he m o de of a d mi nistrati o n (i.e., l o n g acti n g i ntra m usc ular i njecti o n).  T hese 
are:  
C CI


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 3 6  
 
•  Ite m 1 1.  H o w eas y or diffic ult ha ve y o u b ee n fi n di n g y o ur treat me nt t o be 
rece ntl y?  
•  Ite m 1 2.  H o w satisfie d are y o u wit h t he a m o u nt of disc o mf ort or pai n i n v ol ve d 
wit h y o ur prese nt f or m of treat me nt?  
Ps yc h o metric a nal yses fr o m t hree datas ets ( o ne fr o m t he U K, o ne fr o m t he U S A a n d o ne 
fr o m t he L A T T E-2 trial) re veal t hat t he a d diti o n of t w o ite ms i n t he ori gi nal versi o n of 
t he HI V T S Q is s uita ble a n d d oes n ot re d uce t he o verall vali dit y of t he q uesti o n naire.  T he 
c urre nt st u d y will be usi n g t he HI V T S Qs (stat us v ersi o n) a n d t he HI V T S Qc (c ha n ge 
versi o n) of t his rece ntl y de vel o pe d HI V T S Q 1 2 -it em q uesti o n naire. T he HI V T S Q 1 2 -
ite m q uesti o n naire retai ns t he o pti o n of calc ulati n g t he t otal sc ore as if it o nl y ha d t he 
ori gi nal 1 0 ite ms (as t h e ori gi nal 1 0 ite ms are i ncl u de d i n t he HI V -T S Q 1 2). I n a d diti o n, it 
all o ws f or cal c ulati o n of a n 1 1 -ite m scale s c ore i n cl u di n g t he “eas y/ diffi c ult” ite m (ite m-
1 1). T he “ p ai n/ disc o mf ort” ite m (ite m -1 2) will be i ncl u de d i n t he q uesti o n naire as a 
sta n d-al o ne ite m t o e val u ate p ote ntiall y p ai nf ul i njecta bles. T h ese meas ures will assess 
c ha n ge i n treat me nt satisfacti o n o ver ti me (i n t he sa me partici pa nts) a n d c o m pare 
treat me nt satisfacti o n bet wee n treat me nt gr o u ps. 
T he Perce pti o n of I njecti o n ( PI N ) q uesti o n nair e e x pl ores t he b ot her of pai n at t he 
i njecti o n site a n d I S R, a n xiet y bef ore a n d aft er i nj ecti o n, willi n g ness t o recei ve a n HI V 
i njecta ble treat me nt t he f oll o wi n g visit a n d satisfacti o n wit h t he m o de of tr eat me nt 
a d mi nistrati o n of i n di vi d uals recei vi n g i njecti o n a n d perce pti o ns of i n di vi d uals ass ociate d 
wit h recei vi n g i njecti o ns.  T he PI N q uesti o n naire was deri ve d fr o m t he Vacci nes' 
Perce pti o n of I nje cti o n ( V A PI) q uesti o n naire [C he vat , 2 0 0 9], a n d a da pte d f or HI V-
i nfecte d patie nts w h o will recei ve t h e C A B L A a n d R P V L A re gi me n. T his meas ure 
c o ntai ns 2 1 ite ms t hat meas ure pai n at i njecti o n site, l ocal site reacti o ns, i m pact o n 
f u ncti o ni n g a n d willi n g n ess t o p urs ue i njecta ble tr eat me nt o utsi de of a cli nical trial.  
Sc ores ra n ge fr o m 1 t o 5, a n d q uesti o ns are p hrase d i n s uc h  a wa y as t o e ns ure t hat 1 
al wa ys e q uat e d wit h t he m ost fa v o ura ble perce pti o n of vacci n ati o n, a n d 5 t he m ost 
u nfa v o ura bl e.  
 
We will c o n d uct ( o pti o nal) q ualitati ve i nter vie ws wit h S O L A R I n vesti gat ors/ S u b -
I n v esti gat ors a n d/or site staff  t o e val uat e t he reas o ns f or i n vesti gat ors i n t he trial t o use, 
or n ot t o use, t he oral lea d -i n p hase bef ore starti n g ca b ote gra vir i njecti o ns. T he s pecific 
ai m of t he pr o p ose d st u d y is t o de vel o p a better u n dersta n di n g fr o m i n vesti gat ors of t he 
fact ors t hat ha v e dri ve n a n d ma y c o nti n ue t o dri ve L A A R T decisi o ns re gar di n g usi n g 
O LI vers us  D TI. T hes e w o ul d be c o n d ucte d u n der a se p arat e I R B a p pr o ve d c o nse nt  
C CI


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 3 7  
 
( w here necessar y). I n vesti gat ors’ p artici pati o n i n t he i nter vie ws w o ul d be v ol u ntar y a n d 
res ults are a n o n y m o us a n d re p orte d i n a n a g gre gat e d f or mat. 
8. 1 1. 1.  
V al u e E vi d e n c e a n d O ut c o m e s E n d p oi nt s ( S e c o n d ar y) 
All P R Os will be perf or me d at t he s pecifi e d ti me p oi nts as liste d i n t he S o A  i n Secti o n 
1. 3 . 
•  T he “ Prefere nce” q uesti o n naire will assess prefere nce f or C A B L A + R P V L A 
e ver y 2 m o nt hs c o m pare d t o a n oral BI C si n gle ta blet re gi me n as well as reas o ns 
f or prefere nce. 
•  C ha n ge fr o m M o nt h 2 i n Di me nsi o n sc ores (e. g., “ B ot her of I S Rs”, “ Le g 
m o ve me nt”, “ Slee p ”, a n d “ Acce pta nce  of I S Rs ”) a n d i n di vi d ual ite m sc ores 
assessi n g p ai n d uri n g i njecti o n, a n xiet y bef ore a n d after i njecti o n, willi n g ness t o 
be i njecte d i n t he f ut ur e a n d o verall satisfacti o n wit h m o de of a d mi nistrati o n o ver 
ti me usi n g t he Perce pti o n of i njecti o n q uesti o n nair e ( PI N).  
•  Pr o p orti o n of partici pa nts c o nsi deri n g pai n a n d l o cal reacti o ns f oll o wi n g i njecti o n 
t o be e xtre mel y or ver y acce pta bl e base d o n t he acce pta bilit y sc ore o v er ti me 
usi n g t he Perce pti o n of i njecti o n q uesti o n naire ( PI N).  
•  C ha n ge fr o m Baseli ne ( Da y 1) i n t ota l “treat me nt satisfacti o n” sc ore, a n d 
i n di vi d ual ite m sc ores of t he HI V T S Qs. 
•  C ha n ge i n treat me nt satisfacti o n o ver ti me a n d i n di vi d ual ite m sc ores ( usi n g t he 
HI V T S Qc) . 
8. 1 2.  
Bi o m ar k er s  
Bl o o d a n d uri ne are b ei n g c ollecte d t o perf or m r e nal a n d b o ne bi o mar ker assess me nts. I n 
a d diti o n t o meas ure me nts of ser u m cre ati ni ne, esti mate d G F R, a n d uri n ar y e x creti o n of 
al b u mi n, pr otei n, creati ni ne a n d p h os p hate, a d diti o nal re nal bi o mar k ers i ncl u de:  
Re nal bi o mar kers : 
•  C ystati n C ( bl o o d),  
•  Reti n ol Bi n di n g Pr otei n ( R B P, bl o o d/ uri ne)  
•  Beta -2 -Micr o gl o b uli n ( B 2 M, bl o o d/ uri ne).  
C CI


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 3 8  
 
B o ne  bi o mar kers : 
•  B o ne -s p ecific al kali ne p h os p hatase 
•  Pr oc olla ge n t y p e 1 N -pr o pe pti de  
•  T y pe 1 c olla ge n cr oss -li n ke d C-tel o pe pti de 
•  Oste ocalci n  
•  2 5 h y dr o x y -Vita mi n D  
I ns uli n, H b A 1 c, a n d H O M A-I R 
Si nce t he i nte nti o n is t o utilize t hese bi o mar kers f or researc h p ur p oses a n d t he cli nical 
si g nifica n ce of t h ese res ults is u ncertai n, t he S p o ns or will n ot be re p orti n g real ti me 
res ults of t hese ass ess me nts t o t he i n vesti gat or e x ce pt f or Cystati n C a n d 2 5 h y dr o x y -
vita mi n D , I ns uli n, H b A 1c a n d H O M A-I R as per Ta ble 4 . 
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
St ati sti c al H y p ot h e s e s  
T he st u d y is t o de m o nstr ate t he n o n -i nf eri or a nti viral acti vit y of C A B L A + R P V L A 
e ver y 2  m o nt hs  c o m pare d t o a BI K si n gle ta bl et r e gi me n a d mi nistere d o nce dail y o v er 1 2  
m o nt h s i n s u p presse d HI V-1 i nfect e d a ntiretr o viral t hera p y ( A R T) -e x perie n ce d 
partici pa nts.  
N o n -i nferi orit y ca n be c o ncl u de d if t he u p per li mit of a t w o-si de d 9 5 % c o nfi de nce 
i nter val f or t he differe nce i n pr o p orti o n of partici pa nts wit h HI V-1 R N A ≥ 5 0 c/ m L at 
M o nt h 1 2  bet wee n t he t w o treat me nt ar ms ( C A B L A + R P V L A –  BI K) is l ess t ha n 4 %.   
Let p c, pb be t he pr o p orti o n of partici pa nts wit h HI V -1 R N A  ≥ 5 0 c/ m L i n t he C A B 
L A + R P V L A a n d BI K ar ms res pecti vel y, t he n t he pri mar y statistical h y p ot h esis ca n be 
writte n as f oll o ws:  
H 0:  pc - p b ≥ 4 % vs. H 1: pc - p b < 4 %  
C CI
C CI
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
139 
 
9.2. 
Sample Size Considerations 
9.2.1. 
Sample Size Determination 
Sample size was determined based on desired study power. A total of 654 enrolled 
participants will be randomized in a 2:1 ratio to receive either CAB LA + RPV LA or 
BIK treatment. Assuming the true proportion of participants with HIV-RNA ≥ 50 c/mL is 
2% for CAB LA+RPV LA injectable regimen and 1% for the BIK arm, a non-inferiority 
margin of 4% and a 2.5% one-sided significance level, the study will provide 
approximately 85% power to demonstrate non-inferiority of CAB LA+RPV LA to BIK 
in term of proportions participants with HIV-1 RNA ≥ 50 c/mL at Month 12 (per FDA’s 
snapshot algorithm for assessing HIV-1 RNA ≥ 50 c/mL).  Details of this calculation 
along with a couple of another sample size scenarios were provided in Table 7. 
Note: "Enrolled" means a participant's, or their legally acceptable representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process. Potential participants who are screened for the purpose of determining eligibility 
for the study, but do not participate in the study, are not considered enrolled, unless 
otherwise specified by the protocol. 
Assuming a possible 15% of screen failure, a total of ~770 would need to be recruited to 
achieve ~654 participants to be enrolled and randomized. 
Table 7 
Sample Size and Power Scenarios 
Assumptions 
Sample Size 
Power* to reject H0 at α=2.5% 
pc 
pb 
NI Margin 
CAB LA+RPV LA 
BIK 
2% 
1% 
4% 
390 
195 
80% 
2% 
1% 
4% 
436 
218 
85% 
2% 
1% 
4% 
509 
255 
90% 
* Power was calculated using PASS 2019 Non-inferiority Tests for the Difference Between Two Proportions with 
Miettinen & Nurminen Likelihood Score Test Statistics. 
 
9.2.2. 
Sample Size Assumptions 
9.2.2.1. 
Rational for non-inferiority margin 
According to the FDA’s 2015 guidance document (Human Immunodeficiency Virus-1 
Infection: Development of ART Drugs for Treatment, November 2015), the margin for 
switch trials is driven by the largest clinically tolerable virologic failure rate. Per the FDA 
document, typical rates of virologic failure seen in switch studies range from 1% to 3% 
and a margin of 4% for virologic failure rate is considered tolerable [CDER, 2015].   
9.2.2.2. 
Proportion of participants with HIV-1 RNA ≥ 50 c/mL assumptions 
It was assumed 1% and 2% for the proportion of participants with HIV-1 RNA ≥ 50 c/mL 
in BIK and CAB LA + RPV LA respectively. These assumptions were based on the 
following historical data. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
140 
 
Table 8 
Observed Proportion of Participants with HIV-1 RNA ≥ 50 c/mL 
Study 
Treatment Arm 
Month 12 Proportion of 
participant with HIV-1 RNA ≥ 
50 c/mL 
ATLAS-2Ma 
CAB LA+RPV LA 
9/522 (1.7%) 
GS-US-380-1844b 
B/FTC/TAF 
3/282 (1.1%) 
GS-US-380-1878c 
B/FTC/TAF 
5/290 (1.7%) 
a. 
GSK/ViiV Study 207966 Study Week 48 Clinical Study Report [GlaxoSmithKline Document Number 
2019N406358_00, 2019] 
b. 
Molina, 2018.  
c. 
Daar, 2018.  
 
9.2.3. 
Sample Size Sensitivity 
Figure 5 shows sensitivity of the required sample size to the true failure rate for the BIK 
arm assuming 2% failure rate in the CAB LA + RPV LA arm and a 4% non-inferiority 
margin.  
Figure 5 
Power and Sample Size Sensitivity to BIK Failure Rate 
 
9.3. 
Populations for Analyses 
The following populations are defined: 
9.3.1. 
Intent-to-Treat Exposed (ITT-E) Population 
This population will consist of all randomized participants who receive at least one dose 
of study medication. Participants will be assessed according to their randomized 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
141 
 
treatment, regardless of the treatment they receive. Unless stated otherwise, the ITT-E 
Population will be used for efficacy analyses. 
9.3.2. 
Per-Protocol 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. 
9.3.3. 
Safety Population 
The Safety Population will consist of all randomly assigned participants who receive at 
least one dose of study drug. Participants will be assessed according to actual treatment 
received. Unless otherwise stated, the Safety Population will be used for safety analyses. 
9.3.4. 
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. 
9.4. 
Statistical Analyses 
The statistical analysis plan will be finalized prior to database freeze and it will include a 
more technical and detailed description of the statistical analyses described in this 
section. This section is a summary of the planned statistical analyses of the most 
important endpoints including primary and key secondary endpoints. 
The study design is open label.  However, the central ViiV/GSK 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 Month 6 interim analysis. 
9.4.1. 
Primary Analyses 
For the primary efficacy analysis, the difference between the two randomized arms for 
the proportion of participants with HIV-1 RNA ≥50 c/mL at Month 12 (OLI and 
BIK)/Month 11 (D2I) (according to FDA snapshot algorithm) and its confidence interval 
will be calculated and be adjusted to the study stratifications using Cochran-Mantel 
Haenszel (CMH) weights. All CIs will be two-sided. For this analysis, four strata will be 
formed according to the combinations of levels of the study stratification factors: 
- 
Gender at birth: female 
- 
Gender at birth: male 
- 
BMI: <30 kg/m2 
- 
BMI: 30 kg/m2 
 
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: 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
142 
 
If nk is the number of CAB LA + RPV LA treated participants, mk is the number of BIK 
treated participants, and Nk = nk + mk is the total number of participants in the kth 
stratum, then the CMH estimate is given by 
 


=
k
k
k
cmh
W
d
W
d
ˆ
ˆ
 
where 
 
k
k
k
k
N
m
n
W
=
 
are CMH weights and 
 k
dˆ
 are estimates of the differences in response rates between the 
two treatment arms, pc-pb, for the kth stratum. The corresponding two-sided 95% CI will 
be calculated as: 
 
using the variance estimator 
 
)
ˆ
r(
aˆ
v
cmh
d
, 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 statistical analysis plan. 
Female participants randomized to CAB + RPV LA who become pregnant while in the 
study are allowed to continue. Female participants randomized to BIK will not be 
allowed to continue. For the FDA snapshot algorithm-related efficacy analysis at key 
time points (Month 5/6 and Month 11/12), viral load data after confirmed pregnancy may 
be “censored”, to minimize bias between the treatment and the comparator arm. Further 
sensitivity analysis may be performed as necessary. Data handling details will be 
provided in the Reporting Analysis Plan. 
9.4.2. 
Safety and Secondary Analyses 
The proportion of participants with plasma HIV-1 RNA <50 c/mL using the Snapshot 
algorithm is a key outcome at Months 6 and 12 (OLI and BIK)/Months 5 and 11 (D2I) 
and will be judged against a pre-specified non-inferiority margin of -12%. 
Changes from baseline in CD4+ lymphocyte count and in CD4+/CD8+ lymphocyte 
counts ratio and resistance data will be summarized. The incidence of HIV-1 disease 
progression (AIDS and death) will be presented. 
The proportion of participants with plasma HIV-1 RNA <50 c/mL using the Snapshot 
algorithm and changes from baseline in CD4+ lymphocyte count will be summarized by 
subgroups (e.g., age, gender and race) 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 4 3  
 
T he o bser ve d cas e dataset will be t he pri mar y dataset use d f or a n al ysis of safet y 
e n d p oi nt s. 
E x p os ure t o st u d y me di cati o n, meas ure d b y t he n u m ber of wee ks o n st u d y dr u g, will be 
s u m marize d b y treat me nt gr o u p. T h e pr o p orti o n of partici pa nt s re p orti n g A Es will be 
ta b ulate d f or eac h tr eat m e nt gr o u p. T he f oll o wi n g s u m maries of A Es will be pr o vi de d: 
•  I n ci de nce a n d se v erit y of all A Es  
•  I n ci de nce a n d se v erit y of treat me nt relat e d A Es 
•  I n ci de nce a n d se v erit y of A Es lea di n g t o wit h dra wal 
•  I n ci de nce of S A Es 
 
La b orat or y a n d vital si g ns data will be s u m marize d b y visit a n d treat me nt gr o u p. I n 
a d diti o n, t he n u m ber a n d perce nt a ge of p artici pa nt s wit h gra d e d la b orat or y t o xicities 
( base d o n D AI D S cat e g ories) will be s u m marize d b y treat me nt gr o u p. T he pr o p orti o n of 
partici pa nt s e x perie nci n g c ha n ges fr o m Baseli ne i n t heir Nati o nal C h olester ol E d ucati o n 
Pr o gra m ( N C E P) li pi d cate g ori es will be s u m mari ze d b y treat me nt ar m. F urt her details of 
safet y a n al ys es will be i ncl u de d i n t he R A P. 
9. 4. 3.  
H e alt h O ut c o m e A n al y s e s  
T he Prefere n ce, PI N, HI V T S Qs a n d HI V T S Qc, 
 
 will be s u m marize d as detaile d i n Secti o n 8. 1 1 . Details of t he 
a nal ys es  t o be perf or me d will be s pecifie d i n t he R A P. 
9. 4. 4.  
Vir al G e n ot y pi n g/ P h e n ot y pi n g A n al y s e s  
T he i nci de nce of o bser ve d ge n ot y pic a n d p he n ot y pic resista nce t o st u d y A R T will be 
s u m marize d b y treat me nt ar m f or partici pa nt s meeti n g c o nfir m e d vir ol o gi c wit h dra wal 
criteria. D etails of t he a n al yses t o b e perf or me d will be s pecifie d i n t he R A P.  
9. 4. 5.  
P h ar m a c o ki n eti c A n al y si s  
Plas ma C A B a n d R P V c o nce ntrati o n data will be liste d a n d s u m marize d  b y wee k, da y 
a n d pla n ne d sa m pli n g ti me i n b ot h ta b ular a n d gra p hical f or ms. P K para m eters will be 
s u m marize d as well if a v aila ble. 
9. 5.  
I nt eri m A n al y s e s 
T he mai n a nal ysis will be c o n d ucte d t o e val uate t he pri mar y o bjecti ve of t he pr ot oc ol 
w he n all partici pa nts  h a v e c o m plete d t heir M o nt h 1 2 ( O LI a n d BI K)/ M o nt h 1 1 ( D 2I) 
visit. A n i nteri m a nal ysis will be c o n d ucte d w h e n all partici pa nts ha ve c o m plete d t heir 
M o nt h 6 ( O LI a n d BI K)/ M o nt h 5 ( D 2I) visit. T o mi ni mise bias, t he M o nt h 6 i nteri m 
res ults will n ot be s hare d wit h a n y p artici pa nt a n d wit h m ost i n vesti gat ors. H o we ver, 
w he n a le a d a ut h or(s) f or a p ote ntial a bstract prese ntati o n of t he M o nt h 6  i nteri m res ults 
C CI
C CI
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
144 
 
is (are) identified, that investigator(s) and the other co-authors on the abstract will have 
access to the interim results prior to its presentation. No other investigators will have 
knowledge of this data prior to the last participant completing their last visit for the 
primary Month 12 analysis. A Month 6 interim analysis abstract may be submitted to a 
conference for consideration only if the conference convenes after the Month 12 data 
collection has been completed.  
The interim analyses will include analyses on the primary and secondary efficacy 
endpoints, as well as key safety endpoints. Full details of the interim analyses will be 
specified in the Reporting and Analysis Plan (RAP). 
Further data cuts and analyses may be conducted as necessary to support regulatory 
submissions, publications or for other purposes. Additionally, information collected on 
pregnant participants as collected in the eCRF may be reported descriptively or listed on 
an interim basis (see Appendix 6 for further details).  No adjustment for multiplicity 
caused by repeated analysis on the primary endpoint will be made as the interim analysis 
will be secondary.  Type I error rate will not be inflated for the treatment comparison at 
the final analysis as non-inferiority will not be assessed at the interim. 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
145 
 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
Prior to initiation of a site, ViiV/GSK will obtain favorable opinion/approval from the 
appropriate regulatory agency to conduct the study in accordance with International 
Conference on Harmonisation (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. 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences (CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC by the investigator 
and reviewed and approved by the IRB/IEC before the study is initiated.  
Any amendments to the protocol will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants.  
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as required 
by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
146 
 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorized representative and answer all 
questions regarding the study.  
• 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study.  
• 
A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative.  
Participants who are rescreened are required to sign a new ICFGSK (alone or working 
with others) may use participant’s coded study data and samples and other information to 
carry out this study; understand the results of this study; learn more about the study 
intervention or about the study disease; publish the results of these research efforts; work 
with government agencies or insurers to have the study intervention approved for medical 
use or approved for payment coverage.  
The ICF may contain a separate section that addresses the use of participant data and 
remaining samples for optional further research. Where approved by the IRB/IEC, the 
investigator or authorised designee will inform each participant of the possibility of 
further research. Participants will be told that they are free to refuse to participate and 
may withdraw their consent at any time and for any reason during the storage period. A 
separate tick box may be required to document a participant's agreement to allow any 
participant data and/or remaining leftover samples to be used for further research. 
Participants who decline further research will tick the corresponding “No” box. 
10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred.  
The participant must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure must 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
147 
 
also be explained to the participant who will be required to give consent for their data to 
be used as described in the informed consent.  
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities 
10.1.5. 
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. 
10.1.6. 
Dissemination of Clinical Study Data 
• Study information from this protocol will be posted on publicly available clinical 
trial registers before enrolment of participants begins. 
• 
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. 
• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
Publication Policy 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
148 
 
• 
The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.  
• 
The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements. 
10.1.7. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF.  
• 
Guidance on completion of the CRF will be provided in  
• 
Quality tolerance limits (QTLs) will be pre-defined in the (location) to identify 
systematic issues that can impact participant safety and/or reliability of study 
results.  These pre-defined parameters will be monitored during and at the end of 
the study and all deviations from the QTLs and remedial actions taken will be 
summarized in the clinical study report. 
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan and contracts. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
149 
 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor.  
10.1.8. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the CRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
• 
Definition of what constitutes source data can be found in Monitoring plan and 
contract. 
10.1.9. 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform 
the Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
150 
 
by the applicable regulatory requirements. The Investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up 
10.1.10. 
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 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. 
10.1.11. 
Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials Registers and 
Publication 
• Study information from this protocol will be posted on publicly available 
clinical trial registers before enrolment of participants begins. 
• 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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
151 
 
• 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. 
• A manuscript will be progressed for publication in the scientific literature if 
the results provide important scientific or medical knowledge. 
Publication Policy 
• 
The results of this study may be published or presented at scientific meetings. 
If this is foreseen, the investigator agrees to submit all manuscripts or 
abstracts to the sponsor before submission. This allows the sponsor to protect 
proprietary information and to provide comments.  
• 
The sponsor will comply with the requirements for publication of study 
results. In accordance with standard editorial and ethical practice, the sponsor 
will generally support publication of multicenter studies only in their entirety 
and not as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
152 
 
10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.2.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
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 study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
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 intervention administration 
even though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses 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. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfill the definition 
of an AE or SAE.  
 
Events NOT Meeting the AE Definition  
• 
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 participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
153 
 
of the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
• 
Situations in which 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. 
 
10.2.2. 
Definition of SAE 
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). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
o Results in death 
o Is life-threatening 
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. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 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 outpatient setting. Complications that occur during 
hospitalization are AE. 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. 
Results in persistent or significant disability/incapacity 
• 
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 with 
or prevent everyday life functions but do not constitute a substantial disruption. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
154 
 
Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 
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 events 
should usually be considered serious. 
• 
Examples of such events include 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. 
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 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. 
 
10.2.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF 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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
155 
 
10.2.4. 
Recording and Follow-Up of AE and SAE 
AE 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) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
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 case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records 
before submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
• 
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. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 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 causes sufficient discomfort and interferes with normal 
everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is 
assessed as severe should not be confused with an SAE. Severe is a category 
utilized for rating the intensity of an event; and both AE and SAE can be 
assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
156 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/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 underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in 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 in which 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 before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as medically indicated or as 
requested by GSK to elucidate the nature and/or causality of the AE or SAE as 
fully as possible. 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 CRF. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
157 
 
10.2.5. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and 
verification of the relationship of each SAE to IP/study participation (causality) 
within 72 hours of SAE entry into the eCRF. 
• 
After the study is completed at a given site, the electronic data collection tool 
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, then the site can report this information on a paper 
SAE form (see next section) or to the medical monitor/SAE coordinator by 
telephone. 
• 
Contacts for SAE reporting can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page. 
 
SAE Reporting to GSK via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the medical monitor or the SAE coordinator. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found at this beginning of the protocol on the 
Sponsor/Medical Monitor Contact Information page. 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
158 
 
10.3. 
Appendix 3:  CDC Classification for HIV-1 Infection (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/L, 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/L, 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/L, 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/L 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 
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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
159 
 
• 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. 
Reference 
CDC. Revised Surveillance Case Definition for HIV Infection – United States, 2014. 
MMWR 2014; 63 (RR-03);1-10. 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
160 
 
10.4. 
Appendix 4: Division of AIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events Version 2.1, March 
2017 
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. 
10.4.1. 
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. 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
161 
 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
162 
 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
163 
 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
164 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
165 
 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
166 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
167 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
168 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
169 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
170 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
171 
 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
172 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
173 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
174 
 
 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
175 
 
 
 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
176 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
177 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
178 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
179 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
180 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
181 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
182 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
183 
 
 
 
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 
2.1. [March 2017]. Available from: 
https://rsc.tech-res.com/docs/default-source/safety/daids-ae-grading-table-mar2017.pdf 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
184 
 
10.5. 
Appendix 5: Contraceptive Guidance 
10.5.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the 
participant’s medical records, medical examination, or medical history interview. 
3. 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, confirmation with 
more than one FSH measurement is required.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen 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. 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
185 
 
10.5.2. 
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 9 
Table 9 
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 
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.  
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
186 
 
10.6. 
Appendix 6:  Information and Guidance for Managing 
Pregnant Participants 
10.6.1. 
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 8.3.4.  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. 
• 
WOCBP should only be included after a confirmed menstrual period and a 
negative highly sensitive serum pregnancy test  
• 
Additional pregnancy testing should be performed as per the study Time and 
Events Table. Pregnant participants who remain in the study do not need 
pregnancy testing during the study, for the duration of their pregnancy. 
• 
Pregnancy testing will be performed whenever a menstrual cycle is missed or 
when pregnancy is otherwise suspected  
• 
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.  
10.6.2. 
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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
187 
 
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 
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 WHO 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 
213500 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.  
10.6.3. 
Background 
At the time of finalizing this protocol, there have been 25 pregnancies reported during the 
CAB/RPV LA P3 development program (including 6 during PK tail and 5 during OLI) 
with 8 pregnancies leading to live births (including 3 pregnancies exposed during the PK 
tail of treatment and 1 pregnancy exposure occurring during CAB oral lead-in) and 5 on-
going pregnancies. 
• 
A total of 12 pregnancy losses (11 of these occurring during the first trimester) 
• 
Missed abortions: 2 (one of these was a twin anembryonic pregnancy) 
• 
Elective abortions (no medical indication): 5 
• 
Elective abortion for nausea and vomiting: 1 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
188 
 
• 
Spontaneous abortions: 4 (1 late spontaneous abortion at 23/40; severe 
Intrauterine growth restriction [IUGR], placental insufficiency; presence of risk 
factors) 
No reported congenital anomalies 
10.6.4. 
Benefit/Risk Assessment 
Discuss with the 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] at 1-800-258-4263. 
10.6.4.1. 
Cabotegravir 
Cabotegravir use in pregnant females 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. 
Animal Data (pre-clinical)  
Cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1000 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 1000 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 
2000 mg/kg/day from Gestation Days 7 to 19. No drug-related fetal toxicities were 
observed at 2000 mg/kg/day (approximately 0.7 times the exposure in humans at the 
RHD). 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
189 
 
In a rat pre- and postnatal development study, cabotegravir was administered orally to 
pregnant rats at 0, 0.5, 5, or 1000 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 1000 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 (1000 mg/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 NTDs with exposure to CAB 
+ RPV LA during pregnancy, NTDs were associated with dolutegravir, another integrase 
inhibitor. A preliminary analysis of an ongoing birth outcome surveillance study in 
Botswana involving women exposed to DTG, a different molecule in the same integrase 
class of medications as CAB, identified 4 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 woman who started DTG 
during pregnancy had a neural tube defect, out of 2824 women.  More recently, data from 
the Tsepamo study was updated.  In April 2020, the Tsepamo study team provided 
interim data from the study, which included available data through to 29 February 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 6 NTDs in 4569 (0.13%) 
deliveries in mothers taking non-DTG regimens at conception, of which 5 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%).  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
190 
 
A causal relationship of these events to the use of DTG has not been established.  
The incidence of NTDs in the general population ranges from 0.5-1 case per 1000 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. 
10.6.4.2. 
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 
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 MACDP 
In a clinical trial, total oral rilpivirine exposures were generally lower during pregnancy 
compared with the postpartum period. Refer to Edurant Prescribing Information for 
additional information on rilpivirine. 
10.6.5. 
Clinical Considerations 
10.6.5.1. 
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, plasma PK 
samples of CAB and RPV will be obtained at every study visit for Q8W and Q4W during 
the pregnancy. Additionally, all other scheduled assessments, including viral load 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 9 1  
 
m o nit ori n g, will c o nti n ue as reflecte d i n as d escri b e d i n t he pr ot oc ol i n t he S O A  (see 
Secti o n 1. 3 ) 
Fi g ur e 6  
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 
A 
L 2 
A  
 ( + H C G)
A  
 (- H C G)
A  
 (- H C G)
A  
 (- H C G)
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
192 
 
10.6.5.2. 
 Use of Supplements with CAB + RPV LA 
During pregnancy, additional supplements including vitamins, minerals and other 
mediations including over the counter (OTC) medications 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 drug drug interactions (DDIs) that may occur with study 
medications and other agents used during pregnancy. 
10.6.5.2.1. 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. 
10.6.5.3. 
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 2.3.3 
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 
MACDP. 
Refer to Section 10.6.4.1 and Section 10.6.4.2 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 WOCBP, 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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
193 
 
receive CAB + RPV LA injections, once the new pregnancy ICF addendum is signed by 
the participant.  
10.6.6. 
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 care provider is responsible for HIV care and will collaborate and 
share information with the participant’s obstetric care provider, discuss the participant’s 
participation in this study, the necessary procedures at delivery, to share HIV 
information, and to collect birth and infant outcomes from the participant’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 
participant 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 participant 
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, as described in the 
protocol in the SoA (see Section 1.3) 
10.6.6.1. 
Plasma HIV-1 RNA 
Women who become pregnant while on study and consent to stay on study will have viral 
load (VL) testing obtained at every study visit during pregnancy and at the first post-
partum visit. 
10.6.6.2. 
Safety Assessments 
Pregnancy related complications and diagnoses, and outcomes will be captured as AEs 
and SAEs as outlined in the protocol in Section 8.3.2. 
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 participant 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 participant must agree to use contraception to avoid a ‘new’ pregnancy (See 
Appendix 6). 
Any SAE occurring in association with the 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 GSK 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 9 4  
 
1 0. 6. 6. 3.  
P h ar m a c o ki n eti c s  
All pre g n a nt partici p a nt s w h o elect t o re m ai n i n t he st u d y will ha ve a d diti o nal P K pre-
d ose sa m pli n g o btai ne d at eac h st u d y visit. Eac h P K bl o o d dra w f or pre g n a nc y P K will 
c o m prise of t he f oll o wi n g:  
•  C A B P K - 2 m L  ( pr otei n b o u n d a nal ysis) 
•  C A B P K - 9 m L  ( pr otei n u n-b o u n d a nal ysis)  
•  R P V P K - 2 m L    
 
A fi nal P K sa m ple f or ca b ote gra vir  a n d ril pi viri ne c o nce ntr ati o ns  will o btai ne d at t he first 
p ost part u m L A visit. All P K sa m ples will  be c ollecte d pri or t o t he sc h e d ule d L A 
i njecti o n. T he pre-d os e P K sa m ple is t o be c ollect e d wit hi n 1 5 mi n utes pri or t o t he L A 
d ose, o n t he da y of t he st u d y visit.  
Please refer t o t he S P M f or P K sa m ple c ollecti o n, pr ocessi n g, a n d s hi p pi n g i nstr ucti o ns. 
T he act ual d ate a n d ti me of eac h P K s a m ple c ollecti o n will be rec or de d i n t he e C R F.  
 
 
Data c ollecte d o n C R F fr o m pre g n a nt partici p a nts will be re p orte d as detail e d i n a 
se parat e secti o n of t he a n al ysis pla n or s e parate a n al ysis pla n a n d a d diti o nall y ma y be 
p o ole d wit h ot her st u dies.  
 
 
C CI


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
195 
 
10.7. 
Appendix 7: Genetics 
Genetic Research Objectives and Analyses 
The objectives of the genetic research are to investigate a relationship between genetic 
variants and:  
• Response to medicine, including CAB + RPV or any concomitant medicines;  
• HIV-1 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 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 participant who is enrolled in the clinical study can participate in genetic research. 
Any participant who has received an allogeneic bone marrow transplant must be excluded 
from 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  prior 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 participant has been 
randomized 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-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
196 
 
the participant 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 
participant 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. 
Participant Withdrawal from Study 
If a participant who has consented to participate in genetic research withdraws from the 
clinical study for any reason other than being lost to follow-up, the participant 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.  
If a participant withdraws consent for genetic research or requests sample destruction for 
any reason, the investigator must complete the appropriate documentation to request 
sample destruction within the timeframe specified by ViiV/GSK and maintain the 
documentation in the site study records.  
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 participant 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 
participant does not meet the entry criteria for participation in the study, then the 
investigator should instruct the participant 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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
197 
 
and sample reconciliation process.  In this instance a sample destruction form will not be 
available to include in the site files.  
Provision of Study Results and Confidentiality of Participant’s Genetic Data 
ViiV/GSK may summarize the genetic research results in the CSR, or separately, and 
may publish the results in scientific journals.  
ViiV/GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the 
participant, family members, insurers, or employers of individual genotyping results that 
are not known to be relevant to the participant’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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
198 
 
10.8. 
Appendix 8: Liver Safety: Required Actions, Follow-up 
Assessments and Study Intervention Guidelines 
10.8.1. 
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. (Table 10; Figure 7). 
  
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. 
10.8.2. 
VSLC Decision Process for Drug Restart Approval or Disapproval 
• Principal Investigator (PI) requests consideration of drug re-initiation for a 
participant stable or improving on IP, who exhibits liver chemistry elevation 
meeting participant stopping criteria, which is transient, non-drug-related, and 
liver chemistries have improved to normal or are within 1.5x Baseline and ALT< 
3xULN depending on baseline ALT as per Section 7.1.3.1.1.  
• GSK Medical Monitor and GCSP Physician to review the participant’s diagnosis 
restart risk factors (Hepatotoxicity Panel consultation is available) and complete 
checklist (Table 10). 
– 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 ReviewTeam Leader, Safety Development Leader, or Senior Safety 
Physician 
• MDL and PPL 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
199 
 
• Request is taken to VSLC for final decision 
 
Table 10 
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<3xULN 
 
Yes 
No 
Is participant 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 patient’s current resistance profile 
 
 
Previous drug history 
 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
200 
 
Figure 7 
VSLC process for drug restart approval or disapproval 
 
Participant 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 <3xULN (depending on Baseline ALT) 
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 participant 
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 restart 
outcome 
VSLC notified of restart outcome 
 
 
 
PI promptly informed of decision 
 
10.8.3. 
Medical monitor, GCSP Physician and PI actions for Restart 
following VSLC decision 
10.8.3.1. 
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 (associated with bilirubin>2xULN or jaundice, or INR1.5), 
SAEs or fatalities which occur following a drug or restart. must be immediately 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 0 1  
 
re p orte d t o Li ne M a na ge me nt i ncl u di n g, V S L C C hair, V P Gl o bal Me dical 
Strate g y a n d E U Q u alifie d Pers o n f or P har mac o vi gila nce.  
1 0. 8. 3. 2.  
PI A cti o n s:  
•  
T he PI m ust o btai n Et hics C o m mittee or I nstit uti o nal Re vie w B o ar d a p pr o val of 
dr u g restart, as re q uir e d.  
•  
If V S L C a p pr o ves dr u g restart, t he patie nt m ust si g n a n e w i nf or m e d c o nse nt 
c o ntai ni n g a clear descri pti o n of p ossi ble be nefits a n d ris ks of dr u g a d mi nistrati o n 
i ncl u di n g rec urre nt, m ore se vere li ver i nj ur y or p ossi ble deat h. 
•  T ar gete d dr u g dr u g rest art c o nse nt f or m m ust be use d.  
•  
T he patie nt’s i nf or me d c o nse nt m ust be rec or de d i n t he st u d y c hart, a n d t h e dr u g 
a d mi nistere d at a gree d d ose, as c o m m u nicate d b y Me dical M o nit or.  
•  
Li ver c he mistries m ust b e f oll o we d o nce wee kly f or ‘rest art’ c ases  f or a 
mi ni m u m of o ne m o nt h a n d t hereafter f or as l o n g as cli nicall y i n dicate d f oll o wi n g 
dr u g re -i nitiati o n.  If partici pa nt e x hi bits pr ot oc ol-defi ne d li ver c he mistr y 
ele vati o ns, I P s h o ul d be disc o nti n ue d as pr ot oc ol s pecifie d.  
•  
Me dical M o nit or a n d t he Et hics C o m mittee or I nstit uti o nal Re vie w B oar d m ust 
be i nf or me d of t he p atie nt’s o utc o me f oll o wi n g d r u g restart. 
Dr u g Rest art O utc o mes T a ble Te m pl ate  
T o be c o m plete d/ u p d ate d a n d pr o vi de d t o V S L C wit h e ac h e ve nt rec o r de d acr oss 
st u dies a n d i n dic ati o ns 
Dr u g Rest art O utc o mes T a ble –  U p d ate wit h e ac h e ve nt  
Pr ot o c ol #  
P arti ci p a nt #  
R e st art ?  
S af et y o ut c o m e*  
Dr u g  b e n efit  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
R est art s afet y o utc o mes:  
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.


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
202 
 
10.9. 
Appendix 9: AEs, ADEs, SAEs, SADEs, USADEs and 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 and the European Medical Device Regulation (MDR) 2017/745 for 
clinical device research (if applicable).  
• 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 GSK medical devices provided for use in the study (see Section 6.1.3 for the 
list of GSK medical devices). 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
203 
 
10.9.1. 
Definition of Medical Device AE and ADE 
Medical Device AE and ADE Definition  
• 
A medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether or not considered related to the investigational medical device. 
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 an investigational medical device. This definition includes events 
related to the investigational medical device or comparator and events related to the 
procedures involved except for events in users or other persons, which only include 
events related to investigational devices. 
• 
An adverse device effect (ADE) is defined as an AE related to the use of an 
investigational medical device. This definition includes any AE resulting from 
insufficient or inadequate instructions for use, deployment, implantation, installation, 
or operation, or any malfunction of the investigational medical device as well as any 
event resulting from use error or from intentional misuse of the investigational 
medical device. 
 
10.9.2. 
Definition of Medical Device SAE, SADE and USADE 
A Medical Device SAE is any serious adverse event that: 
a. 
Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
o A life-threatening illness or injury. 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. 
o A permanent impairment of a body structure or a body function. 
o Inpatient or prolonged hospitalization. Planned hospitalization for a pre-existing 
condition, or a procedure required by the protocol, without serious deterioration 
in health, is not considered an SAE. 
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
o Chronic disease (MDR 2017/745). 
c. 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of any infectious agent via a medicinal product 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
204 
 
Serious adverse device effect (SADE) definition 
• A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE. 
• Any device deficiency that might have led to an SAE if appropriate action had not 
been taken, intervention had not occurred, or circumstances had been less fortunate. 
Unanticipated serious adverse device effect (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is defined 
as a serious adverse device effect that by its nature, incidence, severity or outcome 
has not been identified in the current version of the risk analysis report  
 
10.9.3. 
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 inadequacy of the information supplied by the 
manufacturer. 
 
10.9.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies 
AE, SAE and Device Deficiency Recording 
• 
When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator 
to review all documentation (e.g., hospital progress notes, laboratory reports, and 
diagnostics reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE/device deficiency information 
in the participant’s medical records, in accordance with the investigator’s normal 
clinical practice, and on the appropriate form. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK and ViiV  in lieu of completion of the GSK/AE/SAE/device 
deficiency form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK or ViiV. 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 GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
205 
 
the individual signs/symptoms) will be documented as the AE/SAE. 
• 
For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the deficiency. 
o A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency. This includes any amendment to the device design to prevent 
recurrence. 
Assessment of Intensity 
• 
The investigator will make an assessment of intensity for each AE/SAE/device 
deficiency reported during the study and assign it to one of the following categories:  
• Mild:  Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• Moderate:  Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL). Instrumental ADL 
refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
• Severe:  Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting 
self care ADL. Self care ADL refers to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden. 
 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency. The investigator will use 
clinical judgment to determine the relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE/device deficiency, the investigator must document in the medical 
notes that he/she has reviewed the AE/SAE/device deficiency and has provided an 
assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
206 
 
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 before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE/SAE/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 GSK to 
elucidate the nature and/or causality of the AE/SAE/device deficiency as fully as 
possible. 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 form. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 
10.9.5. 
Reporting of SADEs 
SADE 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.  
• 
Any device deficiency that is associated with an SAE must be reported to the 
manufacturer of the device (if known) within 24 hours after the investigator 
determines that the event meets the definition of a device deficiency. 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
207 
 
10.10. 
Appendix 10: Recommendation for Assessment of Waist 
Circumference, Hip Circumference and Weight (Adapted 
from WHO STEPS Surveillance Manual, 2017) and for 
Resting Blood Pressure 
10.10.1. 
Waist Circumference 
Equipment  
To take waist circumference measurements you will need a: 
• Constant tension tape (for example, Figure Finder or Myo Tape Body Tape 
Measure); 
o Tape measures will be provided for the study 
• 
Chair or coat stand for participants to place their clothes. 
Privacy 
A private area is necessary for this measurement. This could be a separate room, or an area 
that has been screened off from other people. 
Preparing the participant 
This measurement should be taken without clothing, meaning, directly over the skin. 
If this is not possible, the measurement may be taken over light clothing (for example, a 
hospital gown, an undergarment or thin t-shirt). Thick or bulky clothing must be removed.  
Body shaping garments are not allowed to be worn during this measurement. 
How to take the measurement 
We recommend having the same study staff performing the measurement across visits for 
individual study participants. 
This measurement should be taken: 
• at the end of a normal expiration; 
• 
with the arms relaxed at the sides; 
• at the midpoint between the lower margin of the last palpable rib and the top of 
the iliac crest (hip bone) (Figure 8). 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
208 
 
Figure 8 
Location of Midpoint for Waist Circumference Measurement  
 
Procedure 
Follow the steps below to measure the waist circumference of a participant: 
1. Standing to the side of the participant, locate the last palpable rib and the top of 
the hip bone. You may ask the participant to assist you in locating these points on 
their body. 
2. Wrap the tension tape around the participant and position the tape at the midpoint 
of the last palpable rib and the top of the hip bone, making sure to wrap the tape 
over the same spot on the opposite side. 
Note: Check that the tape is horizontal across the back and front of the participant 
and as parallel with the floor as possible. 
3. Ask the participant to: 
• stand with their feet together with weight evenly distributed across both feet; 
• hold the arms in a relaxed position at the sides; 
• breathe normally for a few breaths, then make a normal expiration. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
209 
 
4. Measure waist circumference and read the measurement at the level of the tape to the 
nearest 0.1 cm, making sure to keep the measuring tape snug but not tight enough to 
cause compression of the skin. 
5. Record the measurement, in centimetres to one decimal place, within the eCRF. 
• 
Note: Measure once and record. 
 
10.10.2. 
Hip Circumference 
Equipment 
To take hip circumference measurements you will need a: 
• Constant tension tape (for example, Figure Finder or Myo Tape Body Tape 
Measure); 
o Tape measures will be provided for the study 
• Chair or coat stand for participants to place their clothes. 
Privacy 
A private area is necessary for this measurement. This could be a separate room, or an 
area that has been screened off from other people. Hip measurements are taken 
immediately after waist circumferences. 
Preparing the participant 
This measurement should be taken without clothing, that is, directly over the skin. 
If this is not possible, the measurement may be taken over light clothing (for example, a 
hospital gown or an undergarment). Thick or bulky clothing must be removed.  Body shaping 
garments are not allowed to be worn during this measurement. 
How to take the measurement 
We recommend having the same study staff performing the measurement across visits for 
individual study participants. 
This measurement should be taken: 
• 
with the arms relaxed at the sides 
• 
at the maximum circumference over the buttocks. 
Procedure 
Follow the steps below to take hip circumference measurements. 
1. Stand to the side of the participant and wrap the tension tape around them. 
2. Position the measuring tape around the maximum circumference of the buttocks. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
210 
 
3. Ask the participant to: 
• Stand with their feet together with weight evenly distributed over both feet; 
• 
Hold their arms relaxed at the sides. 
4. Check that the tape position is horizontal all around the body and snug without 
constricting. 
5. Measure hip circumference and read the measurement at the level of the tape to the 
nearest 0.1 cm. 
6. Record the measurement, in centimetres to one decimal place, within the eCRF.  
Note: Measure once and record. 
 
10.10.3. 
Weight 
Equipment 
To measure weight, you will need a weighing scale, (such as a Tanita BC-587 or Tanita 
BC-730 scale). Alternatively, a BMI scale measuring both height and weight (e. g. 
Growth Management Scale) can be used. 
Ensure the scale has been regularly calibrated according to the manufacturer instructions 
and that calibration documentations are filed and available to the study CRA as required. 
We recommend using the same scale across visits for individual study participants. 
We recommend having the same study staff performing the measurement across visits for 
individual study participants. 
We recommend that the time of day a participant’s weight is measured is consistent for 
every participant at the site within the study. (ex. If measured at 10 a.m. at initial 
measurement, attempt to have the participant measured at 10 a.m. at subsequent visits). 
Set up requirements 
Make sure the scales are placed on a firm, flat surface. Do not place the scales on: 
• 
carpet 
• 
a sloping surface 
• 
a rough, uneven surface. 
Set up scales 
Follow the steps below before measuring the weight of a participant: 
1. Make sure the scale is on a firm, flat surface. 
2. Turn on the scale and wait until the display shows 0.0. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
211 
 
Procedures 
Follow the steps below to measure the weight of a participant: 
1. Ask the participant to remove their footwear (shoes, slippers, sandals, etc). They 
should also take off any heavy belts and remove all objects out of their pockets 
(example:  mobile phones, wallets, coins). 
2. Ask the participant to step onto scale with one foot on each side of the scale. 
3. Ask the participant to: 
• stand still 
• 
face forward 
• place arms on the side and 
• wait until asked to step off. 
Record the weight in kilograms to one decimal place in the eCRF. 
 
References 
[WHO STEPS Surveillance Manual, 2017; 3-5-9 to 3-5-13.] 
10.10.4. 
Resting Blood Pressure 
General instructions 
• Ensure that healthcare professionals taking blood pressure measurements have 
adequate initial training and periodic review of their performance. 
• Healthcare providers must ensure that devices for measuring blood pressure are 
properly validated, maintained and regularly recalibrated according to 
manufacturers' instructions. 
• When measuring blood pressure in the clinic or in the study site, standardise the 
environment and provide a relaxed, temperate setting, with the person quiet and 
seated, and their arm outstretched and supported. Use an appropriate cuff size for 
the person's arm. 
• Measure the blood pressure in one arm (in semi-supine* position or seated after 5 
minutes rest).   
*Semi-supine position: Laying /sitting back (at 45 angle or variations) in a relaxed 
position with feet touching a flat surface. 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
212 
 
10.11. 
Appendix 11:  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 
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.  
10.11.1. 
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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
213 
 
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. 
 
10.11.2. 
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 participant-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. 
 
10.11.3. 
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: 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
214 
 
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) 
 
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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
215 
 
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. 
10.11.4. 
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. 


T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 1 6  
 
•  Pleas e refer t o y o ur C R A or l ocal st u d y m a na ger f or s u p p ort wit h t he D T P 
pr ocess, e ns uri n g refere n ce t o c urre nt s p o ns or g ui da nce a n d arra n ge m e nt of a 
c o urier t hat ca n s u p p ort s hi p me nt of I M P directl y t o partici pa nts.  
 
1 0. 1 1. 5.  
C O VI D -1 9 E x p eri m e nt al A g e nt s  
If a n y treat ments f or C O VI D -1 9 are pla n ne d f or a st u d y partici p a nt, please c o ns ult wit h 
t he st u d y me dical m o nit or t o e ns ure t hat rele va nt dr u g i nteracti o ns are c o nsi dere d a n d t o 
e ns ure t hat c o nti n ue d st u d y partici pati o n re mai ns a p pr o priate.  
1 0. 1 1. 6.  
C O VI D -1 9 S p e cifi c D at a C a pt ur e  
1 0. 1 1. 6. 1.  C a pt uri n g C O VI D -1 9 S p e cifi c Pr ot o c ol D e vi ati o n s  
Please refer t o y o ur st u d y pr oce d ure ma n ual f or s pecific det ails o n ca pt uri n g pr ot oc ol 
de viati o ns as a res ult of C O VI D -1 9.  
 
1 0. 1 1. 6. 2.  C a pt uri n g C O VI D -1 9 S p e cifi c A E s a n d S A E s  
It is i m p orta nt f or t he st u d y te a m t o descri be C O VI D-1 9 relate d a d v erse e v e nts/seri o us 
a d verse a n d t heir i m pact o n st u d y data a n d o utc o mes. Sta n dar dizati o n of case defi niti o ns 
will facilitate f ut ure d ata a nal ysis.  
Please use t he f oll o wi n g g ui da n ce:  
1.  A Es s h o ul d c o nti n ue t o be e val uat e d as t o w het her t he y meet S A E criteri a as 
defi ne d i n t he pr ot oc ol, a n d if s o, s u b mitte d acc or di n g t o esta blis he d S A E 
re p orti n g re q uir e me nts. S A Es a n d A Es s h o ul d be s u b mitte d f oll o wi n g us ual 
st u d y pr oce d ures a n d ti meli nes.  
 
2.  W he n a n i n -pers o n cli nic visit is n ot  p ossi ble, please c o n d uct a re m ote tele h ealt h 
visit t o assess f or, a n d d o c u me nt a n y A Es/ S A Es.  
 
3.  I n v esti gat ors s h o ul d use t he W H O defi niti o n t o classif y C O VI D-1 9 cases. T he 
defi niti o n bel o w, rele ase d Marc h 2 0, 2 0 2 0, re pres e nts a ti me p oi nt f or 
sta n dar dize d collecti o n. We rec o g nize defi niti o ns are li kel y t o c o nti n ue t o 
e v ol ve. W he n re p orti n g b ot h seri o us a n d n o n - seri o us a d verse e ve nts (relat e d 
t o C O VI D-1 9 i nfecti o n, i n vesti gat ors s h o ul d use t he f oll o wi n g Ver bati m 
ter ms:  
 
4.  Sites s h o ul d c o ntact t he st u d y Me dical M o nit or f or q uesti o ns relate d t o defi niti o ns 
a n d re p orti n g, a n d d ecisi o ns ar o u n d i m pact t o st u d y dr u g c o nti n uati o n.  
 
P P D


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
217 
 
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:  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
218 
 
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. 
 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
219 
 
10.12. 
Appendix 12: Country-specific requirements 
10.12.1. 
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 may 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 4- month recruitment period, and with treatment anticipated to be 
commercially available by approximately 4Q 2021, the Extension Phase is anticipated to 
conclude around the same time. During this time, participants will be monitored on Q2M 
to ensure they continue to derive clinical benefit from CAB LA + RPV LA. 
Based on the request from Medicines and Healthcare Products Regulatory Agency 
(MHRA) in United Kingdom, to adjust the Exclusion Criteria Number 11 regarding the 
participants with a risk of seizures excluded or not in this study and the responsibility of 
the Investigator making the decision. 
Exclusion Criteria # 11: 
11.   
Participants determined by the Investigator to have a high risk of seizures, 
including participants who had a seizure within the last year without a 
clear aetiology, or had seizures within the last 12 months while receiving 
anti-seizure medications will be excluded.  Participants with a distant 
history of seizure without recent seizure activities, or any participant with 
a history of a controlled seizure disorder while on treatment who has been 
seizure free and off the anti-seizure medications for >12 months may be 
enrolled if the Investigator believes the risk of seizure recurrence is low.  
Other participants with a prior seizure history may be discussed with the 
Medical Monitor prior to participant’s enrolment 
10.12.2. 
Ireland  
This requirement has been included as a recommendation by the Health Product 
Regulatory Authority (HPRA) in Ireland.  
Section 10.11.1 (Changes to Study Visits and Study Procedures) states the following: 
“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-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
220 
 
In Ireland this can be submitted as an urgent safety measure or amendment as appropriate 
as described at the following link: http://www.hpra.ie/homepage/medicines/regulatory-
information/clinical-trials/covid-19-(coronavirus)-and-cts/guidance-on-the-management-of-
clinical-trials-during-covid-19/. 
10.12.3. 
France (FRA) 
This requirement has been included based on requests from the Agence nationale de 
sécurité du médicament et des produits de santé (ANSM) to adjust the Inclusion and 
Exclusion criteria regarding the INI and NNRTI resistance mutations excluded in this 
study in accordance to the EU review process of the Marketing Authorisation 
Application.  
Exclusion Criteria #27 
27. Known or suspected presence of any major INI or NNRTI resistance mutations, 
except for K103N as defined by the IAS-USA resistance guidelines [IAS-USA, 
2019] by any historical resistance test result. 
Note: Prior genotypic resistance testing (genotyping of plasma vRNA and/or 
PBMC vDNA) is not required but if available it must be provided to ViiV, 
after screening and before randomization according to guidance in the SPM, 
to provide direct evidence of no pre-existing exclusionary resistance 
mutations. You must wait for the study virologists to confirm the lack of 
exclusionary resistance mutations, which will be provided before the 
screening window closes. Details regarding baseline or prior resistance data 
must be noted in the source documentation 
10.12.4. 
Germany (DEU) 
Based on the request from the German Lead Ethics Committee: to remove study 
intervention rechallenge. 
Based on the request from the German Competent Authority, the Federal Institute for 
Drugs and Medical Devices (BfArM): to amend Exclusion Criteria 31 
Exclusion Criteria 31: 
31.  Alanine aminotransferase (ALT) ≥ 5x the upper limit of normal (ULN) or 
ALT ≥3x ULN and bilirubin ≥1.5 x ULN (with > 35% direct bilirubin) 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
221 
 
10.13. 
Appendix 13:  Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 02, 8-SEP-2021 
Overall Rationale for Amendment 2: 
The primary reason for protocol amendment 02 is to address and clarify comments raised 
during the course of the study and to implement country specific changes following 
regulatory review  
Section # and Name 
Description of Change 
Brief Rationale 
Headers 
Change of protocol reference 
number 
Due to sponsor protocol writing 
procedure changes 
Section 1.1 and Section 3 
- Objectives and 
Endpoints 
Minor rephrase of first 
secondary objective 
 
Section 1.3 SoA 
Clarification to SoA (and 
footnotes):  
-addition of ISR Assessment 
for IM injection at Month 13 
in BIK to Direct to Inject 
Extension phase  
-removal of CV assessments 
at months 1 through 6 
- BIK to Oral Lead In – 
Extension Phase table: 12 
Lead ECG, removed 
“triplicated at Day 1 pre-dose 
-clarification to footnote “e” 
footnote “n”:  addition of 
biomarkers in line with 
protocol body 
-footnote “u”: clarification for 
pregnant participants 
-addition of footnote “gg” – 
History of cosmetic 
procedures during the study 
For clarification purposes 
Section 2 - Introduction  
Removal of phrase stating 
CABENUVA now approved in 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
222 
 
Section # and Name 
Description of Change 
Brief Rationale 
there are currently no 
approved two-drug regimen 
selected regions 
Section 2.1.2 – Weight 
Gain 
Addition of metabolic 
syndrome classification  
To clarify which participants meets 
metabolic syndrome 
Section 2.3.1 Risk 
Assessment 
• Dolutegravir 
data/Rationale for 
Risk updated. 
• Rilpivirine LA update 
 
Updated safety information  
Section 3 – Objectives 
and Endpoints 
Replace “…activity…” with 
“…response with the use …” 
in secondary objective 
For clarification purposes   
Section 4.1.2 – 
Maintenance Phase 
(Direct to Inject [no oral 
lead-in]) 
Define window for second 
injection 
To clarify dosing windows for first 
and second injections 
Section 4.1.3.2 – 
Participants Entering from 
the BIK arm 
Define window for second 
injection 
For clarification purposes 
Section 4.1.4 LTFU Phase 
– IM Regimen Only 
New text added 
For clarification purposes 
Section 4.2 – Type and 
Number of Participants 
Inclusion of approximately 
20% females 
Adjust the target based on real 
world evidence. 
Section 4.5 End of Study 
Definitions 
Updated terminology 
For clarification purposes 
Section 5.1 - Inclusion 
Criteria 
Inclusion Criteria 5 - 
Clarification that no other 
ART class other than INI 
regimen are allowed  
 
For clarification purposes 
Section 5.2 – Exclusion 
Criteria 
Exclusion Criteria 2 – specify 
documented viral load is 
required 
For clarification purposes 
Section 5.5.2- Cosmetic 
Addition of new section 
To inform participants who had 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
223 
 
Section # and Name 
Description of Change 
Brief Rationale 
Surgery 
cosmetic surgery during the course 
of the study what happens to their 
data during analyses. 
Section 6.1.3 – Medical 
Devices 
Addition of Medical Devices 
Section 
Regulatory request with 
CABENUVA approval in selected 
countries 
Section 6.4 – Dosage and 
Administration 
Addition of text in table and 
footnote. 
 
Section 6.9.1. – IM Dosing  Rephrasing of visit windows 
 
For clarification purposes. 
Section 6.11.1 - Prohibited 
Medications and Non-
Drug Therapies 
Addition of Rifampicin to 
Rifampin in “concurrent with 
BIK” sub-section 
In line with “concurrent with CAB 
and/or RPV” sub-section  
Section 7.1 – Participant 
Discontinuation/withdrawal 
from the Study 
Addition of reference to BIK 
in second bullet 
Rephrasing pregnancy text 
for BIK participants 
For clarification purposes 
Section 7.1.3. General 
Guidance on Restart 
Removal of rechallenge text. 
Rechallenge option removed. 
Section 7.1.7.1 HIV-1 
RNA Blips 
Specify key analysis 
timepoints 
For clarification purposes 
Section 8.2.1 – Clinical 
Evaluations 
Rephrase to “An ECG 
machine that automatically 
calculates the heart rate and 
measures PR, QRS, QT, and 
QTc  intervals is preferred 
(and RR if calculated 
manually),” 
To align with electronic Data 
Capturing From 
Section 8.2.5 – 
Electrocardiograms 
Deletion of 2 hour post-dose 
ECG in BIK arm 
For clarification purposes and 
alignment to SoA 
Section 8.3.6 - Pregnancy  Added text throughout all 
sections to allow participants 
who become pregnant (on 
CAB+RPV) to remain in the 
study: 
To allow participants who become 
pregnant to remain in the study. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
224 
 
Section # and Name 
Description of Change 
Brief Rationale 
 
Section 8.3.8 – Medical 
Device Deficiencies 
Added new sections detailing 
the medical device 
deficiencies reporting 
requirements. 
Added medical device deficiency 
reporting requirements. 
Section 8.5.2 PK Sample 
Collection 
Addition of: Pregnant 
participants will have 
additional PK samples 
collected during the duration 
of the pregnancy. See 
Appendix 6 for details. 
To allow participants who become 
pregnant to remain in the study. 
Section 8.11 - Value 
Evidence and Outcomes 
Endpoints  
Changes to last paragraph 
To allow optional qualitative 
surveys for Investigators  
Section 8.12 - Biomarkers 
Added Insulin, HbA1c and 
HOMA-IR to last paragraph 
To align with Table 4 (Safety 
Laboratory Assessments) 
footnotes  
Section 9.4.1 – Primary 
Analysis  
Addition of paragraph at end 
of section 
Describing statistical 
considerations for pregnant 
participants on CAB+RPV LA 
Section 9.5 – Interim 
Analysis  
Rephrasing of first and last 
paragraph 
For clarification purposes 
Section 10.1.3 – Informed 
Consent Process 
Changes to last paragraph 
For clarification purposes 
Section 10.5.2 
Contraceptive Guidance 
 
 
 
 
Deleted Footnote B of Table 
8 
Change to One highly effective 
contraceptive method should be 
utilized for 30 days prior to first 
dose of study medication and for at 
least 52 weeks after D/C of CAB 
LA and RPV LA 
Section 10.6 – Appendix 6 
Addition of new Appendix 
“Information and Guidance 
for Managing Pregnant 
Participants” 
To allow participants who become 
pregnant to remain in the study (on 
CAB+RPV only). 
Section 10.8 – Appendix 8 
Removal of Rechallenge 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
225 
 
Section # and Name 
Description of Change 
Brief Rationale 
guidelines. 
Section 10.8 - Appendix 9 
Addition of new Appendix 9 
“AEs, ADEs, SAEs, SADEs, 
USADEs and Device 
Deficiencies: Definition and 
Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting in Medical Device 
Studies” 
Regulatory request with 
CABENUVA approval in selected 
countries 
Section 10.12.2 -Ireland 
Addition of Ireland Country 
Specific Request 
In reply to Health Product 
Regulatory Authority (HPRA)  
Section 10.13 – Appendix 
13: Protocol Amendment 
History 
Addition of changes from 
Global Protocol Amendment 
1 and rationale Local 
Protocol Amendments 01 in 
France, GBR and Germany  
 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
226 
 
 
Amendment 01, 30-JUN-2020 
Overall Rationale for Amendment 1: 
The primary reason for protocol amendment 01 is to add minor clarifications to address 
study completion, PK collection, and endpoint timings.  Country-specific details were 
added to Appendix 10 to address UK MHRA requirements.  The protocol short title was 
updated.  Corrections to typographical errors in protocol text and title were made 
throughout. 
Section # 
and Name 
Description of Change 
Brief Rationale 
Short 
Protocol Title 
Adjusted to more representative for 
the study on title page and 
synopsis 
To conform to guidelines set forth in the 
eTrack User Guide 
 
Section 1.3:  
SoA footnote 
‘u’ and ‘g’ 
PK sample acquisition clarified in 
footnote  
Added specific weight related 
measurements to collect in eCRF 
To remove any confusion of how many PK 
samples to acquire for participants who 
receive OLI at start of Maintenance and 
Extension. Also, important for specific 
weight related measurements to be 
captured to ensure reason to collect in 
eCRF is supported. 
Section 3: 
Objectives 
and 
Endpoints 
and 
throughout 
the protocol 
as applicable 
Clarification of when participants 
reach endpoints  
To provide clarity that only one sample per 
product is required. 
 
Section 4.5; 
End of Study 
definition 
Update of completion scenarios to 
be inclusive of Month 13 
Section 7.1 and Section 4.5 were 
contradictory and needed to be aligned. 
Section 6.3.2; 
Blinding 
Added language regarding blinding 
and when data will be viewed by 
ViiV/GSK staff 
To conform to analysis plan for study 
Section 8.2.1; 
Clinical 
Evaluations 
Added language that points site 
staff to SRM for appropriate 
measures to capture regarding 
weight gain 
To provide clarity on location of measures 
to collect 


TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
227 
 
Section # 
and Name 
Description of Change 
Brief Rationale 
Section 8.2.5; 
ECG/Section 
1.3 SoA 
footnote ‘i’ 
Added clarity to when ECGs were 
performed based on randomized 
arm 
To provide clarity on ECG procedures 
Section 8.5.2 
Removal of requirement of Pre-
dose samples for LTFU visits 
Participant is off drug and a PK sample can 
be taken at any time during LTFU visit 
Section 9.1; 
Statistical 
Hypotheses 
Updated language to terminology 
used in this study (Q8W to Q2M; 
Week 48 to Month 12) 
To keep terminology the same throughout 
document.  
Section 9.4; 
Statistical 
Analysis 
Added language regarding blinding 
and when data will be viewed by 
ViiV/GSK staff 
To conform to analysis plan for study 
Section 
10.10; 
Country 
specific 
requirements 
Added UK country-specific details  
UK has specific details necessary to meet 
regulatory requirements 
Section 
10.11; 
Protocol 
Amendment 
History 
Added appendix to protocol 
Added per protocol template requirements 
Throughout 
protocol 
Minor typographical and grammar 
errors addressed 
Since minor, no need to list individually. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
228 
 
Amendment 01 / France 01, 16-NOV-2020 
Overall Rationale for Country-Specific Amendment:  
Based on requests from the:  
• Agence nationale de sécurité du médicament et des produits de santé (ANSM) in 
France, to adjust the Exclusion criteria number 27 regarding the major INI and 
NNRTI resistance mutations excluded in this study.  
• French Ethics committee, to adjust the introduction as few biotherapies are 
proposed to simplify patients treatment.   
Section # 
and Name 
Description of Change 
Brief Rationale 
Section 2 
Introduction  
Removal of while the phrase  “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 patients with HIV” from 
the second paragraph 
This request was required for France  
Section 5.2 
Exclusion 
Criteria 
Adjustments to include major INI 
and NNRTI resistance mutations 
This amendment was required for France  
 
 
 
 
Amendment 1/GBR-1: 20-NOV-2020 
Overall Rationale for Country-Specific Amendment:  
Based on the request from Medicines and Healthcare Products Regulatory Agency 
(MHRA) in United Kingdom, to adjust the Exclusion Criteria Number 11 regarding the 
participants with a risk of seizures excluded or not in this study and the responsibility of 
the Investigator making the decision. 
  
Section # 
and Name 
Description of Change 
Brief Rationale 
Section 5.2 
Exclusion 
Adjustments to clearly define the 
exclusion criteria and clarify the 
responsibility of the Investigator to 
This amendment was required for United 
Kingdom  


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
229 
 
Section # 
and Name 
Description of Change 
Brief Rationale 
Criteria 
make the decision regarding 
enrolment eligibility 
Section 10.10 
Appendix 10: 
Country-
specific 
requirements 
Additions to specify the UK 
requirement on Exclusion Criteria 
Number 11 
This amendment was required for United 
Kingdom 
 
Amendment 01 / DEU01, 12-JAN-2021 
Overall Rationale for Country-Specific Amendment: Based on the request from the 
German Lead Ethics Committee: to remove study intervention rechallenge. 
Based on the request from the German Competent Authority, the Federal Institute for 
Drugs and Medical Devices (BfArM): to amend Exclusion Criteria 31 
 
Section # 
and Name 
Description of Change 
Brief Rationale 
Section 5.2 
Expand Exclusion Criteria 31  
parameters 
BfArM requirement 
Section 7.1.3 
Restart 
Section 10.7 
Appendix 7: 
Liver Safety: 
Required 
Actions, 
Follow-up 
Assessments 
and Study 
Intervention 
Restart 
Guidelines 
Deleted study intervention 
rechallenge after stopping 
treatment for liver criteria 
Ethics Committee requirement 
 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
230 
 
10.14. 
Appendix 14: Abbreviations and Trademarks 
3TC 
Lamivudine, EPIVIR 
ABC 
Abacavir, ZIAGEN 
ABC/3TC 
Abacavir/lamivudine, EPZICOM, KIVEXA 
ADE 
Adverse device effect 
ADL 
Activities of Daily Living 
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 
N-acetyl-para-aminophenol 
APR 
Antiretroviral Pregnancy Registry 
ARV 
Antiretroviral 
ART 
Antiretroviral therapy 
ATLAS 2M 
Antiretroviral Therapy as Long Acting Suppression every 2 
Months 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AUC(0-) 
Area under the concentration curve from 0 hours to the time 
of next dosing 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CAB 
Cabotegravir 
CAB LA 
Cabotegravir long-acting 
c/mL 
Copies/milliliter 
cART 
Combination antiretroviral therapy 
CCR5 
C-C chemokine receptor type 5 
CD4 
Cluster of Differentiation 4 
CD8 
Cluster of Differentiation 8 
CDC 
Centers for Disease Control and Prevention 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
Cmax 
Maximum concentration 
CMH 
Cochran-Mantel Haenszel 
ConART 
Concomitant Antiretroviral Therapy 
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 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
231 
 
COVID-19 
Coronavirus Disease 2019 
DDI 
Drug Drug Interaction 
DAIDS 
DILI 
Division of Acquired Immunodeficiency Syndrome 
Drug induced liver injury 
DNA 
Deoxyribonucleic acid 
DRE 
Disease-Related Events 
DRV 
Darunavir 
DTG 
Dolutegravir, TIVICAY 
DVT 
Deep vein thrombosis 
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 
FDA 
Food and Drug Administration 
FDC 
Fixed-dose combination 
FTC 
Emtricitabine 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 
HAART 
Highly active antiretroviral therapy 
HbsAg 
Hepatitis B surface Antigen 
HAT-QoL 
HIV/AIDS-targeted quality of life 
HBV 
Hepatitis B virus 
HCG 
human chorionic gonadotrophin 
HCV 
Hepatitis C virus 
HDL 
High density lipoprotein 
HDPE 
High density polyethylene 
HIV 
Human immunodeficiency virus  
HIV TSQ 
HIV treatment satisfaction questionnaire 
HLA 
Human leukocyte antigen 
HSR 
Hypersensitivity reaction 
IAS 
International AIDS Society 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IDMC 
Independent data monitoring committee 
IEC 
Independent Ethics Committee 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
INI 
Integrase inhibitor 
INR 
International normalized ratio 
INSTI 
Integrase strand transfer inhibitor 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
232 
 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT-E 
Intent-to-treat exposed 
IUD 
Intrauterine device 
IUGR 
Intrauterine growth restriction 
IRT 
Interactive response technology 
ISR 
Injection Site Reaction 
LA 
Long Acting 
LDL  
Low density lipoprotein 
LPV 
Lopinavir 
LPV/r 
Lopinavir-ritonavir 
LTFU 
Long-Term Follow-Up 
MACDP 
Metropolitan Atlanta Congenital Defext Program  
MCV 
Mean corpuscular volume 
MDR 
Medical Device Regulation 
MedDRA 
Medical dictionary for regulatory activities 
Mg 
Milligram 
Mg/dL 
Milligram 
MRHD 
Maximum recommended oral human dose 
MSD=F 
Missing, switch, or discontinuation equals failure 
MTCT 
Mother to child transmission  
NTD 
Neural tube defect 
NNRTI 
Non-nucleoside reverse transcriptase inhibitor 
NRS 
Numeric Rating Scale 
NRTI 
Nucleoside reverse transcriptase inhibitor 
OLI 
Optional Oral Lead In  
OTC 
Over the counter 
PI 
Protease inhibitor 
PIN 
Perception of Injection 
PK 
Pharmacokinetic 
PP 
Per-protocol 
PRO 
Protease 
PRTD 
Proximal Renal Tubule Dysfunction 
PSRAE 
Possible suicidality-related adverse event 
QTc 
Corrected QT interval  
Q8W 
Every 8 weeks 
Q4W 
Every 4 weeks 
RAL 
Raltegravir 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cell 
RBP 
Retinol Binding Protein 
RHD 
Recommended human dose 
RNA 
Ribonucleic acid 
RPR 
Rapid plasma reagin 
RPV 
Rilpivirine, Edurant 
RPV LA 
Rilpivirine long-acting 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
233 
 
RT 
Reverse transcriptase 
RTV 
Ritonavir 
SAE 
Serious adverse event 
SADE 
Serious adverse device effect 
SJS 
Stevens-Johnson syndrome 
SOC 
Standard of Care 
SPM 
Study Procedures Manual 
SRM 
Study Reference Manual 
STR 
Single tablet regimen 
SVW 
Suspected Virologic Withdrawal 
TDF 
Tenofovir disoproxil fumarate 
TEN 
Toxic epidermal necrolysis 
TMC278 
Tibotec Medicinal Compound 278 
TSQ 
Treatment Satisfaction Questionnaire 
ULN 
Upper limit of normal 
US 
United States 
USADE 
Unanticipated Serious Adverse Device Effect 
VAPI 
Vaccines’ Perception of Injection 
VAS 
Visual Analog Scale 
VL 
Viral load 
VSLC 
ViiV Safety and Labelling Committee 
WBC 
White blood cell 
WOCBP 
Women of childbearing potential 
 
Trademark Information 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by the ViiV 
Healthcare 
EPIVIR 
 
Biktarvy 
EPZICOM/KIVEXA 
 
Edurant 
TRIUMEQ 
 
GenoSure 
TRIZIVIR 
 
PhenoSense 
ZIAGEN 
 
Monogram Biosciences 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
234 
 
11. 
REFERENCES 
Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury: the 
attractive hazard.  Expert Opin Drug Saf.  2009; 8:709-714. 
Antiretroviral Therapy Cohort Collaboration (ART-CC).  Durability of first ART 
regimen and risk factors for modification, interruption or death in HIV-positive patients 
starting ART in Europe and North America 2002-2009.  AIDS 2013; 27:803-813. 
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. 
Arribas J, Clumeck N, Nelson M, Hill A, van Delft Y, Moecklingoff C.  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 P, Landman R, Rich J, Mallolas J, Martinez-Rebollar M, 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; 15:785-92. 
Bierman WF, van Aqtamael MA, Nijhuis M, Danner SA, Boucher CA. HIV 
monotherapy with ritonavir-boosted protease inhibitors: a systematic review. AIDS, 2009; 
23(3):279-91. 
Biktarvy Prescribing Information, August 2019. 
Bourgi K, Jenkins C, Rebeiro PF, Lake JE, Moore RD, Mathews W.C, et al. Greater 
weight gain among treatment-naïve persons starting integrase inhibitors. Conference on 
Retroviruses and Opportunistic Infections, Seattle, abstract 670, 2019. 
CDER: Center for Drug Evaluation and Research. Human Immunodeficiency Virus-1 
infection: developing antiretroviral drugs for treatment – guidance for industry. US 
DHHS FDA. November 2015. 
Centers for Disease Control and Prevention (CDC) Revised surveillance case definition 
for HIV infection-United States, 2014.  MMWR Recomm Rep 2014;63 (RR-03):1-10. 
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. 
Daar ES, DeJesus E, Ruane P, Crofoot G, Oguchi G, Creticos C, et al. Efficacy and 
safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide 
from boosted protease inhibitor-based regimens in virologically suppressed adults with 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
235 
 
HIV-1:  48 week results of a randomized, open-label, multicenter, phase 3, non-
inferiority trial.  Lancet HIV. 2018. 5:e347-56. 
Debroy P, Sim M, Erlandson KM, Falutz J, Prado CM, Brown TT, et al. Progressive 
increases in fat mass occur in adults living with HIV on antiretroviral therapy, but 
patterns differ by sex and anatomic depot. J Antimicrob Chemother. 2019 Apr; 74(4): 
1028–1034. 
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 December 18, 2019. Available at: 
https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed 20 
Jan 2020. 
Edurant Prescribing Information, May 2021 
European Association for the Study of the Liver.  EASL Clinical Practice Guidelines: 
Drug-induced Liver Injury. J Hepatol 2019 Jun 70 (6), 1222-1261. 
GlaxoSmithKline Document Number 2013N168152_09: A Phase IIb Study Evaluating a 
Long-Acting Intramuscular Regimen of GSK1265744 plus TMC278 For the 
Maintenance of Virologic Suppression Following an Induction of Virologic Suppression 
on an Oral regimen of GSK1265744 plus Abacavir/Lamivudine in HIV-1 Infected, 
Antiretroviral Therapy-Naive Adult Subjects, LATTE-2.  Effective date: November 2017 
GlaxoSmithKline Document Number 2017N326521_02: A Phase IIIb, Randomized, 
Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, 
Safety, and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine 
Administered Every 8 Weeks or Every 4 Weeks in HIV-1-infected Adults who are 
Virologically Suppressed, ATLAS 2M. Effective date: July 2018 
GlaxoSmithKline Document Number 2018N380094_00: A Phase IIb Study Evaluating a 
Long-Acting Intramuscular Regimen of GSK1265744 plus TMC278 for The 
Maintenance of Virologic Suppression Following an Induction of Virologic Suppression 
on an Oral regimen of GSK1265744 plus Abacavir/Lamivudine in HIV-1 Infected, 
Antiretroviral Therapy-Naive Adult Subjects. Week 160 - Clinical Study Report. 
Effective date:  March 2019. 
GlaxoSmithKline Document Number 2019N406358_00: A Phase IIIb, Randomized, 
Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, 
Safety, and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine 
Administered Every 8 Weeks or Every 4 Weeks in HIV-1-infected Adults who are 
Virologically Suppressed, Week 48 CSR.  Effective date:  December 19, 2019 
GlaxoSmithKline Document Number 2019N421460_00.  Population pharmacokinetic 
evaluation of cabotegravir Q8W regimen.  Effective date: 09-Dec-2019 
GlaxoSmithKline Document Number  RPS-CLIN-004375: Clinical Investigator’s 
Brochure for Cabotegravir Annual IB Update Version 11. Effective date:  February 2021. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
236 
 
Grundy SM, Hansen B, Smith SC, Cleeman JI, Kahn RA. Clinical management of 
metabolic syndrome: report of the American Heart Association/National Heart, Lung, and 
Blood Institute/American Diabetes Association Conference on scientific issues related to 
management. Circulation. 2004 Feb;109:551-556 
Hill A, McCann KM, Pilkington V, Moorhouse MA, Sokhela S, Serenata CM, et al. Risk 
of metabolic syndrome, diabetes, and cardiovascular disease in ADVANCE trial (abstract 
#81), CROI 2020 on March 10, 2020. 
Hunt CM, Contraceptive Technology. 20th edition.  Atlanta, Georgia: Ardent Media, 
Inc., 2011: 50.  Table 3-2.  Hepatol 2010; 52:2216-2222. 
Hunt CM, Papay JI, Stanulovic V, Regev A. Drug rechallenge following drug-induced 
liver injury. Hepatology. 2017 Aug;66(2):646-654. 
ICH E2A: International Conference on Harmonisation Tripartite Guideline:  Clinical 
Safety Data Management: Definitions and Standards for Expedited Reporting (1994). 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA et al. 
Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen 
overdose and acute liver failure. Drug Metab Dispos 2009;37(8):1779-1784. 
Janssen Document Number EDMS-ERI-198151177. Rilpivirine Population 
Pharmacokinetics Report.  A phase IIIb, randomized, multicenter, parallel-group, non-
inferiority, open-label study evaluating the efficacy, safety and tolerability of long-acting 
cabotegravir plus long-acting rilpivirine administered every 8 weeks or every 4 weeks in 
HIV-1-infected adults who are virologically suppressed-Study 207966 (ATLAS 2M)-
Week 48 Analysis.  Effective date:  19-Dec-2019. 
Kerchberger AM, Sheth AN, Angert CD, Mehta CC, Summers NA, Ofotukun I, et al. 
Integrase strand transfer inhibitors are associated with weight gain in women. Conference 
on Retroviruses and Opportunistic Infections, Seattle, abstract 672, 2019. 
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et.al. A new 
equation to estimate glomerular filtration rate.  Ann Int Med. 2009; 150: 604-12. 
McCann K, Moorhouse M, Sokhela S, Daniel W, Venter F, Serenata C, et al. The 
ADVANCE clinical trial: changes from baseline to week 96 in DXA-assessed body 
composition in TAF/FTC + DTG compared to TDF/FTC + DTG, and TDF/FTC/EFV. 
17th European AIDS Conference, Basel, Switzerland, abstract PS3, 2019 
McComsey GA, Eron JJ, Santiago S, Mounzer K, Moyle G, Vanig T, et al. Weight gain 
during treatment among 3,468 treatment experienced adults with HIV. Conference on 
Retroviruses and Opportunistic Infections, Seattle, abstract 671, 2019. 
McGowan I, Siegel A, Engstrom J, Nikiforov A, Duffill K, Edick S, et al. Persistence of 
rilpivirine following single dose of long-acting injection. 21st International AIDS 
Conference (AIDS 2016). July 18-22, 2016. Durban, South Africa. Abstract TUAC0103. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
237 
 
Molina J, Ward D, Brar I, Mills A, Stellbrink H, Lopez-Cortes L, et al. Switching to 
fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus 
abacavir and lamivudine in virologically suppressed adults with HIV-1:  48 week results 
of a raondmised, double-blind, multicentre, active-controlled, phase 3, non-inferiority 
trial. Lancet HIV. 2018; 5: e357–65 
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, et al. Drug-induced liver injury 
following positive 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. 
Rilpivirine Clinical Investigator Brochure (RPV IB), Edition 12, Effective Date: July 
2021. 
Sato T. On the variance estimator for the Mantel-Haenszel risk difference. Biometrics. 
1989. 45(4), 1323-1324. 
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. 
UNAIDS, 2019, Geneva Switzerland, AIDS Data 
Vallet-Pichar A, Mallet M, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, et al. 
FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection.  Comparison 
with liver biopsy and fibrotest. Hepatology. 2007:46(1) 32-36. 
Wensig AM, Calvez V, Ceccherini-Silberstein F, Charpentier C, Gunthard HF, Paredes 
R, et al. IAS-USA 2019 update of the drug resistance mutations in HIV-1.  Top Antivir 
Med. 2019;27(3):111-121. 
Woodcock A, Bradley C. Validation of the HIV Treatment Satisfaction Questionnaire 
(HIVTSQ). Quality of Life Research. 2001: 10, 517-531. 
Woodcock A, Bradley C. Validation of the revised 10-item HIV Treatment Satisfaction 
Questionnaire status version (HIVTSQs) and the new change version (HIVTSQc). Value 
in Health. 2006: 9(5) 320-333. 
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. 


TMF-14364917  
CONFIDENTIAL 
 
 
 
213500 
 
 
 
 
238 
 
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 
 
 

SAP_001.pdf: 
Reporting and Analysis Plan 
 
 
 
Study ID:  213500 
 
Official Title of Study:  Reporting and Analysis Plan Amendment 1 for 213500:  
A Phase IIIb, Randomized, Multicenter, Active-controlled, Parallel group, Non-inferiority, 
Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-
acting Cabotegravir Plus Long-acting Rilpivirine Administered Every Two Months from a 
Bictegravir/emtricitabine/tenofovir alafenamide Single Tablet Regimen in HIV-1 Infected 
Adults who are Virologically Suppressed. 
 
IND No.: 109,678 
 
EudraCT No.: 2020-002623-11 
 
Date of Document: 10-May-2023  
 
 
 


 
C O N FI D E N TI A L  
T h e G S K  gr o u p of c o m p a ni e s  
 
2 1 3 5 0 0  
 
1  
 
Di visi o n  
: W orl d wi de  De vel o p me nt  
I nf or m ati o n T y pe 
: Re p orti n g a n d A nal ysis Pla n  ( R A P) 
 
Title  
: Re p orti n g a n d A nal ysis Pla n A me n d me nt 1 f or 2 1 3 5 0 0:  A 
P hase III b, Ra n d o mize d, M ultice nter, Acti ve -c o ntr olle d, 
Parall el gr o u p, N o n -i nf eri orit y, O pe n-la bel St u d y 
E val uati n g t he Efficac y, Safet y, a n d T olera bilit y of 
S witc hi n g t o L o n g -acti n g Ca b ote gra vir Pl us L o n g -acti n g 
Ril pi viri ne A d mi nistere d E ver y T w o M o nt hs fr o m a  
Bicte gra vir/e mtri cita bi ne/te n of o vir alafe na mi de Si n gle 
Ta blet Re gi me n i n HI V -1 I nfect e d A d ults w h o are 
Vir ol o gicall y S u p presse d  
C o m p o u n d N u m ber  : G S K 1 2 6 5 7 4 4  
Cli nic al St u d y 
I de ntifier 
: 2 1 3 5 0 0  
Effecti ve D ate  
: Refer t o D oc u m e nt date  
 
Descri pti o n:  
•  
T he p ur p ose of t his R A P is t o descri be t he pla n ne d a nal ys es a n d o ut p ut t o b e 
i ncl u de d i n t he Cli nical St u d y Re p ort f or Pr ot oc ol 2 1 3 5 0 0.  
•  
T his R A P descri be s t he statistical a nal ys es re q uir e d f or t he i nteri m a nal ysis w he n 
all partici pa nts ha ve c o m plete d t heir M o nt h 6 ( O LI a n d BI K)/ M o nt h 5 ( D 2I) visit . 
•  
T h e R A P  als o pr o vi des  t he c o nte nt of t he Pri mar y M o nt h 1 2 ( O LI a n d 
BI K)/ M o nt h 1 1 ( D 2I) St atistical A nal ysis C o m plete ( S A C) deli vera ble.  
•  
T he sec o n d a me n d me nt pr o vi des t he c o nte nt of t h e E n d of St u d y ( E o S) re p orti n g.  
 
R A P A ut h or(s):  
A ut h or  
D ate  
Le a d  
 
  
Refer t o D oc u m e nt 
Date  
Pri nci pal Statisticia n (HI V, Cli nical Statistics ) 
 
C o p yri g ht 2 0 2 3  t he G S K  gr o u p of c o m pa nies. All ri g hts res er ve d.  U na ut h orise d c o p yi n g 
or use of t his i nf or mati o n is pr o hi bite d.
P P D


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2  
 
Cli nic al St atistics & Cli nic al Pr o gr a m mi n g Li ne A p pr o v als  
( Met h o d: P h ar m a T M F e Si g n at ure) 
A p pr o ver  
 
 (HI V, Cli nical  Statistics ) 
 
 
P P D
P P D


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
3  
 
T A B L E O F C O N T E N T S  
P A G E  
1.  
I N T R O D U C TI O N ...................................................................................................... 7  
2.  
S U M M A R Y O F K E Y P R O T O C O L I N F O R M A TI O N  .................................................. 8  
2. 1.  
C h a n g e s t o t h e Pr ot o c ol D efi n e d St ati sti c al A n al y si s Pl a n  ............................ 8  
2. 2.  
St u d y O bj e cti v e( s) a n d E sti m a n d( s) / E n d p oi nt( s)  ......................................... 9  
2. 3.  
St u d y D e si g n  .............................................................................................. 1 2  
2. 4.  
St ati sti c al H y p ot h e s e s / St ati sti c al A n al y s e s  ............................................... 1 3  
3.  
P L A N N E D A N A L Y S E S  .......................................................................................... 1 4  
3. 1.  
I nt eri m A n al y s e s ......................................................................................... 1 4  
3. 2.  
Fi n al A n al y s e s  ............................................................................................ 1 4  
3. 3.  
E n d of St u d y ( E O S) A n al y s e s  ..................................................................... 1 4  
4.  
A N A L Y SI S P O P U L A TI O N S  ................................................................................... 1 5  
4. 1.  
Pr ot o c ol D e vi ati o n s  ..................................................................................... 1 6  
5.  
C O N SI D E R A TI O N S F O R D A T A A N A L Y S E S A N D D A T A H A N D LI N G 
C O N V E N TI O N S  ..................................................................................................... 1 7  
5. 1.  
St u d y Tr e at m e nt & S u b -gr o u p Di s pl a y D e s cri pt or s  ..................................... 1 7  
5. 2.  
B a s eli n e D efi niti o n s  .................................................................................... 1 7  
5. 3.  
M ulti c e ntr e St u di e s  ..................................................................................... 1 8  
5. 4.  
E x a mi n ati o n of C o v ari at e s, Ot h er Str at a a n d S u b gr o u p s  ............................ 1 8  
5. 4. 1.  
C o v ari at e s a n d Ot h er Str at a  ........................................................ 1 8  
5. 4. 2.  
E x a mi n ati o n of S u b gr o u p s a n d C o v ari at e s  .................................. 1 8  
5. 5.  
M ulti pl e C o m p ari s o n s a n d M ulti pli cit y  ......................................................... 2 1  
5. 5. 1.  
Pri m ar y A n al y si s  .......................................................................... 2 1  
5. 5. 2.  
Ot h er C o m p ari s o n s of I nt er e st  ..................................................... 2 2  
5. 5. 3.  
S e c o n d ar y C o m p ari s o n s  .............................................................. 2 2  
5. 6.  
Ot h er C o n si d er ati o n s f or D at a A n al y s e s a n d D at a H a n dli n g 
C o n v e nti o n s  ................................................................................................ 2 3  
6.  
S T U D Y P O P U L A TI O N A N A L Y S E S  ....................................................................... 2 3  
6. 1.  
O v er vi e w of Pl a n n e d St u d y P o p ul ati o n A n al y s e s  ........................................ 2 3  
7.  
E F FI C A C Y A N A L Y S E S  .......................................................................................... 2 5  
7. 1.  
Pri m ar y Effi c a c y A n al y s e s  .......................................................................... 2 5  
7. 1. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 2 5  
7. 1. 2.  
S u m m ar y M e a s ur e  ...................................................................... 2 5  
7. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 2 5  
7. 1. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 2 6  
7. 1. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 2 6  
7. 2.  
S e c o n d ar y Effi c a c y A n al y s e s  ...................................................................... 2 9  
7. 2. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 2 9  
7. 2. 2.  
S u m m ar y M e a s ur e  ...................................................................... 2 9  
7. 2. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 2 9  
7. 2. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 2 9  
7. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 3 0  
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
4  
 
8.  
S A F E T Y A N A L Y S E S  ............................................................................................. 3 4  
8. 1.  
A d v er s e E v e nt s A n al y s e s  ........................................................................... 3 4  
8. 2.  
A d v er s e E v e nt s of S p e ci al I nt er e st A n al y s e s  .............................................. 3 8  
8. 2. 1.  
A n al y s e s f or I nj e cti o n Sit e R e a cti o n A d v er s e E v e nt s  ................... 4 0  
8. 3.  
Cli ni c al L a b or at or y  ...................................................................................... 4 0  
8. 4.  
Bi o m ar k er A n al y s e s  .................................................................................... 4 1  
8. 4. 1.  
B o n e Bi o m ar k er s  ......................................................................... 4 1  
8. 4. 2.  
R e n al Bi o m ar k er s  ........................................................................ 4 3  
8. 5.  
Ot h er S af et y A n al y s e s  ................................................................................ 4 4  
8. 5. 1.  
E C G  ............................................................................................. 4 4  
8. 5. 2.  
M et a b oli c S y n dr o m e  .................................................................... 4 5  
8. 5. 3.  
A nt hr o p o m etri c pr ofil e  .................................................................. 4 6  
8. 5. 4.  
H O M A -I n s uli n R e si st a n c e ............................................................ 4 6  
9.  
P O P U L A TI O N P H A R M A C O K I N E TI C ( P O P P K) A N A L YS E S  .................................. 4 8  
1 0.  P H A R M A C O KI N E TI C A N A L Y S E S  ......................................................................... 4 8  
1 1.  P H A R M A C O D Y N A MI C ( A N D  / O R BI O M A R K E R) A N AL Y S E S  ............................. 4 8  
1 2.  P H A R M A C O KI N E TI C / P H A R M A C O D Y N A MI C A N A L Y S E S  ................................. 4 8  
1 3.  H E A L T H O U T C O M E S A N A L Y SI S  ......................................................................... 4 8  
1 3. 1.  E n d p oi nt/ V ari a bl e s  ...................................................................................... 4 8  
1 3. 2.  S u m m ar y M e a s ur e  ..................................................................................... 4 9  
1 3. 3.  P o p ul ati o n of I nt er e st  .................................................................................. 4 9  
1 3. 4.  Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ............................... 4 9  
1 3. 5.  St ati sti c al A n al y s e s / M et h o d s  .................................................................... 5 0  
1 3. 5. 1.  
St ati sti c al M et h o d ol o g y S p e cifi c ati o n  ........................................... 5 1  
1 4.  VI R O L O G Y  ............................................................................................................ 5 4  
1 5.  R E F E R E N C E S  ....................................................................................................... 5 6  
1 6.  A P P E N DI C E S  ........................................................................................................ 5 8  
1 6. 1.  A p p e n di x  1: Pr ot o c ol D e vi ati o n M a n a g e m e nt a n d D efi niti o n s f or P er 
Pr ot o c ol P o p ul ati o n  ..................................................................................... 5 8  
1 6. 1. 1.  
E x cl u si o n s fr o m P er Pr ot o c ol P o p ul ati o n  ..................................... 5 8  
1 6. 2.  A p p e n di x 2: S c h e d ul e of A cti viti e s  .............................................................. 6 0  
1 6. 3.  A p p e n di x 3: A s s e s s m e nt Wi n d o w s  ............................................................. 7 4  
1 6. 3. 1.  
D efi niti o n s of A s s e s s m e nt Wi n d o w s f or A n al y s e s  ........................ 7 4  
1 6. 3. 2.  
D efi niti o n s of A s s e s s m e nt Wi n d o w s f or D at a Ot h er t h a n 
H e alt h O ut c o m e s  ......................................................................... 7 5  
1 6. 3. 3.  
A s s e s s m e nt Wi n d o w f or St u d y C o n cl u si o n  .................................. 8 7  
1 6. 3. 4.  
A s s e s s m e nt Wi n d o w f or H e alt h O ut c o m e D at a  ........................... 8 7  
1 6. 3. 5.  
M ulti pl e  a s s e s s m e nt s  wit hi n a n A n al y si s Wi n d o w  ........................ 8 9  
1 6. 4.  A p p e n di x 4: St u d y P h a s e s a n d Tr e at m e nt St at e  ......................................... 9 0  
1 6. 4. 1.  
St u d y P h a s e s  .............................................................................. 9 0  
1 6. 4. 2.  
St u d y P eri o d s  .............................................................................. 9 4  
1 6. 4. 3.  
Tr e at m e nt St at e  ........................................................................... 9 6  
1 6 . 4. 4. 
C o m bi ni n g Tr e at m e nt P h a s e s a n d St at e s  .................................... 9 7  
1 6. 5.  A p p e n di x 5: D at a Di s pl a y St a n d ar d s & H a n dli n g C o n v e nti o n s  .................... 9 8  
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5  
 
1 6. 5. 1.  
R e p orti n g Pr o c e s s  ....................................................................... 9 8  
1 6. 5. 2.  
R e p orti n g St a n d ar d s  .................................................................... 9 8  
1 6. 6. 
A p p e n di x 6: D eri v e d a n d Tr a n sf or m e d D at a  ............................................. 1 0 0  
1 6. 6. 1.  
G e n er al  ...................................................................................... 1 0 0  
1 6. 6. 2.  
St u d y P o p ul ati o n  ........................................................................ 1 0 3  
1 6 . 6. 3. 
Effi c a c y  ...................................................................................... 1 0 6  
1 6. 6. 4.  
S af et y  ........................................................................................ 1 0 8  
1 6. 6. 5.  
P h ar m a c o ki n eti c  ........................................................................ 1 1 4  
1 6. 6. 7.  
Vir al G e n ot y p e a n d P h e n ot y p e  .................................................. 1 1 9  
1 6. 7. 
A p p e n di x 7: R e p orti n g St a n d ar d s f or Mi s si n g D at a  ................................... 1 2 3  
1 6. 7. 1.  
Pr e m at ur e Wit h dr a w al s  .............................................................. 1 2 3  
1 6. 7. 2.  
H a n dli n g of Mi s si n g D at a  ........................................................... 1 2 3  
1 6. 8.  A p p e n di x 8: V al u e s of P ot e nti al Cli ni c al I m p ort a n c e  ................................. 1 2 6  
1 6. 9.  A p p e n di x 9: S n a p s h ot Al g orit h m D et ail s  ................................................... 1 2 7  
1 6. 1 0.  A p p e n di x 1 0: V ari a bl e s D efi n e d f or Ti m e t o E v e nt A n al y si s  ...................... 1 3 4  
1 6. 1 1.  A p p e n di x 1 1: I d e ntifi c ati o n of A d v er s e E v e nt s of S p e ci al I nt er e st 
( A E SI) ....................................................................................................... 1 3 6  
1 6. 1 1. 1.  H e p ati c S af et y Pr ofil e  ................................................................ 1 3 6  
1 6. 1 1. 2.  H y p er s e n siti vit y R e a cti o n s ( H S R)  .............................................. 1 3 9  
1 6. 1 1. 3.  R a s h  .......................................................................................... 1 4 0  
1 6. 1 1. 4.  Pr ol o n g ati o n of t h e C orr e ct e d Q T I nt er v al of t h e E C G i n 
S u pr at h er a p e uti c D o s e s  ............................................................ 1 4 1  
1 6. 1 1. 5.  S ui ci d al I d e ati o n/ B e h a vi o ur  ....................................................... 1 4 1  
1 6. 1 1. 6.  D e pr e s si o n  ................................................................................ 1 4 2  
1 6. 1 1. 7.  Bi p ol ar Di s or d er  ......................................................................... 1 4 3  
1 6. 1 1. 8.  P s y c h o si s  .................................................................................. 1 4 3  
1 6. 1 1. 9.  M o o d Di s or d er s  ......................................................................... 1 4 5  
1 6. 1 1. 1 0.  A n xi et y  ....................................................................................... 1 4 6  
1 6. 1 1. 1 1.  Sl e e p Di s or d er s  ......................................................................... 1 4 9  
1 6. 1 1. 1 2.  I nj e cti o n Sit e R e a cti o n s (I S R) .................................................... 1 5 2  
1 6. 1 1. 1 3.  S ei z ur e s a n d S ei z ur e -li k e E v e nt s .............................................. 1 5 2  
1 6. 1 1. 1 4.  W ei g ht G ai n  ............................................................................... 1 5 5  
1 6. 1 1. 1 5.  R h a b d o m y ol y si s  ........................................................................ 1 5 6  
1 6. 1 1. 1 6.  P a n cr e atiti s  ................................................................................ 1 5 7  
1 6. 1 1. 1 7.  I m p a ct o n Cr e ati ni n e .................................................................. 1 5 7  
1 6. 1 1. 1 8.  S af et y i n Pr e g n a n c y  ................................................................... 1 5 9  
1 6. 1 2.  A p p e n di x 1 2: I d e ntifi c ati o n of C O VI D -1 9 A d v er s e E v e nt s  ......................... 1 6 0  
1 6. 1 3.  A p p e n di x 1 3: D at a H a n dli n g f or Pr e g n a nt S u bj e ct s  .................................. 1 6 1  
1 6. 1 4.  A p p e n di x 1 4: A b br e vi ati o n s & Tr a d e M ar k s  .............................................. 1 6 2  
1 6. 1 4. 1.  A b br e vi ati o n s  ............................................................................. 1 6 2  
1 6. 1 4. 2.  Tr a d e m ar k s  ............................................................................... 1 6 4  
1 6 . 1 5. A p p e n di x 1 5: Li st of D at a Di s pl a y s ............................................................ 1 6 5  
1 6. 1 5. 1.  D at a Di s pl a y N u m b eri n g  ............................................................ 1 6 5  
1 6. 1 5. 2.  M o c k E x a m pl e S h ell R ef er e n ci n g  .............................................. 1 6 5  
1 6. 1 5. 3.  D eli v er a bl e s  ............................................................................... 1 6 5  
1 6. 1 5. 4.  St u d y P o p ul ati o n T a bl e s  ............................................................ 1 6 6  
1 6. 1 5. 5.  Effi c a c y T a bl e s  .......................................................................... 1 6 9  
1 6. 1 5. 6.  Effi c a c y Fi g ur e s  ......................................................................... 1 7 6  
1 6 . 1 5. 7. S af et y T a bl e s  ............................................................................. 1 7 7  
1 6. 1 5. 8.  S af et y Fi g ur e s  ........................................................................... 1 9 2  
1 6. 1 5. 9.  H e alt h O ut c o m e T a bl e s  ............................................................. 1 9 5  
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
6 
 
16.15.10. Virology Tables .......................................................................... 199 
16.15.11. ICH Listings ............................................................................... 201 
16.15.12. Non-ICH Listings ........................................................................ 204 
16.16. Appendix 16: Example Mock Shells for Data Displays .............................. 210 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
7  
 
1.  
I N T R O D U C TI O N 
T he p ur p ose of t his r e p orti n g a n d a n al ysis pla n ( R A P) is t o descri be t he a n al yses t o b e 
i ncl u de d i n t he Cli nical St u d y Re p ort f or Pr ot oc ol: 
Re vi si o n C hr o n ol o g y:  
2 0 1 9 N 4 2 5 7 25 _ 0 0 
2 7 -M A Y -2 0 2 0  
Ori gi nal  
2 0 1 9 N 4 2 5 7 25 _ 0 1  
3 0 -J U N-2 0 2 0  
T h e pri mary r e as o n for pr ot ocol a m en d m e nt 0 1 is t o a d d 
mi n or cl arific ati o ns t o a ddr ess st u dy c o mpl etio n, P K 
c oll ecti on, a n d e n d p oi nt ti mi ngs. C o u ntry-s p ecific d et ails 
w er e a d d e d to A p p e n dix 10 t o a d dr ess U K M H R A  
r e q uir e me nts. T h e pr otoc ol s hort titl e w as u p dat e d.  
C orr ecti o ns t o ty p o gr ap hical err ors i n prot oc ol t ext a n d titl e 
w er e m a d e  thr o u g h out. 
T M F -1 2 4 7 34 0 7  
0 8 -S E P -2 0 2 1  
T h e pri mary r e as o n for pr ot ocol a m en d m e nt 0 2 is t o a d dr ess 
a n d clarify c o m m e nts r ais e d  duri n g t h e c o urs e of th e stu dy 
a n d t o i m pl e m e nt c o u ntry sp ecific c h an g es f ollo wi n g  
r e g ul at ory r evi e w. 
T M F -1 4 3 6 49 1 7  
1 0 -F E B -2 0 2 2  
T h e pri mary r e as o n for pr ot ocol a m en d m e nt 0 3 is t o a d dr ess 
a n d clarify c o m m e nts r ais e d duri n g t h e c o urs e of th e stu dy.  
T hi s fi r st a m e n d m e nt i n cl u de s a m e n d me nt s t o t h e ori gi nall y a p pr o v e d R A P eff e ctiv e 2 7 D e c 2 0 2 1 . T h e 
f oll o wi ng c h an g es w ere m a de pri or t o t he M 1 2 pri mary  a nalysis:  
M aj or  ( a pplic a ble t o M1 2 o nly): 
•  
U p d at e d pri m ary a n alysis  p o pul ati o n t o  mI T T -E  excl u din g subj ects fr o m sit e 
 
•  
A d d e d m o difi ed C V F  ( m C V F) p o p ul ati o n exclu di ng s u bj ects fr o m sit e 
 
•  
U p d at e d t h at P er Pr ot ocol ( P P) will b e bas e d o n mI T T -E  
•  
U p d at e d i n Ap p e n dix 1 5 a n alysis po p ul ati o n for t h e M 1 2 an alysis t a bl es  
 
Mi n or  (ty p o corr ecti o ns, cl arificati o ns, a d diti o n al dis pl ays  an d f or m at c h a n g es ): 
•  
U p d at e d i n Sectio n 2. 2  i n co nsist e ncy wit h u p d ates in pr ot ocol a m en d m e nt 3 
•  
U p d at e d i n Ap p e n dix 2  
•  
U p d at e d i n Sectio n 8. 4  th at “I nt er acti ons bet w e e n tr e at m e nt a n d e ac h of t he c ov ari ates will n ot b e 
ass ess e d” F or M M R M m od els.  
•  
U p d at e d t h e titl e f or t h e listi n g “ Listi ng of HI V-1 Ass oci at e d Co n diti ons “ to “Listi n g of St a g e 3 HI V -1 
Ass oci at e d C o nditio ns ”. 
•  
U p d at e d t h e titl e f or S af ety Fi gur e 3. 2 “ Pl ot of I nci d enc e of Mai nt e n anc e P h as e Dr u g -R el ate d 
I nj ecti o n Site R e acti o n A dverse Ev e nts by Visit ( Ov erall an d C o m m o n)” by a d di n g “ Dr u g -Rel at e d” 
t o t h e titl e f or accur acy 
•  
U p d at e d t h e titl e f or S af ety Fi gur e 3. 3 “ Pl ot of I nci d enc e of Gr a d e 3 -5 Mai nt en a nce P h ase Dr u g -
R el at e d I nj ecti o n Site R e acti on A dv erse Ev e nts by Visit ( Over all a nd C o m mo n)” by a d din g “ Dr u g -
R e l at e d” t o th e titl e f or accur acy 
•  
U p d at e d t h e titl e f or S af ety Fi gur e 3. 9 “ Pl ot of I nci d enc e of Mai nt e n anc e P h as e Dr u g -R el ate d 
I nj ecti o n Site R e acti o n A dverse Ev e nts by Str ata a n d Visit ( Ov er all a nd C o m mo n) - C A B an d/ or 
R P V” by a d di ng “ Dr u g -R el at ed” t o t h e titl e f or accur acy 
P P D
P P D


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
8  
 
•  
Cl arifi e d S af ety Ta bl e 3. 6 4 “ Su m m ary of P erce nt of S ubj ects wit h M et a b olic Sy n dr o me a nd Risk 
F act ors” is f or “ M aint e n a nc e Ph as e”  
•  
R e m ov e d th e o utp ut “ Pr o p ortio n of S u bjects wit h Pl as m a HI V -1 R N A < 2 c/ m L –  O bserv e d C as e 
A n alysis ( M ai nt en a n ce P h ase)” 
•  
M ov e d  t h e listin g of net ass ess m e nt d at a int o se p ar at e listi ngs f or C V F a n d n o n-C V F s ubjects du e 
t o s p ac e li mit i n t h e o ut p ut fil es ( 2 extra listi ngs a dd e d) 
•  
Divi d e d t h e fig ur e “P atie nt Pr ofil e Pl ot of Cli nic al Di a g nosis Fact ors for P ati ents wit h  M et abolic 
Sy n dr o m e at A ny Ti m e Poi nt ” t o s e p arat e fig ur es for O LI, D 2I a n d BI K d u e t o s pac e li mit  i n t h e 
o ut p ut  fil es (2 extra fi g ures a dd e d) 
•  
C orr ect e d  a ty p o  i n S ecti o n 16. 1 5. 9  t h at t h e a nalysis p o p ul atio n f or H e alth O utc o mes t abl e 6. 13  
“ Pr o p orti o n of S u bj ects Sc ori ng E ac h O pti on i n t he 
 Qu esti o n n air e at M ont h 1 3” 
is “ Ext ensi on S witc h” i nste a d of I T T-E.  
•  
A d d e d i n S ecti on 1 6. 15. 9  “ St atistic al A n alysis of HI V T S Qs - C h a n g e fr o m M aint e n a nc e B as eli ne 
( Day 1) i n Tot al Tr eat m ent S atisf acti o n Sc or e a nd i n divid u al it e ms 5 (co nv e ni ent), 6 (fl exi ble) a n d 
1 0 (c o nti n u e) ( M ai nte n a nc e Ph as e) by B as eli n e Sc or e Gr o up” a n d “ S u m m ary of S hift i n  
 
”. 
•  
U p d at e d d escripti o n  i n t he 
 q u esti o nn air e i n S ectio n 1 6.6. 6  t o ali gn wit h e C R F 
w or di n g . 
•  
C orr ect e d t hat t h e an alysis p op ul ati on f or listi n g “ Listi ng of Plas m a P K C o nc e ntr ati o ns at 
Wit h dr a w al” will b e I T T -E.  
•  
A d d e d i n S ecti on 1 6. 15. 1 2  “Listi n g of All Plas ma P K C o nc e ntr ati o ns f or C V F S u bj ects” . 
•  
A d d e d clarific ati on i n S ecti on 1 6. 1 5. 1 2  t h at t he f oll o wi n g t w o dis plays will n ot b e pr o d uc e d if n o 
s u bj ect b ec o m es pr e gn a nt on Q 2 M: " Listi n g of S el ect e d La bor at ory D at a f or S u bjects W h o 
B ec a m e Pr eg n a nt D uri n g t h e St u dy", " Listi n g of Pl as m a P K Co nc e ntr ati o ns f or S u bjects Wh o 
B ec a m e Pr eg n a nt D uri n g t h e St u dy".  
•  
A d d e d clarific ati on o n dat a h an dli n g str at egy f or Q 2 M s u bj ects w h o b ec o m e pr e g n ant o n stu dy i n 
S ecti o n  1 6. 1 3 . 
T h e s e c o n d  a m e n d m e nt i n cl u d e s a m e n d me nt s t o t h e R A P a m e n d m e nt #1 eff e cti ve 15 -J u n -2 0 2 2, t he 
f oll o wi n g c ha n g e s w er e m a d e: 
S ecti o n 1 6. 5  w as u p d ate d  t o pr ovi d e a d diti o n al d et ails of t h e pl a n n e d a n alys es a n d d at a displ ays f or 2 13 5 0 0  
E O S Fi n al re p ortin g.  
2.  
S U M M A R Y O F K E Y P R O T O C O L I N F O R M A TI O N  
2. 1.  
C h a n g e s t o t h e Pr ot o c ol D efi n e d St ati sti c al A n al y si s Pl a n  
D ue t o critical a u dit fi n di n gs at site  
 relate d t o critical i ncl usi o n/e xcl usi o n criteria 
vi olati o ns a n d maj or  G C P n o n -c o m plia nce ( re p orti n g letter t o F D A s u b mitte d), effi cac y 
data fr o m t his site is dee me d u nrelia ble a n d as s u c h t he M 1 2 pri mar y a nal ysis p o p ulati o n 
will e x cl u de all 1 1 ra n d o mize d site partici pa nts ( mI T T -E). Efficac y a n al ysis i n t he “ mI T T -
E” p o p ulati o n will be c o nsi dere d pri mar y. A d diti o nal (se nsiti vit y) efficac y a n al yses will 
be perf or me d f or t he I T T -E p o p ulati o n a n d t his a nal ysis 
will be c o nsi dere d 
sec o n dar y/s u p p orti ve. Safet y a nal yses 
will re mai n as pla n ne d a n d 
will i ncl u de all 
ra n d o mize d s u bjects w h o recei ve d at least o ne d ose of st u d y treat me nt ( Safet y). F or 
vir ol o g y ta bles (if a p plica ble) a n d o ne efficac y ta ble, t he m C V F p o p ulati o n will be 
s u m marize d e x cl u di n g a n y s u bject fr o m t he site. All listi n gs a n d s u bject -le vel fi g ures will 
be pr o d uce d as pla n ne d, wit h o ut e x cl usi o n of t he site, w here a p plica ble. See A p pe n di x 1 5 . 
N ote t his u p date is ma de after t he M o nt h 6 b ut pri or t o t he M 1 2 a nal ysis t heref ore s uc h 
c ha n ges are o nl y a p plica ble t o t he M 1 2 a nal ysis.  
C CI
C CI
P P D
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
9 
 
2.2. 
Study Objective(s) and Estimand(s) / Endpoint(s) 
Objectives 
Estimands/Endpoints 
Primary 
To demonstrate the non-inferior antiviral activity of 
CAB LA + RPV LA every two months compared to 
a BIK single tablet regimen administered once 
daily over 12 months in suppressed HIV-1 infected 
antiretroviral therapy (ART)-experienced 
participants 
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 Month 12 (OLI and BIK)/Month 11 (D2I) (Intent-
to-Treat Exposed [ITT-E] population) 
Secondary 
To demonstrate the antiviral and immunologic 
response with the use of CAB LA + RPV LA every 
2 months compared to a BIK single tablet regimen 
administered once daily 
Proportion of participants with plasma HIV-1 RNA 
<50 c/mL (c/mL) at Month 6 and Month 12 (OLI 
and BIK)/Month 5 and Month 11 (D2I) using the 
FDA Snapshot algorithm (Intent-to-Treat Exposed 
[ITT-E] population) 
Proportion of participants with protocol-defined 
confirmed virologic failure (CVF) through Month 6 
and Month 12 (OLI and BIK)/Month 5 and Month 
11 (D2I). 
Proportion of participants with HIV-RNA greater 
than or equal to 50 c/mL as per FDA Snapshot 
algorithm at Month 6, and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I) 
Absolute values and changes from Baseline in viral 
load and CD4+ cell count over time including 
Month 6 and Month 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I) 
To assess viral resistance in participants 
experiencing protocol-defined confirmed virologic 
failure  
Incidence of treatment emergent genotypic and 
phenotypic resistance to CAB, RPV, BIC, FTC, and 
TAF through Month 6 and Month 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I). 
To evaluate renal (in urine and blood) and bone (in 
blood) biomarkers in participants treated with CAB 
LA + RPV LA compared to BIK 
Change from Baseline (Day 1) in renal and bone 
biomarkers at Months 6 and 12 (OLI and 
BIK)/Month 5 and Month 11 (D2I). 
To evaluate Metabolic Syndrome for participants 
treated with CAB + RPV and BIK 
Change from Baseline in proportions of 
participants with Metabolic syndrome at Months 6 
and 12 (OLI and BIK)/Month 5 and Month 11 (D2I) 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
10 
 
Objectives 
Estimands/Endpoints 
To evaluate insulin resistance in participants 
treated with CAB LA + RPV LA compared to BIK 
Change from Baseline (Day 1) in homeostasis 
model of assessment-insulin resistance (HOMA-
IR) at Months 6 and 12 (OLI and BIK)/Month 5 and 
Month 11 (D2I). 
To assess preference for CAB LA + RPV LA 
administered every 2 months compared to a BIK 
single tablet regimen administered once daily  
 
Preference for CAB LA + RPV LA every 2 months 
compared to a BIK single tablet regimen will be 
assessed using a preference questionnaire at 
Month 12 (OLI )/Month 11 (D2I) (or Withdrawal). 
To assess patient reported treatment satisfaction, 
and injection tolerability. 
Change from baseline (Day 1) in total “treatment 
satisfaction” score, and individual item scores of 
the HIV Treatment Satisfaction Status 
Questionnaire (HIVTSQs) at Month 6 and Month 
12 (OLI and BIK)/Month 5 and Month 11 (D2I), (or 
Withdrawal) 
Change in treatment satisfaction over time using 
the HIV Treatment Satisfaction Change 
Questionnaire HIVTSQc total score and individual 
item scores at Month 12 (OLI and BIK)/Month 11 
(D2I) (or Withdrawal). 
Change from Month 2 in Dimension scores 
(“Acceptance of ISRs”, “Bother of ISRs”, “Leg 
movement”, “Sleep”) 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) will be assessed using 
the Perception of injection questionnaire (PIN) at 
Months 2, 6, and 12 (OLI)/Months 1, 5, 11 (D2I) (or 
Withdrawal)  
Safety 
To evaluate the safety and tolerability of CAB LA + 
RPV LA every 2 months compared to a BIK single 
tablet regimen administered once daily 
Incidence and severity of AEs and laboratory 
abnormalities over time including Month 6 and 
Month 12 (OLI and BIK)/Month 5 and Month 11 
(D2I). 
Proportion of participants who discontinue 
treatment due to AEs over time including Month 6 
and Month 12 (OLI and BIK)/Month 5 and Month 
11 (D2I). 
Change from Baseline in laboratory parameters 
over time including Month 6 and Month 12 (OLI 
and BIK)/Month 5 and Month 11 (D2I). 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 1  
 
O bj e cti ve s  
E sti m a n d s/ E n d p oi nt s  
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
12 
 
 
2.3. 
Study Design 
Overview of Study Design and Key Features 
Design 
Features 
• 
The Solar Study (213500) is a Phase IIIb, randomized, open-label, active-
controlled, multicenter, parallel-group, non-inferiority study designed to assess the 
antiviral activity and safety of a two-drug regimen of CAB LA + RPV LA 
administered every 2 months compared with maintenance of BIK.   
• 
The study comprises a Screening Phase (up to 35 days), a Maintenance Phase, 
and an Extension Phase. Any participant who receives at least one dose of CAB LA 
CCI


 
CONFIDENTIAL 
 
 
 
213500 
 
13 
 
Overview of Study Design and Key Features 
and/or RPV LA and discontinues the CAB LA + RPV LA regimen for any reason will 
enter the Long-term Follow-up Phase on suppressive HAART for at least 52 weeks 
after the last dose of CAB LA and/or RPV LA. 
Dosing 
• 
Maintenance Phase:  
- 
CAB LA (600 mg) + RPV LA (900 mg) IM every 2 months 
- 
Oral BIK once daily   
• 
Extension Phase:  
- 
CAB LA (600 mg) + RPV LA (900 mg) IM every 2 months 
Time & 
Events 
• 
[Refer to Appendix 2] 
Treatment 
Assignment 
• 
Maintenance Phase: Approximately 654 subjects randomized 2:1 to CAB LA + RPV 
LA vs. Oral BIK. Subjects randomized to receive CAB LA + RPV LA may choose to 
begin oral therapy with CAB 30 mg + RPV 25 mg once daily (OLI) prior to 
administration of CAB LA + RPV LA, or transition directly to injections (D2I).  
• 
Extension Phase: if meeting eligibility requirements, subjects randomized to CAB 
LA + RPV LA will continue to have access to their randomized regimen; subjects 
randomized to BIK will have the option to either continue study participation by 
switching to CAB LA + RPV LA, or complete the study at Month 12. 
• 
GSK RandAll NG will be used to generate randomization schedules. 
• 
Stratified Randomization by participants’ Baseline BMI (< 30 kg/m2 ,  30 kg/m2) 
and Gender at Birth (female, male). 
Interim 
Analysis 
• 
An interim analysis will be conducted when all participants have completed their 
Month 6 (OLI and BIK)/Month 5 (D2I) visit.  
• 
The main analysis will be conducted to evaluate the primary objective of the 
protocol at Month 12(OLI and BIK)/Month 11(D2I). 
• 
Further data cuts and analyses may be conducted as necessary in order to support 
regulatory submissions and publications. 
 
 
2.4. 
Statistical Hypotheses / Statistical Analyses 
The study is to demonstrate the non-inferior antiviral activity of CAB LA + RPV LA 
(Q2M) every 2 months compared to a BIK single tablet regimen administered once daily 
over 12 months in suppressed HIV-1 infected antiretroviral therapy (ART)-experienced 
participants. 
Non-inferiority will be concluded if the upper limit of a two-sided 95% confidence 
interval for the difference in proportion of participants with HIV-1 RNA ≥ 50 c/mL at 
Month 12 (OLI and BIK)/Month 11 (D2I) between the two treatment arms (Q2M - BIK) 
is less than 4%. Note that efficacy data for the primary endpoint from the OLI subjects at 
Month 12 and from the D2I subjects at Month 11 will be combined for the Q2M arm 
when assessing non-inferiority. 
Let pc, pb be the proportion of participants with HIV-1 RNA ≥ 50 c/mL in the CAB 
LA+RPV LA (Q2M) and BIK arms respectively, then the primary statistical hypothesis 
can be written as follows: 
H0:  pc - pb ≥ 4% vs. Ha: pc - pb < 4% 


 
CONFIDENTIAL 
 
 
 
213500 
 
14 
 
3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
An interim analysis will be conducted when all participants have completed their Month 
6 (OLI and BIK)/Month 5 (D2I) visit, focusing on the interim efficacy and key secondary 
efficacy endpoints, as well as key safety endpoints.  
To minimise bias, the Month 6 interim results will not be shared with any participant and 
with most investigators. However, when a lead author(s) for a potential abstract 
presentation of the Month 6 interim results is (are) identified, that investigator(s) and the 
other co-authors on the abstract will have access to the interim results prior to its 
presentation. No other investigators will have knowledge of this data prior to the last 
participant completing their last visit for the primary Month 12 analysis. A Month 6 
interim analysis abstract may be submitted to a conference for consideration only if the 
conference convenes after the Month 12 data collection has been completed.  
Further data cuts and analyses may be conducted as necessary to support regulatory 
submissions, publications or for other purposes. Additionally, information collected on 
pregnant participants as collected in the eCRF may be reported descriptively or listed. 
The Month 12 analysis will be primary. No adjustment for multiplicity caused by 
repeated evaluation of the primary endpoint will be made as the Month 6 interim analyses 
will be secondary.  
3.2. 
Final Analyses 
The primary Month 12 analysis will be conducted to evaluate the primary objective of the 
protocol when all participants have completed their Month 12 (OLI and BIK)/Month 11 
(D2I) visit. These analyses will be performed after the completion of the following 
sequential steps: 
1. All participants have completed their Month 12 (OLI and BIK)/Month 11 (D2I) visit 
as defined in the protocol and had a re-test if necessary 
2. All required database cleaning activities have been completed and final database 
release (DBR), source data lock (SDL) and database freeze (DBF) have been 
declared by Data Management. 
3. All criteria for unblinding the randomization codes have been met.  
4. Randomization codes have been distributed according to RandAll NG procedures. 
3.3. 
End of Study (EOS) Analyses 
A final End-of-Study analysis will be conducted when all subjects have completed the 
study. 
Details of which outputs will be produced at End of Study can be found in Section 16.5. 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 5  
 
4.  
A N A L Y SI S P O P U L A TI O N S  
P o p ul ati o n  
D efi niti o n / Crit eri a  
A n al y s e s E v al uat e d  
S cr e e n e d  
•  
A ll p artici p ants w h o w ere scree n e d f or eli gi bility . 
•  
S u bj ects m ay b e r e -scr ee n e d o nc e a nd will b e 
assi gn e d a n e w s u bj ect n u m ber . 
•  
F or dis positi o n dis pl ays, exc ept f or t h e listi n g of 
s u bj ects w h o w ere r escr e e n ed, o nly th e l at est r e-
scr e e ni n g dat a will b e inclu d ed. 
•  
St u dy P o p ul ati on  
E nr oll e d  
•  
All p artici p ants w h o p ass e d scr e e ni n g a n d e nter e d 
t h e st u dy.  
•  
N ot e scr e eni n g f ailur es ( wh o nev er p ass e d 
scr e e ni n g ev e n if r escr e e n ed) a n d p artici pa nts 
scr e e ne d b ut n ev er e nr oll e d int o t h e stu dy ar e 
excl ud e d fr o m t h e Enr oll ed p op ul ati on  as t h ey di d 
n ot e nt er th e stu dy.  
•  
St u dy P o p ul ati on  
Ra n d o miz e d  
 
•  
A ll p artici p ants  w h o w ere r a n do mly assi g n e d  t o 
tr e at m e nt i n t he st udy. 
•  
T his p op ul ati o n will b e b as ed o n t h e tr eat m e nt t h e 
p articip a nt w as r a n d o mize d t o.  
•  
St u dy P o p ul ati on  
S af ety  
•  
All r a n d o mize d p articip a nts w h o r ec eiv e d at l e ast 
o n e d os e of st u dy tr e at me nt.  
•  
T his p op ul ati o n will b e b as ed o n t h e  act u al  
tr e at m e nt t h e p artici p a nt r ec eiv e d. 
•  
N ot e: p artici p a nts w h o w er e not r a n d o miz ed b ut 
r ec eive d at l e ast o n e dos e of st u dy tr e at m e nt will 
b e list e d se p ar at ely. 
•  
S af ety  
•  
Vir ol o gy (if 
a p plic a bl e)  
I nt e nt-t o-Tr eat 
Ex p os e d (I T T -E)  
•  
All r a n d o mize d p articip a nts w h o r ec eiv e at l e ast 
o n e d os e of I P duri n g th e M aint e n a nc e P h ase of 
t h e st u dy ( o n or aft er D ay 1). 
•  
P artici pa nts will b e a n alyz ed acc or din g t o th e 
r a n d o miz e d tre at m ent r e g ardless of t h e act u al 
tr e at m e nt r ec eiv e d. 
•  
St u dy P o p ul ati on  
•  
Effic acy   
M o difie d I nte nt -
t o-Tr e at ( mI T T -
E)  
•  
All I T T -E s ubj ects exclu di n g t hos e fr o m site
 •  
St u dy P o p ul ati on  
•  
Effic acy  
•  
H e alt h 
O utc o m es  
P er -Pr ot oc ol 
( P P) 
•  
All  p artici p ants i n t h e m I T T-E p o p ul ati o n  exc ept  
m aj or pr ot oc ol viol at ors.   
•  
Pr ot oc ol d eviati o ns t h at excl u de s u bjects fr o m th e 
P er -Pr ot oc ol  p o p ulati o n ar e d efi n e d in S ecti o n 4. 1 
( Pr ot oc ol D evi ati o ns) a n d A p pe n dix 1  ( Pr ot ocol 
D evi ati on M a na g e me nt a nd D efi nitio n f or P er -
Pr ot oc ol P op ul ati o n).  
•  
Effic acy 
( S e nsitivity 
A n alysis)  
Ext e nsio n S witch 
( E S) 
•  
All r a n d o mize d s ubj ects fr o m BI K ar m w h o r eceiv e 
at l e ast o n e d os e of C A B a n d/or R P V d uri n g t h e 
Ext e nsio n P h as e of th e stu dy.   
•  
P artici pa nts will b e ass ess e d acc or di n g t o act ual 
tr e at m e nt r ec eiv e d d uri n g t h e Ext e nsio n P h as e.  
•  
S af ety a nd 
effic acy f or BI K 
s u bj ects 
s witc hin g t o 
Ext e nsio n Q2 M  if 
a p plic a bl e  
 
P P D


 
CONFIDENTIAL 
 
 
 
213500 
 
16 
 
Population 
Definition / Criteria 
Analyses Evaluated 
 
Pharmacokinetic 
(PK) 
• 
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 with at least 1 non-missing PK assessment 
(Non-quantifiable [NQ] values will be considered as 
non-missing values). 
• 
Note: 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. 
• 
PK (Pregnant 
subjects on Q2M 
arm only for this 
RAP) 
Confirmed 
Virologic Failure 
(CVF) 
• 
All participants in the ITT-E population who met 
Confirmed Virologic Failure (CVF) 
• 
CVF during the Maintenance and/or Extension 
Phases is defined as: Rebound as indicated by two 
consecutive plasma HIV-1 RNA levels 200 c/mL 
(Day 1 values not applicable) after prior 
suppression to <200 c/mL 
• 
Virology 
• 
Efficacy 
 
 
Modified 
Confirmed 
Virologic Failure 
(mCVF) 
• 
All participants in the mITT-E population who met 
Confirmed Virologic Failure (CVF) 
• 
Note this population is only applicable to summary 
tables 
• 
Virology 
• 
Efficacy 
 
Long-term 
Follow-up 
(LTFU) 
• 
Discontinued subjects who have received at least 
one dose of CAB LA and/or RPV LA and have met 
any of the following criteria:  
- 
have at least one Long-term Follow-up phase clinic 
visit, 
- 
have filled out the LTFU phase conclusion form,  
- 
or have indicated the continuation to LTFU phase in 
the subject continuation form. 
• 
Safety 
Refer to Appendix 15: List of Data Displays which details the population used for each display. 
 
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. 


 
CONFIDENTIAL 
 
 
 
213500 
 
17 
 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations which may lead to exclusion from the analysis population(s) 
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 
Treatment Group Descriptions 
RandAll NG Randomization System 
Data Displays for Reporting  
Code 
Description 
Description 
Order in TLF  
A 
CAB LA + RPV LA Q2M  
Q2M 
1 
B 
BIK QD 
BIK 
2 
 
Note: Treatment comparisons will be displayed as follows using the descriptors as specified: Q2M vs. BIK (Q2M – 
BIK)  
 
The following sub-display may be used as appropriate under the Q2M treatment group as 
noted in Appendix 15: List of Data Displays. 
 
Data Display for 
Reporting 
Order for sub-display 
For subjects randomized to Q2M during the 
Maintenance Phase 
OLI 
1 
D2I 
2 
 
In data displays of Extension Phase data for the Extension Switch population who 
switched from BIK, “Switch Q2M” will be used. In displays where sub study treatment 
will be displayed, descriptors are as shown below. 
 
Data Display for 
Reporting 
Order for sub-display 
Extension Phase data for the Extension Switch 
population (Switch Q2M) 
Switch OLI 
1 
Switch D2I 
2 
 
5.2. 
Baseline Definitions 
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment with a non-missing value, including those from unscheduled 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 8  
 
visits . If ti me is n ot c ollecte d, Da y 1 assess me nts are ass u me d t o b e ta ke n pri or t o first 
d ose a n d use d as b aseli ne . 
Electr ocar di o gra ms ( E C Gs) are t o be perf or me d i n tri plicate  pri or t o first d ose  o n Da y 1 . 
T he b aseli ne v al ue f or a n E C G para meter will be t he mea n of t he l ast pre -tr eat me nt set of 
assess me nts fr o m t he sa me date.  
U nless ot her wise state d, if baseli ne dat a is missi n g n o deri vati o n will be perf or me d a n d 
baseli ne will be set t o missi n g . 
 
5. 3.  
M ulti c e ntr e St u di e s  
Data will be s u m marize d f or all ce ntr es c o m bi ne d. C o u ntr y ma y  be tr eate d  
 
 a nal ys es of t he pri mar y efficac y e n d p oi nt ( HI V-1 R N A ≥5 0 
c/ m L) as descri be d i n Secti o n 7. 1. 5. 1 . a n d sec o n d ar y efficac y e n d p oi nt ( HI V-1 R N A < 5 0 
c/ m L) as descri be d i n Secti o n  7. 2. 5. 1 . 
 
 
 
5. 4.  
E x a mi n ati o n of C o v ari at e s , Ot h er Str at a a n d S u b gr o u p s 
5. 4. 1.  
C o v ari at e s  a n d Ot h er Str at a  
T he list of c o variates a n d ot her strata ma y be use d i n descri pti ve s u m maries a n d statistical 
a nal ys es, s o me of w hic h ma y als o b e use d f or s u b gr o u p a n al ys es.  A d diti o n al c o variates of 
cli nical i nterest ma y als o be c o nsi dere d  f or a d diti o nal a nal ys es o n Healt h O utc o mes a n d 
Bi o mar ker a nal ys es . 
Cat e g ory  
D et a il s 
Str at a  
•  
F or t h e pr o porti o n of p articip ants wit h pl as m a HI V -R N A gr e at er t h a n or e q u al t o 
5 0 c/ mL p er F D A S n a ps h ot alg orit h m at M ont h 1 2 ( O LI an d BI K)/ M o nt h 1 1 
( D2I) ( pri m ary e n d poi nt), a stratifi e d a n alysis wit h C oc hr a n-M a nt el H ae nsz el 
( C M H) w ei g hts will b e us e d t o a dj ust t h e pri m ary tr e at me nt co m p aris o n wit h t h e 
r a n d o miz atio n strat a corr es p on di n g t o G e nd er  at B irt h (f e mal e, m al e) a n d 
B as eli ne B MI  ( <30 k g/ m 2, 3 0 k g/ m 2).  
•  
A si mil ar a p pro ac h will be used t o a dj ust t he a n alysis of t h e pr o p orti on  of 
p articip a nts wit h HI V -1 R N A <5 0 c/ mL ( p er t he F D A’s S n apsh ot al g orit h m) at 
M o nt h 12 ( O LI a n d BI K)/ Mo nt h 1 1 ( D 2I) 
•  
T h e a n alys es as d escri b ed a bov e will als o b e ap plie d i n t h e int eri m an alysis f or 
k ey effic acy en d p oi nts at M o nth 6 ( O LI a n d BI K)/ Mo nt h 5 ( D 2I).  
Cov ari at es  
S e e d et ails in S ecti o n 5.4. 2 
 
5. 4. 2.  
E x a mi n ati o n of S u b gr o u p s  a n d C o v ari at e s  
T he f oll o wi n g is a list of s u b gr o u ps t hat ma y be use d i n d escri pti ve s u m maries a n d 
statistical a nal ys es. A d diti o nal s u b gr o u ps of cli nical i nterest ma y als o be c o nsi dere d.  
C CI
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
19 
 
• 
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, 2019), factors defining a subgroup 
population may be put in three categories: 
1. Factors with strong reason to expect an inconsistent response to treatment 
across the different levels of the factor to an extent that would make an overall 
assessment uninterpretable. In this case separate trials should usually be 
planned. 
2. Factors with reason to consider it prognostic for outcome, or at least some 
biological plausibility or external evidence such that an inconsistent response 
might be observed. In this study, stratified randomization 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. 
3. Factors with good argumentation why consistency of response to treatment is 
plausible or for which there is absence of pharmacological rationale and 
absence of clinical evidence from which to determine the plausibility of 
consistent drug effects. The impact of factor(s) falling into this category will be 
explored. 
Subgroup Category 
Subgroup and Subgroup Levels  
EMA Subgroup Category 2: 
Randomization Strata 
• 
Baseline BMI: <30 kg/m2, 30 kg/m2 
• 
Gender at Birth: female, male 
 
For analysis purposes, randomization strata will be derived using 
eCRF data (which may differ 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 
- 
Descriptive summaries: < 35, 35 - < 50, ≥ 50 
- 
Statistical analyses: < 50, ≥ 50 
- 
FDAAA: ≤18, 19 - 64, ≥ 65  
- 
EMA: 18 - 64, 65 - 84, ≥ 85  
 
• 
Race 


 
CONFIDENTIAL 
 
 
 
213500 
 
20 
 
Subgroup Category 
Subgroup and Subgroup Levels  
EMA Subgroup Category 2: 
- 
White; Non-White  
- 
Black/ African American; Non- Black/ African 
American 
- 
White, Black/African American, Other  
For statistical modelling of biomarkers, use White, 
Black/African American vs. Other.  
For other statistical modelling, use White vs Non-White. 
 
• 
Country (not used for statistical modelling) 
- 
Canada 
- 
United Kingdom 
- 
Ireland 
- 
France 
- 
Germany 
- 
Spain 
- 
Italy 
- 
Switzerland 
- 
Austria 
- 
Netherlands 
- 
Belgium 
- 
Japan 
- 
Australia 
- 
United States 
 
• 
Region 
North America, Europe, Rest of World 
 
• 
Baseline CD4+ cell count (cells/mm3) 
- 
 <350, 350 to <500, ≥ 500 cells/mm3 
 
• 
Derived Maintenance Baseline (Day 1) Centres for 
Disease Control and Prevention (CDC) category: 
- 
Stage I, Stage II, Stage III 
 
• 
Baseline HIV-1 Subtype (if available at the time of the 
analysis) 
- 
A, A1, AE, AG, B, C, Other 
 
• 
INI Regimen prior to BIK 
- 
Raltegravir, Elvitegravir, Dolutegravir, none.  
• 
Duration of Prior ART (including BIK) use before study entry 
(<1 year, 1 - <2, 2 - <3 ,3-<4, >=4 years) 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
21 
 
Subgroup Category 
Subgroup and Subgroup Levels  
EMA Subgroup Category 2: 
EMA Subgroup Category 3: 
ISR-related: 
Needle length 
For the maximum toxicity grade of each preferred term of the 
common ISR (pain, induration, nodules and any other ISR with 
>=5% subjects in the Q2M treatment arm) during the maintenance 
phase: 
• 
Needle Length for Last CAB Injection prior to and including 
the onset date of the earliest corresponding CAB ISR with 
maximum toxicity grade during the Maintenance Phase: 
(<1.5, 1.5 to <2, ≥2 inch); 
• 
Needle Length for Last RPV Injection prior to and including 
the onset date of the earliest corresponding RPV ISR with 
maximum toxicity grade during the Maintenance Phase: 
(<1.5, 1.5 to <2, ≥2 inch ); 
 
Note: If there is no ISR of interest reported during maintenance 
phase for a subject, the needle length of last injection during 
maintenance phase will be used in the summary. 
 
 
5.5. 
Multiple Comparisons and Multiplicity 
There are no planned adjustments for multiple comparisons or multiplicity.  
 
5.5.1. 
Primary Analysis 
The primary comparison of interest is the comparison between CAB LA + RPV LA (Q2M) 
and BIK for the primary endpoint in the mITT-E population at Month 12 (OLI and 
BIK)/Month 11 (D2I). The primary comparison will be made at a one-sided 2.5% level of 
significance. Treatment with CAB LA + RPV LA (Q2M) will be declared non-inferior to 
BIK if the upper bound of a two-sided 95% confidence interval for the difference (Q2M – 
BIK) in proportion of participants with HIV-1 RNA ≥ 50 c/mL is below 4%. 
If the primary analysis demonstrates non-inferiority, then a superiority hypothesis will be 
tested at the two-sided 5% level of significance. Superiority favoring CAB LA + RPV LA 
(Q2M) will be declared if the upper limit of the confidence interval is below 0% for the 
mITT-E population analysis. If superiority is declared, the p-value for superiority will also 
be calculated.  
No multiple comparison adjustment is necessary for testing non-inferiority followed by 
superiority (conditional on achieving significance in the non-inferiority test) 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. 


 
CONFIDENTIAL 
 
 
 
213500 
 
22 
 
Subjects who became pregnant during the study will be allowed to continue CAB LA + 
RPV LA (Q2M) treatment, while those who became pregnant on BIK will be withdrawn. 
To minimize bias, a “while on-treatment” strategy will be implemented. Viral load data 
collected after confirmed pregnancy will not be evaluated for summary tables and 
statistical analysis in the primary analysis (see Appendix 13: Data Handling for Pregnant 
Subjects).  
 
5.5.2. 
Other Comparisons of Interest 
The following sensitivity analysis will also be performed for consistency with the results 
from the primary analysis: 
• Same analysis as described above with the PP population  
• Same analysis as described above with the ITT-E population  
• Same analysis as described above with all data as observed (not applicable if no 
subject on the Q2M arm becomes pregnant) 
 
5.5.3. 
Secondary Comparisons 
If the primary comparison of interest (Section 5.5.1) using the mITT-E population 
demonstrates non-inferiority of CAB LA + RPV LA (Q2M) compared to BIK at the 
primary analysis timepoint, then the following key secondary comparisons using the 
mITT-E population will be tested: 
• Treatment comparisons between the two arms (Q2M – BIK) with respect to the 
proportion of participants with HIV-1 RNA < 50 copies/mL at Months 12 (OLI and 
BIK)/Month 11 (D2I) (defined by the US FDA snapshot algorithm), including the 
two-sided 95% confidence interval. If the lower limit of the confidence interval for 
the difference in response rates (Q2M-BIK) lies above -12% then non-inferiority can 
be concluded.  
• Sensitivity analysis as described in Section 5.5.2 in the PP population and with all 
data observed will also be performed, for secondary comparisons. Additional 
comparisons of clinical interest between two treatment arms may also be performed 
as supportive analyses.  
• In addition to the primary and the key secondary comparisons, the comparisons 
between two treatment arms for HIVTSQs (Treatment Satisfaction Status Score), 
HIVTSQc (Treatment Satisfaction Change score), the statistical test on change in PIN 
acceptance score within the Q2M arm over time using a two-sided 5% level of 
significance will also be performed as supportive analyses. 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
23 
 
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: 
Section 
Component 
16.3 
Appendix 3: Assessment Windows  
16.4 
Appendix 4: Study Phases and Treatment State 
16.5 
Appendix 5: Data Display Standards & Handling Conventions 
16.5 
Appendix 6: Derived and Transformed Data 
16.7 
Appendix 7: Reporting Standards for Missing Data 
16.8 
Appendix 8: Values of Potential Clinical Importance 
16.9 
Appendix 9: Snapshot Algorithm Details 
16.10 
Appendix 10: Variables Defined for Time to Event Analysis 
16.11 
Appendix 11: Identification of Adverse Events of Special Interest (AESI) 
16.12 
Appendix 12: Identification of COVID-19 Adverse Events 
16.13 
Appendix 13: Data Handling for Pregnant Subjects 
 
6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the Intent-to-Treat Exposed population, 
unless otherwise specified. Note in the Month 12 analysis, mITT-E will be used in 
summary tables. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and exposure and treatment compliance will be based on GSK Core Data Standards.   
Table 1 provides an overview of the planned study population analyses, with full details 
of data displays presented in Appendix 15: List of Data Displays 


 
CONFIDENTIAL 
 
 
 
213500 
 
24 
 
Table 1 
Overview of Planned Study Population Analyses  
Display Type 
Data Displays Generated 
Table 
Listing 
Randomization 
Randomization [1] 
 
Y[2] 
Subject Disposition 
Study Populations [3] 
Y 
 
Study Recruitment [3] 
Y 
 
Reasons for Screening Failures [3] 
Y 
Y 
Age categories 
Y 
 
Subject Disposition 
Y[4][5] 
 
Reasons for Withdrawal 
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 Entry 
Y 
 
CDC Classification of HIV infection (2014) at Maintenance 
Baseline (Day 1) 
Y 
 
Distribution of CD4+ Cell Counts at Screening and Maintenance 
Baseline (Day 1) 
Y 
 
HIV Risk Factors 
Y 
 
Medical Conditions, Concomitant Medications & Antiretroviral Therapy 
Medical Conditions (Current/Past) [8] 
Y 
 
Medical Conditions: Sub-conditions (Current/Past) [9] 
Y  
 
Concomitant Medications (non-ART) 
Y[10] 
 
Prior Antiretroviral Therapy 
Y 
Y 
Concomitant Antiretroviral Therapy during Maintenance Phase 
 
Y 
ART Medications Received during LTFU Phase 
 
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 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
25 
 
NOTES: 
• 
T = Tables, L = Listings, Y = Display Generated, 
1. 
Based on Randomized population 
2. 
One listing of participants randomized but not treated, and one listing of planned and actual treatment strata. 
3. 
All Subjects screened population. 
4. 
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. 
5. 
Analysis of subject disposition may be performed for each study Phase separately if applicable, as well as for 
overall study conclusion. 
6. 
Age and ethnicity collected at Screening; weight, height and BMI collected at Day 1, 
7. 
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. 
8. 
Medical conditions will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
9. 
Sub conditions include Cardiac, Gastrointestinal, Metabolism and Nutrition, Psychiatric, Renal and Urinary, and 
Nervous system Conditions. 
10. Summarised by Ingredient combinations. 
11. Dispensation information (dates and number of tablets dispensed and returned). 
 
7. 
EFFICACY ANALYSES 
7.1. 
Primary Efficacy Analyses 
7.1.1. 
Endpoint / Variables 
The primary objective of the study is to demonstrate the non-inferior antiviral activity of 
CAB LA + RPV LA every two months (Q2M) compared to a BIK single tablet regimen 
administered once daily over 12 months in suppressed HIV-1 infected antiretroviral 
therapy (ART)-experienced participants. The primary endpoint is 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 Month 12 (OLI and BIK)/Month 
11 (D2I). 
7.1.2. 
Summary Measure 
Difference between the two treatment groups (Q2M – BIK) in the proportion of 
participants with HIV-RNA 50 c/mL at Month 12 (OLI and BIK)/Month 11(D2I) (as 
defined by the US FDA snapshot algorithm) and its two-sided 95% confidence interval 
will be produced. Note for the Q2M arm, primary endpoint data from the Q2M OLI 
subjects at Month 12 and data from the Q2M D2I subject at Month 11 will be combined 
for demonstration of non-inferiority. 
7.1.3. 
Population of Interest  
The primary efficacy analyses will be based on the modified Intent-To-Treat Exposed 
(mITT-E) population, unless otherwise specified. 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
26 
 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
As defined by the Snapshot algorithm, HIV-RNA  50 copies/mL is determined by the 
last available on-treatment HIV-1 RNA measurement 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 copies/mL at time of discontinuation, or who change study treatment not permitted 
per protocol prior to the analysis window are classified as having HIV-RNA  50 
copies/mL. 
A “while on-treatment” strategy will be implemented when a Q2M subject becomes 
pregnant on study but is allowed to continue. Viral load data collected after confirmed 
pregnancy will not be evaluated for summary tables and statistical analysis in the primary 
analysis. Additional sensitivity analysis including all observed data may be performed to 
assess consistency. See Appendix 13: Data Handling for Pregnant Subjects for details. 
7.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 15: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
7.1.5.1. 
Statistical Methodology Specification 
Primary Statistical Analysis 
Endpoint / Variables 
• 
Proportion of participants with plasma HIV-RNA greater than or equal to 50 copies/mL at Month 
12 (OLI and BIK)/Month 11 (D2I) per Snapshot algorithm for the mITT-E population. 
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 
(refer to analysis window defined in Section 16.3). 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 Appendix 9: Snapshot Algorithm Details 
Model Specification 
• 
The primary efficacy endpoint will be analysed using a stratified analysis with Cochran-Mantel-
Haenszel (CMH) weights, adjusting for the randomization strata BMI (<30, 30 kg/m2) and 
Gender at Birth (female, male) 


 
CONFIDENTIAL 
 
 
 
213500 
 
27 
 
• 
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 stratum as follows: 
o Baseline BMI < 30 kg/m2 and Male Gender at Birth 
o Baseline BMI < 30 kg/m2 and Female Gender at Birth 
o Baseline BMI  30 kg/m2 and Male Gender at Birth 
o Baseline BMI  30 kg/m2 and Female Gender at Birth 
 
• 
If nk is the number of CAB LA + RPV LA (Q2M) treated participants, mk is the number of BIK 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, pQ2M-
pBIK, for the kth stratum. 
 
• 
The corresponding two-sided 95% CI will be calculated as 
 
where the variance estimator [Sato, 1989] consistent in both sparse data and large strata 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
−
+
−
=
 
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  50 c/mL at Month 12 (OLI 
and BIK)/Month 11 (D2I) per FDA Snapshot for the Q2M and BIK arm, respectively, for the kth stratum. 


=
k
k
k
cmh
W
d
W
d
ˆ
ˆ
k
k
k
k
N
m
n
W
=
 
)
ˆ
r(
a ˆ 
v 
96 
. 
1
ˆ
cmh 
cmh 
d 
d 

 
 
k
dˆ


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 8  
 
M o d el R e s ult s Pr e se nt ati o n  
•  
A dj ust e d C M H esti m at e of t h e diff er e nc e i n t h e pr op orti on of p articip a nts wit h “HI V -1 R N A ≥5 0 ” 
b et w e e n e ac h tr e at m e nt gr o u p ( Q 2 M – BI K ) a n d corr es po n din g 9 5 % c o nfid e nc e i nt erv al.  
•  
N o n -i nf eri ority will b e c o ncl u ded if t h e u p p er bo u n d of t h e t w o-si d e d 9 5 % confi de nc e i nt erv al ( CI) 
f or t h e C M H a dj ust ed differ e nce i n pr o porti o n of p articip a nts wit h ‘ HI V -1 R N A ≥5 0’  i n t he C A B L A 
+ R P V L A ( Q 2 M) gr ou p mi n us pr o p orti on of p articip a nts wit h ‘ HI V -1 R N A ≥5 0’  i n th e BI K  gr ou p is 
l ess th a n 4 %.    
•  
If t h e a n alysis s h o ws n o n-i nf eri ority, t h e n a s u p eri ority hyp oth esis will b e t est e d at t h e t w o-si d e d 
5 % l evel of si g nific a nc e. S u p eri ority fav ori n g C A B L A + R P V L A ( Q 2 M) will b e d ecl ar e d if t he 
u p p er li mit of t h e c o nfid e nce i nt erv al is b el o w 0 % for t h e m I T T-E p o p ul ati o n an alysis.  If 
s u p eri ority is decl are d, t h e p-val u e f or s u p eri ority will als o b e c alcul at ed. 
S u b gr o u p A n al y s e s  
•  
Tr e at m e nt H et er o g e neity acr oss r a n do miz atio n str at a:  
o  T h e w ei g ht ed l e ast sq u ar es c hi -s q u ar ed st atistic [Fl eiss , 1 981] will be us ed t o t est f or 
o n e -w ay h o m o g en eity acr oss th e l evels of e ac h c at e g oric al vari a bl e, wit h e ac h 
c at e g oric al v aria bl e c o nsi d er ed s e p ar at ely.  
o  F oll o wi n g L ui a n d K elly [ Lui , 20 0 0] ½ will b e a d d e d t o e ac h cell i n a ny str at a f or w hich 
t h e str atu m-s pecific r at e esti mat es of eit h er p Q 2 M  or p BI K  ar e zer o or o n e, a n d t ests will 
b e o n e -si d e d.  
o  A ny h et er og e n eity f ou n d t o b e st atistically sig nific a nt will be ex pl or ed a n d if n ec ess ary, 
r es ults will b e r e p ort e d f or e ach l ev el of t he c ate g oric al v ari abl e. I nv esti g atio n of 
h et er o g e neity will be c onfi n e d t o t h e pri m ary  e n d p oi nt . T ests of h o m og e n eity will b e 
a ss ess e d at t h e o n e-si d e d 1 0 % l ev el of si g nific a nc e. 
 
S e n siti vit y A n al ys e s  
•  
P er -P r ot oc ol p o p ulati o n a n alysis: 
T o assess t h e i m p act of i m p ort a nt pr ot oc ol d eviati o ns, statistic al an alysis will b e r e pe at e d usi n g 
t h e P er-P r ot ocol p o pul ati o n a nd c o m par e d f or c o nsiste ncy wit h t h e r es ults fr o m th e pri m ary 
m I T T-E p o p ul ati on a n alysis.  
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
29 
 
• 
All Data as Observed: 
This analysis will include all observed data including those collected after confirmed pregnancy, 
in the mITT-E population. 
• 
Efficacy Sensitivity: 
This analysis will be based on the ITT-E population at Month 12. 
 
7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoint / Variables 
The key secondary efficacy endpoint is proportion of participants with plasma HIV-1 
RNA <50 c/mL (c/mL) at Month 12 (OLI and BIK)/Month 11(D2I) using the FDA 
Snapshot algorithm. 
Other secondary efficacy endpoints are listed below: 
• 
Proportion of participants with plasma HIV-1 RNA <50 c/mL (c/mL) at Month 6 
(OLI and BIK)/Month 5 (D2I). 
 
• 
Proportion of participants with plasma HIV-1 RNA ≥50 c/mL (c/mL) at Month 6 
(OLI and BIK)/Month 5(D2I) 
• 
Proportion of participants with protocol-defined confirmed virologic failure (CVF) 
through Month 6 and Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I). 
 
• 
Changes from Baseline in viral load and CD4+ cell count over time including Month 
6 and Month 12 (OLI and BIK)/Month 5 and Month 11 (D2I) 
7.2.2. 
Summary Measure 
Binary endpoints: difference in the proportion of participants with HIV-RNA ≥ 50 c/mL 
(or < 50 c/mL) as defined by the US FDA snapshot algorithm at specified time point 
between treatment groups (Q2M – BIK) will be produced. 
Continuous endpoints (e.g. CD4+ cell count): descriptive summary statistics per GSK 
data standards will be produced. 
7.2.3. 
Population of Interest  
The secondary efficacy analyses will be based on the Intent-to-Treat Exposed (ITT-E) 
population, unless otherwise specified. Note in the Month 12 analysis, mITT-E will be 
used in summary tables. 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events 
As defined by the snapshot algorithm, only 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.  


 
CONFIDENTIAL 
 
 
 
213500 
 
30 
 
A “while on-treatment” strategy will be implemented as described in Section 7.1.4. Same 
approach will be applied to efficacy tables for protocol-defined confirmed virologic 
failure (CVF) and CD4+ cell count. Data after confirmed pregnancy will not be evaluated 
for the summary tables unless otherwise noted, but will be included in the listings if 
applicable. 
7.2.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 15: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
7.2.5.1. 
Statistical Methodology Specification 
Key Secondary Statistical Analysis  
Endpoint / Variables 
• 
Proportion of participants with plasma HIV-RNA < 50 copies/mL at Month 12(OLI and 
BIK)/Month11(D2I) per Snapshot algorithm for the mITT-E population. 
• 
Proportion of participants with plasma HIV-RNA < 50 copies/mL at Month 6(OLI and BIK)/Month 
5(D2I) per Snapshot algorithm for the ITT-E population. 
• 
Proportion of participants with plasma HIV-RNA 50 copies/mL at Month 6(OLI and BIK)/Month 
5(D2I) per Snapshot algorithm for the ITT-E population. 
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 Section 16.3). 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 Appendix 9: Snapshot Algorithm Details  
Model Specification 
• 
As specified in Section 7.1.5.1, with outcome being “HIV-1 RNA <50 c/mL” or “HIV-1 RNA ≥50 
c/mL”   
Model Results Presentation 
• 
Adjusted CMH estimate of the difference in the proportion of participants with ‘HIV-1 RNA <50’ 
or with ‘HIV-1 RNA 50’ between two treatment groups (Q2M – BIK) and corresponding 95% 
confidence interval.  
• 
Non-inferiority will be concluded if the lower bound of the two-sided 95% confidence interval (CI) 
for the CMH adjusted difference (Q2M – BIK) in proportion of participants with ‘HIV-1 RNA <50’ 
is greater than -12% at Month 12 (OLI and BIK)/Month 11 (D2I).   
Subgroup Analyses 
• 
Treatment Heterogeneity across randomization strata at Month 12 (OLI and BIK)/Month 11 (D2I) 
As specified in Section 7.1.5.1, with outcome being “HIV-1 RNA <50 c/mL” or “HIV-1 ≥50 c/mL” 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
3 1  
 
S e n siti vit y a n d S u p p orti v e A n al y s e s  
•  
P er -P r ot oc ol p o p ulati o n a n alysis: 
T o assess t h e i m p act of i m p ort a nt pr ot oc ol d eviati o ns, statistic al an alysis will b e r e pe at e d usi n g 
t h e P er-P r ot ocol p o pul ati o n a nd c o m par e d f or c o nsiste ncy wit h t h e r es ults fr o m th e pri m ary I T T-
E p o p ul ati o n a nalysis.  N ot e f or M o nt h 12, P P p o p ul ati on is bas e d o n t h e  mI T T -E p o p ul ation . 
•  
All D at a as O bs erv ed : 
T his a nalysis will i nclu d e all o bs erv e d d at a  i nclu di n g t h ose c oll ect ed aft er c o nfir m e d pr e g n ancy, 
i n t h e I T T-E p o p ulati o n.  N ot e for M o nt h 1 2, t his a nalysis will b e b as ed o n th e mI T T -E p o p ulati o n.  
•  
Effic acy S e nsitivity:  
T his a nalysis will be b as e d o n t h e I T T-E p o pul atio n at M o nt h 1 2.  
 
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
3 2  
 
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
3 3  
 
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
34 
 
8. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety population, unless otherwise specified. A 
“while on-treatment” strategy which considers data collected after confirmed pregnancy 
non-evaluable in the Q2M arm will be implemented for selected analysis including 
clinical laboratory, biomarker, and metabolic analysis. See Appendix 13: Data Handling 
for Pregnant Subjects for details. Note for safety-related reporting including adverse 
events and ECG, all observed data will be included. 
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. Table 3 below 
provides an overview of the planned analyse with further details of data displays 
provided in Appendix 15: List of Data Displays.  
Table 3 
Overview of Adverse Events Analyses 
Endpoint 
 
Absolute 
 
Change from Maintenance 
Baseline 
Max Post 
Maintenance Baseline 
Summary 
Individual 
Stats 
Analysis 
Summary Individual Summary 
Individual 
T 
F 
F 
L 
T 
T 
F 
F 
L 
T 
F 
F 
L 
Exposure 
Extent of Exposure[1] 
Y 
 
 
Y[2] 
 
 
 
 
 
 
 
 
 
Adherence to Dosing 
Schedule [1] 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Dosing Errors and IP 
Device Malfunctions 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
Injection Needle  
Length and Gauge 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events[3] 
All AEs by SOC and 
PT 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
All AEs by SOC, PT 
and Toxicity 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
All Drug-Related AEs 
by SOC and PT 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
All Drug-Related AEs 
by SOC, PT and 
Toxicity 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Common AEs by 
frequency [5] 
Y 
Y[6] 
 
 
 
 
 
 
 
 
 
 
 
Common Grade 2-5 
AEs [5] by frequency 
Y 
 
 
 
 
 
 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
35 
 
Endpoint 
 
Absolute 
 
Change from Maintenance 
Baseline 
Max Post 
Maintenance Baseline 
Summary 
Individual 
Stats 
Analysis 
Summary Individual Summary 
Individual 
T 
F 
F 
L 
T 
T 
F 
F 
L 
T 
F 
F 
L 
Drug-related Grade 2-
5 AEs  
Y 
 
 
 
 
 
 
 
 
 
 
 
 
All AEs 
 
 
 
Y[4] 
 
 
 
 
 
 
 
 
 
Serious and other significant adverse events 
All SAEs by SOC and 
PT 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Reason for 
Considering as a 
Serious Adverse 
Event (FDA) 
 
 
 
Y  
 
 
 
 
 
 
 
 
 
All Drug-Related SAEs 
by SOC and PT 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Fatal SAEs  
 
 
 
Y 
 
 
 
 
 
 
 
 
 
Non-Fatal SAEs 
Y 
 
 
Y 
 
 
 
 
 
 
 
 
 
Drug-related non-fatal 
SAEs 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
AEs Leading to 
Withdrawal/Permanent 
Discontinuation of IP 
Y 
 
 
Y 
 
 
 
 
 
 
 
 
 
Common Non-serious 
AEs by SOC and PT 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects and Number 
of occurrences of 
SAEs, Fatal SAEs, 
and Drug-related 
SAEs  
Y 
 
 
 
 
 
 
 
 
 
 
 
 
AESI 
Depression, Suicidal 
and Self-Injury AEs by 
Prior History 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
AESI by SOC and PT 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Characteristics of 
AESI 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Syncope and 
Presyncope AE 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Suicidality assessment 
PSRAE 
 
 
 
Y[7] 
 
 
 
 
 
 
 
 
 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
3 6  
 
E n d p oi nt  
 
A b s ol ut e  
 C h a n g e fr o m M ai nt e n a n c e 
B a s eli n e  
M a x P o st 
M ai nt e n a n ce B a s eli ne 
S u m m ary  
I n divid u al 
St ats 
A n alysis  
S u m m ary  I n divid u al S u m m ary  
I n divid u al 
T  
F  
F  
L  
T  
T  
F  
F  
L  
T  
F  
F  
L  
Col u m bi a s uici dality 
(e C -S S R S ) 
Y  
 
 
 
 
 
 
 
 
 
 
 
 
I nj e cti o n Sit e  R e acti o n A d v er s e E v e nt s [ 12] 
I S R A Es ( Ev e nt-L ev el) 
[ 1 7] 
Y  
 
 
 
 
 
 
 
 
 
 
 
 
I S R A Es ( S u bj ect-
L ev el)  [ 18]  
Y  
 
 
 
 
 
 
 
 
 
 
 
 
I S R A Es ( S u bj ect-
L ev el) by Visit a nd 
S ev erity  
Y  
Y [ 1 9] 
 
 
 
 
 
 
 
 
 
 
 
M axi m u m I S R A E 
Gr a d e by N e e dle 
L e n gt h [ 21] 
Y  
 
 
 
 
 
 
 
 
 
 
 
 
L a b orat ory: C h e mi str y a n d H e m at ol o g y  
Cli nic al C h e mistry  
 
 
 
 
 
Y  
 
 
 
Y  
 
 
 
Li pi ds  
 
 
 
 
 
Y  
 
 
 
 
 
 
 
N C E P s hifts i n li pi ds  
 
 
 
 
 
 
 
 
 
Y [ 8] 
 
 
 
He m at ol o gy  
 
 
 
 
 
Y  
 
 
 
Y  
 
 
 
L a b orat ory: Uri n al y si s (r e g ar dl e s s of f a sti n g st at u s)  
Uri n e Di pstick  
Y  
 
 
 
 
 
 
 
 
 
 
 
 
Uri n e C o nc e ntr ati o n  
 
 
 
 
 
Y  
 
 
 
 
 
 
 
Pr ot ei n uri a  
 
 
 
 
 
 
 
 
 
Y [ 8] 
 
 
 
L a b orat ory: He p at o bili ar y  
Liv er Ass ess m ent  
 
 
 
Y [ 1 4] 
 
 
 
 
 
 
 
 
 
He p at o bili ary 
A b n or m ality crit eria  
Y  
 
 
Y  
 
 
 
 
 
 
 
 
 
Liv er Ch e mistri es  
 
 
 
Y [ 1 1] 
 
 
 
 
 
 
Y [ 9] 
 
 
L a b orat ory: Bi o m ar k er s  
B o n e m arkers  
 
 
 
 
Y  
Y [ 1 0] 
 
 
 
 
 
 
 
Re n al m ark ers  
 
 
 
 
Y  
Y [ 1 0] 
 
 
 
 
 
 
 
H O M A -I R, i ns uli n a n d 
H b A 1c  
 
 
 
 
Y [ 1 6] 
Y  
 
 
 
 
 
 
 
E C G  
E C G fi n di ngs  
Y  
 
 
Y  
 
 
 
 
 
 
 
 
 
C CI
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
3 7  
 
E n d p oi nt  
 
A b s ol ut e  
 C h a n g e fr o m M ai nt e n a n c e 
B a s eli n e  
M a x P o st 
M ai nt e n a n ce B a s eli ne 
S u m m ary  
I n divid u al 
St ats 
A n alysis  
S u m m ary  I n divid u al S u m m ary  
I n divid u al 
T  
F  
F  
L  
T  
T  
F  
F  
L  
T  
F  
F  
L  
E C G v al u es  
 
 
 
Y [ 2 2] 
 
Y  
 
 
 
 
 
 
 
Q T C v al ues by 
Cat e g ory  
Y  
 
 
 
 
Y  
 
 
 
 
 
 
 
Ot h er  
Vit al Si g ns  ( B P, H R, 
t e m p) 
 
 
 
Y  
 
Y  
 
 
 
 
 
 
 
W ei g ht , H eig ht a nd 
B MI  
Y  
 
 
Y  
 
Y  
 
 
 
 
 
 
 
W aist Circ u mf ere nc e 
a n d Hi p 
Circ u mf er enc e   
Y  
 
 
Y  
 
Y  
 
 
 
 
 
 
 
T a nit a Scal e 
Ass ess m e nts ( B o dy 
F at  P erc e nta g e , B o ne 
Mi n er al M ass, M uscl e 
M ass, T ot al B o dy 
W at er  P erc e nt a g e ) 
Y  
 
 
Y  
 
Y  
 
 
 
 
 
 
 
A b ac avir H S R  
 
 
 
Y [ 1 3] 
 
 
 
 
 
 
 
 
 
P artici pa nts w h o 
b ec a me Pr e g n a nt  
 
 
 
Y  
 
 
 
 
 
 
 
 
 
P ati e nt Pr ofil es  
 
 
 
Y [ 2 0] 
 
 
 
 
 
 
 
 
 
M et a b olic Sy n dr o m e  
Y  
 
Y  
Y  
 
Y  
 
 
 
 
 
 
 
 
N O T E S:  
•  
T = T a bl e, F = Fi g ur es, L = Listi n gs, Y = Y es dis pl ay g e n er at e d.  
•  
St ats A n alysis = Dis pl ays  r el at e d t o a ny f or m al st atistic al a n alys es (i. e. m o d elli n g) c o n d uct e d. 
•  
S u m m ary = R e pr es e nts T F L r el at e d t o a ny s u m m ari es (i. e. d escri ptiv e st atistics) of t h e o bs erv e d r a w d at a. 
•  
I n divi d u al = R e pr es e nts F L r el at e d t o a ny dis pl ays of i n divi d u al p artici p a nt o bs erv e d r a w d at a.  
1.  
R ef er t o S ecti o n 1 6. 6. 2  a n d S ecti o n 1 6. 6. 4  f or d efi ni n g e xt e nt of e x p os ur e a n d a d h er e nc e t o d osi n g i nt erv als .  
2.  
I ncl u d es r e as o n f or a ny d os e c h a n g e/i nt err u pti o n. 
3.  
F or A Es r e p ort e d m or e t h a n o nc e by a p artici p a nt, t h e m ost s ev er e i nt e nsity will b e i ncl u d e d.  Se p ar at e s u m m ary 
t a bl es i ncl u di n g a n d excl u di n g i nj ecti o n sit e a dv ers e r e acti o ns. 
4.  
L isti n g of all A Es i ncl u di n g v er b ati m t ext a n d pr ef err e d t er m , a n d listi n g of s u bj ect n u m b ers f or i n divi d u al A Es.  
5.  
C o m m o n A Es ar e t h os e wit h ≥5 % i nci d e nc e i n Q 2 M  or BI K s u m m aris e d by fr e q u e ncy. 
6.  
Pl ots of i nci d e nc e r at es a n d r el ativ e risk wit h 9 5 % CI f or Q 2 M vs. BI K.  
7.  
F o ur P S R A E listi n gs: Ev e nt a n d D escri pti o n ( Secti o n 1  a n d S ecti o n 2 ), P ossi bl e C a us e ( Secti o n 3 ), Secti o n 4  a n d 
S ecti o n 5  - S ecti o n 8 . 
C CI
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
3 8  
 
8.  
S hift t a bl e s u m m arisi n g M ai nt e n a nc e B as eli n e ( D ay 1) vs. m axi m u m M ai nt e n a nc e P h as e r es ult . 
9.  
Sc att er pl ot of b as eli n e vs. m axi m u m p ost -b as eli n e f or A L T  a n d BI L T . Sc att er pl ot of m axi m u m A L T vs. m axi m u m 
Bilir u bi n.  
1 0.  B o n e m ark ers: B o n e -s p ecific alk ali n e p h os p h at as e, pr oc oll a g e n ty p e 1 N -pr o p e pti d e, ty p e 1 c oll a g e n cr oss -li nk e d 
C -t el o p e pti d e, ost e oc alci n, 2 5 hy dr oxy-Vit a mi n D . R e n a l m ark ers: Cyst ati n C; Bet a -2 -Micr o gl o b uli n; R eti n ol 
Bi n di n g Pr ot ei n ( R B P).  
.  
1 1.  F or su bj ects m e eti n g h e p at o bili ary la b a b n or m ality crit eri a. 
1 2.  R e p e at f or C A B/ R P V, C A B, R P V r es p ectiv ely.  
1 3.  S e p ar at e lis ti n gs f or ex p os ur e t o a b ac avir, hist ory of dr u g all er gi es, f a mily c o n diti o ns, ski n r as h, sy m pt o ms, vit al 
si g ns, i n divi d u al sy m pt o ms a n d di a g n ostic c at e g ory assi g n m e nt.  If n o hy p ers e nsitivity t o a b ac avir is o bs erv e d, 
t h e n o nly o n e bl a nk listi n g will b e pr ovi d e d f or t h e ex p os ur e t o a b ac avir.  
1 4.  S e p ar at e listi n gs f or ev e nt  r e p orti n g, R U C A M sc or e, bi o psy, i m a gi n g, s u bst a nc e us e a n d m e dic al c o n diti o ns.  
1 6.  St atistic al a n alysis will b e p erf or m e d f or H O M A-I R.  
1 7.  Ev e nt -l ev el s u m m ary: P erc e nt a g es b as e d o n t ot al n u m b er of I S R ev e nts i ncl u di n g distri b uti o n of gr a d e, d ur ati o n, 
a n d ev e nt c h ar act eristics . 
1 8.  S u bj ect -L ev el s u m m ary: C h ar act eristics of I S R A E ( Ov er all a n d by C o m m o n I S Rs); P erc e nt a g e b as e d o n n u m b er 
of p artici p a nts; I ncl u d es distri b uti o n of gr a d e a n d m ax gr a d e, ev e nt c h ar act eristics, n u m b er of ev e nts p er s u bj ect, 
r at e of n u m b er of ev e nts p er i nj ecti o n visit. 
1 9.  A c orr es p o n di n g pl ot f or all gr a d es a n d a s e p ar at e pl ot f or gr a d e 3 -5 ev e nts will b e pr o d uc e d . 
2 0.  P ati e nt pr ofil es ar e n ot pl a n n e d  b ut  c a n b e pr o d uc e d p ost h oc, as n ec ess ary.  
2 1.  Pl e as e r ef er t o S ecti o n 5. 4  f or d eriv ati o n of n e e dl e l e n gt h us e d i n t his s u m m ary. 
2 2.  F or s u bj ects wit h a ny v al u e of p ot e nti al cli nic al i m p ort a nc e . 
 
8. 2.  
A d v er s e E v e nt s of S p e ci al I nt er e st  A n al y s e s  
A d verse e ve nts of s pecial i nterest ( A E SI) are det er mi ne d f or C A B a n d/ or R P V base d o n 
pre -cli nic al a n d cli nical e x perie nce, al o n g wit h i nf or mati o n f or t he I nte gras e I n hi bit or 
class of HI V m e dicati o ns a n d R P V safet y pr ofile. Ta ble 4  s h o ws t he c urre ntl y i de ntifie d 
A E SI, dr u g(s) of I nterest a n d t he reas o ns f or i ncl usi o n. C ha n ges t o t he Me d D R A 
dicti o nar y m a y occ ur bet wee n t he start of t he st u d y a n d t h e ti me of re p orti n g a n d/ or 
e mer gi n g data fr o m o n g oi n g st u dies ma y hi g hli g ht a d diti o nal  a d verse e ve nts of s pecial 
i nterest, t heref ore t he list of ter ms t o be use d f or eac h e v e nt of i nterest a n d t he s pecific 
e ve nts of i nterest will be base d o n t he safet y re vi e w tea m ( S R T) a gree me nts i n place at 
t he ti me of re p orti n g. 
A s u m mar y b y s yste m or ga n  class a n d preferre d ter m will be pr o vi de d f or eac h of A E SI. 
T he c haract eristics of e v e nt occ urre nces d uri n g t h e mai nte na nce p hase will be 
s u m marize d f or A E SIs. F or De pressi o n, a n xiet y a n d s uici dal i deati o n/ be ha vi o ur A E SI, a 
s u m mar y b y s yste m or ga n class, ma xi m u m D AI D S t o xicit y gra de a n d pri or hist or y of 
s uici dal i deati o n will be pr o vi de d.  
T he details of t he c urre nt pla n ne d gr o u pi n g, i ncl u di n g Sta n dar dize d Me d D R A Q uer y 
( S M Q) val ues (as a p plica ble), a n d pla n ne d dis pla ys are pr o vi de d i n  A p pe n di x 1 1 : 
I d e ntificati o n of A d v erse E ve nts of S pecial I nterest ( A E SI) a n d A p pe n di x 1 5 : List of 
Data Dis p la ys. 
C CI
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
39 
 
Table 4 
Adverse Events of Special Interest 
Adverse Events of Special Interest 
Drug(s) of 
Interest 
Reason for Inclusion 
Hepatic Safety Profile: Assessment of Risk of 
hepatoxicity 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Hyperglycemia 
CAB 
Class, Regulatory Interest 
Hypersensitivity Reactions (HSR) 
CAB 
Class, Regulatory Interest, 
Occurs in HIV population 
Rash 
RPV 
Class, Regulatory Interest, 
Occurs in HIV population 
Prolongation of the Corrected QT Interval of the 
ECG in Supratherapeutic Doses 
RPV 
Non-clinical, Clinical, 
Regulatory Interest 
Suicidal Ideation/Behaviour 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Depression 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Bipolar Disorder 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Psychosis 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Mood Disorders 
CAB+RPV 
Clinical, Class, Regulatory 
Interest 
Anxiety 
CAB+RPV 
Clinical, Class, Regulatory 
Interest 
Sleep Disorders 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Injection Site Reactions (ISR) from Study Drug 
Injections [1] 
CAB+RPV 
Clinical 
Seizures and Seizure-like Events 
CAB 
Clinical, Regulatory Interest 
Weight Gain 
CAB 
Clinical, Class 
Rhabdomyolysis 
CAB 
Clinical, Class 
Pancreatitis 
CAB 
Clinical, Therapeutic Area, 
More prevalent in HIV 
population 


 
CONFIDENTIAL 
 
 
 
213500 
 
40 
 
Adverse Events of Special Interest 
Drug(s) of 
Interest 
Reason for Inclusion 
Impact on Creatinine 
CAB+RPV 
Regulatory Interest, 
Therapeutic Area, More 
prevalent in HIV population 
Safety in Pregnancy 
CAB 
Regulatory Interest, Class 
NOTE: 
[1] A separate analysis will be performed for ISRs from study drug injections as described in Section 8.2.1 
 
8.2.1. 
Analyses for Injection Site Reaction Adverse Events 
Injection Site Reaction (ISR) adverse events of interest are those from study drug 
injections. For the summary of ISR 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), associated to CAB and/or RPV, or 
stratification by subgroup (such as needle length, refer to Section 5.4.2). 
ISRs (based on investigator discretion) from study drug injections 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 
the causal agent cannot be determined in cases where both drugs are given on one side or 
the ISR is reported non-specifically, then the attribution to a specific causal agent will 
remain unknown. 
Common ISR adverse events during the Maintenance Phase are defined by MedDRA 
preferred terms including injection site pain, injection site induration, injection site 
nodules and preferred terms of any other ISR with ≥5% participants in the Q2M arm. The 
same set of common terms will be applied to ‘overall’ (CAB and/or RPV), CAB alone, 
RPV alone. 
ISRs will be attributed to the needle length specifically based on the side of injection 
administration and the side of the reported ISR (as collected in the eCRF). If the needle 
length cannot be determined due to both drugs given on the same side with different 
needle lengths, then the attribution to a needle length will remain unknown. 
 
8.3. 
Clinical Laboratory 
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. 


 
CONFIDENTIAL 
 
 
 
213500 
 
41 
 
For women who became pregnant on study, a data listing for selected parameters 
including the following will be provided. Additional parameters of interest may also be 
listed if applicable. 
Clinical Chemistry: Creatinine, GFR, Glucose, HCG 
Hematology: HbA1C, Hemoglobin,Hematocrit, Mean Corpuscular Volume, Platelets, 
Erythrocytes, Lymphocytes, Neutrophils, Basophils, Monocytes, Eosinophils 
Immunology: CD4+ cell count, CD8+ cell count, CD4/CD8 cell count ratio, 
CD4/Lymphocytes, CD8/Lymphocytes 
Urinalysis: Albumin/Creatinine, Glucose, Ketones, Occult Blood, Protein, 
Protein/Creatinine, Erythrocytes  
 
8.4. 
Biomarker Analyses 
Biomarker analysis (renal, bone, inflammation) will not be performed at the Month 6 
interim analysis, and will only be performed when all expected data through Month 12 
(OLI and BIK)/Month 11 (D2I) has been received from the laboratory. Statistical 
estimates for each planned visit will be provided in the Month 12 primary analysis using 
the MMRM model as describe in the below sections unless otherwise noted. The details 
of the planned displays are in Appendix 15: List of Data Displays. 
8.4.1. 
Bone Biomarkers 
Statistical Analyses 
Endpoints 
• Change from Maintenance Baseline (Day 1) in the following bone markers at Month 6 (OLI and 
BIK)/Month 5 (D2I) and at Month 12 (OLI and BIK)/Month 11 (D2I): 
° 
Bone-specific alkaline phosphatase 
° 
Procollagen type 1 N-propeptide 
° 
Type 1 collagen cross-linked C-telopeptide 
° 
Osteocalcin 
° 
25 hydroxy-Vitamin D 
Covariates 
• 
Baseline Value (continuous, log-transformed) 
• 
Gender at Birth (male, female) 
• 
Baseline BMI(<30 kg/m2, >=30 kg/m2)  
• 
Age (Continuous)  
• 
Race (White, Black/African American, Other) 
• 
Smoking Status (Never, Former, Current) 
• 
Vitamin D use (Yes vs no) 


 
CONFIDENTIAL 
 
 
 
213500 
 
42 
 
Data Handling 
• 
OC (Observed Case) dataset will be used. 
Model Specification 
• 
Analysis values will be log-transformed (including the baseline value).  
• 
The change in the log-transformed data from Maintenance baseline (i.e. log(value/ baseline value) or 
log(value) – log(baseline value)) for each bone marker will be analysed for the comparison between 
the two treatment arms.  
• 
MMRM (Mix Model Repeated Measures) model with the observed margins (OM) option within PROC 
MIXED in SAS will be used including treatment group plus the above covariates, with visit as the 
repeated factor.  
 
• 
The Kenward and Roger method for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used. 
 
• 
No assumptions about the correlations between a subject’s values will be made (the correlation 
matrix for within-subject errors will be unstructured). This will be estimated by treatment group by 
specifying “type=UN” and “group=treatment” options in the SAS MMRM models.  
 
• 
In the event that this model fails to converge, alternative correlation structures may be considered 
such as CSH or CS. Akaike's Information Criteria (AIC) will be used to assist with the selection of 
covariance structure if needed. 
 
• 
The repeated measures analysis will assume that the treatment difference can vary between visits 
(i.e. a treatment*visit interaction will be included in the model). Estimates and 95% confidence 
intervals will be produced for each visit.  
 
Model Checking & Diagnostics 
• 
Model assumptions will be applied, but appropriate adjustments maybe made based on the data. 
 
• 
Distributional assumptions underlying the model used for analysis may be examined by obtaining a 
normal probability plot of the residuals and a plot of the residuals versus the fitted values (i.e. 
checking the normality assumption and constant variance assumption of the model respectively) to 
gain confidence that the model assumptions are reasonable. 
 
• 
If there are any departures from the distributional assumptions, alternative models will be explored 
using appropriately transformed data. 
Model Results Presentation 
• 
For each treatment: Adjusted geometric means (for ratio to Maintenance BL) and 95% CI. 
Exponential transformation on the estimates from the MMRM model (based on the log-transformed 
data) will reflect the mean ratio of values post-baseline vs. Maintenance BL for each treatment arm. 
This ratio can then be translated into percent change from maintenance baseline (Day 1) (e.g. the 
ratio bbM12/bbbl = 1.3 can be translated into 30% increase from baseline). 
 
• 
For treatment comparison: Adjusted geometric mean ratio between the two treatment groups 
(Q2M/BIK), 95% CI and p-value. This ratio can then be translated into percent comparisons in the 
ratio (value/baseline value) between Q2M vs. BIK (e.g. Q2M/BIK = 1.2 can be translated into 20% 
higher in the Q2M change from baseline ratio compared with BIK). 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
43 
 
• 
Interactions between treatment and each of the covariates will not be assessed but may be explored 
post hoc. 
Sensitivity Analyses 
• 
Not applicable 
Subgroup Analyses 
• 
Not applicable 
 
8.4.2. 
Renal Biomarkers  
Statistical Analyses 
Endpoints 
• 
Change from Maintenance Baseline (Day 1) in the following renal markers at Month 6 (OLI and 
BIK)/Month 5 (D2I) and at Month 12 (OLI and BIK)/Month 11 (D2I): 
° 
Cystatin C 
° 
Retinol Binding Protein (RBP) 
° 
Beta-2-Microglobulin (B2M)  
Covariates  
• 
Baseline Value (continuous) 
• 
Gender at Birth (male, female) 
• 
Baseline BMI(<30 kg/m2, >=30 kg/m2)  
• 
Age (continuous) 
• 
Race (White, Black/African American, Other) 
• 
Hypertension (Yes vs no) 
• 
Diabetes (Yes vs no) 
 
Note:  
Hypertension is defined as having a medical history of hypertension or use of medication treating 
hypertension (current and past).  
Diabetes is defined as having a medical history of Diabetes or use of medication treating Diabetes (current 
and past) or fasting glucose at ≥ 126 mg/dL with HbA1c > 6.5% at Day 1.  
Data Handling 
• 
OC (Observed Case) dataset will be used.  
Model Specification 
• 
Same as in Section 8.4.1 
Model Checking & Diagnostics 
• 
Same as in Section 8.4.1 
Model Results Presentation 
• 
Same as in Section 8.4.1 
Sensitivity Analyses 
• 
Not applicable 
Subgroup Analyses 
• 
Not applicable 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
4 4  
 
8. 5.  
Ot h er S af et y A n al y s e s  
T he a nal yses o f n o n -la b orat or y safet y test res ults i ncl u di n g E C Gs a n d vital si g n s will be 
base d o n  G S K C ore D ata Sta n dar ds , u nless ot her wise s pecifie d. T h e details of t he 
pla n ne d  dis pla ys are pres e nte d i n  A p pe n di x 1 5 : List of Data Dis plays . 
 
8. 5. 1.  
E C G  
E C G Val ues of P ote ntial Cli nical I nterest are defi n e d as a Q Tc of > 5 0 0 msec or i ncreas e 
fr o m baseli ne i n Q T c ≥ 6 0 msec.  
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
45 
 
8.5.2. 
Metabolic Syndrome 
Diagnosis of Metabolic Syndrome is defined as follows per joint interim statement of the 
International Diabetes Federation Task Force on Epidemiology and Prevention; National 
Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; 
International Atherosclerosis Society; and International Association for the Study of 
Obesity. Three abnormal findings out of the five risk factors would qualify a person for 
the metabolic syndrome(waist circumference, triglycerides, HDL, BP and fasting 
glucose) at each planned time point. See Section 16.6.4 for cutoff details. Percent of 
subjects diagnosed with metabolic syndrome will be produced. Patient profile as well as 
listing of clinical diagnosis factors over time may also be provided for those who are 
diagnosed with metabolic syndrome. 
 
Statistical Analyses 
Endpoints 
• 
Proportion of subjects with metabolic syndrome at Month 6 (OLI and BIK)/Month 5 (D2I) and at 
Month 12 (OLI and BIK)/Month 11 (D2I) 
Covariates  
 
• 
Baseline CD4+ cell count (continuous) 
• 
Gender at Birth (male, female) 
• 
Baseline BMI(<30 kg/m2, >=30 kg/m2) 
• 
Age (35-<50, >=50, <35 years)  
• 
Race (White, Black/African American, Other) 
• 
Smoking Status (Never, Current, Former) 
• 
Hypertension (Yes vs no) 
• 
Baseline Triglyceride (High vs. Normal) 
• 
Baseline HDL (Low, High vs Normal) 
• 
Baseline HOMA-IR (2 to <3, 3 to <4, >=4 vs <2) 
Note: Hypertension is defined as having a medical history of hypertension or use of medication treating 
hypertension (current and past) 
Data Handling 
• 
OC (Observed Case) dataset will be used. 
Model Specification 
• 
A logistic regression model will be performed on the proportion of subjects with metabolic syndrome 
at Month 6(OLI and BIK)/5(D2I) and at Month 12(OLI and BIK)/11(D2I) adjusting for the covariates 
as above. 
Model Checking & Diagnostics 
• 
Upon delivery of data, an assessment regarding the amount of missing data will be made. If the 
amount of missing outcome data considered as a result of other impacts such as COVID-19 is 
substantial, the logistic regression analysis may not be performed. 
 
• 
If the percent of subjects are below 5% of the total number of subjects (observed data), or if 
complete or quasi-complete separation is observed in the data, then the analysis may not be 
performed. 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
4 6  
 
St ati sti c al A n al y se s  
M o d el R e s ult s Pr e se nt ati o n  
•  
O d ds rati os, c onfi d e nc e int ervals a nd p -v al u es will b e pr es ent e d f or all cov ariat es s p ecified i n t h e 
m o d el.  
S e n siti vit y A n al ys e s  
•  
Not a p plic a ble  
S u b gr o u p A n al y s e s  
•  
Not a p plic a ble  
 
8. 5. 3.  
A nt hr o p o m etri c pr ofil e  
Descri pti ve s u m maries will be pr o vi de d  f or t he f oll o wi n g para m eters t o e val uate t he 
meta b olic pr ofile  of s u bj ects :  
•  
Wei g ht, Hei g ht a n d B MI  
•  
W aist circ u mfere n ce  
•  
H i p circ u mfere nce 
•  
 
•  
 
•  
Ta nita scale p ara met ers ( t otal b o d y fat  perce nt , t otal b o d y water p e rce nt, m uscle 
mass, a n d b o ne mi neral mass )  
 
S u bjects wit h c os metic pr oce d ures of t he t ors o/t hi g hs (e x cl u de face/ nec k) i ncl u di n g b ut 
n ot li mite d t o li p os ucti o n/li p osc ul pt ure/i m pla nts will be e x cl u de d fr o m t he a b o ve 
s u m mar y statistics at M o nt h 1 2 ( O LI a n d B I K)/ M o nt h 1 1 ( D 2I). 
D ata c ollecte d aft er i nitiati o n of li pi d -m o dif yi n g a ge nts  o n tr eat me nt  will be c o nsi dere d 
n o n -e val ua ble f or a nt hr o p o metric pr ofile s u m mari es  ( w hile o n-tr eat me nt strate g y). 
8. 5. 4.  
H O M A -I n s uli n R e si st a n c e 
H O M A -I ns uli n Resista n ce a n al ysis will o nl y b e p erf or me d w he n all e x pect e d data 
t hr o u g h M o nt h 1 2 ( O LI a n d BI K)/ M o nt h 1 1 ( D 2I) has bee n recei ve d fr o m t he la b orat or y. 
Statistical esti mates f or eac h pla n ne d visit will be pr o vi de d i n t he M o nt h 1 2 pri mar y 
a nal ysis usi n g t he M M R M m o del as descri be i n t he bel o w secti o ns u nless ot her wise 
n ote d. T he details of t he pla n ne d dis pla ys are i n A p pe n di x 1 5 : List of Dat a Dis pla ys. 
St ati sti c al A n al y se s  
E n d p oi nt s  
•  
Ch a n g e fr o m b aseli ne i n H O M A -I R at M o nt h 6 ( O LI a n d BI K)/ M o nt h 5 ( D2I) a n d at M o nt h 12 ( O LI 
a n d BI K)/ M o nth 1 1 ( D 2I)  
 
N ot e: t h e f oll o wi n g s u bj ects will b e excl u d e d fr o m t h e st atistic al a n alysis:  
° 
di a b etic or h av e t ak e n a n a nti -di a b etic m e dic ati o n u p t o scr e e ni n g  
° 
f asti n g gl uc os e > 1 2 6 m g/ dl a n d H b A 1 C > 6. 5 % at D ay 1 
° 
h av e h a d a c os m etic pr oc e d ur e i ncl u di n g li p os ucti o n/li p osc ul pt ur e of t h e t hi g hs, b utt ocks, hi ps a n d/ or 
a b d o m e n  
 
C o v ari at e s  
C CI
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
47 
 
Statistical Analyses 
 
• 
Baseline Value (continuous) 
• 
Gender at Birth (male, female) 
• 
Baseline BMI(<30 kg/m2, >=30 kg/m2) 
• 
Age (Continuous)  
• 
Race (White, Black/African American, Other) 
• 
Smoking Status (Never, Current, Former) 
• 
Hypertension (Yes vs no) 
Note: Hypertension is defined as having a medical history of hypertension or use of medication treating 
hypertension (current and past) 
Data Handling 
• 
OC (Observed Case) dataset will be used. 
Model Specification 
• 
Same as in Section 8.4.1 
Model Checking & Diagnostics 
• 
Same as in Section 8.4.1 
Model Results Presentation 
• 
Same as in Section 8.4.1 
Sensitivity Analyses 
• 
Logistic regression models will be performed on the proportion of subjects with HOMA-IR >=2, >=3 
or >=4 at Month 12(OLI and BIK)/11(D2I) adjusting for the same covariates as specified in the 
MMRM analysis (without visit or interaction terms and without log transformation for the baseline 
value). Odds ratios, confidence intervals and p-values will be presented for all covariates specified in 
the model.  
• 
Upon delivery of data, an assessment regarding the amount of missing data will be made. If the 
amount of missing HOMA-IR outcome data considered as a result of other impacts such as COVID-
19 is substantial, the logistic regression analysis may not be performed. 
• 
If the percent of subjects above any of the cutoffs are below 5% of the total number of subjects 
(observed data), or if complete or quasi-complete separation is observed in the data, then the 
analysis may not be performed. 
Subgroup Analyses 
• 
Not applicable 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
48 
 
9. 
POPULATION PHARMACOKINETIC (POPPK) 
ANALYSES 
Not applicable. 
 
10. 
PHARMACOKINETIC ANALYSES 
PK data collected for pregnant participants and at withdrawal visits for all subjects will 
be listed given data availability. Other PK samples are put to storage and there is no 
planned PK analysis at the time of the interim or the primary analysis. Future amendment 
will be made if pharmacokinetic data are to be explored further in the future.  
 
11. 
PHARMACODYNAMIC (AND / OR BIOMARKER) 
ANALYSES 
Not applicable. 
 
12. 
PHARMACOKINETIC / PHARMACODYNAMIC 
ANALYSES 
There is no plan for PK/PD analysis for the interim or the Month 12 primary analysis. 
Analysis details will be provided in future amendments if necessary. 
 
13. 
HEALTH OUTCOMES ANALYSIS 
13.1. 
Endpoint/Variables 
 
• 
Absolute values and Change from baseline in total “treatment satisfaction” score, and 
individual item scores of the HIV Treatment Satisfaction Status Questionnaire 
(HIVTSQs) at Month 12 (OLI and BIK)/Month 11 (D2I), and at Month 6(OLI and 
BIK)/Month 5(D2I). 
 
• 
Change in treatment satisfaction using the HIV Treatment Satisfaction Change 
(HIVTSQc) questionnaire at Month 12 (OLI and BIK)/Month 11 (D2I)(or 
withdrawal). 
 
• 
Preference for CAB LA + RPV LA every 2 months compared to an oral BIK single 
tablet regimen as well as reasons for preference at Month 12 (OLI)/Month 11 (D2I).  
 
• 
Change from Month 2(OLI)/Month 1(D2I) in Dimension scores (e.g., “Bother of 
ISRs”, “Leg movement”, “Sleep”, and “Acceptance of ISRs”) and in individual item 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
4 9  
 
sc ores ass essi n g p ai n d uri n g i njecti o n, a n xiet y bef ore a n d after i njecti o n, willi n g ness 
t o be i njecte d i n t he f ut ur e a n d o verall satisfacti o n wit h m o de of a d mi nistrati o n o ver  
ti me usi n g t he Perce pti o n of i njecti o n q uesti o n nair e ( PI N) at M o nt h 1 2 ( O LI a n d 
BI K)/ M o nt h 1 1 ( D 2I), a n d at M o nt h 6( O LI a n d BI K)/ M o nt h 5( D 2I).  
1 3. 2.  
S u m m ar y M e a s ur e  
Mea n treat me nt differe nce ( Q 2 M –  BI K) i n c ha n ge fr o m da y 1 ( baseli ne) at visits of 
i nterest f or HI V T S Qs a n d HI V T S Qc. 
 
Mea n c ha n ge at visits of i nterest f or C ha n ge fr o m M o nt h 2( O LI) / M o nt h 1 ( D 2I) i n PI N 
Di me nsi o n a n d i n di vi d ual ite m sc ores.  
 
1 3. 3.  
P o p ul ati o n of I nt er e st  
T he pri mar y healt h o utc o mes a nal yses will  be bas e d o n t he I nte nt -t o-Treat E x p ose d 
p o p ulati o n, u nless ot her wise s pecifie d.  
 
 N ote i n t he M o nt h 1 2 a nal ysis, m I T T-E will be us e d i n s u m mar y 
ta bles. 
 
1 3. 4.  
Str at e g y f or I nt er c urr e nt ( P o st-R a n d o mi z ati o n) E v e nt s  
If a partici pa nt disc o nti n ues treat me nt pri or t o t he ti me p oi nt of i nterest s uc h t hat t here is 
n o e val ua ble o n -treat me nt assess me nt f or t he ti me p oi nt of i nterest, t he data will n ot be 
c o m p ute d or i m p ute d.  Assess me nt wi n d o w sl otti n g ma y  b e i m ple me nte d f or u nsc he d ule d 
a n d wit h dra w al visits per Secti o n 1 6. 3. 4 . 
C CI
C CI
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5 0  
 
1 3. 5.  
St ati sti c al A n al y s e s / M et h o d s  
E n d p oi nt s  
A b s ol ut e  
C h a n g e fr o m M ai nt e n a n c e Ba s eli n e  
St ats A n alysis  S u m m ary  I n divid u al St ats A n alysis  S u m m ary  I n divid u al 
T  
F  
L 
T  
F  
F  
L 
T  
F  
L 
T  
F  
F  
L 
Tre at m e nt Sati sf a cti o n S c ore ( HI V T S Q s) at Da y 1, M o nt h 6( O LI a n d BI K)/ M o nt h 5( D2I), M o nt h 1 2 
( O LI a n d BI K)/ M o nt h 1 1 ( D 2I)  
I n divi d ual It e m 
Sc or es  by visit  
 
 
 
Y  
 
 
 
Y [ 3] 
 
 
Y  
 
 
 
 
T ot al Tr e at me nt 
S atisf actio n Scor e  
 
 
 
Y  
 
 
 
Y   
 
Y  
 
 
 
Tre at m e nt Sati sf a cti o n S c ore C h a n g e ( HI V T S Q c) at D ay 1, M o nt h 1 2 ( O LI a n d BI K)/ M o nt h 1 1( D2I)  
I n divi d ual It e m 
Sc or es  
 
 
 
Y  
 
 
 
 
 
 
 
 
 
 
Tr e at m e nt 
S atisf actio n Scor e 
C h a n ge  
Y  
 
 
Y  
 
 
 
 
 
 
 
 
 
 
Tre at m e nt Pr ef er e n c e f or C A B L A + R P V L A e v er y 2 m o nt h s c o m p are d t o a n or al BI K  si n gl e t a bl et 
r e gi m e n a s w ell a s r e a s o n s f or pr ef er e n c e 
Tr e at m e nt: Ev ery 2 
M o nt hs  vs D aily Or al 
BI K  
 
 
 
Y  
 
 
 
 
 
 
 
 
 
 
 
Re as o ns f or 
Pr ef er e nc e  
 
 
 
Y  
 
 
 
 
 
 
 
 
 
 
P er c e pti o n of I nj e cti o n ( PI N)  at M o nt h 2( O LI a n d BI K)/ M o nt h 1( D2I), M o nt h 6( O LI a n d BI K)/ M o nt h 
5( D2I), M o nt h 1 2 ( O LI a n d BI K)/ M o nt h 1 1 ( D 2I)  –  Q 2 M o nly  
I n divi d ual It e m 
Sc or es  ( A nxiety 
B ef or e, P ain, 
S atisf actio n, A nxi ety 
Aft er, Willi n g n ess)  
 
 
 
Y  
 
 
 
 
 
 
Y [2 ] 
 
 
 
Di m e nsi o n sc or es 
( e. g., “ B ot h er of 
I S Rs”, “L e g 
m ov e m e nt”, “ Sl e e p”, 
a n d “ Acc e pta nc e of 
I S Rs”) 
Y [1 ] 
 
 
Y  
 
 
 
 
 
 
Y [2 ] 
 
 
 
 
I n divi d ual 
Q u esti on n air e 
Sc or es ( 2 1 it e ms)  
 
 
 
Y  
 
 
 
 
 
 
 
 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5 1  
 
E n d p oi nt s  
A b s ol ut e  
C h a n g e fr o m M ai nt e n a n c e Ba s eli n e  
St ats A n alysis  S u m m ary  I n divid u al St ats A n alysis  S u m m ary  I n divid u al 
T  
F  
L 
T  
F  
F  
L 
T  
F  
L 
T  
F  
F  
L 
N O T E S:  
T a bl e 1  T = T a bl e, F = Fi g ur e, L = Listi n gs, Y = Dis pl ay g e n er at e d.  
T a bl e 2  St ats A n alysis = R e pr es e nts T F L r el at e d t o a ny f or m al st atistic al a n alys es (i. e. m o d elli n g) c o n d uct e d.  
T a bl e 3  S u m m ary = R e pr es e nts T F L r el at e d t o a ny s u m m ari es (i. e. d escri ptiv e st atistics) of t h e o bs erv e d r a w d at a. 
T a bl e 4  I n divi d u al = R e pr es e nts F L r el at e d t o a ny dis pl ays of i n divi d u al p artici p a nt o bs erv e d r a w d at a. 
 
1.  
St atistic al a n alysis (i. e. p -v al u e) pr o d uc e d o nly f or t h e acc e pt a nc e sc or e c o m p ari n g t o M o nt h 2( O LI)/ M o nt h 1( D 2I).  
2.  
C h a n g e  v ers us M o nt h 2( O LI)/ M o nt h 1( D 2I) f or PI N.  
3.  
I n divi d u al it e ms 5 (c o nv e ni e nt), 6 (fl exi bl e) a n d 1 0 (c o nti n u e). 
 
1 3. 5. 1.  
St ati sti c al M et h o d ol o g y S p e cifi c ati o n  
Details of t h e pla n n e d dis pla ys are pr o vi de d i n A p pe n di x 1 5 : List of Data Dis pla ys a n d 
will be base d o n G S K Data Sta n dar ds a n d statistical pri nci ples.  
U nless ot her wise s pecifie d, e n d p oi nts/ varia bles defi ne d i n Secti o n 1 3. 1  will be s u m marise d 
usi n g des cri pti ve statistics  a n d gra p hicall y prese nte d ( w here a p pr o pri ate).  O bser ve d dat a 
will be use d f or s u m mari es a n d statistical a nal ysis u nless ot her wise n o te d. 
1 3. 5. 1. 1.  
HI V T S Q s  
St ati sti c al A n al ys es  
HI V T S Q S  
E n d p oi nt s  
C h a n ge fr o m M ai nt e na nce B as eli n e ( D ay 1) at M o nth 6( O LI a nd BI K)/ M o nth 5( D2I) a n d at 
M o nt h 1 2 ( O LI an d BI K)/ M ont h 1 1 ( D 2I)  i n:  
 
•  HI V T S Qs t ot al tr eat m e nt s atisf acti o n scor e  
•  I n divi d ual HI V T S Qs it e ms 5 (c o nv e nie nc e), 6 (fl exi bl e), 1 0 (c o nti n ue) 
 
C o v ari at es  
B as eli n e sc or e(c onti n uo us)  
G e n der at Birt h ( m al e, f e m al e)  
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
52 
 
Statistical Analyses 
Baseline BMI(<30 kg/m2, >=30 kg/m2) 
Age (<50, >=50 Years) 
Race (white, non-white) 
Model Specification 
• 
Month 6(OLI and BIK)/Month 5(D2I) Analysis: ANCOVA (analysis of covariance) model will 
be used for Maintenance Phase data including treatment group plus above covariates. 
 
• 
Month 12 (OLI and BIK)/Month 11 (D2I) Analysis: MMRM (Mixed Model Repeated 
Measures) will be used including treatment group plus above covariates. No assumptions 
will be made about the correlations between subject readings (i.e. the correlation matrix for 
within-subject errors is unstructured):  
 
• MMRM (Mix Model Repeated Measures) model with the observed margins (OM) option 
within PROC MIXED in SAS will be used including treatment group plus the above 
covariates, with visit as the repeated factor.  
 
• The Kenward and Roger method for approximating the denominator degrees of freedom and 
correcting for bias in the estimated variance-covariance of the fixed effects will be used. 
 
• No assumptions about the correlations between a subject’s value will be made (the 
correlation matrix for within-subject errors will be unstructured). This will be estimated by 
treatment group by specifying “type=UN” and “group=treatment” options in the SAS MMRM 
models.  
 
• In the event that this model fails to converge, alternative correlation structures may be 
considered such as CSH or CS. Akaike's Information Criteria (AIC) will be used to assist 
with the selection of covariance structure if needed. 
 
• The repeated measures analysis will assume that the treatment difference can vary between 
visits (i.e. a treatment*visit interaction will be included in the model) . Estimates and 95% 
confidence intervals will be produced for each visit. 
 
Dataset 
• 
OC (Observed Case) dataset (with data slotting for the withdrawal/unscheduled visits) will 
be used. see Section 16.3.4 for details. No additional imputations will be used.  
Model Results Presentation 
• 
Adjusted means for each treatment group with 95% CI 
• 
Adjusted treatment difference (Q2M-BIK), 95% CI and the associated p-value for difference 
• 
Interaction between treatment and the baseline score  
 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5 3  
 
1 3. 5. 1. 2.  
HI V T S Q c  
St ati sti c al A n al ys es  
HI V T S Q c  
E n d p oi nt  
•  
Tr e at m e nt S atisfacti o n Sc ore ( C h a ng e) at M o nth 1 2 ( OLI an d BI K)/ M o nt h 1 1 ( D 2I)  
C o v ari at es  
G e n der at Birt h ( m al e, f e m al e)  
B as eli n e B MI( < 3 0 k g/ m 2, > =3 0 k g/ m2) 
A g e ( < 50, > =5 0 Y ears)  
R ac e ( w hit e, n on -w hit e)  
M o d el S p e cific ati o n  
•  
A n a n alysis of v ari a nce ( A N O V A) m o del will b e use d with a bov e cov ariates 
 
•  
A dj ust ed p oi nt esti m at es will b e d eriv e d as L S M E A N S usi n g t he o bs erv ed m ar gi ns ( O M) 
o pti on wit hi n P R O C MI X E D i n S A S.  
 
•  
I nt er actio ns b et w ee n tr e at me nt a n d e ach of t he c ovariates will n ot be assess ed u nl ess 
 
 t he pri m ary e nd p oint hi g hli ghts si g nifica nt int er acti o ns. In 
t his sit u atio n, t h e i nt er acti o n(s) of i nt er est m ay be assess e d a n d, if n ecess ary, r esults will b e 
r e p ort ed i n th e cli nic al st u dy r e p ort. If i nter acti ons ar e f o u n d t o b e si gnific a nt ( p < 0.10), 
r es ults m ay b e pr ese nte d se p ar ately by su bgr o u p. 
 
D at a s et  
•  
O C ( O bs erv e d Cas e) dat aset ( wit h d at a slotti ng f or th e wit h dr a w al/ unsc h ed ul ed visits) will 
b e use d. s e e S ectio n 1 6. 3. 4  f or d et ails. N o a dditi o n al i mp ut ati o ns will b e us ed.  
M o d el R e s ult s Pr e se nt ati o n  
•  
A dj ust ed m e ans  for e ach tre at m e nt gr ou p wit h  9 5 % CI  
•  
A dj ust ed tr eat m e nt differ e nc e ( Q 2 M -BI K), 9 5 % CI a nd th e associ at ed p -val u e for diff er e nce 
 
1 3. 5. 1. 3.  
PI N  
St ati sti c al A n al ys es  
PI N  ( Q 2 M ar m o nly) 
E n d p oi nt s  
C h a n ge fr o m M ont h 2( O LI) /M o nt h 1 (D 2I)  i n th e PI N acce pt a nc e scor e at: 
•  
M o nt h 1 2( O LI) /M ont h 1 1 (D2I)  
•  
M o nt h 6( O LI) /M o nt h 5 (D 2I)  
St ati sti c al T e st  
•  
T h e Wilc ox o n Si g n e d -R a nk T est will b e use d t o ev al u a bl e w h eth er t he c h a ng e fr o m M o nt h 
2 /M o nth 1 t o M ont h 6( O LI) /M o nt h 5 (D 2I) , an d to M o nt h 1 2( O LI) /M ont h 1 1 (D 2I) , r esp ectiv ely, 
is st atistic ally differ e nt fr o m z er o b ase d o n a t w o-si de d si g nific a nc e l ev el of 0. 0 5. Se p ar ate 
t ests will b e p erf or med f or th e c ha ng e at eac h ti me p oint. 
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
54 
 
Statistical Analyses 
Dataset 
• 
OC (Observed Case) dataset (with data slotting for the withdrawal/unscheduled visits) will 
be used. see Section 16.3.4 for details. No additional imputations will be used. 
Results Presentation 
• 
Summary statistics at each analysis timepoint and p-value for each comparison. 
 
14. 
VIROLOGY 
Given data availability, the virology analyses will mainly use genotype and phenotype 
data based on plasma sample for CVF population, unless otherwise specified. Summary 
tables (if applicable) will be based on the mCVF population. Listings will include all 
CVFs in this study. Additional analyses for HIV-1 resistance may be carried out on 
peripheral blood mononuclear (PBMC) samples and/or on stored blood samples from 
relevant time points. 
If pre-treatment genotypic/phenotypic results are available from both the central 
laboratory and Monogram Biosciences, then Monogram assays will take precedence.  
Table 5 provides an overview of the planed analyses. Further details of the planned 
displays are provided in Appendix 15: List of Data Displays and will be based on GSK 
Data Standards and statistical principles.  
Table 5 
Overview of Planned Virology Analysis 
Endpoint  
Absolute 
Summary 
Individual 
T 
F 
F 
L 
Genotypic resistance at time of CVF[1] 
Prevalence of Resistance Mutations 
Y [2] 
 
 
Y 
Prevalence of Genotypic Susceptibility 
Y 
 
 
 
Phenotypic resistance at time of CVF[1] 
Prevalence of Phenotype   
Y [3] 
 
 
Y 
Fold Change to CAB, RPV and BIC 
Y 
 
 
Y[4] 
IN, PR/RT Replication Capacity [5] 
 
 
 
Y 
Other 
Viral load, Genotypic and Phenotypic data for 
Participants with genotype and/or phenotype 
data for CVF and non-CVF participants  
 
 
 
Y[4] 
Net Assessment 
Y 
 
 
 
NOTES: 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 


 
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
5 5  
 
•  
S u m m ary = R e pr es e nts T F L r el at e d t o a ny s u m m ari es (i. e. d escri ptiv e st atistics) of t h e o bs erv e d r a w d at a. 
•  
I n divi d u al = R e pr es e nts F L r el at e d t o a ny dis pl ays of i n divi d u al p artici p a nt o bs erv e d r a w d at a.  
•  
If l ess t h a n 5 C V Fs ar e o bs erv e d d uri n g t h e m ai nt e n a nc e p h as e i n t h e mI T T-E p o p ul ati o n, s u m m ary t a bl es 
m ay n ot b e pr o d uc e d. All d at a will b e pr ovi d e d i n listi n gs i n t his c as e.  
 
1.  
C V F  d efi n e d by t w o c o ns ec utiv e pl as m a HI V -1 R N A l ev els 2 0 0 c/ m L aft er pri or s u p pr essi o n t o < 2 0 0 c/ m L. T h e 
first of t h es e t w o c o ns ec utiv e visits is d efi n e d as ‘ s us p ect e d’, a n d t h e 2 n d is d efi n e d as “c o nfir m e d”. Sa m pl e 
us e d f or r esist a nc e t esti n g is t ak e n at t h e s us p ect e d visit, a n d o nly t est e d o nc e vir ol o gic f ail ur e at a s u bs e q u e nt 
visit is c o nfir m e d. If t h e t est f ails wit h t h e s a m pl e at t h e s us p ect e d visit,  it will b e r e p ort e d as ‘ n o d at a’.  
 
 
2.  
N u m b er a n d p erc e nt a g e of p artici p a nts wit h I NI r esist a nc e m ut ati o ns or m aj or r esist a nc e m ut ati o ns i n t h e 
cl ass es of N N R TI, N R TI, PI, r es p ectiv ely, as d efi n e d i n S ecti o n 1 6. 6. 7 . 
3.  
S e p ar at e o ut p uts by p h e n oty pic s usc e pti bility a n d by n u m b er of dr u gs t o w hic h p artici p a nts ar e p h e n oty pic 
r esist a nt, p arti ally s e nsitiv e or s e nsitiv e. 
4.  
F ol d c h a n g e t o C A B, R P V a n d BI C will b e i ncl u d e d i n t h e listi n g f or vir al l o a d, g e n oty pic a n d p h e n oty pic d at a f or 
p artici p a nts wit h g e n oty p e a n d/ or p h e n oty p e d at a f or C V F a n d n o n -C V F p artici p a nts.  
5.  
I N: i nt e gr as e; P R: Pr ot e as e; R T: r ev ers e tr a nscri pt as e 
 
 
C CI


 
CONFIDENTIAL 
 
 
 
213500 
 
56 
 
15. 
REFERENCES 
Alberti KGMM et al. Harmonizing the metabolic syndrome: a joint interim statement of 
the International Diabetes Federation Task Force on Epidemiology and Prevention; 
National Heart, Lung, and Blood Institute; American Heart Association; World Heart 
Federation; International Atherosclerosis Society; and International Association for the 
Study of Obesity. Circulation. 2009;120:1640 –1645. 
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, 31 January 2019 
FDA Guidance for Industry: Human Immunodeficiency Virus-1 Infection: Developing 
Antiretroviral Drugs for Treatment, Nov 2015 
Fleiss J.L. Statistical Methods for Rates and Proportions. 2nd ed. New York:John Wiley; 
1981. 
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. 


 
CONFIDENTIAL 
 
 
 
213500 
 
57 
 
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. 
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.  
Wensing AM et al, 2019 Update of the Drug Resistance Mutations in HIV-1, Volume 27 
Issue 3 July/August 2019. 
 


 
CONFIDENTIAL 
 
 
 
213500 
 
58 
 
16. 
APPENDICES 
16.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population  
16.1.1. 
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. Month 12 or Month 6), 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. Note exclusion category # 2 
below will only be applied in the Month 12 analysis. Other categories will be applied in 
both Month 6 and Month 12 analysis. 
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* 
For Month 12 analysis only: 
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, meeting the following conditions during the Maintenance Phase: 
1. Two or more injection intervals affected by over dosage deviations, for example 
• 
Extra injection or excessive volume administered 
• 
Length of time between injections less than 21 days between the first and 
second injections (between M1 and M2 for OLI; between Day 1 and M1 for 
D2I), or less than 52 days for all subsequent dosing intervals, excluding split 
doses up to the analysis visit of interest (M12 for OLI /M11 for D2I) 
 
* 21 = 28 – 7; 52 = 28 + 31 – 7 (smallest possible dosing interval allowed – 7 days) 
 
 
2. 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. Month 12 for OLI and BIK/Month11for 
D2I), where the % of non-compliance is calculated as: 
(total number of non-compliant dosing days / total number of intended exposure days) * 
100% 


 
CONFIDENTIAL 
 
 
 
213500 
 
59 
 
Number 
Exclusion Description 
Where : 
• 
Total number of intended exposure days = 
date of the last analysis timepoint snapshot viral load (up to Injection Study 
Day 372 for OLI subjects, up to Study Day 372 for D2I subjects and up to 
Study Day 378 for BIK subjects) – Start Date of Study Treatment + 1 
 
• 
Total number of non-compliant dosing days up to the analysis timepoint visit 
(or date of IP discontinuation/ withdrawal, whichever is earlier), is derived as 
follows: 
BIK Arm:  
o Duration of interruptions in BIK arm for reasons other than treatment-
related adverse events/laboratory abnormalities (based on Exposure 
eCRF forms) 
 
Q2M Arm:  
o Length of time (in days) in excess until next injection from date of 
dosage/administration deviation potentially resulting in under dosage. 
Examples include: 
- less than 3 ml administered 
- early stop of oral bridging prior to the next planned injection  
 
o Length of time (in days) in excess beyond 31 days between the first and 
second injections and beyond 69 days for all subsequent dosing intervals.  
 
* 69 = 31+ 31 + 7 (largest possible dosing interval allowed + 7 days) 
- For those with oral bridging (OB), length of time (in days) is calculated 
between the start of oral bridging and the preceding injection 
 
o Interrupted days in oral study treatment (oral lead-in or oral bridging) if 
the oral dose has been interrupted for 3 or more consecutive days and 
the primary interruption reason is not adverse event or laboratory 
abnormality (based on the eCRF Exposure forms). 3 days will be 
assumed if such interrupted days are not available in the database. 
 
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). 
* Note: Category 02 is only applicable to the Month 12 analysis. 
 


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 0  
 
1 6. 2.  
A p p e n di x 2: S c h e d ul e of A cti viti e s  
Ti m e a n d E v e nt s T a bl e f or C A B L A + R P V L A Or al L e a d I n ( O LI) P arti ci p a nt s:  
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
2  
4  
6  
8  
1 0  
1 2  
Q 2 M aft er 
M o nt h 1 2  
Writt e n I nf or m e d C o ns e nt  
X  
 
 
 
 
 
 
 
 
 
 
 
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X  
X d  
 
 
 
 
 
 
 
 
 
 
R a n d o miz ati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
D e m o gr a p hy  
X  
 
 
 
 
 
 
 
 
 
 
 
M e dic al Hist ory e 
X  
 
 
 
 
 
 
 
 
 
 
 
C ar di ov asc ul ar risk ass ess m e nt e 
X  
X  
 
 
 
 
 
 
X  
 
X  
 
M e dic ati o n Hist ory/ Pri or A R T hist ory  
X  
 
 
 
 
 
 
 
 
 
 
 
Sy p hilis s er ol o gy + r efl ex R a pi d Pl as m a 
R e a gi n ( R P R)  
X  
X  
 
 
 
 
 
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d 
M e dic al Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
X  
 
X  
X  
X  
 
 
X  
 
X  
 
W aist Circ u mf er e nc e  
 
X  
 
X  
X  
X  
 
 
X  
 
X  
 
Hi p Circ u mf er e nc e  
 
X  
 
X  
X  
X  
 
 
X  
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h 
X  
X  
 
X  
X  
X  
 
 
X  
 
X  
 
1 2 -l e a d E C Gi  
(tri plic ate at D ay 1 pr e-d os e) 
X  
X  
X  
 
 
 
 
 
X  
 
X  
 
C D C HI V -1 st a g e ff 
X  
X  
 
 
 
 
 
 
 
 
 
 
HI V Ass oci at e d C o n diti o ns  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
A Es, S A Es, C o nc o mit a nt M e dic ati o ns  
X j 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 1  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
2  
4  
6  
8  
1 0  
1 2  
Q 2 M aft er 
M o nt h 1 2  
C ol u m bi a S uici d e S ev erity R ati n g Sc al e 
( e C-S S R S)  k 
X  
X  
 
X  
 
X  
 
 
X  
 
X  
 
Cli nic al c h e mistry a n d H e m at ol o gy  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Pr e g n a ncy T esti n g l 
S  
U  
U  
U  
U  
U  
U  
U  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st or a g e ( S) m  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
HI V -1 R N A l o w c o py s a m pl e  
 
X  
 
 
 
 
 
 
X  
 
 
 
C D 4 + c ell c o u nt  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
X  
 
 
 
X  
 
 
X  
 
X  
 
Uri n alysis n 
 
X  
X  
 
 
X  
 
 
X  
 
X  
 
F asti n g L a bs  
Gl uc os e, C h ol est er ol ( T ot al, H D L a n d 
L D L) a n d Tri glyc eri d es o 
 
X  
 
 
 
X  
 
 
X  
 
X p 
 
H e p atitis B ( H Bs A g), A nti -H Bc, a n d A nti -
H Bs A G, H e p atitis C  
( a nti-H C V A b)  
X  
 
 
 
 
 
 
 
 
 
 
 
P T/ P T T/I N R  
X  
X  
 
 
 
 
 
 
 
 
 
 
W h ol e Bl o o d ( Vir ol o gy)  
 
X  
 
 
 
X  
 
 
X  
 
X  
 
P B M Cs q  
 
X  
 
 
 
X  
 
 
X  
 
X  
 
I ns uli n, H b A 1c a n d r e n al, a n d b o n e 
bi o m ark er a n alyt es ( bl o o d uri n e) r 
 
X  
 
 
 
X  
 
 
X  
 
X x 
 
G e n etics s a m pl e t 
 
X  
 
 
 
 
 
 
 
 
 
 
P K s a m pli n g u 
( S) = St or a g e o nly 
 
 
S  
S  
S  
S  
S  
S  
S  
 
X  
S  
Or al C A B a n d Or al R P V Dis p e ns ati o n v 
 
X  
 
 
 
 
 
 
 
 
 
 
C CI
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 2  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
2  
4  
6  
8  
1 0  
1 2  
Q 2 M aft er 
M o nt h 1 2  
I P acc o u nt a bility ( Pill C o u nts)  
 
 
X  
 
 
 
 
 
 
 
 
 
I M tr e at m e nt a d mi nistr ati o n w  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
 
 
HI V T S Qs cc 
 
X  
 
 
 
X  
 
 
X  
 
X d d  
 
HI V T S Qc cc 
 
 
 
 
 
 
 
 
X  
 
X d d  
 
Pr ef er e nc e cc  
 
 
 
 
 
 
 
 
X  
 
X d d  
 
PI N cc 
 
 
 
X  
 
X  
 
 
X  
 
X d d  
 
Hist ory of C os m etic pr oc e d ur es g g 
 
 
 
 
 
 
 
 
X  
 
X  
 
 
C CI
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 3  
 
Ti m e a n d E v e nt s T a bl e f or C A B L A + R P V L A Dir e ct t o I nj e cti o n ( D 2I) P arti ci p a nt s:  
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
3  
5  
7  
9  
1 1  
Q 2 M aft er 
M o nt h 1 1  
Writt e n I nf or m e d C o ns e nt  
X  
 
 
 
 
 
 
 
 
 
 
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X  
X d  
 
 
 
 
 
 
 
 
 
R a n d o miz ati o n  
 
X  
 
 
 
 
 
 
 
 
 
D e m o gr a p hy  
X  
 
 
 
 
 
 
 
 
 
 
M e dic al Hist ory e 
X  
 
 
 
 
 
 
 
 
 
 
C ar di ov asc ul ar risk ass ess m e nt e 
X  
X  
 
 
 
 
 
X  
 
 
 
M e dic ati o n Hist ory/ Pri or A R T hist ory  
X  
 
 
 
 
 
 
 
 
 
 
Sy p hilis s er ol o gy + r efl ex R a pi d Pl as m a 
R e a gi n ( R P R)  
X  
X  
 
 
 
 
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d 
M e dic al Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
X  
X  
X  
X  
 
 
X  
 
X  
 
W aist Circ u mf er e nc e  
 
X  
X  
X  
X  
 
 
X  
 
X  
 
Hi p Circ u mf er e nc e  
 
X  
X  
X  
X  
 
 
X  
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h 
X  
X  
X  
X  
X  
 
 
X  
 
X  
 
1 2 -l e a d E C Gi  
(tri plic ate at D ay 1 pr e-d os e) 
X  
X  
 
 
 
 
 
X  
 
X  
 
C D C HI V -1 st a g e ff 
X  
X  
 
 
 
 
 
 
 
 
 
HI V Ass oci at e d C o n diti o ns  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
A Es, S A Es, C o nc o mit a nt M e dic ati o ns  
X j 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C ol u m bi a S uici d e S ev erity R ati n g Sc al e  
( e C-S S R S)  k 
X  
X  
X  
 
X  
 
 
X  
 
X  
 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 4  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
3  
5  
7  
9  
1 1  
Q 2 M aft er 
M o nt h 1 1  
Cli nic al c h e mistry a n d H e m at ol o gy  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Pr e g n a ncy T esti n g l 
S  
U  
U  
U  
U  
U  
U  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st or a g e ( S) m  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
HI V -1 R N A l o w c o py s a m pl e  
 
X  
 
 
 
 
 
X  
 
 
 
C D 4 + c ell c o u nt  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
X  
 
 
X  
 
 
X  
 
X  
 
Uri n alysis n 
 
X  
X  
 
X  
 
 
X  
 
X  
 
F asti n g L a bs: Gl uc os e, C h ol est er ol 
( T ot al, H D L a n d L D L) a n d 
Tri glyc eri d es o 
 
X  
 
 
X  
 
 
X  
 
X p 
 
H e p atitis B ( H Bs A g), A nti -H Bc, a n d 
A nti -H Bs A G, H e p atitis C ( a nti -H C V A b)  
X  
 
 
 
 
 
 
 
 
 
 
P T/ P T T/I N R  
X  
X  
 
 
 
 
 
 
 
 
 
W h ol e Bl o o d ( Vir ol o gy)  
 
X  
 
 
X  
 
 
X  
 
X  
 
P B M Cs q  
 
X  
 
 
X  
 
 
X  
 
X  
 
I ns uli n, H b A 1c a n d r e n al, a n d b o n e 
bi o m ark er a n alyt es ( bl o o d uri n e) r 
 
X  
 
 
X  
 
 
X  
 
X x 
 
G e n etics s a m pl e t 
 
X  
 
 
 
 
 
 
 
 
 
P K s a m pli n g u ( S) = St or a g e o nly 
 
 
S  
S  
S  
S  
S  
S  
 
X  
S  
I M tr e at m e nt a d mi nistr ati o n  
 
X  
X  
X  
X  
X  
X  
X  
X  
 
 
HI V T S Qs cc 
 
X  
 
 
X  
 
 
X  
 
X d d  
 
HI V T S Qc cc 
 
 
 
 
 
 
 
X  
 
X d d  
 
Pr ef er e nc e cc  
 
 
 
 
 
 
 
X  
 
X d d  
 
C CI
C CI
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 5  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
E xt e n si o n 
P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
D a y 1 b  
M o nt h  
1 c 
3  
5  
7  
9  
1 1  
Q 2 M aft er 
M o nt h 1 1  
PI N cc 
 
 
X  
 
X  
 
 
X  
 
X d d  
 
Hist ory of C os m etic pr oc e d ur es g g 
 
 
 
 
 
 
 
X  
 
X  
 
 
 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 6  
 
Ti m e a n d E v e nt s T a bl e f or BI K P arti ci p a nt s:  
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
D a y 1 b  
M o nt h  
2  
4  
6  
8  
1 0  
1 2 b b  
Writt e n I nf or m e d C o ns e nt  
X  
 
 
 
 
 
 
 
 
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X  
X d  
 
 
 
 
 
 
 
R a n d o miz ati o n  
 
X  
 
 
 
 
 
 
 
D e m o gr a p hy  
X  
 
 
 
 
 
 
 
 
M e dic al Hist ory e 
X  
 
 
 
 
 
 
 
 
C ar di ov asc ul ar risk ass ess m e nt e 
X  
X  
 
 
 
 
 
X  
 
M e dic ati o n Hist ory/ Pri or A R T hist ory  
X  
 
 
 
 
 
 
 
 
Sy p hilis s er ol o gy + r efl ex R a pi d Pl as m a R e a gi n ( R P R)  
X  
X  
 
 
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d M e dic al 
Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
X  
X  
X  
X  
 
 
X  
X  
W aist Circ u mf er e nc e  
 
X  
X  
X  
X  
 
 
X  
X  
Hi p Circ u mf er e nc e  
 
X  
X  
X  
X  
 
 
X  
X  
Vit al Si g ns ( B P, H R, T e m p er at ur e) h 
X  
X  
X  
X  
X  
 
 
X  
X  
1 2 -l e a d E C Gi  
(tri plic ate at D ay 1 pr e-d os e) 
X  
X  
 
 
 
 
 
X  
X  
C D C HI V -1 st a g e ff 
X  
X  
 
 
 
 
 
 
 
HI V Ass oci at e d C o n diti o ns  
 
X  
X  
X  
X  
X  
X  
X  
X  
A Es, S A Es, C o nc o mit a nt M e dic ati o ns  
X j 
X  
X  
X  
X  
X  
X  
X  
X  
C ol u m bi a S uici d e S ev erity R ati n g Sc al e ( e C -S S R S)  k 
X  
X  
X  
 
X  
 
 
X  
X  
Cli nic al c h e mistry a n d H e m at ol o gy  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Pr e g n a ncy T esti n g l 
S  
U  
U  
U  
U  
U  
U  
U  
S  
HI V -1 R N A  a n d s a m pl e f or st or a g e ( S) m  
X  
X  
X  
X  
X  
X  
X  
X  
X  
HI V -1 R N A l o w c o py s a m pl e  
 
X  
 
 
 
 
 
X  
 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 7  
 
Pr o c e d ure  
Scr e e ni n g Vi sit a  
M ai nt e n a n c e P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
D a y 1 b  
M o nt h  
2  
4  
6  
8  
1 0  
1 2 b b  
C D 4 + c ell c o u nt  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
X  
 
 
X  
 
 
X  
X  
Uri n alysis n 
 
X  
 
 
X  
 
 
X  
X  
F asti n g L a bs  
Gl uc os e, C h ol est er ol ( T ot al, H D L a n d L D L) a n d 
Tri glyc eri d es o 
 
X  
 
 
X  
 
 
X  
X p 
H e p atitis B ( H Bs A g), A nti -H Bc, a n d A nti -H Bs A G, 
H e p atitis C  
( a nti-H C V A b)  
X  
 
 
 
 
 
 
 
 
P T/ P T T/I N R  
X  
X  
 
 
 
 
 
 
 
W h ol e Bl o o d ( Vir ol o gy)  
 
X  
 
 
X  
 
 
X  
X  
P B M Cs q  
 
X  
 
 
X  
 
 
X  
X  
I ns uli n, H b A 1c a n d r e n al, a n d b o n e bi o m ark er a n alyt es 
( bl o o d uri n e)r 
 
X  
 
 
X  
 
 
X  
X x 
G e n etics s a m pl e t 
 
X  
 
 
 
 
 
 
 
BI K Dis p e ns ati o n  
 
X  
X  
X  
X  
X  
X  
X a a 
 
I P acc o u nt a bility ( Pill C o u nts) 
 
 
X  
X  
X  
X  
X  
X  
 
HI V T S Qs cc 
 
X  
 
 
X  
 
 
X  
X d d  
HI V T S Qc cc 
 
 
 
 
 
 
 
X  
X d d  
Hist ory of C os m etic pr oc e d ur es g g 
 
 
 
 
 
 
 
X  
X  
 
C CI
C CI
C CI
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 8  
 
Ti m e a n d E v e nt s T a bl e f or BI K t o Or al L e a d  I n –  E xt e n si o n P h a s e:  
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
M o nt h  
1 3  
1 4  
1 5  
Q 2 M Aft er 
M o nt h 1 5  
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X d  
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d M e dic al 
Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
 
 
 
X  
 
W aist Circ u mf er e nc e  
 
 
 
 
X  
 
Hi p Circ u mf er e nc e  
 
 
 
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h 
 
 
 
 
X  
 
1 2 -l e a d E C Gi  
 
 
 
 
 
X  
 
HI V Ass oci at e d C o n diti o ns  
X  
X  
X  
X  
X  
X  
A Es, S A Es, C o nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
 
X  
X  
X  
X  
X  
Cli nic al c h e mistry a n d H e m at ol o gy  
X  
X  
X  
X  
X  
X  
Pr e g n a ncy T esti n g l 
S  
U  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st or a g e ( S) m  
X  
X  
X  
X  
X  
X  
C D 4 + c ell c o u nt  
 
X  
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
 
 
 
X  
 
Uri n alysis n 
 
X  
 
 
X  
 
F asti n g L a bs  
Gl uc os e, C h ol est er ol ( T ot al, H D L a n d L D L) a n d 
Tri glyc eri d es o 
 
X  
 
 
X  
 
W h ol e Bl o o d ( Vir ol o gy)  
 
 
 
 
X  
 
P B M Cs q  
 
 
 
 
X  
 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
6 9  
 
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
M o nt h  
1 3  
1 4  
1 5  
Q 2 M Aft er 
M o nt h 1 5  
P K s a m pli n g u 
( S) = St or a g e o nly 
 
S  
S  
 
X  
S  
Or al C A B a n d Or al R P V Dis p e ns ati o n v 
X  
 
 
 
 
 
I P acc o u nt a bility ( Pill C o u nts) 
X  
X  
 
 
 
 
I M tr e at m e nt a d mi nistr ati o n w  
 
X  
X  
X  
 
 
 
 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 0  
 
Ti m e a n d E v e nt s T a bl e f or BI K t o Dir e ct t o I nj e cti o n –  E xt e n si o n P h a s e:  
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p  z 
M o nt h  
1 3  
1 4  
Q 2 M Aft er M o nt h 
1 4  
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X d  
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d M e dic al 
Ass ess m e nt f 
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
 
 
X  
 
W aist Circ u mf er e nc e  
 
 
 
X  
 
Hi p Circ u mf er e nc e  
 
 
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h 
 
 
 
X  
 
1 2 -l e a d E C Gi  
 
 
 
 
X  
 
HI V Ass oci at e d C o n diti o ns  
X  
X  
X  
X  
X  
A Es, S A Es, C o nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
X  
X  
X  
X  
X  
Cli nic al c h e mistry a n d H e m at ol o gy  
X  
X  
X  
X  
X  
Pr e g n a ncy T esti n g l 
S  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st or a g e ( S) m  
X  
X  
X  
X  
X  
C D 4 + c ell c o u nt  
 
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
 
 
X  
 
Uri n alysis n 
 
X  
 
X  
 
F asti n g L a bs  
Gl uc os e, C h ol est er ol ( T ot al, H D L a n d L D L) a n d 
Tri glyc eri d es o 
 
X  
 
X  
 
W h ol e Bl o o d ( Vir ol o gy)  
 
 
 
X  
 
P B M Cs q  
 
 
 
X  
 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 1  
 
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p  z 
M o nt h  
1 3  
1 4  
Q 2 M Aft er M o nt h 
1 4  
P K s a m pli n g u 
( S) = St or a g e o nly 
 
S  
 
X  
S  
I P acc o u nt a bility ( Pill C o u nts) 
X  
 
 
 
 
I M tr e at m e nt a d mi nistr ati o n w  
X  
X  
X  
 
 
 
S af ety F oll o w U p Visit:  C o n d uct a p pr oxi m at ely 4 w e eks aft er t h e l ast d os e of I P.  R e q uir e d o nly if t h e p artici p a nt h as o n g oi n g A Es or l a b a b n or m aliti es at t h e l ast o n-st u dy visit.  T his 
visit m ay b e c o n d uct e d by t el e p h o n e. 
N ot e: B P –  Bl o o d pr ess ur e, H R –  H e art R at e, B MI –  Bo dy M ass I n d ex, H D L –  Hi g h D e nsity Li p o pr ot ei n , L D L –  L o w D e nsity Li p o pr ot ei n, P T - Pr ot hr o m bi n Ti m e, P T T - P arti al 
T hr o m b o pl asti n Ti m e, I N R - I nt er n ati o n al n or m aliz e d r ati o, P B M C –  p eri p h er al bl o o d m o n o n ucl e ar c ell, R N A –  Ri b o n ucl eic aci d, H b A 1c = Glyc at e d h e m o gl o bi n, H Bs A g = h e p atitis B 
s urf ac e a ntig e n, H C V = h e p atitis C vir us, HI V -1 = h u m a n i m m u n o d efici e ncy vir us ty p e 1.  
a.  
C o m pl et e all Scr e e ni n g ass ess m e nts wit hi n 3 5 d ays.  Partici p a nts m ay b e gi n t h e M ai nt e n a nc e P h as e as s o o n as all Scr e e ni n g ass ess m e nts ar e c o m pl et e.  P artici p a nts m ay b e 
r escr e e n e d onc e a n d will b e assi g n e d a n e w p artici p a nt n u m b er.  
b.  
F or p artici p a nts w h o el ect t o p artici p at e i n t h e or al l e a d i n p eri o d, or al C A B 3 0 m g + R P V 2 5 m g will b e a d mi nist er e d a n d t h e  or al l e a d will st art o n D ay 1.  F or p artici p a nts w h o 
c h o os e t o g o dir ectly i nto i nj ecti o ns, t h e first l o a di n g d os e will b e a d mi nist er e d o n D ay 1. Visits f or p artici p a nts o n t h e BI K ar m ar e ex p ect e d t o oc c ur ev ery 5 6 d ays as pr oj ect e d 
acc or di n g t o t h e D ay 1 visit.  T h er e is a 3 d ay visit wi n d o w, fr o m t h e pr oj ect e d visit d at e ( M ai nt e n a nc e P h as e of t h e st u dy).  
c. 
F or p artici p a nts w h o el ect t o p artici p at e i n t h e or al l e a d i n p eri o d, t h e first l o a di n g d os e will b e a d mi nist er e d a n d t h e or a l l e a d i n will e n d.  F or p artici p a nts w h o c h o os e t o g o dir ectly 
i nt o i nj ecti o ns, t h e s ec o n d l o a di n g d os e will b e a d mi nist er e d.   
d.  
C o nfir m ati o n of eli gi bility t o c o nti n u e t h e M ai nt e n a nc e P h as e, a n d eli gi bility t o e nt er t h e Ext e nsi o n Ph as e.  
e.  
C oll ect f ull r o uti n e m e dic al hist ory pl us (r e p ort at B as eli n e visit): HI V risk f act ors ( m ay b e c oll ect e d at a l at er st u dy  visit), c ar di ov asc ul ar risk f act ors ( ass ess m e nts i ncl u d e s m oki n g 
st at us a n d hist ory, f a mily hist ory of c ar di ac ev e nts), r ec e nt [ 6  m o nt hs] illicit dr u g us e, i ntr av e n o us dr u g us e, g astr oi nt esti n al dis e as e, m et a b olic, psyc hi atric, r e n al, b o n e, a n d 
n e ur ol o gic dis or d ers.  At M o nt h 1 1 ( D 2I)/ 1 2 ( O LI a n d BI K), ass ess m e nts i ncl usiv e of s m oki n g st at us, alc o h ol us e a n d illicit d r u g us e si nc e t h e st art of t h e st u dy will b e 
a d mi nist er e d.  
f. 
P hysic al ex a ms s h o ul d b e c o n d uct e d as p art of n or m al r o uti n e cli nic al c a r e.  M e dic al ass ess m e nts i ncl u d e a ny d ecisi o ns t h e st u dy st aff m ust m ak e f or p artici p a nts m a n a g e m e nt 
a n d/ or c ar e of p artici p a nt.   
g.  
H ei g ht c oll ect e d at B as eli n e D ay 1 o nly.  R ec o m m e n d e d pr oc e d ur es t o m e as ur e w ei g ht, w aist a n d hi p circ u mf er e nc e c a n b e f o u n d i n pr ot oc ol  S ecti o n 1 0. 1 0.  W ei g ht r el at e d 
m e as ur e m e nts t o b e c oll ect e d ar e w ei g ht, b o dy f at %, t ot al b o dy w at er %, m uscl e m ass, a n d b o n e mi n er al m ass.  
h.  
M e as ur e vit al si g ns aft er a b o ut 5 mi n ut es of r est i n a s e mi -s u pi n e p ositi o n. 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 2  
 
i. 
A 1 2 -l e a d E C G will b e p erf or m e d aft er r esti n g i n a s e mi-s u pi n e p ositi o n f or at l e ast 5 mi n ut es.  E C Gs will b e p erf or m e d pr e -d os e. E C G pr e -d os e will b e p erf or m e d i n tri plic at e at 
D ay 1.  A 2 -h o ur p ost -d os e E C G will als o b e p erf or m e d at D ay 1 ( D 2I), M o nt h 1 ( O LI) a n d M o nt h 1 2 ( O LI)/ M o nt h 1 1 ( D 2I) f or p artici p a nts r ec eivi n g C A B L A + R P V L A wit h a n 
all o w a bl e wi n d o w of  3 0 mi n ut es.  
j. 
O nly S A Es r el at e d t o st u dy p artici p ati o n or t o a c o nc o mit a ntly a d mi nist er e d Vii V/ G S K pr o d uct will b e c oll ect e d b et w e e n o bt ai n i n g i nf or m e d c o ns e nt a n d a d mi nistr ati o n of st u dy 
dr u g at D ay 1.  
k. 
O n D ay 1, t h e e C -S S R S  is t o b e a d mi nist er e d pri or t o r a n d o miz ati o n.  T h e e C-S S R S will b e c o m pl et e d at t h e b e gi n ni n g of t h e visit f oll o wi n g a d mi nistr ati o n of ot h er P R Os r e q uir e d 
pri or t o i nj ecti o ns.  T h e e C -S S R S is n ot r e q uir e d d uri n g t h e Wit h dr a w al visit if wit h dr a w al occ urs d uri n g t h e Ext e nsi o n Ph as e.  
l. 
W o m e n of c hil d b e ari n g p ot e nti al o nly.  S =s er u m, U = uri n e.  Pr e g n a ncy ev e nts will b e c a pt ur e d st arti n g at D ay 1 f oll o wi n g i niti al ex p os ur e t o st u dy dr u g .  S er u m pr e g n a ncy t est c a n 
s u bstit ut e f or uri n e pr e g n a ncy t est if l oc ally r e q uir e d b ut m ust b e a p pr o pri at ely ti m e d t o c o nfir m pr e g n a ncy st at us pri or t o r a n d o miz ati o n a n d first I M a d mi nistr ati o n.  If t h e uri n e t est 
is p ositiv e, p erf or m a s er u m t est a n d d o n ot a d mi nist er i nj ecti o n.  T h e fr e q u e ncy of pr e g n a ncy t ests s h o ul d b e p erf or m e d acc or di n g t o l oc al l e g al r e q uir e m e nts.  
m.  M o nt h 1 2 ( O LI a n d BI K) a n d M o nt h 1 1 ( D 2I) HI V -1 R N A r et est ( wit hi n 4 w e eks) f or r es ults > 5 0 c/ m L will b e c a pt ur e d as u nsc h e d ul e d visit.   Pl as m a f or st or a g e s a m pl es will b e 
us e d f or p ossi bl e f ut ur e a n alys es.  
n.  
A m or ni n g s p eci m e n is pr ef err e d.  T o ass ess bi o m ark ers: uri n e al b u mi n/cr e ati ni n e r ati o; uri n e pr ot ei n/cr e ati ni n e r ati o; uri n e  p h os p h at e; b et a -2 -micr o gl o b uli n; a n d r eti n ol bi n di n g 
pr ot ei n.   
o.  
A n ov er ni g ht f ast is pr ef err e d; h o w ev er, a mi ni m u m of a 6 -h o ur f ast is acc e pt a bl e.  
p.  
O nly c oll ect if t h e Wit h dr a w al visit occ urs at M o nt h 6 or M o nt h 1 2 ( O LI a n d BI K); M o nt h 5 or M o nt h 1 1 ( D 2I).  
q.  
W h ol e bl o o d/ P B M C c oll ecti o n s a m pl es m ay b e us e d f or vir ol o g ic a n alys es.  P B M Cs will b e c oll ect e d at b as eli n e D ay 1, M o nt h 6, M o nt h 1 2, or Wit h dr a w al if pri or t o M o nt h 1 2 ( O LI 
a n d BI K). P B M Cs will b e c oll ect e d at b as eli n e D ay 1, M o nt h 5, M o nt h 1 1, or Wit h dr a w al if pri or t o M o nt h 1 1 ( D 2I)  
r. 
Bl o o d s a m pl e f or i ns uli n, H b A 1c, a n d r e n al a n d b o n e bi o m ark er ass ess m e nts:  R e n al:  Cyst ati n C; B et a -2 -Micr o gl o b uli n; R eti n ol Bi n di n g Pr ot ei n ( R B P); B o n e:  b o n e s p ecific 
alk ali n e p h os p h at as e, pr oc oll a g e n ty p e 1 -N -pr o p e pti d e, ty p e 1 c oll a g e n cr oss -li nk e d C-t el o p e pti d e, ost e oc alci n, 2 5 hy dr oxy-Vit a mi n D.  
s. 
Bl o o d s a m pl e f or
 
t. 
I nf or m e d c o ns e nt f or g e n etic r es e arc h m ust b e o bt ai n e d b ef or e s a m pl e c oll ecti o n.  Sa m pl e m ay b e c oll ect e d at a ny visit aft er si g ni n g i nf or m e d c o ns e nt, b ut pr ef er a bly at t h e D ay 1 
visit. 
u.  
O n e bl o o d s a m pl e f or C A B a n d R P V e a c h t o b e c oll e ct e d at e ac h P K ti m e p oi nt .  At M o nt h 1, f or p artici p a nts w h o el ect e d t o p artici p at e i n t h e Or al L e a d i n, a n d M o nt h 1 4 f or 
p artici p a nts w h o w er e r a n d o miz e d t o BI K a n d s witc h e d t o C A B L A + R P V L A i n t h e Ext e nsi o n Ph as e a n d will p artici p at e i n t h e Or al L e a d i n, Pr e d os e P K s a m pl es ar e t o b e 
c oll ect e d: P RI O R t o t h e fi n al or al d os e of C A B + R P V. F or pre g n a nt p arti ci p a nt s  ( o n C A B + R P V ar m): t w o bl o o d s a m pl es f or C A B a n d o n e R P V s a m pl e at e ac h P K ti m e p oi nt. 
R ef er t o pr ot oc ol Secti o n 1 0. 6. 6. 3.  
v. 
P artici p a nts w h o el ect e d t o p artici p at e i n t h e Or al L e a d i n b ef or e s witc hi n g t o C A B L A + R P V L A i nj ecti o ns, will t ak e fi n al d os e of or al l e a d -i n r e gi m e n i n t h e cli nic at t h e M o nt h 
1/ M o nt h 1 4 visit a n d b e gi n i nj ecti o ns.   
w.  If p ossi bl e, i nj ecti o ns s h o ul d b e s p ac e d a p pr oxi m at ely 2 c m fr o m o n e a n ot h er a n d fr o m t h e sit e of a ny pr evi o us i nj ecti o n a n d or a ny i nj ecti o n sit e r e acti o n.  Bri n g R P V L A t o 
a p pr oxi m at ely r o o m t e m p er at ur e pri or t o i nj ecti n g.  Ti m e a n d l oc ati o n of i nj ecti o n (ri g ht or l eft) as w ell as n e e dl e l e n gt h u s e d will b e c oll ect e d i n t h e e C R F.  T h e first i nj ecti o n c a n 
b e p erf or m e d b ef or e c e ntr al l a b res ults b ec o m e av ail a bl e a n d s af ety p ar a m et ers ar e r evi e w e d .  
x. 
C oll ect s a m pl e f or t h es e ass ess m e nts O N L Y if t h e Wit h dr a w al visit occ urs at M o nt hs 6 a n d 1 2 ( O LI a n d BI K); M o nt h 5 a n d 1 1 ( D 2 I). 
y. 
R ef er t o S ec ti o n 7. 1  of t h e pr ot oc ol f or a d diti o n al i nf or m ati o n o n p erf or mi n g wit h dr a w al ass ess m e nts  
z. 
P artici p a nts r ec eivi n g o n e or m or e i nj ecti o ns wit h C A B L A a n d/ or R P V L A will b e ass ess e d wit h cli nic visits at M o nt hs 3, 6, 9 a n d 1 2 d uri n g t h e L o n g -T er m F oll o w -U p P h as e  
a a.  BI K dis p e ns ati o n ( 1 -m o nt h s u p ply) f or p artici p a nts w h o pl a n o n e nt eri n g i nt o t h e Ext e nsi o n Ph as e.  P artici p a nts w h o d o n ot e nt er t h e Ext e nsi o n P h a s e or d o n ot wis h t o tr a nsiti o n 
t o t h e c o m m erci al s u p ply will n ot r ec eiv e 1-m o nt h s u p ply at M 1 2 . 
C CI


C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 3  
 
b b.  D at a fr o m visit will b e us e d t o d et er mi n e p artici p a nt’s eli gi bility t o e nt er t h e Ext e nsi o n Ph as e of st u dy.  If p artici p a nt el ects t o e nt er t h e Ext e nsi o n P h as e,  d et er mi n e if t h e p artici p a nt 
will el ect t o st art i nj ecti o ns i m m e di at ely or st art wit h or al l e a d i n.  
cc. All P R Os ar e r ec o m m e n d e d t o b e a d mi nist er e d b ef or e ot h er ass ess m e nts a n d i nj ecti o ns t ak e pl ac e at e ac h d esi g n at e d visit.  
d d.  O nly c oll ect e d if Wit h dr a w al visit  occ urs d uri n g t h e M ai nt e n a nc e P h as e.  
ff. 
W h e n ass essi n g C D C st a g e at Scr e e ni n g/ B as eli n e, c o nsi d er o nly t h e l at est av ail a bl e C D 4 T -c ell c o u nt, exc e pt w h e n t h e p artici p a nt h a d a n activ e St a g e 3 ev e nt 6 m o nt hs pri or t o 
Scr e e ni n g.  
g g.  At M o nt h 1 1 ( D 2I)/ M o nt h 1 2 ( O LI or BI K) or wit h dr a w al, ( d e p e n di n g w hic h is s o o n er) p artici p a nts will b e ask e d if a ny c os m etic pr oc e d ur es w er e p erf or m e d d uri n g t h e c o n d uct of 
t h e st u dy. 
 
C CI


CONFIDENTIAL 
 
 
 
213500 
 
74 
 
16.3. 
Appendix 3: Assessment Windows 
16.3.1. 
Definitions of Assessment Windows for Analyses 
Unless otherwise noted, laboratory data, vital signs, ECGs, Health Outcomes 
assessments, 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. The target 
Study Day or target Injection Study Day for is defined in Section 16.3.2.  
For parameters which are not scheduled to be assessed at a particular visit, 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” 
and “on-treatment” time points and in data listings, as well any algorithms that make use 
of additional data (e.g., snapshot). 
Maintenance phase assessments are assigned based on the Maintenance Phase Study Day, 
respectively. Extension phase assessments are assigned based on the Maintenance Phase 
Study day for subjects continuing CAB LA + RPV LA dosing (Q2M) into the Extension 
Phase, and based on the Extension Phase Study Day for subjects switching from the BIK 
arm to CAB LA + RPV LA dosing (Switch Q2M) for the Extension phase. Long-term 
Follow-up phase assessments are assigned based on the LTFU study day. See Section 
16.6.1 for derivation of Maintenance, Extension and LTFU Study Day. 
 
 


 
C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 5  
 
1 6. 3. 2.  
D efi niti o n s of A s s e s s m e nt Wi n d o w s f or D at a Ot h er t h a n H e alt h  O ut c o m e s  
1 6. 3. 2. 1.  
 A s s e s s m e nt Wi n d o w s f or S cr e e ni n g, M ai nt e n a n c e a n d E xt e n si o n P h a s e D at a –  Q 2 M O LI S u bj e ct s  
 
All P ara m et er s e x c e pt f or w h er e 
n ot e d [d]  
A n al y si s Wi n d o w  
T ar g et  
St u d y D a y  
T ar g et 
I nje cti o n  
St u d y  D a y  
A n al y si s 
Ti m e p oi nt 1  
A n al y si s 
Ti m e p oi nt  
2  
N ot e s  
 
St u dy D ay  1  
St u dy d ay of 
t h e e arli est 
r ec or d 
 
Scr e e ni n g  
Scr e e ni n g  
Scr e e ni n g  
 
L ast av ail a bl e r ec or d e d v al u e u p 
t o a n d i ncl u di n g t h e d at e of first 
M ai nt e n a nc e P h as e d os e of I P  
1  
 
M ai nt e n a nc e 
Bas eli n e ( D ay 1)  
M ai nt e n a nc e 
B as eli n e ( D ay 1)  
M ai nt e n a nc e 
B as eli n e ( D ay 1)  
P ost -d os e E C G  
V al u e t ak e n p ost -d os e  
1  
 
D ay 1 ( P ost D os e)  
D ay 1( P ost D os e)  
D ay 1( P ost D os e)  
 
I nj ecti o n St u dy D ay   1 5  a n d  
 St u dy D ay ≥2  
F or t h os e wit h O LI o nly: 2 < = 
St u dy D ay < = St u dy D ay  of L ast 
Or al D os e + 1  
3 1  
1  
M o nt h 1  
M o nt h 1  
I nj ecti o n 1 
Uri n alysis  
I nj ecti o n St u dy D ay  4 2 a n d  
 St u dy D ay ≥2  
F or t h os e wit h O LI o nly: 2 < = 
St u dy D ay < = St u dy D ay of L ast 
Or al D os e + 1  
P ost -d os e E C G  
V al u e t ak e n p ost -d os e M o nt h 1  
 
1 6   I nj ecti o n St u dy D ay   6 0  
6 1  
3 1  
M o nt h 2  
M o nt h 2  
I nj ecti o n 2 
 
6 1   I nj ecti o n St u dy D ay  1 2 0  
 
1 2 1  
9 1  
M o nt h 4  
M o nt h 3/ 4  
I nj ecti o n 3 
 
1 2 1  I nj ecti o n St u dy D ay  1 8 0  
1 8 1  
1 5 1  
M o nt h 6  
M o nt h 5/ 6  
I nj ecti o n 4 
Uri n alysis [a], C D 8, C D 4/ C D 8 r ati o, f asti n g 
gl uc os e a n d li pi ds [b], w ei g ht, h ei g ht, B MI, 
W aist a n d Hi p  Circ u mf er e nc e, Vit al 
Si g ns,
, I ns uli n, H b A 1c, H O M A -I R, 
1 2 1  I nj ecti o n St u dy D ay  1 9 2  
 
C CI


 
C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 6  
 
All P ara m et er s e x c e pt f or w h er e 
n ot e d [d]  
A n al y si s Wi n d o w  
T ar g et  
St u d y D a y  
T ar g et 
I nje cti o n  
St u d y  D a y  
A n al y si s 
Ti m e p oi nt 1  
A n al y si s 
Ti m e p oi nt  
2  
N ot e s  
R e n al, B o n e a n d  
 
 
1 8 1  I nj ecti o n St u dy D ay  2 4 0  
2 4 1  
2 1 1  
M o nt h 8  
M o nt h 7/ 8  
I nj ecti o n 5 
 
2 4 1  I nj ecti o n St u dy D ay  3 0 0  
3 0 1  
2 7 1  
M o nt h 1 0  
M o nt h 9/ 1 0  
I nj ecti o n 6 
 
3 0 1  I nj ecti o n St u dy D ay  3 6 0  
3 6 1  
3 3 1  
M o nt h 1 2  
M o nt h 1 1/ 1 2  
I nj ecti o n 7 
Uri n alysis [a], C D 8, C D 4/ C D 8 r ati o, f asti n g 
gl uc os e a n d li pi ds [b], w ei g ht, h ei g ht, B MI, 
W aist a n d Hi p Circ u mf er e nc e, Vit al 
Si g ns, 
, I ns uli n, H b A 1c, R e n al, 
B o n e a n d 
c] 
3 0 1  I nj ecti o n St u dy D ay  3 7 2  
 
 
3 6 1  I nj ecti o n St u dy D ay  4 2 0  
 
F or t h os e w h o di d n ot c o nti n u e 
t o Ext e nsi o n aft er c o m pl eti n g 
M ai nt e n a nc e P h as e:  
3 6 1  I nj ecti o n St u dy D ay  
I nj ecti o n St u dy D ay of: m ax( L ast 
I nj ecti o n D at e + 6 7, D at e of L ast 
Or al D os e + 1)  
 
4 2 1  
3 9 1  
M o nt h 1 4  
M o nt h 1 3/ 1 4  
I nj ecti o n 8 
 
( 3 0* m - 5 9)  I nj ecti o n St u dy 
D ay  ( 3 0* m ) 
3 0* m + 1  
3 0* m - 2 9  
M o nt h 1 6, 1 8, etc.  
M o nt h m -1/ m  
I nj ecti o n ( m/ 2 + 1) 
If s u bj e ct p er m a n e ntl y dis c o nti n u e d st u d y tr e at m e nt: 
 
S u bj e ct re c ei v e d at l e a st 1 
i nj e cti o n of I P: 
D at e > mi n( L T F U A R T st art 
d at e, m ax( L ast I nj ecti o n D at e + 
6 7, D at e of L ast Or al D os e + 1))  
S u bj e ct re c ei v e d oral 
C A B/ R P V o nl y:  
D at e > ( D at e of L ast or al 
C A B/ R P V D os e + 1)  
 
 
F oll o w -u p  
F oll o w -u p  
F oll o w -u p  
C CI
C CI
C CI
C CI


 
C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 7  
 
N O T E S:  
•  
A n alysis wi n d o ws ar e a p pli e d aft er d at a h as b e e n assi g n e d t o t h e M ai nt e n a nc e P h as e a n d Ext e nsi o n P h as e as d efi n e d i n S ecti o n 1 6. 4. 1  
•  
St u dy d ay a n d i nj ecti o n st u dy d ay is d efi n e d i n S ecti o n 1 6. 6. 1  
•  
F oll o w -u p will b e d er iv e d o nly f or p artici p a nts w h o p er m a n e ntly disc o nti n u e d st u dy tr e at m e nt. 
•  
L ast or al d os e m ay b e C A B/ R P V or S O C A R T Or al Bri d gi n g w h er e C A B/ R P V is n ot av ail a bl e d u e t o C O VI D -1 9 i m p act.  
•  
T ar g et I nj ecti o n St u dy D ay is o nly a p plic a bl e t o Q 2 M O LI s u bj ects  
 
[ a] Ur i n al y si s: All p ar a m et ers pr ovi d e d by t h e c e ntr al l a b or at ory u n d er t h e c at e g ory of uri n alysis.  
[ b] Li pi d s : C h ol est er ol, H D L C h ol est er ol Dir ect, L D L C h ol est er ol C alc ul ati o n, L D L C h ol est er ol Dir ect, T ot al C h ol est er ol/ H D L C h ol est er ol R ati o, Tri glyc eri d es  
[c]B o n e M ar k ers:  B o n e -s p ecific alk ali n e p h os p h at as e, Pr oc oll a g e n ty p e 1 N -pr o p e pti d e, Ty p e 1 c oll a g e n cr oss -li nk e d C-t el o p e pti d e, Ost e oc alci n, 2 5 hy dr oxy-Vit a mi n D; R e n al 
M ar k ers:  Cyst ati n C, R eti n ol Bi n di n g Pr ot ei n, B et a -2 -Micr o gl o b uli n; 
 
. 
[ d] A n alysis wi n d o ws f or p ar a m et ers wit h s p ars e c oll ecti o n ar e n ot e d.   
 
C CI


 
C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 8  
 
1 6. 3. 2. 2.  
A s s e s s m e nt Wi n d o w s f or S cr e e ni n g, M ai nt e n a n c e a n d E xt e n si o n P h a s e D at a –  Q 2 M D 2I S u bj e ct s  
 
All P ara m et er s e x c e pt f or w h er e 
n ot e d [c] 
A n al y si s Wi n d o w  
T ar g et St u d y D a y  
A n al y si s 
Ti m e p oi nt 1  
A n al y si s 
Ti m e p oi nt 2  
N ot e s  
 
St u dy D ay  1  
St u dy d ay of t h e e arli est r ec or d  
Scr e e ni n g  
Scr e e ni n g  
Scr e e ni n g  
 
L ast av ail a bl e r ec or d e d v al u e u p 
t o a n d i ncl u di n g t h e d at e of first 
M ai nt e n a nc e P h as e d os e of I P  
1  
M ai nt e n a nc e 
Bas eli n e ( D ay 1)  
M ai nt e n a nc e 
B as eli n e ( D ay 1)  
I nj ecti o n 1 
p ost -d os e E C G  
V al u e t ak e n p ost -d os e  
1  
D ay 1 ( P ost 
D os e)  
D ay 1( P ost D os e)  
I nj ecti o n 1 
 
2  St u dy D ay  6 0  
3 1  
M o nt h 1  
M o nt h 1  
I nj ecti o n 2 
Uri n alysis  
2  St u dy D ay  7 2  
 
6 1  St u dy D ay  1 2 0  
9 1  
M o nt h 3  
M o nt h 3/ 4  
I nj ecti o n 3 
 
1 2 1  St u dy D ay  1 8 0  
1 5 1  
M o nt h 5  
M o nt h 5/ 6  
I nj ecti o n 4 
Uri n alysis [a], C D 8, C D 4/ C D 8 r ati o, f asti n g 
gl uc os e a n d li pi ds[b], w ei g ht, h ei g ht, B MI, 
W aist a n d Hi p Circ u mf er e nc e, Vit al 
Si g ns, 
, I ns uli n, H b A 1c, R e n al, 
B o n e a n d 
 
1 2 1  St u dy D ay  1 9 2  
 
1 8 1  St u dy D ay  2 4 0  
2 1 1  
M o nt h 7  
M o nt h 7/ 8  
I nj ecti o n 5 
 
2 4 1  St u dy D ay  3 0 0  
2 7 1  
M o nt h 9  
M o nt h 9/ 1 0  
I nj ecti o n 6 
 
3 0 1  St u dy D ay  3 6 0  
3 3 1  
M o nt h 1 1  
M o nt h 1 1/ 1 2  
I nj ecti o n 7 
Uri n alysis [a], C D 8, C D 4/ C D 8 r ati o, f asti n g 
gl uc os e a n d li pi ds [b], w ei g ht, h ei g ht, B MI, 
W aist a n d Hi p Circ u mf er e nc e, Vit al 
Si g ns, 
 I ns uli n, H b A 1c, R e n al, 
B o n e a n d 
 
3 0 1  St u dy D ay  3 7 2  
C CI
C CI
C CI
C CI


 
C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
7 9  
 
All P ara m et er s e x c e pt f or w h er e 
n ot e d [c] 
A n al y si s Wi n d o w  
T ar g et St u d y D a y  
A n al y si s 
Ti m e p oi nt 1  
A n al y si s 
Ti m e p oi nt 2  
N ot e s  
 
3 6 1  St u dy D ay  4 2 0  
 
F or t h os e w h o di d n ot c o nti n u e 
t o Ext e nsi o n aft er c o m pl eti n g 
M ai nt e n a nc e P h as e:  
3 6 1  St u dy D ay  m ax( L ast 
I nj ecti o n D at e + 6 7, D at e of L ast 
Or al D os e + 1))  
 
3 9 1  
M o nt h 1 3  
M o nt h 1 3/ 1 4  
I nj ecti o n 8 
 
( 3 0* m - 2 9)  St u dy D ay  
( 3 0* m + 3 0) 
3 0* m + 1  
M o nt h 1 5, 1 7, 
etc.  
M o nt h m/ m + 1  
I nj ecti o n (( m + 3)/ 2) 
If s u bj e ct p er m a n e ntl y dis c o nti n u e d st u d y tr e at m e nt: 
 
D at e > mi n( L T F U A R T st art 
d at e, m ax( L ast I nj ecti o n D at e + 
6 7, D at e of L ast Or al D os e + 1))  
 
F oll o w -u p  
F oll o w -u p  
F oll o w -u p  
N O T E S:  
•  
A n alysis wi n d o ws ar e a p pli e d aft er d at a h as b e e n assi g n e d t o t h e M ai nt e n a nc e P h as e a n d Ext e nsi o n P h as e as d efi n e d i n S ecti o n 1 6. 4. 1  
•  
St u dy d ay is d efi n e d i n S ecti o n 1 6. 6. 1  
•  
F oll o w -u p will b e d eriv e d o nly f or p artici p a nts w h o p er m a n e ntly disc o nti n u e d st u dy tr e at m e nt.  
•  
L ast or al d os e m ay b e C A B/ R P V or S O C A R T Or al Bri d gi n g w h er e C A B/ R P V is n ot av ail a bl e d u e t o C O VI D -1 9 i m p act.  
 
[ a] Uri n al y si s:  All p ar a m et ers pr ovi d e d by t h e c e ntr al l a b or at ory u n d er t h e c at e g ory of uri n alysis.  
[ b] Li pi d s : C h ol est er ol, H D L C h ol est er ol Dir ect, L D L C h ol est er ol C alc ul ati o n, L D L C h ol est er ol Dir ect, T ot al C h ol est er ol/ H D L C h ol est er ol R ati o,  Tri glyc eri d es  
[c]B o n e M ar k ers:  B o n e -s p ecific alk ali n e p h os p h at as e, Pr oc oll a g e n ty p e 1 N -pr o p e pti d e, Ty p e 1 c oll a g e n cr oss -li nk e d C-t el o p e pti d e, Ost e oc alci n, 2 5 hy dr oxy-Vit a mi n D; R e n al 
M ar k ers:  Cyst ati n C, R eti n ol Bi n di n g Pr ot ei n, B et a -2 -Micr o gl o b uli n; 
 
 
[ d] A n alysis wi n d o ws f or p ar a m et ers wit h s p ars e c oll ecti o n ar e n ot e d.   
 
 
 
C CI


 
C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
8 0  
 
1 6. 3. 2. 3.  
A s s e s s m e nt Wi n d o w s f or S cr e e ni n g a n d M ai nt e n a n c e P h a s e D at a – BI K  
All P ara m et er s e x c e pt f or w h er e 
n ot e d [d]  
A n al y si s Wi n d o w  
T ar g et St u d y D a y  
A n al y si s 
Ti m e p oi nt 1  
A n al y si s 
Ti m e p oi nt 2  
N ot e s  
 
St u dy D ay  1  
St u dy d ay of t h e e arli est r ec or d  
Scr e e ni n g  
Scr e e ni n g  
 
 
L ast av ail a bl e r ec or d e d v al u e u p 
t o a n d i ncl u di n g t h e d at e of first 
M ai nt e n a nc e P h as e d os e of I P  
1  
M ai nt e n a nc e 
Bas eli n e ( D ay 
1)  
M ai nt e n a nc e 
B as eli n e ( D ay 1)  
 
p ost -d os e E C G  
V al u e t ak e n p ost -d os e  
1  
D ay 1 ( P ost 
D os e)  
D ay 1( P ost D os e)  
 
 
2  St u dy D ay  8 4  
5 7  
M o nt h 2  
M o nt h 2  
 
 
8 5  St u dy D ay  1 4 0  
1 1 3  
M o nt h 4  
M o nt h 3/ 4  
 
 
1 4 1   St u dy D ay  1 9 6  
1 6 9  
M o nt h 6  
M o nt h 5/ 6  
 
Uri n alysis [a], C D 8, C D 4/ C D 8 r ati o, f asti n g 
gl uc os e a n d li pi ds [b], w ei g ht, h ei g ht, B MI, 
W aist a n d Hi p Circ u mf er e nc e, Vit al 
Si g ns, 
, I ns uli n, H b A 1c, R e n al, 
B o n e a n d 
1 4 1   St u dy D ay  2 1 0  
 
1 9 7   St u dy D ay  2 5 2  
2 2 5  
M o nt h 8  
M o nt h 7/ 8  
 
 
2 5 3   St u dy D ay  3 0 8  
2 8 1  
M o nt h 1 0  
M o nt h 9/ 1 0  
 
 
3 0 9   St u dy D ay  3 5 0  
3 3 7  
M o nt h 1 2  
M o nt h 1 1/ 1 2  
 
Uri n alysis [a], C D 8, C D 4/ C D 8 r ati o, f asti n g 
gl uc os e a n d li pi ds[b], w ei g ht, h ei g ht, B MI, 
W aist a n d Hi p Circ u mf er e nc e, Vit al 
Si g ns, 
, I ns uli n, H b A 1c, R e n al, 
B o n e a n d
[c] 
3 0 9   St u dy D ay  3 7 8  
 
 
3 5 1  St u dy D ay  St u dy D ay  of 
L ast M ai nt e n a nc e BI K D os e + 1  
3 6 5  
M o nt h 1 3  
M o nt h 1 3/ 1 4  
 
If s u bj e ct p er m a n e ntl y dis c o nti n u e d st u d y tr e at m e nt: 
 
D at e > ( D at e of L ast BI K D os e 
+ 1)  
 
F oll o w -u p  
F oll o w -u p  
 
N O T E S:  
•  
A n alysis wi n d o ws ar e a p pli e d aft er d at a h as b e e n assi g n e d t o t h e M ai nt e n a nc e P h as e as d efi n e d i n Secti o n 1 6. 4. 1  
C CI
C CI
C CI
C CI


 
C O N FI D E N TI A L  
2 1 3 5 0 0  
 
 
8 1  
 
•  
N ot e f or t h e BI K ar m, t h e “ev ery t w o m o nt hs” ar e i m pl e m e nt e d as “ ev ery 5 6 d ays ”, t h er ef or e t h e a n alysis wi n d o ws ar e a dj ust e d acc or di n g t o t h e act u al visit sc h e d ul es i nst e a d 
of n o mi n al.  
•  
St u dy d ay is d efi n e d i n S ecti o n 1 6. 6. 1  
•  
F oll o w -u p will b e d eriv e d o nly f or p artici p a nts w h o p er m a n e ntly disc o nti n u e d st u dy tr e at m e nt.  
 
[ a] Uri n al y si s:  All p ar a m et ers pr ovi d e d by t h e c e ntr al l a b or at ory u n d er t h e c at e g ory of uri n alys is. 
[ b] Li pi d s : C h ol est er ol, H D L C h ol est er ol Dir ect, L D L C h ol est er ol C alc ul ati o n, L D L C h ol est er ol Dir ect, T ot al C h ol est er ol/ H D L C h ol est er ol R ati o, Tri glyc eri d es  
[c]B o n e M ar k ers:  B o n e -s p ecific alk ali n e p h os p h at as e, Pr oc oll a g e n ty p e 1 N -pr o p e pti d e, Ty p e 1 c o ll a g e n cr oss-li nk e d C-t el o p e pti d e, Ost e oc alci n, 2 5 hy dr oxy-Vit a mi n D; R e n al 
M ar k ers:  Cyst ati n C, R eti n ol Bi n di n g Pr ot ei n, B et a -2 -Micr o gl o b uli n; 
 
. 
[ d] A n alysis wi n d o ws f or p ar a m et ers wit h s p ars e c oll ecti o n ar e n ot e d.   
 
C CI


 
CONFIDENTIAL 
213500 
 
 
82 
 
16.3.2.4. 
Assessment Windows for Extension Phase Data – BIK subjects Switching to CAB LA + RPV LA (Switch Q2M) and 
choose OLI (Switch OLI) 
All Parameters except 
for where noted[c] 
Analysis Window 
Target 
Extension 
Study Day 
Target 
Extension 
Injection 
Study Day 
Analysis 
Timepoint 1 
Analysis 
Timepoint 2 
Notes 
 
Last available recorded value up to and 
including the date of first Extension Phase dose 
of CAB/RPV 
1 
 
Extension 
Baseline 
(Month 13) 
Extension Baseline 
(Month 13) 
 
 
Extension Injection Study Day  15 and 
Extension Study day ≥2 
For those with Ext OLI only: 2<= Extension 
Study Day<= Extension Study Day of Last 
Extension Oral Dose +1 
31 
1 
Month 14 
Month 14 
Extension Injection 1 
Urinalysis[a], fasting 
glucose and lipids[b] 
Extension Injection Study Day  42 and 
Extension Study day ≥2 
For those with Ext OLI only: 2<= Extension 
Study Day<= Extension Study Day of Last 
Extension Oral Dose +1 
 
16  Extension Injection Study Day  60 
61 
31 
Month 15 
Month 15 
Extension Injection 2 
 
61  Extension Injection Study Day  120 
121 
91 
Month 17 
Month 16/17 
Extension Injection 3 
 
121  Extension Injection Study Day  180 
181 
151 
Month 19 
Month 18/19 
Extension Injection 4 
 
(30*(m-14) - 29)  Extension Injection Study 
Day  (30*(m -14)+ 30) 
30*(m-13) + 1 
30*(m-14) + 1 
Month 21, 23, 
etc. 
Month m-1/m 
Extension Injection 
(m-11)/2 
If subject permanently discontinued study treatment: 
 
Subject received at least 1 injection of IP: 
Date > min(LTFU ART start date, max(Last 
Injection Date + 67, Date of Last Oral Dose + 
1)) 
 
Subject received oral CAB/RPV only: 
Date> (Date of Last oral Dose +1) 
 
 
 
Follow-up 
Follow-up 
 
 


 
CONFIDENTIAL 
213500 
 
 
83 
 
NOTES: 
• 
Analysis windows are applied after data has been assigned to the Extension Phase as defined in Section 16.4.1 
• 
Extension Study day and Extension Injection Study Day is defined in Section 16.6.1 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
• 
Last oral dose may be CAB/RPV or SOC ART Oral Bridging where CAB/RPV is not available due to COVID-19 impact. 
• 
Target Extension Injection Study Day is only applicable to Switch Q2M subjects who choose OLI during the Extension Phase 
 
 
[a] Urinalysis: All parameters provided by the central laboratory under the category of urinalysis. 
[b] Lipids: Cholesterol, HDL Cholesterol Direct, LDL Cholesterol Calculation, LDL Cholesterol Direct, Total Cholesterol/HDL Cholesterol Ratio, Triglycerides 
[c] Analysis windows for parameters with sparse collection are noted.   
 
 
 
 


 
CONFIDENTIAL 
213500 
 
 
84 
 
16.3.2.5. 
Assessment Windows for Extension Phase Data –BIK subjects Switching to CAB LA + RPV LA (Switch Q2M) and 
choose D2I (Switch D2I) 
All Parameters except 
for where noted[c] 
Analysis Window 
Target Extension Study Day 
Analysis 
Timepoint 1 
Analysis 
Timepoint 2 
Notes 
 
Last available recorded value up to and 
including the date of first Extension Phase dose 
of CAB/RPV 
1 
Extension 
Baseline 
(Month 13) 
Extension Baseline 
(Month 13) 
 
Extension Injection 1 
 
2  Study Day  60 
31 
Month 14 
Month 14 
Extension Injection 2 
Urinalysis[a], fasting 
glucose and lipids[b] 
2  Study Day  72 
 
61  Study Day  120 
91 
Month 16 
Month 16/17 
Extension Injection 3 
 
121  Study Day  180 
151 
Month 18 
Month 18/19 
Extension Injection 4 
 
(30*(m-13) - 29)  Study Day  (30*(m -13)+ 
30) 
30*(m-13) + 1 
Month 20, 22, 
etc. 
Month m/m+1 
Extension Injection 
(m-10)/2 
If subject permanently discontinued study treatment: 
 
Date > min(LTFU ART start date, max(Last 
Injection Date + 67, Date of Last Oral Dose + 
1)) 
 
 
 
Follow-up 
Follow-up 
 
NOTES: 
• 
Analysis windows are applied after data has been assigned to the Extension Phase as defined in Section 16.4.1 
• 
Extension Study day is defined in Section 16.6.1 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
• 
Last oral dose may be CAB/RPV or SOC ART Oral Bridging where CAB/RPV is not available due to COVID-19 impact. 
 
[a] Urinalysis: All parameters provided by the central laboratory under the category of urinalysis. 
[b] Lipids: Cholesterol, HDL Cholesterol Direct, LDL Cholesterol Calculation, LDL Cholesterol Direct, Total Cholesterol/HDL Cholesterol Ratio, Triglycerides 
[c] Analysis windows for parameters with sparse collection are noted.   


 
CONFIDENTIAL 
213500 
 
 
85 
 
16.3.2.6. 
Assessment Windows for Summary of Snapshot Data - Data assigned to Maintenance Phase Only 
Snapshot Analysis Windows 
(If no on-treatment viral load data in default window, use expanded window) 
Analysis 
Timepoint 1 
Analysis 
Timepoint 2 
Default[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) 
Maintenance 
Baseline (Day 1) 
CAB LA + RPV LA (OLI) 
Injection Study Day  15 and Study Day ≥2 
For those with OLI only: 2<= Study Day<= 45 
Injection Study Day  42 and Study Day ≥2 
For those with OLI only: 2<= Study Day<= Study Day of 
Last Oral Dose +1 
Month 1 
Month 1 
16  Injection Study Day  60 
16  Injection Study Day  72 
Month 2 
Month 2 
61  Injection Study Day  120 
61  Injection Study Day  132 
Month 4 
Month 3/4 
109  Injection Study Day  192 
109  Injection Study Day  192 
Month 6 
Month 5/6 
181  Injection Study Day  240 
181  Injection Study Day  252 
Month 8 
Month 7/8 
241  Injection Study Day  300 
241  Injection Study Day  312 
Month 10 
Month 9/10 
289  Injection Study Day  372 
289  Injection Study Day  372 
Month 12 
Month 11/12 
CAB LA + RPV LA (D2I) 
2  Study Day  60 
2  Study Day  72 
Month 1 
Month 1 
61  Study Day  120 
61  Study Day  132 
Month 3 
Month 3/4 
109  Study Day  192 
109  Study Day  192 
Month 5 
Month 5/6 
181  Study Day  240 
181  Study Day  252 
Month 7 
Month 7/8 
241  Study Day  300 
241  Study Day  312 
Month 9 
Month 9/10 
289  Study Day  372 
289  Study Day  372 
Month 11 
Month 11/12 
BIK Arm 
2  Study Day  84 
2  Study Day  98 
Month 2 
Month 2 
85  Study Day  140 
85  Study Day  154 
Month 4 
Month 3/4 
127  Study Day  210 
127  Study Day  210 
Month 6 
Month 5/6 
197  Study Day  252 
197  Study Day  266 
Month 8 
Month 7/8 
253  Study Day  308 
253  Study Day  322 
Month 10 
Month 9/10 
295  Study Day  378 
295  Study Day  378 
Month 12 
Month 11/12 
NOTES: 
o Apply Snapshot analysis windows only to viral load data that is on-treatment within the Maintenance Phase (See Section 16.4.2). 


 
CONFIDENTIAL 
213500 
 
 
86 
 
o An on-treatment viral load assessment may be assigned to more than one snapshot analysis window. 
a. 
 6 Week window is always used at key analysis timepoints (Month 5/6 and Month 11/12). For other analysis timepoints, if no viral load data in default window, expand 
upper bound to +6 weeks.  
 


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
8 7  
 
1 6. 3. 2. 7.  
A s s e s s m e nt Wi n d o w s f or S u m m ari e s of L o n g -T er m F oll o w U p P h a s e 
D at a  
A n al y si s Wi n d o w  
A n al y si s 
Ti m e p oi nt  
T ar g et  L T F U  St u d y D a y 
of Wi n d o w  
1  L T F U St u dy D ay  1 3 5  
L T F U M o nt h 3  
9 0  
1 3 6  L T F U Stu dy Day  22 5  
L T F U M o nt h 6  
1 8 0  
2 2 6  L T F U Stu dy Day  31 5  
L T F U M o nt h 9  
2 7 0  
3 1 6  L T F U Stu dy Day  40 5  
L T F U M o nt h 1 2  
3 6 0  
( 3 0* m - 4 4)  L T F U St u dy D ay  ( 3 0* m + 4 5) 
L T F U M o nt h m  
m = 1 5, 1 8,2 1,  
3 0* m 
N O T E S:  
•  
A n alysis wi n d o ws ar e a p pli e d aft er d at a h as b e e n assi g n e d t o t h e L T F U Ph as e as d efi n e d i n Secti o n 1 6. 4. 1 . 
•  
L o n g -T er m F oll o w -U p ( L T F U) St u dy d ay is d ef i n e d i n Secti o n 1 6. 6. 1  
•  
A n ass ess m e nt m ay b e sl ott e d t o b ot h L T F U a n d M ai nt e n a nc e/ Ext e nsi o n P h as e  
 
1 6. 3. 3.  
A s s e s s m e nt Wi n d o w f or St u d y C o n cl u si o n  
T he st u d y c o ncl usi o n a n d P hase c o ncl usi o n rec or ds i n dis p ositi o n data will be 
sl otte d base d o n Secti o n 1 6. 3. 1  f or Mai nte na n ce a n d E xte nsi o n P hase c o ncl usi o n 
rec or ds. H o we v er, if t he disc o nti n uati o n date is p ost-treat me nt ( bas e d o n Secti o n 
1 6. 4. 3 ), t he n t he disc o nti n uati o n will be sl otte d t o t he partici pa nt’s last attai ne d 
o n -treat me nt a n al ysis visit acr oss all assess me nts (e. g. a nal ysis visit 
c orres p o n di n g t o t he last o n -treat me nt la b ass ess me nt), rat her t ha n f oll o w u p. 
1 6. 3. 4.  
A s s e s s m e nt Wi n d o w f or H e alt h O ut c o m e D at a  
1 6. 3. 4. 1.  HI V T S Q s/ HI V T S Q c / PI N/
  
Assess me nts will be assi g ne d t o a nal ysis visits as f oll o ws : 
•  Mai nte na nce Baseli ne ( Da y 1) will be defi n e d as l ast a vaila ble rec or de d val ue u p 
t o a n d i ncl u di n g t he d ate of first Mai nte na nce P hase d ose of st u d y treat me nt 
(e x pecte d t o be c ollecte d at Da y 1).  Bas eli ne is n ot a p plica ble f or PI N, HI V T S Qc 
a n d ot her o ne -ti me q uesti o n naires s uc h as treat me nt prefere nce. 
 
•  If t he n o mi nal visit i de ntifier as ca pt ure d i n t he s o urce dat aset c orres p o n ds t o a 
sc he d ule d c ollecti o n per t he Ti me a n d E ve nts Sc h e d ule (see Secti o n 1 6. 2 ) a n d t he 
assess me nt is c ollecte d i n t he Mai nte na nce P hase ( see Secti o n 1 6. 4. 1. 2 ), t h e n t he 
n o mi nal visit i de ntifier will be ke pt as t he a nal ysis visit (e x cl u di n g Da y 1 w hic h 
will n or mall y be assi g ne d t o Mai nte na nce Bas eli ne ( Da y 1).  
 
•  If t he n o mi nal visit i de ntifier is u nsc he d ule d or wit h dra wal, t he n t he f oll o wi n g 
pr oce d ure will be use d:  
a. Assi g n t he ass ess me nt t o a st u d y P hase acc or di n g t o Secti o n 1 6. 4. 1. 2 . 
Pr ocee d t o ste p b if t he assess me nt is assi g ne d t o t he Mai nte na nce P hase.  
C CI


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
8 8  
 
b.  I d e ntif y t he ‘last n o mi nal visit’ wit h t he H O assess me nt perf or me d pri or 
t o t he u nsc he d ule d/ wit h dra wal visit t o be slotte d.  
c. U nsc he d ule d/ wit h dra wal visit s will be sl otte d t o t he pla n ne d n o mi nal visit 
s u bse q ue nt t o t he ‘last n o mi nal visit’. If t he ‘l ast n o mi nal visits’ d oes n ot 
e xist (e. g. n o rec or ds ori gi nate fr o m a pla n n e d n o mi nal visit), t he n t he 
u nsc he d ule d/ wit h dra wal  visit will be sl ot te d t o t he first pla n ne d n o mi nal 
visit after Da y 1.  If t here is alrea d y a n ori gi n al ( pla n ne d) val ue f or t he 
s u bse q ue nt visit, t he n t he ori gi nal val u e will be sel ecte d i nstea d of a n 
“ u nsc he d ule d ” val ue.   
E x a m ple 1, f or HI V T S Qs,  f or Q 2 M s u bjects wit h O LI, t he pla n ne d n o mi nal visits are 
Da y 1, M o nt h 6 , a n d M o nt h 1 2 . If a partici pa nt has t he ‘last n o mi nal visit’ ( wit h 
HI V T S Qs assess me nt) at M o nt h 6  pri or t o wit h dra wal at M o nt h 8 , t he wit h dra wal 
assess me nt will be sl otte d t o t he s u b se q ue nt pla n n e d n o mi nal visit of M o nt h 1 2 .  
E x a m ple 2, f or HI V T S Qs, f or Q 2 M s u bjects wit h O LI if t here is u nsc he d ul e d visit 
bet wee n M o nt h 6 a n d M o nt h 1 2 , this u nsc he d ule d visit will be sl otte d t o M o nt h 1 2 . I n 
t his case, t here are t w o assess me nts wit h a nal ysis visit e q ual t o M o nt h 1 2  (i.e. t he sl otte d 
val ue a n d t he v al ue at ori gi nal n o mi nal M o nt h 1 2  visit). T he ori gi nal n o mi nal val ue will 
be selecte d f or s u m mar y per t he r ule b el o w f or m ulti ple rec or ds — see Secti o n 1 6. 3. 5 . 
T a bl e 6  
Pl a n n e d N o mi n al Vi sit of H e alt h O ut c o m e D at a  
Q u e sti o n n air e  
D a y 1  
M o nt h 1/ 2 
M o nt h 5/ 6  
M o nt h 1 1/ 12  
PI N  
 
x 
x 
x 
HI V T S Qs  
x 
 
x 
x 
HI V T S Qc  
 
 
 
x 
N O T E S:  
Day 1 visits ar e r ec or d e d as “ B as eli ne” visits i n th e d ata b ase.  
 
1 6. 3. 4. 3.  
Tr e at m e nt Pr ef er e n c e  
T he treat me nt pr efere n ce q uesti o n naire is ta ke n at M o nt h 1 1/ 1 2  a n d wit h dra wal. T he 
n o mi nal visit i de ntifier will be ke pt as t he a nal ysis visit. Data will be re p ort e d se paratel y 
f or M o nt h 1 1/ 1 2 a n d f or wit h dra wal. 
 
C CI
C CI


CONFIDENTIAL 
 
 
 
213500 
 
89 
 
16.3.5. 
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:  
• 
the assessment closest to the window target Study Day (or target Injection Study 
Day if injection study day is used for assessment window slotting); 
• 
if there are multiple assessments equidistant from the target Study Day or target 
Injection 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. For post-dose ECG, the assessment closest to two-hour post 
injection will be used. 
Health outcome assessments: 
• 
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; 
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 be 
included 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 CVF identification, where 
applicable). 
 


CONFIDENTIAL 
 
 
 
213500 
 
90 
 
16.4. 
Appendix 4: Study Phases and Treatment State  
16.4.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
the Treatment Start Date defined in Section 16.6.1. 
AEs will be assigned to study phases as defined in Section 16.4.1.1.  
Laboratory data (efficacy, safety, and virology), HIV associated/ AIDS-defining 
conditions, health outcomes assessments, vital signs, and ECGs will be assigned to study 
phases as defined as in Section 16.4.1.2.  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.   
16.4.1.1. 
Study Phases for AEs 
Study Phase 
Date range 
Screen 
Date < Maintenance Treatment Start Date 
Maintenance 
Q2M Arm (OLI and D2I): 
 
For participants continuing into Extension Phase: 
OLI: Maintenance Treatment Start Date ≤ Date < Date of Nominal Month 14 
Injection Visit  
D2I: Maintenance Treatment Start Date ≤ Date < Date of Nominal Month 13 
Injection Visit  
 
For participants not continuing into Extension Phase: 
Maintenance Treatment Start Date ≤ Date< LTFU ART Start Date (if 
applicable)  
Note:  
- For AEs leading to withdrawal and started on the same date as LTFU ART Start 
Date, Maintenance Phase, instead of Long-term Follow-up phase, will be assigned. 
- LTFU ART start date is not applicable for those who complete maintenance phase 
and transition to commercial supply. 
BIK Arm: 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date ≤ Date < min (Start Date of Extension 
Phase CAB/RPV oral lead-in, Date of first Extension Phase CAB/RPV 
injection) 
 
For participants not continuing into Extension Phase: 
 
Date ≥Maintenance Treatment Start Date 


CONFIDENTIAL 
 
 
 
213500 
 
91 
 
Study Phase 
Date range 
Extension 
Participants continuing maintenance CAB LA + RPV LA into Extension 
Phase 
OLI: Date of Nominal Month 14 Injection Visit ≤ Date < LTFU ART Start Date 
(if applicable)  
D2I: Date of Nominal Month 13 Injection Visit ≤ Date < LTFU ART Start Date 
(if applicable) 
 
Participants Switching from Maintenance BIK Arm to CAB LA + RPV LA: 
 
min (Start Date of Extension Phase CAB/RPV oral lead-in, Date of first 
Extension Phase CAB/RPV injection) ≤ Date < LTFU ART Start Date (if 
applicable) 
 
Note: LTFU ART start date is not applicable for those who transition to commercial 
supply. 
• 
Date = AE Start date 
• 
Maintenance Treatment Start Date: refer to Treatment Start Date in Section 16.6.1 
 
 
16.4.1.2. 
Study Phases for Lab assessments, ECG, Vital Signs, Health 
Outcomes, Protocol Deviations, and HIV associated/AIDS-defining 
conditions  
Study Phase 
Date range 
Screen 
Date ≤ Maintenance Treatment Start Date 
Maintenance 
Q2M Arm: 
 
For participants continuing into Extension Phase: 
OLI: Maintenance Treatment Start Date <Date ≤ Date of Nominal Month 14 
Injection Visit  
D2I: Maintenance Treatment Start Date < Date ≤ Date of Nominal Month 13 
Injection Visit  
 
For participants not continuing into Extension Phase: 
 
Maintenance Treatment Start Date < Date ≤ LTFU ART Start Date (if 
applicable) 
Note: LTFU ART start date is not applicable for those who complete maintenance 
phase and transition to commercial supply. 


CONFIDENTIAL 
 
 
 
213500 
 
92 
 
Study Phase 
Date range 
BIK Arm: 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date < Date ≤ min (Start Date of Extension 
Phase CAB/RPV oral lead-in, Date of first Extension Phase CAB/RPV 
injection) 
 
For participants not continuing into Extension Phase: 
 
Date > Maintenance Treatment Start Date 
Extension 
 
Participants continuing maintenance CAB LA + RPV LA into Extension 
Phase 
OLI: Date of Nominal Month 14 Injection Visit < Date ≤ LTFU ART Start Date 
(if applicable)  
D2I: Date of Nominal Month 13 Injection Visit < Date ≤ LTFU ART Start Date 
(if applicable) 
 
Participants Switching from Maintenance BIK arm to CAB LA + RPV LA: 
min (Start Date of Extension Phase CAB/RPV oral lead-in, Date of first 
Extension Phase CAB/RPV injection) < Date ≤ LTFU ART Start Date (if 
applicable) 
 
Note: LTFU ART start date is not applicable for those who transition to commercial 
supply. 
 
• 
Date = start or assessment date 
• 
Maintenance Treatment Start Date: refer to Treatment Start Date in Section 16.6.1 
 
 
16.4.1.3. 
Long-Term Follow-Up Phase  
Study Phase 
Date range 
Long-Term 
Follow-Up 
Date > max (Last CAB/RPV Injection Date, Last Oral Bridging End Date) 
• 
Date = Assessment/Start Date 
• 
Only applicable to subjects who have received at least 1 injection 
• 
LTFU phase is not applicable for those who transition to commercial supply.Last oral Bridging may be 
CAB/RPV or SOC ART Oral Bridging where CAB/RPV is not available due to COVID-19. 
 
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.  


CONFIDENTIAL 
 
 
 
213500 
 
93 
 
16.4.1.4. 
Study Phases for Concomitant medication/ART 
 
Study Phase 
Date range 
Prior 
Medication Taken < Maintenance Treatment Start Date 
Maintenance[a] 
Q2M Arm (OLI and D2I): 
 
For participants continuing into Extension Phase: 
OLI: Maintenance Treatment Start Date ≤ Medication Taken < Date of 
Nominal Month 14 Injection Visit  
D2I: Maintenance Treatment Start Date ≤ Medication Taken < Date of 
Nominal Month 13 Injection Visit  
 
For participants not continuing into Extension Phase: 
Maintenance Treatment Start Date ≤ Medication Taken < LTFU ART Start 
Date (if applicable) 
Note: LTFU ART start date is not applicable for those who transition to commercial 
supply. 
 
BIK Arm: 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date ≤ Medication Taken < min (Start Date of 
Extension Phase CAB/RPV oral lead-in, Date of first Extension Phase 
CAB/RPV injection) 
 
For participants not continuing into Extension Phase: 
 
Medication Taken ≥Maintenance Treatment Start Date 
Extension[b] 
Participants continuing maintenance CAB LA + RPV LA into Extension 
Phase 
OLI: Date of Nominal Month 14 Injection Visit ≤ Medication Taken < LTFU 
ART Start Date (if applicable) 
D2I: Date of Nominal Month 13 Injection Visit ≤ Medication Taken < LTFU 
ART Start Date (if applicable) 
 
Participants Switching from Maintenance BIK Arm to CAB LA + RPV LA: 
 
min (Start Date of Extension Phase CAB/RPV oral lead-in, Date of first 
Extension Phase CAB/RPV injection) ≤ Medication Taken < LTFU ART Start 
Date (if applicable) 
 
Note: LTFU ART start date is not applicable for those who transition to commercial 
supply. 
 


CONFIDENTIAL 
 
 
 
213500 
 
94 
 
Study Phase 
Date range 
Long-Term 
Follow-Up 
For participants who received at least one CAB and/or RPV Injection: 
 
Medication Taken  LTFU ART Start Date 
 
Note: LTFU phase is not applicable for those who transition to commercial supply. 
 
 
 
[a]: ART stopped on the start date of Maintenance Treatment will be considered a prior medication and will not be 
considered concomitant during the Maintenance Phase. If the stop date of ART medication is completely missing 
and this medication is recorded in eCRF as prior, it will be considered a prior medication and will not be considered 
concomitant during the Maintenance phase. 
 
[b]: ART stopped on the start date of Extension Phase IP will not be assigned to the Extension 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.  
 
16.4.2. 
Study Periods 
Certain displays will be produced for data collected during the oral-lead-in. These period 
variables are defined in the tables below and will be reflected in the datasets with 
separate variables. 


CONFIDENTIAL 
 
 
 
213500 
 
95 
 
16.4.2.1. 
Oral Lead-in Period for AE Data 
Study Period 
Date range 
Maintenance 
Phase Oral 
Lead-in 
Q2M OLI subjects only: 
 
For participants receiving at least one Injection: 
Maintenance Treatment Start Date ≤ Date < Date of First Maintenance Phase 
CAB/RPV Injection  
 
For participants withdrawing prior to first Injection: 
Date  Maintenance Treatment Start Date 
Note that the oral lead-in period is only applicable to the participants who 
received at least one dose of study treatment during the oral lead-in period in 
the study. Oral lead-in period is within the maintenance phase. 
Extension 
Phase Oral 
Lead-in 
Switch Q2M OLI subjects only: 
 
For participants receiving at least one Extension Phase Injection: 
Extension Oral CAB/RPV Start Date ≤ Date < Date of First Extension Phase 
CAB/RP injection  
 
For participants withdrawing prior to first Extension Phase Injection: 
Date  Extension Phase Oral CAB/RPV Start Date 
 
16.4.2.2. 
Oral Lead-in Period for Lab assessments 
 
Study Period 
Date range 
Maintenance 
Phase Oral 
Lead-in 
Q2M OLI subjects only: 
 
For participants receiving at least one Injection: 
Maintenance Treatment Start Date < Date ≤ Date of First Maintenance Phase 
CAB/RPV Injection  
 
For participants withdrawing prior to first Injection: 
Date > Maintenance Treatment Start Date 
Note that the oral lead-in period is only applicable to the participants who 
received at least one dose of study treatment during the oral lead-in period in 
the study. Oral lead-in period is within the maintenance phase. 


CONFIDENTIAL 
 
 
 
213500 
 
96 
 
Extension 
Phase Oral 
Lead-in 
Switch Q2M OLI subjects only: 
 
For participants receiving at least one Extension Phase Injection: 
Extension Oral CAB/RPV Start Date < Date ≤ Date of First Extension Phase 
CAB/RP injection  
 
For participants withdrawing prior to first Extension Phase Injection: 
Date > Extension Oral CAB/RPV Start Date 
 
16.4.3. 
Treatment State 
Within each treatment study phase (i.e. Maintenance, and Extension—based on 
assignment of study phase described in Section 16.4.1), only those assessments which 
occur within the ranges shown below will be considered ‘on-treatment’ for the given 
phase. Note “on-treatment” criteria will not be implemented for adverse event 
summaries. 
Table 7 
Treatment State within Study Phases 
Study Phasea 
Treatment State 
Date Range 
Screen 
Pre-treatment 
All assessments/events within Phase 
Maintenance 
On-treatment 
Q2M Arm:  
 
Date  max (Date of Last Injection Dose + 67, Date 
of Last Oral Dose + 1) 
 
BIK Arm: 
Date  Maintenance ART Stop Date + 1 
Post-treatment 
Q2M Arm:  
Date > max (Date of Last Injection Dose + 67, Date 
of Last Oral Dose + 1) 
 
BIK Arm: 
Date > Maintenance ART Stop Date + 1 
Extension 
On-treatment 
Date  max (Date of Last IP Injection Dose + 67, 
Date of Last Oral Dose + 1) 
Post-treatment 
Date > max (Date of Last IP Injection Dose + 67, 
Date of Last Oral Dose + 1) 
Long-Term 
Follow-up 
On-treatment 
Date  min (LTFU ART start date, max (Date of Last 
IP Injection Date + 67, Date of Last Oral Dose + 1)) 
Post-treatment 
Date > min (LTFU ART start date, max (Date of Last 
IP Injection Date + 67, Date of Last Oral Dose + 1)) 
Note:  
• 
Treatment State is determined after data has been assigned to the study Phases as defined in Section 
16.4.1 


CONFIDENTIAL 
 
 
 
213500 
 
97 
 
• 
The upper bound with last IP injection / last oral dose /Maintenance ART Stop Date should only be 
applied to participants who permanently discontinue from study treatment 
• 
Date = Assessment/Start Date. 
• 
Last oral dose may be CAB/RPV or SOC ART Oral Bridging where CAB/RPV is not available due to 
COVID-19. 
 
 
16.4.4. 
Combining Treatment Phases and States 
On-treatment and Post-treatment assessments and events will be classified as occurring 
during the Maintenance Phase, Extension, or Long-term follow up Phase. 


CONFIDENTIAL 
 
 
 
213500 
 
98 
 
16.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
16.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software or R/RStudio will be used. 
• 
The specific versions of SAS or R packages used to generate the analyses will be detailed in the 
ADRG. 
Reporting Area 
HARP Server 
: us1salx00259 
HARP Compound 
: \ARPROD\GSK1265744\mid213500  
Analysis Datasets  
• Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & 
ADaM IG Version 1.2). 
• 
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 reporting efforts described in the RAP. 
 
16.5.2. 
Reporting Standards 
General 
• 
The current GSK Statistical Display Standards in the GSK Standards Library (IDSL) will be applied 
for reporting, unless otherwise stated (Library 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  
• 
Do not include participant level listings in the main body of the GSK Clinical Study Report. All 
participant level listings should be located in the modular appendices as ICH or non-ICH listings 
Formats 
• 
GSK Statistical Display 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 GSK Standard Statistical Display 
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: 
° 
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:  


CONFIDENTIAL 
 
 
 
213500 
 
99 
 
• 
If space permits, planned and actual time relative to study drug dosing will be shown in listings 
(Refer to GSK Standard Statistical Display Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings.  
Unscheduled Visits 
• 
Unscheduled visits will be slotted to analysis time points as per Section 16.3. 
• 
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 and PDVF 
identification). 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to GSK Standard Statistical Display Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to GSK Standard Statistical Display Principals 7.01 to 7.13. 
 


CONFIDENTIAL 
 
 
 
213500 
 
100 
 
16.6. 
Appendix 6: Derived and Transformed Data 
16.6.1. 
General 


CONFIDENTIAL 
 
 
 
213500 
 
101 
 
Multiple Measurements at One Analysis 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 (or target Injection Study 
Day if injection study day is used for assessment window slotting); 
o if there are multiple assessments equidistant from the target Study Day or target 
Injection 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 ’ 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 as follows: 
 
• 
Maintenance Phase 
° 
For participants randomized to Q2M: Date of first dose of CAB + RPV (oral or injection) entered 
in the IP exposure CRF form. 
° 
For participants randomized to BIK: BIK regimen start date entered in the Maintenance Phase IP 
exposure CRF 
 
• 
Extension Phase  
° 
For participants continuing CAB LA + RPV LA (Q2M):  
- for Q2M OLI: Date of the nominal Month 14 injection date  
- for Q2M D2I: Date of the nominal Month 13 injection date  
° 
For participants switching from BIK to Q2M:  
Date of the nominal Month 13 Q2M injection date (BIK to D2I) or the oral CAB + RPV start date 
entered in the Extension Phase IP exposure CRF (BIK to OLI) 
 
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 Maintenance Phase start date of study treatment 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. 
Injection Study Day (Maintenance Phase) (Only applicable to Q2M OLI subjects) 


CONFIDENTIAL 
 
 
 
213500 
 
102 
 
The Injection Study Day of an event will be derived as the number of days between the date of the event 
and the date of first Maintenance Phase injection as follows: 
if date of event  first Maintenance Phase injection, then 
• 
Injection Study Day = Date of Event – Date of First Maintenance Phase CAB/RPV Injection + 1 
if date of event < first Maintenance Phase injection, then 
• 
Injection Study Day = Date of Event – Date of First Maintenance Phase CAB/RPV Injection 
Note that the date of first Maintenance Phase injection is considered to be on Injection Study Day 1 and 
the day before this is Injection Study Day -1; i.e., there is no Injection Study Day 0. 
Extension 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 
• 
Extension Study Day = Date of Event – Start Date of Extension Phase IP + 1 
if date of event < start date of Extension Phase IP, then 
• 
Extension Study Day = Date of Event – Start Date of Extension Phase IP  
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. 
Extension Injection Study Day (Only applicable to Extension Switch OLI subjects) 
The Extension Phase Injection 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 injection as follows: 
if date of event  date of first Extension Phase injection, then 
• 
Extension Injection Study Day = Date of Event – Date of First Extension Phase CAB/RPV 
Injection + 1 
if date of event < date of first Extension Phase injection, then 
• 
Extension Injection Study Day = Date of Event – Date of First Extension Phase CAB/RPV 
Injection 
Note that the date of first Extension Phase Injection is considered to be on Extension Injection Study Day 
1 and the day before this is Extension Injection Study Day -1; i.e., there is no Extension Phase Injection 
Study Day 0. 
 
Long-Term Follow Up Study Day 


CONFIDENTIAL 
 
 
 
213500 
 
103 
 
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 
• 
LTFU Study Day = Date of Event – End Date of IP 
 
16.6.2. 
Study Population 
Demographics and Baseline Characteristics 
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: 
• 
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) 
• 
BMI is calculated as Weight (kg) / Height (m)2. Height is only collected at Baseline Day 1. 
Hepatitis Status 
• 
Hepatitis status at entry will be based on the assessments prior to/on the start of the study treatment. 
• 
A participant will be considered positive for hepatitis B virus (HBV) if they have a positive surface 
antigen or detectable HBV DNA result. “HBV DNA DETECTED” in the lab comment takes 
precedence over HBV DNA test result for positive hepatitis B status, for example, if a participant has 
HBV test result below level of detection, however, the lab comment shows that HBV DNA detected, 
this participant will be considered positive for hepatitis B. If HBV DNA result is available, it will be 
used to qualify hepatitis B status as positive or negative (positive if ≥ limit of quantification); 
otherwise Hepatitis B status will be determined using the surface antigen result (i.e. “REACTIVE”). 
• 
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 detectable (i.e., ≥ limit of quantification) or not. In the 
absence of an HBV RNA result, Hepatitis C antibody of “REACTIVE” or “BORDERLINE” will qualify 
as Hep C positive. 
Framingham Risk Equation 
• 
The predicted probability, 𝑝̂ , of having a cardiovascular disease (CVD) within the next 10-years 
according to the Framingham formula [D’Agostino, 2008] is 
 
For females: 
 𝑝̂F = 1 – S0(t)exp{ 2.32888 × log(age) + 1.20904 × log(TC) – 0.70833 × log(HDL) + 2.76157 × log(SBPu) + 2.82263 × log(SBPt) +  
0.52873 × Is + 0.69154 × Id – 26.1931}, 
   
For males: 
𝑝̂M = 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}, 


CONFIDENTIAL 
 
 
 
213500 
 
104 
 
Demographics and Baseline Characteristics 
 Where 
 
𝑆0(𝑡) = {0.95012, females
0.88936, 𝑚𝑎𝑙𝑒𝑠 
 
𝐼𝑠= { 1, current smoker
0,          𝑜𝑡ℎ𝑒𝑟𝑤𝑖𝑠𝑒 
𝐼𝑑= { 1,       diabetic
0,   𝑜𝑡ℎ𝑒𝑟𝑤𝑖𝑠𝑒 
 
    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) 
 
• 
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 (Day 1) fasting 
glucose ≥7.00 mmol/L (126 mg/dL) and HbA1C >6.5%. 
• 
Smoking status is collected in the eCRF at Day 1. 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 they will be counted in the highest category of risk in the summary by category. 
• 
Framingham Risk will also be calculated at Month 6 and Month 12. 
° 
Baseline smoking status will be used for the Month 6 calculation. Smoking status collected 
at Month 12 will be used for the Month 12 calculation. 
° 
Diabetic status is defined as: 
1. Current or past is indicated in the medical conditions eCRF for Type 1 or Type 2 
diabetes mellitus, or  
2. At any time prior to and including the analysis timepoint:  
2a. fasting glucose ≥7.00 mmol/L (126 mg/dL) and HbA1C >6.5%, or  
     2b. an adverse event is collected as having “type 1 or type 2 diabetes mellitus” 
° 
“Treated for high blood pressure” at Month 6 and Month 12 is defined as  
1. 
hypertension at baseline or  
2. 
use of medication treating hypertension which started prior to and including the 
analysis time point 
Lipid-modifying Agents 
• 
The following ATC codes correspond to lipid-modifying agents: 
o 
ATC Level 2: C10 
o 
ATC Level 3: C10A, C10B (if Level 2 is not available) 


CONFIDENTIAL 
 
 
 
213500 
 
105 
 
Demographics and Baseline Characteristics 
o 
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 fasting 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 fasting lipid testing date. 
Treatment Compliance 
• 
For defining protocol deviation (i.e. treatment non- compliance) leading to exclusion from the Per 
Protocol population, the total non-compliance days will be calculated (see details in Section 16.1). 
The percentage of the total number of non-compliant days to the Exposure (‘overall exposure’ for 
CAB+RPV treatment) will be used to define protocol deviation leading to exclusion from PP 
Population for the Month 12 analysis due to study treatment non-compliance (i.e. >10%). 
Adherence to CAB/RPV Injection Schedule 
Timeliness of Injections relative to Date of Projected Dosing Visits are assessed by using "actual injection 
visit date - projected visit date from first injection". The injections of interest in adherence analysis are 
those after first injection. For participants who choose oral lead-in (Q2M OLI), the first injection is planned 
at Month 1. For Q2M D2I participants, the first injection is planned at Day 1. 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 2 ml of injection instead of 3 ml due to a dosing error, but this 
participant 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 day 
 0 day  
1 day 
2 to 3 days  
4 to 7 days  
8 to 14 days 
>14 days 
Missed Injection without Oral Bridging 
Missed Injection with Oral Bridging 
Missed Injection with CAB+RPV Oral Bridging 
      Missed Injection with SOC Oral Bridging 


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 0 6  
 
1 6. 6. 3.  
E ffi c a c y 
HI V -1 R N A  
T ar g et D et e ct e d / T ar get N o n -D et e ct e d / S u p er L o w Vir al L o a d Te sti n g  
•  
W h e n a me as ure m e nt of plas m a HI V -1 R N A is b el o w t h e li mit of qu a ntific ati o n (i. e. 4 0 c/ m L) a n d is 
q u alit ativ ely obs erv a bl e t h at will b e de n ot e d as a “ T ar g et D etect e d” m e as ure, w hile HI V -1 R N A 
b el o w t h e li mit of qu a ntific ati on t h at is n ot q u alit ativ ely o bserv a bl e th at will b e de n ot ed as “ T ar g et N ot 
Det ect e d”. A ny m eas ur e m e nts < 4 0 c/ m L c har act eris ed as “ Tar g et N ot D et ect e d” or “ Tar g et 
Det ect e d” will b e c a pt ure d i n th e d at a bas e. 
•  
S u p er L o w viral l oa d will als o be t est e d by Bio M O N T R La bs for vir al l o a ds b el o w t h e li mit of 
q u a ntific ati o n at D ay 1 an d M ont h 1 1/ 1 2.  
C o nfir m e d Vir ol o gi c Fail ur e  
•  T h e d efiniti on of C V F  is pr ovi de d i n t he Pr ot ocol, S ecti o n 7. 1. 6  –  D efi niti o n of Pr ot ocol -D efin e d 
Vir ol o gic F ail ur e  
Tr e at m e nt ( T R D F) a n d Effi c a cy R elat e d ( E R D F) Di s c o nti n u ati o n = F ail ur e  
•  
T h e a n alysis of ti m e t o c onfir me d vir ol o gic f ail ur e ( C V F) or disc o nti n u ati o n d ue t o tr eat m e nt r el at e d 
r e as o ns (i. e., dr u g-r elat e d A E, i nt ol era bility of i njectio ns, pr otoc ol defi n ed s afety st o p pin g crit eri a, or 
l ack of effic acy) will c e ns or partici p ants w h o h av e n ot m et C V F crit eria a n d ar e o n goi n g i n t he st u dy, 
or wh o h av e disc o nti n u e d f or re as o ns ot h er t h a n t hos e rel at ed t o tr e at m e nt. This will b e t h e 
Tr e at m e nt R el at e d Disco nti nuati o n = Fail ur e ( T R D F) d at a.  
C CI


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 0 7  
 
HI V -1 R N A  
•  
P artici pa nts w h o h ave n ot m et C V F crit eri a a n d ar e o n g oi n g in t h e stu dy, or wh o h av e disc onti n u e d 
f or r e as ons ot her t h a n l ack of effic acy, will b e c e ns or e d i n t he a n alysis of t he Efficacy R el at e d 
D isc o nti n u ati o n = Fail ure ( E R D F) d at a. 
•  
Pr o p orti o n of P artici p a nts wit ho ut vir ol o gic ( E R D F) or t ol era bility ( T R D F) f ail ur e will be esti m at e d 
usi n g th e K a pl a n -M ei er n on p ar a m etric m et ho d b as e d on t h e ti m e t o E R D F or T R D F. T he esti m ate d 
pr o p orti on at ti m e p oi nt  of i nt erest will b e pr es e nt ed by tr e at me nt gr o u p, al o ng wit h esti mat ed 
diff er e nc e i n pr o p orti o ns b et we e n tr e at m e nt gro u ps a n d its ass oci at e d t w o -si de d 9 5 % CI. Th e 
esti mat e of th e sta n d ar d err or us e d t o d eriv e c onfi d enc e i nt erv als will be b ase d o n Gr e e n wo o d’s 
f or m ul a [K al bfleisc h , 1 98 0]. 
•  
S e e A p p e n dix 1 0 : V ari a bl es Defi n e d for Ti me t o Eve nt A n alysis f or a d diti o n al d et ails. 
Del a y i n I P I nj e cti o n  
I M d osi n g is ex pect e d t o occ ur ev ery 2 mo nths st arti ng fr o m t h e t hird i nj ecti o n a n d o n w ar ds. Th e 
D el ay i n I P i nj ecti on ( d ays) will b e c alc ul ate d as: 
F or t h e sec o nd i nj ecti o n:  
D el ay i n I P i nj ecti on( d ays) =   I nj ecti o n d ate –  d ate of prec e di ng i nj ectio n  –  31   
F or ot h er i nj ecti ons:  
•  D el ay i n I P i nj ecti on( d ays) =   I nj ecti o n d ate –  d ate of prec e di ng i nj ectio n - 62  
D el ay i n I P i nj ecti on will b e gr o u pe d i nt o: ≤1, 2 -3, 4 -7, > 7 d ays.  
•  
T h e pr op orti on of p artici pa nts wit h HI V -1 R N A ≥5 0 c/ m L at M o nt h 1 2  will b e s u m m ariz e d 
by l ast d el ay i n I P I nj ecti on. T h e l ast d el ay i n I P i nj ecti on will b e t he d elay i n I P i nj ecti o n 
at M o nt h 1 1 ( D 2I) or M ont h 1 2 ( O LI), or t he d el ay i n l ast I P i nj ecti on prior to M o nt h 
1 1 / M o nt h 1 2 if a p artici p a nt d o es n ot r ec eiv e t h eir M o nth 1 1/ 1 2 i nj ecti on (i. e. missi ng 
visit or wit h dr a w al). 
•  
D el ays ar e d efi ne d as m or e t h an 3 1 or 62 d ays for t h e sec o nd a n d th e su bs eq ue nt 
i nj ecti o ns, res p ectiv ely. 
•  
If t her e ar e s u bj ects w h o did n ot r ec eiv e a ny i nj ecti on or r ec eiv e d o nly on e i njecti o n, 
t h e n a dd th e “ N o i nj ecti o n or o nly 1 i njecti o n” c at e g ory. 
 
 
 
C CI


CONFIDENTIAL 
 
 
 
213500 
 
108 
 
16.6.4. 
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 2.1, March 2017, as specified in the 
protocol Appendix 4.  
Potential QTc Interval Prolonging Events of Interest 
Potential QTc Interval Prolonging Events of Interest will be identified based on Standardised 
MedDRA Query (SMQ) for Torsade de pointes/QT prolongation, broad (MedDRA). The terms 
per this reference are listed below.  
 
AE preferred term 
Electrocardiogram QT interval abnormal 
Electrocardiogram QT prolonged 
Long QT syndrome 
Long QT syndrome congenital 
Torsade de pointes 
Ventricular tachycardia 
Cardiac arrest 
Cardiac death 
Cardiac fibrillation 
Cardio-respiratory arrest 
Electrocardiogram repolarisation abnormality 
Electrocardiogram U wave inversion 
Electrocardiogram U wave present 
Electrocardiogram U-wave abnormality 
Loss of consciousness 
Sudden cardiac death 
Sudden death 
Syncope 
Ventricular arrhythmia 
Ventricular fibrillation 
Ventricular flutter 
Ventricular tachyarrhythmia 
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 


CONFIDENTIAL 
 
 
 
213500 
 
109 
 
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     
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: 
 
 
Abbreviations / Units:  
eGFR (estimated glomerular filtration rate) = mL/min/1.73 m2 
age = years 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() = the minimum of CRT/κ or 1 
max() = the maximum of CRT/κ or 1 
CRTmg/dL = serum creatinine concentration in mg/dL. The serum creatinine concentration in 
mg/dL is obtained from GSK standard units of mol/L as CRTmg/dL =0.0113x CRTmol/L.  
Lab Toxicities 
• Toxicities will be based on the Division of AIDS (DAIDS) grading system, Version 2.1, March 
2017, as specified in the protocol of Appendix 4. 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 


CONFIDENTIAL 
 
 
 
213500 
 
110 
 
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 
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 


CONFIDENTIAL 
 
 
 
213500 
 
111 
 
 Percentage change for lipids 
The percentage change from Baseline* is calculated as: 
% Change from BL = 
 
Value at Month X – BL value 
X 100 % 
BL value 
 
*Maintenance or Extension 
Other Safety Endpoints 
Extent of Exposure 
• 
Exposure to CAB+RPV (oral lead-in), CAB LA+RPV LA, BIK will be calculated from the IP eCRF 
pages.   
Maintenance Phase: Q2M 
Exposure to CAB + RPV (oral lead-in) = 
* Q2M OLI subjects only 
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 and include the Month 12 (OLI) or the Month 
11 (D2I) injection 
Overall Exposure to IP (Q2M OLI) = min [Date of latest Maintenance Phase visit up to and 
including Month 14 (OLI), max (Date of last CAB LA + 
RPV LA injection +67, Date of last oral CAB/RPV dose) ] 
– Oral lead-in CAB/RPV Start Date +1  
Overall Exposure to IP (Q2M D2I) = min [Date of latest Maintenance Phase visit up to and 
including Month 13(D2I), max (Date of last CAB LA + 
RPV LA injection +67, Date of last oral CAB/RPV dose) ] 
– CAB LA + RPV LA Start Date +1 
Overall Exposure to Study Treatment 
(OLI) = 
min [Date of latest Maintenance Phase visit up to and 
including Month 14, max (Date of last CAB LA + RPV LA 
injection +67, Date of last oral CAB/RPV dose, Date of 
last oral SOC bridging) ] – Oral lead-in CAB/RPV Start 
Date +1  
Overall Exposure to Study Treatment 
(D2I) = 
min [Date of latest Maintenance Phase visit up to and 
including Month 13, max (Date of last CAB LA + RPV LA 
injection +67, Date of last oral CAB/RPV dose, Date of 
last oral SOC bridging) ] – CAB LA + RPV LA Start Date 
+1 
Maintenance Phase: BIK arm 
Exposure = Min (Date of latest Maintenance Phase visit up to and including Month 13, Maintenance 
Phase Treatment Stop Date, Date of Maintenance Phase Discontinuation) – Maintenance Treatment 
Start Date + 1 
° 
Last oral dose may be CAB/RPV or SOC ART Oral Bridging where CAB/RPV is not available due 
to COVID-19 
° 
Last CAB LA + RPV LA injection / last oral dose is only applicable to participants who 
permanently discontinue from study 


CONFIDENTIAL 
 
 
 
213500 
 
112 
 
Corrected QT (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., 
QT
QTcF
QTcB
3
=
 
 
3
2
QTcB
QT
QTcF

=
 
QTc Values by Category 
The following categories for QTc will be used: 
 
• For absolute QTc values: 
≤450 
>450 to ≤480 
>480 to ≤500 
>500 
 
• For change from baseline in QTc values: 
≤30 
>30 to ≤60 
>60 
 
Columbia Suicide Severity Rating Scale (C-SSRS) (Posner, 2007) 
• Missing data will not have any imputation performed (Nilsson, 2013) 


CONFIDENTIAL 
 
 
 
213500 
 
113 
 
Homeostatic model assessment-Insulin Resistance (HOMA-IR) 
• 
HOMA-IR = (fasting plasma insulin (mU/L) * fasting plasma glucose (mmol/L)) / 22.5. 
• 
HOMA-IR categories will be categorised as follows for the shift table analysis: 
1. <2 
2. 2 to <3 
3. 3 to <4 
4. >=4 
 
All HOMA-IR analyses will be based on fasting values and only patients with post-baseline 
values will be included in analyses (i.e. patients with missing post-baseline HOMA-IR will not be 
included in summary tables or figures). 
The following subjects will be excluded from the HOMA-IR analysis: 
• diabetic as captured on the medical history or have taken an anti-diabetic 
medication (ATC code “A10” (DRUGS USED IN DIABETES)) up to screening 
• fasting glucose >126mg/dl and HbA1C >6.5% at Day 1 
• have had a cosmetic procedure including liposuction/liposculpture of the thighs, 
buttocks, hips and/or abdomen 
 
Metabolic Syndrome 
• 
Diagnosis of Metabolic Syndrome is defined as follows per joint interim statement of the 
International Diabetes Federation Task Force on Epidemiology and Prevention; National 
Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; 
International Atherosclerosis Society; and International Association for the Study of Obesity. 
• 
Three abnormal findings out of the following five qualifies a person for the metabolic 
syndrome: 
o Elevated waist circumference 
Males: ≥102 cm (≥40 in) 
Females: ≥88 cm (≥35 in) 
 
o Elevated triglycerides  
≥150 mg/dL (1.7 mmol/L) 
 
o Reduced HDL-C  
Males: < 40 mg/dL (1.0 mmol/L)  
Females: < 50 mg/dL (1.3 mmol/L) 
 
o Elevated blood pressure (meeting either or both criteria) 
Systolic ≥130 and/or diastolic ≥ 85 mm Hg  
 
o Elevated fasting glucose  
≥ 100 mg/dL 
 


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 1 4  
 
B MI ( F or S hift T a bl e)  
T h e f oll o wi ng c at e gori es will b e us e d f or B MI shift ta bl es: 
 
< N or mal:    < 1 8. 5  k g/ m 2 
N or m al:     18. 5 - < 2 5  kg/ m 2 
Ov er w ei g ht:   25 - < 3 0  k g/ m 2 
O b es e:      > = 30 k g/ m 2 
 
1 6. 6. 5.  
P h ar m a c o ki n eti c  
N/ A.  
1 6. 6. 6.  
H e alt h O ut c o m e s  
HI V T S Q s  
Tr e at m e nt S atisf a cti o n S c 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 p ossi 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 e a d, it will b e tr e at e d 
as a sta nd -al o n e it e m o nly.  
•  Hi g h er sc or es r epr es e nt 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 a n b e missi n g, whic h c an b e i m p ut e d t o refl ect th e me a n of t h e 
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.  
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 
 
  
•  Hi g h er sc or es r epr es e nt 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 e d ( acc or di ng to P ag e 
C CI
C CI
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 1 3 5 0 0  
 
1 1 5  
 
7 of t h e [ HI V T S Q  Us er G ui deli n es, 2 0 16]).  
HI V T S Q c  
Tr e at m e nt S atisf a cti o n S c 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 p ossi 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 e d 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 mpr ove m e nt i n s atisf acti o n with tr eat m e nt; t h e l o w er 
t h e scor e, th e gr e ater t h e det eri or ati on  i n satisf actio n wit h tr e at me nt. A sc or e of 0 re pr es ents 
  
•  A m axi m u m of 5 it e ms c a n b e missi n g, t h e missi n g sc or es will b e i m p ut e d wit h t h e m e a n of 
t h e co m pl et ed it e m scor es. If 6 or m or e it e ms are missi n g, th en t he over all tr e at m ent 
s atisf acti on sc al e sc or e sh oul d not be c o m put e d a n 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 
 
 t o -3 
  
•  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 e ac h as p ect of 
tr e at m e nt an d th e l o wer t h e sc or e, t he gr eat er t h e d et erior ati o n in s atisfacti o n wit h eac h 
as p ect of tr e at m ent.  
PI N  
C CI
C CI
C CI
C CI
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 1 3 5 0 0  
 
1 1 6  
 
Di m e nsi o n Sc ore ( C h ev at , 2 0 08) 
•  D o m ai ns a nd Cl usters  
o  B ot h er 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 1 1, 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 n ot i ncl ud e d i n a ny of t h es 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, 
1 9, 2 0, 2 1) 
 
•  N o ov er all sc or e is c alc ul at e d p er th e g ui da nce  
•  T h e sc or e of a d o m ai n is c alc ul at e d as th e m ea n o f all ite ms wit h t he d o 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 % it e ms c a n b e 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 h e m ea n of th e co m pl et ed it e m sc or es wit hi n t he d o m ai n. T h us, if th e n u m b er of missi n g 
it e ms is ≥3 
 ≥2 
 ≥1 
, t h en th e tot al sc or e f or th e d o m ai n s h oul d n ot be c o m put e d.  
I n divi d ual It e m Sc or es 
•  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
 t o 5 
  
C CI
C CI
C CI
C CI
C CI
C CI
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 1 3 5 0 0  
 
1 1 7  
 
•  L o w er sc or es r e pr es e nt w ors e p erc epti on of i nj ecti on  
•  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 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 CI


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 1 8  
 
C CI


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 1 9  
 
 
1 6. 6. 7.  
V ir al G e n ot y p e a n d P h e n ot y p e 
G e n ot y p e  
A mi n o A ci d C h a n g e s  
•  A m ut atio n is c o nsi d er ed pres e nt w h en ev er th e e nco d ed a mi n o aci d r esi du e diff ers fr o m t h e 
a mi n o aci d t hat w oul d hav e b e en e nc o de d by t he wil d -typ e ( e.g., H X B 2, NL 4 3) co m p ar at or 
g e ne; e. g., Q 1 48 K.  
•  If t he e nc o de d a mi n o aci d is s e e n as a mixt ur e of wil d-ty p e an d m ut a nt a mi n o aci d, e. g., 
Q 1 4 8 Q/ K, t h e m ut ate d a mi no aci d is co nsi der e d pr es ent at th e co d on of i nt erest.  
•  If t he e nc o de d a mi n o aci d is s e e n as a mixt ur e of t w o or m or e a mi n o aci ds, whic h may or 
m ay n ot incl u d e wil d ty pe, e. g., Q1 84 K/ H or Q 1 84 K/ H/ Q, et c., f or th e p ur p oses of c alc ul ati n g 
t h e n u m b er of m utat e d a min o acids, only o ne m utati o n is c o nsi d er ed to b e pr ese nt at t h e 
c o d on of i nt er est. 
R e pr e s e nt ati o n of A mi n o A ci d C h a n g e s  
 
 
M ut ati o n s  
A mi n o a ci d c h a n g e  
T 6 9 S  
Si n gl e m ut ati on fr o m a mi no aci d ' T' (v en dor r ef er enc e) to ' S' (s a m pl e) at c o do n 
' 6 9'  
Q 1 4 8 H/ K/ R  Mixt ur e of a mi no aci d m ut ati o ns ‘ H’, ‘ K’ a nd ‘ R’ (s a m pl e) fr o m a mi n o aci d ‘ Q’ 
(v e n d or r efer e nce) at co do n ‘ 1 4 8’ 
_ 6 9_ 1 T  
First i ns erti o n of a mi n o aci d ' T' (s a m pl e) at c od o n ' 69' 
_ 6 9_ 2 S  
S ec o nd i nserti o n of a mi no aci d ' S' (s a mpl e) at co do n '6 9'  
_ 6 9_ 3 S/ A  
T hir d i ns erti o n of a mixt ur e of a mi n o aci ds ' S' a nd ' A' (sa m pl e) at co d on '6 9'  
L 7 4L/ - 
Mixt ur e of a mi no aci d ' L' (s a m pl e) a n d a d el eti on at c odo n '7 4'  
V 7 5 - 
Si n gl e d el etio n of a mi no acid (s a m pl e) at c o do n ' 7 5'  
 
R e si st a nc e A ss o ciat e d M ut ati o n s  
•  
K n o w n I NI m utati o ns ass ociat e d wit h th e d ev el op m e nt of r esist anc e to BI C, R A L, E V G , C A B 
or D T G:  
 
A mi n o Aci ds i n 
HI V I nt e gr as e f or 
A n alysis  
H 5 1 Y,  T 6 6 A /I/K , E 9 2 Q /V / G, Q9 5 K, T 9 7 A, G 1 1 8 R , F 1 2 1 C/ Y , E 1 3 8 A/ K/ T, 
G 1 4 0 A/ C/ R /S,  Y 1 43 C/ H/ R/ K/ S/ G/ A,  P14 5 S , Q 1 4 6 P , S 14 7 G , Q1 48 H /K /R/ N , 
V 1 5 1 L / A, S 1 53 F/ Y, N 1 5 5 H/ S/ T , E 1 57 Q, G 1 6 3 R/ K, S 23 0 R , D 2 3 2 N, R 2 6 3 K,  
L 6 8 V/I*, L 7 4I / M*, E 1 3 8 D*, V 15 1I*, G 1 93 E* 
Not es : 
C CI


CONFIDENTIAL 
 
 
 
213500 
 
120 
 
• 
Draft listing; may be modified in case of additional substantive data availability. 
• 
INI mutations listed taken from Stanford HIV Resistance Database 
(http://hivdb.stanford.edu/DR/cgi-bin/rules_scores_hivdb.cgi?class=INI cited 22Feb2021) 
• 
INI substitutions listed above in bold had a score of =60. 
*Denotes additional INI mutations added as they were identified during in vitro passage of DTG or 
seen in a previous DTG study in INI-experienced subjects (ING112574). 
• 
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]. 
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, I54M/L/V, Q58E, T74P, L76V, 
V82A/T/F/L/S, N83D, I84V, N88S,L90M 
Note: List generated from IAS_USA Guideline, [Wensing. 2019] 
 
• 
The pre-specified INI Mutations are identified as below: 
• Per the IAS-USA list of mutations (both minor and major) 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  
• 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 
• Mutations per FDA request for Study 201584: Q146L, T124A 
• 
The NNRTI resistance associated mutations (RAMs) are identified per IAS-USA NNRTI 
mutations (IAS-USA 2019 resistance mutations update volume 27 issue 3, 2019): 
• V90I, A98G, L100I, K101E/H/P, K103N/S, V106A/I/M/T, V108I, E138A/G/K/Q/R, V179D/F/L/T, Y181C/I/V, 
Y188C/H/L, G190A/E/S, H221Y, P225H, F227C/L/R, M230I/L, L234I 
• 
The RPV RAMs are identified per IAS-USA NNRTI mutations (IAS-USA 2019 resistance 
mutations update volume 27 issue 3, 2019): 
• 
L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, M230I/L 
 
• 
The NRTI major mutations associated with resistance to BIKTARVY (Emtricitabine and 
Tenofovir, IAS-USA 2019 resistance mutations update volume 27 issue 3, 2019): 
• 
K65R/E/N, K70E, M184V/I 
Phenotype 
Phenotypic Susceptibility  
o 
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 


CONFIDENTIAL 
 
 
 
213500 
 
121 
 
relative to wild-type control virus NL4-3, i.e., FC of sample virus = IC50 of sample virus/IC50 of 
control virus.   
 
o 
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 categorised 
according to FC as shown in Table below (based on Monogram PhenoSense assay). Clinical cutoffs 
(where available) or biological cutoffs by PhenoSense will be used to define the phenotypic 
susceptibility of background treatment by Monogram. PHENOTYP dataset from Monogram contains 
the phenotypic susceptibility information derived from the cutoff listed below. Thus, phenotypic 
susceptibility (i.e. full sensitivity and partial sensitivity) will not be re-derived in our analysis. 
 
o 
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 
NRTI 
(1.4 – 4) a 
Delavirdine 
DLV 
NNRTI 
6.2 
Efavirenz 
EFV 
NNRTI 
3 
Nevirapine 
NVP 
NNRTI 
4.5 
Etravirine 
ETR 
NNRTI 
(2.9-10) a 
Rilpivirine 
RPV 
NNRTI 
2.0 
Doravirine   
DOR   
NNRTI 
3.0 
Fosamprenavir/r 
FPV/r 
PI 
(4-11) a 
Atazanavir 
ATV 
PI 
2.2a 
Atazanavir/r 
ATV/r 
PI 
5.2a 
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 
Bictegravir 
BIC 
INI 
(2.5- 10) 
a. 
clinical cutoff (lower cutoff – higher cutoff).  
 


CONFIDENTIAL 
 
 
 
213500 
 
122 
 
o 
Phenotypic susceptibility to each drug in a subject’s background regimen will be determined by 
applying drug-associated cutoffs as defined by the PhenoSense algorithm to the phenotypic fold 
resistance to that drug at a certain timepoint (e.g. Screening or Baseline).  
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 
Genotypic and Net Assessment Susceptibility 
Genotypic and Net assessment susceptibility to all licensed antiretroviral drugs and CAB will be 
determined from Monogram Inc. Net assessment susceptibility will be reported with the 
categories of ‘resistant’, ‘partially sensitive’, and ‘sensitive’ as what will be performed for 
phenotypic susceptibility. Genotypic susceptibility will be reported with the categories of 
‘resistant’, ‘resistance possible’ and ‘sensitive’. Genotypic and Net assessment susceptibility will 
be assessed at time of CVF using plasma sample, Genotypic susceptibility may be assessed at 
baseline using PBMC. 


CONFIDENTIAL 
 
 
 
213500 
 
123 
 
16.7. 
Appendix 7: Reporting Standards for Missing Data 
16.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Participants are considered to have completed the study if they remain on therapy 
(i.e., have not permanently discontinued IP) and satisfy one of the following: 
- Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including Month 11/12 visits (with or without Month 11/12 study 
treatment) and did not enter the Extension Phase; 
- Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including Month 13, entered and completed the Extension 
Phase (defined as remaining on study until commercial supplies of the CAB LA + 
RPV LA Q8W regimen 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 Follow-Up phase required for participants who receive one or 
more injections with CAB LA or RPV LA, an in-clinic Follow-Up visit will be conducted 
approximately 4 weeks after the last dose of study medication for participants who 
withdraw during the oral lead-in phase and who were randomized to BIK with ongoing 
AEs, serious adverse events (SAEs) and 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 subjects 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. 
 
16.7.2. 
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: 
• 
These data will be indicated by the use of a “blank” in participant listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded from 
the table.  
• 
Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 


CONFIDENTIAL 
 
 
 
213500 
 
124 
 
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. 
16.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant 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. 
• 
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. 
• 
For medications with completely missing start date, they will be considered 
started prior to the maintenance phase treatment start date. 
• 
For medications with completely missing stop date, they will be considered 
ongoing unless recorded in eCRF as prior. 
• 
For ART booster medications, the start and stop dates are not recorded in the 
database (i.e. missing), the dates will be imputed to be the same as the dates 
of their parent medications.  
• 
The recorded partial or missing date will be displayed in listings. 
Health outcomes 
• 
For the summary of individual item scores outputs, missing scores will not be 
computed. 
 


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 2 5  
 
1 6. 7. 2. 2.  
H a n dli n g of Mi s si n g  d at a f or St ati sti c al A n al y si s  
El e m e nt  
R e p orti n g D et ail  
S n a ps h ot  
•  
I n t h e S n a ps h ot d at aset, p artici p a nts wit h o ut HI V-1 R N A d at a i n t h e ass ess m e nt 
wi n d o w f or t h e visit of i nt er est ( d u e t o missi n g dat a or disc o nti n u atio n of I P pri or t o 
t h e visit wi nd o w) d o n ot b elo ng t o ‘ HI V-1 R N A < 5 0 c/ m L ( or < 2 0 0 c/ m L)’. Th e n atur e 
of t h is missi ng d at a will be f urth er cl assifi e d i n S n a ps h ot s u m m ari es as eit h er ‘ HI V-1 
R N A ≥5 0’ or ‘ N o Vir ol o gic D at a at W e ek X’ . S e e A p pe n dix 9 : S n a ps h ot Al g orith m 
D et ails . 
Li pi d 
Ev al u a bl e  
•  
F or s u bjects w it h li pi d-m o difyin g a g e nt us e , li pi d ass ess m ents will b e c onsid er e d 
n o n -ev al u a bl e  ( e q ual t o missi ng) aft er i niti ati o n with o ut a ny i m p ut atio n.  
•  
If p artici p a nts t ak e lipi d m o difyi n g a g ents wit hi n 1 2 w e eks prior t o t h e st art of t h e 
st u dy tre at m ent, all t h e p ost-bas elin e v al u es will b e n o n -ev alu a bl e.  
 
•  
T h e  li pi d ev al u ability r ul es will b e us e d f or t h e f ollo wi n g dis plays:  
   S u m m ary of F asti ng T C/ H D L r ati o C h a ng e fr o m B as eli n e  
S u m m ary of F asti n g Li pids P erc e nt a g e C h a n g es fr o m Bas elin e  
S u m m ary of C h e mistry C h a n ges fr o m B as eli n e  
 
•  
All ot h er dis pl ays of li pi ds (i.e. t oxicity ta bl es a n d N C E P t a bl es) will us e o bs erve d 
f asti n g d at a, wit h o ut c o nsi d erin g li pi d eval u ability. 
 
•  
T h e s a m e r ul e of “li pi d ev alu abl e” will b e a ppli ed t o a nt hr o p o m etric  p ar a met ers as 
s p ecifi e d i n Secti o n 8. 5. 3 : 
- 
W ei g ht, H eig ht a nd B MI  
- 
W aist circ u mf er e nc e s 
- 
Hi p circu mf er enc e  
- 
 
- 
 
- 
T a nit a sc al e par a m eters (t ot al b o dy f at perc e nt, t ot al b ody w at er p erc e nt, 
m uscl e mass, a n d bo n e mi n eral m ass).  
 
C CI
C CI


CONFIDENTIAL 
 
 
 
213500 
 
126 
 
16.8. 
Appendix 8: Values of Potential Clinical Importance 
Element 
Reporting Detail 
Laboratory 
Values and 
Adverse Events 
• 
The DAIDS grading for severity of laboratory toxicities and clinical adverse events 
is included in the protocol.  
• 
The central laboratory will flag lab parameter toxicities directly in the provided 
datasets. 
ECG values  
• 
Defined as QTc > 500 msec or increase from baseline in QTc ≥ 60 msec 
 
 


CONFIDENTIAL 
 
213500 
 
 
127 
 
16.9. 
Appendix 9: Snapshot Algorithm Details 
Detailed Algorithm Steps 
• 
Consider an analysis visit window for Month X as defined in Section 16.3.1 
• 
The HIV-1 RNA threshold of 50, 200 copies/mL will be analysed, respectively, in this study.  
• 
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 participant’s ability to attend clinic visits. The snapshot algorithm is modified to allow for the presentation of full 
scope of COVID-19 relatedness. The analysis window ‘Week 48’ and HIV-1 RNA threshold of ’50 c/mL’ are used for the purpose of illustration. A participant’s 
Snapshot response and reason at Week 48 are categorized as below. 
 
o HIV-1 RNA < 50 c/mL 
o HIV-1 RNA ≥ 50 c/mL 
   Data in window not below threshold 
  Non-COVID-19 related  
Discontinued for lack of efficacy 
Discontinued for other reason while not below threshold 
Change in background therapy* 
  COVID-19 related 
Discontinued for lack of efficacy 
Discontinued for other reason while not below threshold 
Change in background therapy* 
 
o No Virologic Data at Week 48 Window 
  Non-COVID-19 related 
Discontinued study due to AE or death 
Discontinued study for other reasons 
Not evaluated or discontinued due to confirmed pregnancy** 
On study but missing data in window 
                COVID-19 related 
Discontinued study due to AE or death 
Discontinued study for other reason  
On study but missing data in window 


CONFIDENTIAL 
 
213500 
 
 
128 
 
 
• 
Note: since permanent changes in ART are not permitted in this protocol, all such participants who permanently change ART will be considered ‘HIV-1 RNA ≥ 
50 c/mL’ if the change is made prior to an analysis timepoint. Participants with protocol permitted oral bridging treatment, CAB+RPV or SOC (during COVID-19 
pandemic due to the unavailability of the CAB/RPV IM injections and oral CAB+RPV), or a temporary change in ART by mistake prior to an analysis timepoint 
(e.g. participant took the ART different from study treatment during oral lead-in by mistake for a short period of time and then went back to the study treatment) 
will not be considered ‘HIV-1 RNA ≥ 50 c/mL’ due to ‘change in ART’. 
 
• 
The steps in determining response and reasons are indicated in Table below, in the order stated. 
 
• 
*Background therapy is not given to participants while on study. The “change in background therapy” in detailed steps below refers to the “change in ART” in 
this study. 
 
• 
** This category is not needed if no subject on the Q2M arm becomes pregnant and continues in the study. 
 
 
Detailed steps 
Please note that the following scenarios will NOT be penalized per Snapshot algorithm (i.e. please exclude these scenarios from Conditions 1-4). 
• 
Dose reduction, dropping a component, or change in formulation (e.g. ‘Tivicay + Kivexa’ to ‘Triumeq’ with the identical ingredients) 
• 
Protocol permitted temporary oral bridging, or temporary change in ART by mistake 
 
Condition (‘Week 48’ indicates Week 48 window) 
Response  
Reasons 
1. If non-permitted change in background therapy prior to Week 48  
o not due to COVID-19 
HIV-1 RNA ≥ 50  
Change in background therapy (non-
COVID-19 related) 
o due to COVID-19 
HIV-1 RNA ≥ 50 
Change in background therapy 
(COVID-19 related) 
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/mL (NA to this 
study) 
o not due to COVID-19 
HIV-1 RNA ≥ 50  
Change in background therapy (non-
COVID-19 related) 


CONFIDENTIAL 
 
213500 
 
 
129 
 
o due to COVID-19 
HIV-1 RNA ≥ 50 
Change in background therapy 
(COVID-19 related) 
3. If non-permitted change in background therapy during Week 48    
o Last on-treatment VL during Week 48 prior to/on the date of change ≥ 
50 c/mL 
HIV-1 RNA ≥ 50 
Data in window not below 50 
o Last on-treatment VL during Week 48 prior to/on the date of change < 
50 c/mL 
HIV-1 RNA < 50 
 
o No VL during Week 48 prior to/on the date of change and the change in 
background therapy is not due to COVID-19     
HIV-1 RNA ≥ 50 
Change in background therapy (Non-
COVID-19 related) 
o No VL during Week 48 prior to/on the date of change and the change in 
background therapy is due to COVID-19     
HIV-1 RNA ≥ 50  
Change in background therapy 
(COVID-19 related) 
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 
 
 
• The change in background therapy is not due to COVID-19 
HIV-1 RNA ≥ 50 
Change in background therapy (non-
COVID-19 related)  
• The change in background therapy is due to COVID-19 
HIV-1 RNA ≥ 50 
Change in background therapy 
(COVID-19 related) 
4.2 This last on-treatment VL occurs during Week 48 but prior to/on the date of 
change 
HIV-1 RNA ≥ 50 
Data in window not below 50 
5. If none of the above conditions met 
5.1 On-treatment VL available during Week 48  
 
 
• Last on-treatment VL during Week 48 ≥ 50 c/mL 
HIV-1 RNA ≥ 50 
Data in window not below 50 
• Last on-treatment VL during Week 48 < 50 c/mL 
HIV-1 RNA < 50 
 
5.2 No on-treatment VL during Week 48    
 
 
5.2.1 If participants are still on study, i.e. a participant has not permanently 
discontinued the study treatment yet, or if a participant permanently discontinued 
 
 


CONFIDENTIAL 
 
213500 
 
 
130 
 
the study treatment and the upper bound of analysis snapshot window is prior to the
following date:  
 
For Q2M arm:  
Min[max(Date of last CAB/RPV LA Dose + 67, Date of last oral dose+1), 
withdrawal date] 
 
For BIK arm: 
Min (BIK Stop Date + 1, withdrawal date) 
Note: 
• 
Last oral dose: may be CAB/RPV or SOC ART Oral Bridging where 
CAB/RPV is not available due to COVID-19 impact. 
• 
Withdrawal Date: date the participant failed to complete per 
corresponding conclusion form 
5.2.1.1 If no on-treatment VL during Week 48 is not due to COVID-19 
 
 
• If no on-treatment VL is not due to confirmed pregnancy 
No virologic data at 
Week 48 Window 
On study but missing data in window 
(Non-COVID-19 related) 
• If no on-treatment VL is due to confirmed pregnancy (“while on-
treatment”: data not evaluable) 
No virologic data at 
Week 48 Window 
Not evaluated or discontinued due to 
confirmed pregnancy(Non-COVID-19 
related) 
5.2.1.2 If no on-treatment VL during Week 48 is due to COVID-19 
No virologic data at 
Week 48 Window 
On study but missing data in window 
(COVID-19 related) 
5.2.2 If participants withdraw before/during Week 48 due to 
 
 
5.2.2.1 Non-COVID-19 related safety reasons (e.g. AE/death, liver 
chemistry stopping criteria, renal toxicity withdrawal criteria, 
QTc withdrawal criteria etc, as recorded in eCRF Conclusion 
form) 
No virologic data at 
Week 48 Window 
Disc due to AE/death (Non-COVID-19 
related) 


CONFIDENTIAL 
 
213500 
 
 
131 
 
5.2.2.2 COVID-19 related safety reasons (e.g. AE/death, liver 
chemistry stopping criteria, renal toxicity withdrawal criteria, 
QTc withdrawal criteria etc, as recorded in eCRF Conclusion 
form) 
No virologic data at 
Week 48 Window 
Disc due to AE/death (COVID-19 
related) 
5.2.2.3 Non-safety and Non-COVID-19 related reasons (e.g. Lack of 
efficacy, protocol deviation, withdrew consent, loss to follow-
up, study closed/terminated, investigator discretion etc, as 
recorded in eCRF Conclusion Form) 
 
 
° 
Last on-treatment VL <50 c/mL OR no on-treatment VL 
available during study  
 
 
•  Withdrew not due to pregnancy 
No virologic Data at 
Week 48 Window 
Disc for other reasons (Non-COVID-19 
related) 
•  Withdrew due to pregnancy 
No virologic Data at 
Week 48 Window 
Not evaluated or discontinued due to 
confirmed pregnancy(Non-COVID-19 
related) 
° 
Last on-treatment VL ≥ 50 c/mL AND withdrawal due to 
Lack of efficacy 
HIV-1 RNA ≥ 50 
Disc. for lack of efficacy (Non-COVID-
19 related) 
° 
Last on-treatment VL ≥ 50 c/mL AND withdrawal due to 
all other non-safety related reasons 
HIV-1 RNA ≥ 50 
Disc. for other reason while not below 
50 (Non-COVID-19 related) 
5.2.2.4 Non-safety and COVID-19 related reasons (e.g. protocol 
deviation, withdrew consent, loss to follow-up, study 
closed/terminated, investigator discretion etc., 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 (COVID-19 
related) 
• 
Last on-treatment VL ≥ 50 c/mL AND withdrawal due to Lack 
of efficacy 
HIV-1 RNA ≥ 50 
Disc. for lack of efficacy (COVID-19 
related) 
• 
Last on-treatment VL ≥ 50 c/mL AND withdrawal due to all 
other non-safety related reasons 
HIV-1 RNA ≥ 50 
Disc. for other reason while not below 
50 (COVID-19 related) 
• 
Excluding permitted change in background therapy where change or decision to change is made prior to/on the first on-treatment viral result  
 


CONFIDENTIAL 
 
213500 
 
 
132 
 
Examples from FDA guidance 
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. 
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: 
o 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.  
o 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 subject 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 considered an efficacy failure and captured in the HIV-RNA 
greater than or equal to 50 copies/mL row. 
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. 


CONFIDENTIAL 
 
213500 
 
 
133 
 
• 
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. 
Not evaluated due to confirmed pregnancy: 
Q2M subjects who became pregnant on study will be allowed to continue study treatment whereas BIK subjects will be withdrawn. HIV-1 RNA data will be treated as 
non-evaluable after confirmed pregnancy date as recorded on the eCRF, if a pregnant Q2M subject is allowed to continue. 
 


CONFIDENTIAL 
 
213500 
 
 
134 
 
16.10. 
Appendix 10: 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=Study Day 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 and/or standardized 
subreason for discontinuation based on 
Maintenance Conclusion form in the eCRF. 
‘Protocol Defined Safety Stopping Criteria’ includes 
GSK defined liver chemistry stopping criteria, renal 
toxicity criteria and QTc withdrawal criteria. 
Treatment Related AE’ is defined as participants 
who have primary reason for withdrawal =AE and 
who have at least one AE considered drug related 
and leading to withdrawal/permanent 
discontinuation of investigational product. 
CNSR=0 
EVNTDESC= terms in italic, respectively. 
 
For Q2M arm: 
AVAL= min [Study Day of Maintenance Phase Discontinuation, Study day of Starting 
LTFU HAART if applicable, max(Study Day of Last Maintenance Q2M IM Dose + 67, 
Study Day of Last Maintenance Oral Dose + 1)] 
 
For BIK arm: 
AVAL= min [Study Day of Maintenance Phase Discontinuation, Study Day of 
Maintenance IP Stop Date + 1] 
 
 
Note:  
• 
Last Q2M IM / last oral dose/ Maintenance IP Stop Date only applies to 
subjects who permanently discontinue from study treatment. 
• 
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 who did not have premature 
withdrawal from the Maintenance Phase 
CNSR=1 
EVNTDESC=’Censored due to data cutoff for analysis’ 
 


CONFIDENTIAL 
 
213500 
 
 
135 
 
Programming Instructions for the Kaplan-Meier analysis of treatment-related discontinuation equals failure (TRDF) 
Condition 
Censor Status  
Event Description/AVAL 
AVAL = Study Day of last on-treatment date during the maintenance phase, which is 
defined as follows:  
 
For Q2M arm: 
min [Study Day of Month 13(D2I)/14(OLI) Visit, Study Day of Starting LTFU HAART, 
Study Day of Last Contact Date at time of analysis, max(Study Day of Last Maintenance 
Q2M IM Dose + 67, Study Day of Last Maintenance oral dose + 1)] 
 
For BIK arm: 
min [Study Day of Month 13 Visit, Day of Last Contact at time of analysis, Study Day of 
Maintenance IP stop Date + 1] 
 
Note: 
• 
Last Q2M IM / last oral dose/ Maintenance IP Stop Date only applies to 
subjects who permanently discontinue from study treatment 
 
*Last oral dose may be CAB/RPV or SOC ART Oral Bridging where CAB/RPV is not available due to COVID-19 impact. 
 
Note that last injection and last oral dose mentioned above are only applied to participants who permanently discontinued from the study treatment.  
The similar approach will be used to derive for Kaplan-Meier analysis of efficacy-related discontinuation equals failure (ERDF), except that the reason of withdrawal in 
Condition 2 will be restricted to ‘Lack of Efficacy’. 
 


CONFIDENTIAL 
 
 
 
213500 
 
136 
 
16.11. 
Appendix 11: Identification of Adverse Events of Special 
Interest (AESI) 
The adverse events of special interest are identified based on MedDRA coded values 
and/or AE data available in the study database. The PT terms and codes below are from 
MedDRA 24.1. SMQs use narrow terms unless otherwise specified. In case there is a 
change to the version of MedDRA at time of reporting, the coded values based on the 
MedDRA version at the time of reporting will be used. Additional events may be added 
based on the blinded review of AE data collected on study prior to the database freeze. 
16.11.1. 
Hepatic Safety Profile 
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ) 
PT 
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 
Flood syndrome 
10084797 
Gallbladder varices 
10072319 
Gastric variceal injection 
10076237 
Gastric variceal ligation 
10076238 
Gastric varices 
10051012 
Gastric varices haemorrhage 
10057572 
Gastrooesophageal variceal haemorrhage prophylaxis 
10066597 
Hepatectomy 
10061997 
Hepatic atrophy 
10019637 
Hepatic calcification 
10065274 
Hepatic cirrhosis 
10019641 


CONFIDENTIAL 
 
 
 
213500 
 
137 
 
PT 
PT Code 
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 
Immune-mediated cholangitis 
10083406 
Immune-mediated hepatic disorder 
10083521 
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 
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 


CONFIDENTIAL 
 
 
 
213500 
 
138 
 
PT 
PT Code 
Portal hypertensive enteropathy 
10068923 
Portal hypertensive gastropathy 
10050897 
Portal vein cavernous transformation 
10073979 
Portal vein dilatation 
10073209 
Portopulmonary hypertension 
10067281 
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 
Sugiura procedure 
10083010 
Varices oesophageal 
10056091 
Varicose veins of abdominal wall 
10072284 
White nipple sign 
10078438 
Hepatic cytolysis 
10049199 
Spontaneous bacterial peritonitis 
10061135 
 
Hepatitis, non-infectious (SMQ) 
PT 
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 
Hepatitis acute 
10019727 
Hepatitis cholestatic 
10019754 
Hepatitis chronic active 
10019755 
Hepatitis chronic persistent 
10019759 
Hepatitis fulminant 
10019772 
Hepatitis toxic 
10019795 


CONFIDENTIAL 
 
 
 
213500 
 
139 
 
PT 
PT Code 
Immune-mediated hepatitis 
10078962 
Ischaemic hepatitis 
10023025 
Lupus hepatitis 
10067737 
Non-alcoholic steatohepatitis 
10053219 
Radiation hepatitis 
10051015 
Steatohepatitis 
10076331 
Hepatic cytolysis 
10049199 
 
16.11.2. 
Hypersensitivity Reactions (HSR) 
Drug reaction with eosinophilia and systemic symptoms syndrome (SMQ) 
PT 
PT Code 
Drug reaction with eosinophilia and systemic symptoms 
10073508 
Pseudolymphoma 
10037127 
Granulomatous T-cell pseudolymphoma 
10084214 
 
PTs (select)  
PT 
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 
Polymers allergy 
10086347 
 


CONFIDENTIAL 
 
 
 
213500 
 
140 
 
16.11.3. 
Rash 
Severe cutaneous adverse reactions (SMQ) 
PT 
PT Code 
Acute generalised exanthematous pustulosis 
10048799 
Bullous haemorrhagic dermatosis 
10083809 
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 
Erythrodermic atopic dermatitis 
10082985 
Exfoliative rash 
10064579 
Oculomucocutaneous syndrome 
10030081 
SJS-TEN overlap 
10083164 
Skin necrosis 
10040893 
Stevens-Johnson syndrome 
10042033 
Target skin lesion 
10081998 
Toxic epidermal necrolysis 
10044223 
Toxic skin eruption 
10057970 
Generalised bullous fixed drug eruption 
10084905 
Severe cutaneous adverse reaction 
10085778 
 
PTs (Select) 
PT 
PT Code 
Eyelid rash 
10074620 
Genital rash 
10018175 
Mucocutaneous rash 
10056671 
Nodular rash 
10075807 
Perineal rash 
10075364 
Rash 
10037844 
Rash erythematous 
10037855 
Rash generalised 
10037858 
Rash macular 
10037867 
Rash maculo-papular 
10037868 
Rash maculovesicular 
10050004 
Rash morbilliform 
10037870 


CONFIDENTIAL 
 
 
 
213500 
 
141 
 
PT 
PT Code 
Rash papular 
10037876 
Rash rubelliform 
10057984 
Rash scarlatiniform 
10037890 
Rash vesicular 
10037898 
Rash pruritic 
10037884 
Rash follicular 
10037857 
Rash pustular 
10037888 
Drug eruption 
10013687 
 
16.11.4. 
Prolongation of the Corrected QT Interval of the ECG in 
Supratherapeutic Doses 
Torsade de pointes/QT prolongation (SMQ) 
PT 
PT Code 
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 
 
PTs (Selective) 
PT 
PT Code 
Electrocardiogram repolarisation abnormality 
10052464 
 
16.11.5. 
Suicidal Ideation/Behaviour 
Suicide/self-injury (SMQ) 
PT 
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 


CONFIDENTIAL 
 
 
 
213500 
 
142 
 
PT 
PT Code 
Suicidal behaviour 
10065604 
Suicidal ideation 
10042458 
Suicide attempt 
10042464 
Suicide threat 
10077417 
Suspected suicide 
10082458 
Suspected suicide attempt 
10081704 
 
16.11.6. 
Depression 
Depression (excl suicide and self injury) (SMQ) 
PT 
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 
Depression rating scale score increased 
10084390 
Depressive symptom 
10054089 
Discouragement 
10084257 
Dysphoria 
10013954 
Electroconvulsive therapy 
10014404 
Feeling guilty 
10049708 
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 
 


CONFIDENTIAL 
 
 
 
213500 
 
143 
 
16.11.7. 
Bipolar Disorder 
HLGT Manic and Bipolar mood disorders and disturbances 
PT 
PT Code 
Bipolar I disorder 
10004939 
Bipolar II disorder 
10004940 
Bipolar disorder 
10057667 
Cyclothymic disorder 
10011724 
Hypomania 
10021030 
Mania 
10026749 
Manic symptom 
10084119 
 
16.11.8. 
Psychosis 
Psychosis and psychotic disorders (SMQ) 
PT 
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 parasitosis 
10012242 
Delusion of reference 
10012244 
Delusion of replacement 
10012245 
Delusion of theft 
10084030 
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 


CONFIDENTIAL 
 
 
 
213500 
 
144 
 
PT 
PT Code 
Delusional perception 
10012258 
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 
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 


CONFIDENTIAL 
 
 
 
213500 
 
145 
 
PT 
PT Code 
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 
Thought blocking 
10043495 
Thought broadcasting 
10052214 
Thought insertion 
10043496 
Thought withdrawal 
10043497 
Transient psychosis 
10056326 
Waxy flexibility 
10047853 
Negative symptoms in schizophrenia 
10084992 
Pseudohallucination 
10066297 
 
16.11.9. 
Mood Disorders 
HLGT Mood disorders and disturbances 
PT 
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 
Discouragement 
10084257 
Dysphoria 
10013954 
Emotional disorder 
10014551 


CONFIDENTIAL 
 
 
 
213500 
 
146 
 
PT 
PT Code 
Emotional distress 
10049119 
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 
Sibling rivalry disorder 
10086385 
 
16.11.10. Anxiety 
HLGT Anxiety disorders and symptoms 
PT 
PT Code 
Acrophobia 
10000605 
Activation syndrome 
10066817 
Acute stress disorder 
10001084 
Aerophobia 
10080300 
Agitation 
10001497 
Agitation postoperative 
10049989 
Agoraphobia 
10001502 
Akathisia 
10001540 
Algophobia 
10078056 
Animal phobia 
10002518 
Anniversary reaction 
10074066 


CONFIDENTIAL 
 
 
 
213500 
 
147 
 
PT 
PT Code 
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 
Cryophobia 
10082662 
Dermatillomania 
10065701 
Dysmorphophobia 
10049096 
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 surgery 
10084519 
Fear of weight gain 
10016280 
Fear-related avoidance of activities 
10080136 
Generalised anxiety disorder 
10018075 
Glossophobia 
10080077 
Haemophobia 
10073458 


CONFIDENTIAL 
 
 
 
213500 
 
148 
 
PT 
PT Code 
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 
Noctiphobia 
10057946 
Nocturnal fear 
10057948 
Nosocomephobia 
10083993 
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 
 
 
 
213500 
 
149 
 
PT 
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 
Aichmophobia 
10085292 
Olfactory reference syndrome 
10085053 
Frigophobia 
10086104 
Somniphobia 
10085856 
 
16.11.11. Sleep Disorders 
HLGT Sleep Disorders and Disturbances 
PT 
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 
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 


CONFIDENTIAL 
 
 
 
213500 
 
150 
 
PT 
PT Code 
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 
Paradoxical insomnia 
10083337 
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 
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 


CONFIDENTIAL 
 
 
 
213500 
 
151 
 
PT 
PT Code 
Terminal insomnia 
10068932 
Upper airway resistance syndrome 
10063968 
 
HLGT Sleep disturbances (incl subtypes) 
PT 
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 
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 
Sleep apnoea syndrome 
10040979 
Sleep deficit 
10080881 
Sleep inertia 
10067493 
Sleep paralysis 
10041002 


CONFIDENTIAL 
 
 
 
213500 
 
152 
 
PT 
PT Code 
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 
Catathrenia 
10085704 
 
16.11.12. Injection Site Reactions (ISR)  
ISR data available in the database, i.e. data collected from non-serious ISR AE eCRF form and 
collected serious adverse events with ‘STUDY DRUG INJECTION SITE’ included in the AE term. 
16.11.13. Seizures and Seizure-like Events 
Convulsions (SMQ) 
PT 
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 
Alpers disease 
10083857 
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 
CEC syndrome 
10083749 
CDKL5 deficiency disorder 
10083005 
Change in seizure presentation 
10075606 
Clonic convulsion 
10053398 
Congenital bilateral perisylvian syndrome 
10082716 
Convulsion in childhood 
10052391 


CONFIDENTIAL 
 
 
 
213500 
 
153 
 
PT 
PT Code 
Convulsions local 
10010920 
Convulsive threshold lowered 
10010927 
CSWS syndrome 
10078827 
Deja vu 
10012177 
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 
Faciobrachial dystonic seizure 
10084187 
Febrile convulsion 
10016284 
Febrile infection-related epilepsy syndrome 
10079438 
Focal dyscognitive seizures 
10079424 
Frontal lobe epilepsy 
10049424 
Gelastic seizure 
10082918 
Generalised onset non-motor seizure 
10083376 
Generalised tonic-clonic seizure 
10018100 
Glucose transporter type 1 deficiency syndrome 
10078727 
GM2 gangliosidosis 
10083933 
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 
Jeavons syndrome 
10084303 
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 


CONFIDENTIAL 
 
 
 
213500 
 
154 
 
PT 
PT Code 
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 
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 
Hemiconvulsion-hemiplegia-epilepsy syndrome 
10085010 
Juvenile absence epilepsy 
10085031 
Parietal lobe epilepsy 
10085326 
Epilepsy of infancy with migrating focal seizures 
10086114 
Photosensitive seizure 
10086294 
PURA syndrome 
10085882 
Epilepsia partialis continua 
10015034 
 


CONFIDENTIAL 
 
 
 
213500 
 
155 
 
PTs (Selective) 
PT 
PT Code 
Confusional state 
10010305 
Loss of consciousness 
10024855 
Syncope 
10042772 
Sopor 
10058709 
Stupor 
10042264 
Altered state of consciousness 
10050093 
Depressed level of consciousness 
10012373 
Consciousness fluctuating 
10050093 
 
16.11.14. Weight Gain 
HLT General nutritional disorders NEC (Selective) 
PT 
PT Code 
Abdominal fat apron 
10077983 
Overweight 
10033307 
Abnormal weight gain 
10000188 
Central obesity 
10065941 
Obesity 
10029883 
 
PTs (Select) - Physical examination procedures and organ system status 
PT 
PT Code 
Weight abnormal 
10056814 
Weight increased 
10047899 
Waist circumference increased 
10064863 
Body mass index abnormal 
10074506 
Body mass index increased 
10005897 
 
PTs (Select) - General Signs and Symptoms 
PT 
PT Code 
Fat tissue increased 
10016251 
Sarcopenic obesity 
10083992 
 


CONFIDENTIAL 
 
 
 
213500 
 
156 
 
16.11.15. Rhabdomyolysis 
Rhabdomyolysis/myopathy (SMQ) 
PT 
PT Code 
Muscle necrosis 
10028320 
Myoglobin blood increased 
10028625 
Myoglobin blood present 
10059888 
Myoglobin urine present 
10028631 
Myoglobinaemia 
10058735 
Myoglobinuria 
10028629 
Myopathy 
10028641 
Myopathy toxic 
10028648 
Necrotising myositis 
10074769 
Rhabdomyolysis 
10039020 
Thyrotoxic myopathy 
10081524 
Muscle infarction 
10086278 
 
PTs (Selective) - Muscle Disorders 
PT 
PT Code 
Myalgia 
10028411 
Myositis 
10028653 
 


CONFIDENTIAL 
 
 
 
213500 
 
157 
 
16.11.16. Pancreatitis 
Acute pancreatitis (SMQ) 
PT 
PT Code 
Cullen's sign 
10059029 
Grey Turner's sign 
10075426 
Haemorrhagic necrotic pancreatitis 
10076058 
Immune-mediated pancreatitis 
10083072 
Ischaemic pancreatitis 
10066127 
Oedematous pancreatitis 
10052400 
Pancreatic abscess 
10048984 
Pancreatic cyst drainage 
10082531 
Pancreatic haemorrhage 
10033625 
Pancreatic phlegmon 
10056975 
Pancreatic pseudoaneurysm 
10081762 
Pancreatic pseudocyst 
10033635 
Pancreatic pseudocyst drainage 
10033636 
Pancreatic pseudocyst haemorrhage 
10083813 
Pancreatic pseudocyst rupture 
10083811 
Pancreatitis 
10033645 
Pancreatitis acute 
10033647 
Pancreatitis haemorrhagic 
10033650 
Pancreatitis necrotising 
10033654 
Pancreatitis relapsing 
10033657 
Pancreatorenal syndrome 
10056277 
Subacute pancreatitis 
10084554 
Walled-off pancreatic necrosis 
10085347 
 
16.11.17. Impact on Creatinine 
Acute renal failure (SMQ) 
PT 
PT Code 
Acute kidney injury 
10069339 
Acute phosphate nephropathy 
10069688 
Anuria 
10002847 
Azotaemia 
10003885 
Continuous haemodiafiltration 
10066338 
Dialysis 
10061105 
Foetal renal impairment 
10078987 
Haemodialysis 
10018875 


CONFIDENTIAL 
 
 
 
213500 
 
158 
 
PT 
PT Code 
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 
Subacute kidney injury 
10081980 
 
Renal Failure and Impairment 
PT 
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 
Renal impairment 
10062237 
Renal impairment neonatal 
10049776 
Renal injury 
10061481 


CONFIDENTIAL 
 
 
 
213500 
 
159 
 
PT 
PT Code 
Scleroderma renal crisis 
10062553 
Traumatic anuria 
10044501 
16.11.18. Safety in Pregnancy 
Use AE terms co-reported in pregnancy exposures to CAB and/or RPV. 
 


CONFIDENTIAL 
 
 
 
213500 
 
160 
 
16.12. 
Appendix 12: Identification of COVID-19 Adverse Events 
COVID-19 adverse events are identified based on MedDRA coded values and/or AE 
referenced in the COVID-19 Coronavirus Infection assessment. PT terms and codes 
below are from MedDRA 24.1. In case there is a change to the version of MedDRA at 
time of reporting, the coded values based on the MedDRA version at the time of 
reporting will be used. Additional events may be added based on the blinded review of 
AE data collected on study prior to the database freeze. 
PT 
PT Code  
Asymptomatic COVID-19 
10084459 
COVID-19 
10084268 
COVID-19 pneumonia 
10084380 
Suspected COVID-19 
10084451 
SARS-CoV-2 carrier 
10084461 
SARS-CoV-2 test positive 
10084271 
Multisystem inflammatory syndrome 
10086091 
Multisystem inflammatory syndrome in adults 
10085850 
Multisystem inflammatory syndrome in children 
10084767 
SARS-CoV-2 viraemia 
10084640 
Post-acute COVID-19 syndrome 
10085503 
Coronavirus infection 
10051905 
Coronavirus test positive 
10070255 
Coronavirus pneumonia 
10084381 
 
 
 
 


C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
1 6 1  
 
1 6. 1 3.  
A p p e n di x 1 3: D at a H a n dli n g f or Pr e g n a nt S u bj e ct s  
T he S O L A R  st u d y all o ws pre g na nt s u bjects o n t h e Q 2 M ar m t o c o nti n ue C A B L A + 
R P V L A  treat me nt, w hile t h ose w h o beca me pre g na nt o n t he BI K ar m will be wit h dra w n. 
T o mi ni mize bias, f or s u m mar y ta bl es, if Q 2 M s u bjects c o nti n ue w hile bei n g pre g na nt , 
data after date of c o nfir m e d pre g na n c y (as rec or de d i n t he e C R F E O S pre g na nc y f or m) 
will n ot be e val ua ble f or pre g na nt Q 2 M s u bjects wit h d oc u me nte d e vi de nce c o nfir mi n g 
pre g na nc y  u nl ess t he c o nfir mati o n occ urs pri or t o or o n t he sa me da y as ter mi nati o n of 
pre g na nc y (as r ec or de d o n t he E O S pre g na n c y f or m a n d t he A E f or m, r es p ecti vel y) 
wit hi n t he sa m e ti me peri o d bet wee n t w o st u d y visits . T he a b o ve data ha n dli n g strate g y 
will n ot be i m ple me nte d o n t he f oll o wi n g:   
 
•  All a d verse e ve nts  
•  E C G/ Q Tc a nal ysis  
•  Vital si g ns  
•  e C-S S R S  
•  
 
•  Healt h O utc o mes  
•  Vir ol o g y  
 
N ote all o bser ve d d ata c ollecte d f or all pre g na nt s u bjects  will be i ncl u de d i n t he listi n gs.  
F or st u d y o utc o mes bas e d o n t he F D A s n a ps h ot al g orit h m, a n a d diti o nal s u b -cate g or y 
will be a d de d u n der “ N o Vir ol o gic Data”: N ot e val uate d  or disc o nti n ue d d u e t o 
c o nfir me d pre g na nc y.  Viral l oa d aft er c o nfi r me d pre g na nc y of a Q 2 M s u bject will n ot be 
e val uate d f or s na ps h ot o utc o mes ( Se e A p pe n di x 9 : S na ps h ot Al g orit h m Details ).  
Se nsiti vit y a n al ysis i ncl u di n g all data ( all data as o bser ve d ) will be pr o vi de d f or t he 
f oll o wi n g s na ps h ot-b ase d a nal ysis  is a p plica ble: 
•  S u m mar y of St u d y O utc o mes ( 5 0 c/ m L t hres h ol d)  
•  S u m mar y of A n al ysis f or Pr o p orti o n of S u bjects wit h Plas ma HI V -1 R N A > = 5 0 
c/ m L (or  < 5 0 c/ ml)  
•  Pr o p orti o n of S u bjects wit h Plas ma HI V -1 R N A > = 5 0 c/ m L ( or < 5 0 c/ ml) b y 
Visit  
 
If n o Q 2 M s u bject be ca m e pre g na nt o n st u d y, t he n t he “w hile o n -tr eat me nt” strate g y will 
n ot be necess ar y a n d t heref ore n o s e nsiti vit y a nal ysis will be perf or me d , a n d t he 
a d diti o nal s u b -cate g or y me nti o ne d a b o ve will n ot be nee d e d.  
 
C CI


CONFIDENTIAL 
 
 
 
213500 
 
162 
 
16.14. 
Appendix 14: Abbreviations & Trade Marks 
16.14.1. 
Abbreviations 
Abbreviation 
Description 
3TC 
Lamivudine, EPIVIR 
ABC 
Abacavir, ZIAGEN 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
AIC 
Akaike's Information Criteria 
AIDS 
Acquired immunodeficiency syndrome 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
A&R 
Analysis and Reporting  
BIK 
Bictegravir/emtricitabine/tenofovir alafenamide Single Tablet 
Regimen 
BMI 
Body Mass Index 
BP 
Blood Pressure 
CAB 
Cabotegravir 
CAB LA 
Cabotegravir long-acting 
CD4  
Cluster of Differentiation 4 
CD8  
Cluster of Differentiation 8 
CDC 
Centers for Disease Control and Prevention 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CMH 
Cochran-Mantel Haenszel 
COVID-19 
Coronavirus Disease 2019 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale  
CTR 
Clinical Trial Register 
CVF 
Confirmed Virologic Failure 
mCVF 
Modified Confirmed Virologic Failure 
c/mL 
Copies/milliliter 
D2I 
Direct to Inject 
DAIDS 
Division of Acquired Immunodeficiency Syndrome 
DBF 
Database Freeze 
DBR 
Database Release 
DNA 
Deoxyribonucleic acid 
DOB 
Date of Birth 
DP 
Decimal Places 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Record Form 


CONFIDENTIAL 
 
 
 
213500 
 
163 
 
Abbreviation 
Description 
eGFR 
Estimated Glomerular Filtration Rate 
EMA 
European Medicines Agency 
ERDF 
Efficacy Related Discontinuation Failure 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure 
Requirements 
GSK 
GSK 
HAART 
Highly active antiretroviral therapy 
HBV 
Hepatitis B virus 
HbA1c 
Glycated hemoglobin 
HbsAg 
Hepatitis B surface Antigen 
HCV 
Hepatitis C virus 
HDL 
High density lipoprotein 
HIV 
Human Immunodeficiency Virus  
HIVTSQc 
Change Version of HIV Treatment Satisfaction Questionnaire 
IDMC 
Independent Data Monitoring Committee  
IDSL 
Integrated Data Standards Library (GSK Standards Library) 
IM 
Intramuscular 
IMMS 
International Modules Management System 
INI 
Integrase Inhibitor 
INR 
International normalized ratio 
INSTI 
Integrase strand transfer inhibitor 
IP 
Investigational Product 
ISR 
Injection Site Reaction 
ITT 
Intent-To-Treat 
ITT-E 
Intent-To-Treat Exposed 
mITT-E 
Modified Intent-To-Treat Exposed 
LA 
Long Acting 
LDL 
Low density lipoprotein 
LPV 
Lopinavir 
LPV/r 
Lopinavir-ritonavir 
LTFU 
Long-Term Follow-Up 
MMRM 
Mixed Model Repeated Measures 
NNRTI 
Non-nucleoside Reverse Transcriptase Inhibitor 
NRTI 
Nucleoside Reverse Transcriptase Inhibitor 
OLI 
Oral Lead In 
PBMC 
Peripheral Blood Mononuclear Cell 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamic 
PDMP 
Protocol Deviation Management Plan 
PI 
Protease Inhibitor 
PIN 
Perception of Injection 
PK 
Pharmacokinetic 


CONFIDENTIAL 
 
 
 
213500 
 
164 
 
Abbreviation 
Description 
PopPK 
Population PK 
PP 
Per Protocol 
PRO 
Protease 
PTT 
Partial Thromboplastin Time 
PSRAE 
Possible suicidality-related adverse event 
Q2M 
Every 2 Months 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAL 
Raltegravir 
RAMOS 
Randomization & Medication Ordering System  
RAP 
Reporting & Analysis Plan 
RBP 
Retinol Binding Protein 
RNA 
Ribonucleic acid 
RPR 
Rapid plasma reagin 
RPV 
Rilpivirine, Edurant 
RPV LA 
Rilpivirine long-acting 
RT 
Reverse transcriptase 
RTV 
Ritonavir 
SAE 
Serious Adverse Event 
SAC 
Statistical Analysis Complete 
SDSP 
Study Data Standardization Plan 
SDTM 
Study Data Tabulation Model 
SMQ 
Standardised MedDRA Query 
SOC 
System Organ Class or Standard of Care 
SOP 
Standard Operation Procedure 
SRM 
Study Reference Manual 
TDF 
Tenofovir disoproxil fumarate 
TFL 
Tables, Figures & Listings  
TRDF 
Treatment Related Discontinuation Failure  
ULN  
Upper limit of normal 
16.14.2. 
Trademarks 
 
Trademarks of the GSK Group of 
Companies 
 
Trademarks not owned by the GSK 
Group of Companies 
EPIVIR 
 
Biktarvy 
EPZICOM/KIVEXA 
 
Edurant 
TRIUMEQ 
 
GenoSure 
TRIZIVIR 
 
Monogram Biosciences 
ZIAGEN 
 
PhenoSense 
 
 
SAS 
 


CONFIDENTIAL 
 
 
 
213500 
 
165 
 
16.15. 
Appendix 15: List of Data Displays 
16.15.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.n 
1.1 to 1.n 
Efficacy 
2.1 to 2.n 
2.1 to 2.n 
Safety 
3.1 to 3.n 
3.1 to 3.n 
Pharmacokinetic* 
4.1 to 4.n 
4.1 to 4.n 
Health Outcomes 
6.1 to 6.n 
6.1 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 
 
* For the Month 12 analysis, only listings will be provided for the Pharmacokinetic section. 
The numbers for Table/Figures are reserved for future reports if applicable. 
 
16.15.2. 
Mock Example Shell Referencing 
Nonstandard specifications will be referenced as indicated and if required example mock-
up displays will be provided in Appendix 16: Example Mock Shells for Data Displays or 
in a separate document:  
Section 
Description 
HL 
Headline  
M6 
Month 6 (OLI and BIK)/Month 5 (D2I) 
M12 
Month 12 (OLI and BIK)/Month 11 (D2I) 
 
16.15.3. 
Deliverables 
Delivery [Priority] [1,3] 
Description 
Month 6 
Interim analysis when all participants have completed their Month 6 (OLI 
and BIK)/Month 5 (D2I) visit[2] 
Month 12 
Primary analysis when all participants have completed their Month 12 (OLI 
and BIK)/Month 11 (D2I) visit 
EOS 
Final End of Study analysis  
NOTES:  
1. 
Indicates priority (i.e. order) in which displays will be generated for the reporting effort 
2. 
Will not be shared with any participant and with most investigators. See Section 3.1 for details. 
3. 
The Month 6(OLI and BIK)/Month 5(D2I) and the Month 12(OLI and BIK)/Month 11(D2I) analyses may also be 
referred to as the “Month 6” and “Month 12” analysis, respectively.  
 


 
CONFIDENTIAL 
 
 
213500 
 
166 
 
16.15.4. 
Study Population Tables 
Note analysis population below has been updated to reflect the M12 analysis plan. In the Month 6 analysis, ITT-E was used prior to this 
amendment. 
Study Population Tables 
No. 
Population 
GSK Standard  / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
Screened 
ES6 
Summary of Screening Status and 
Reasons for Screen Failures 
 
M6, M12 
1.2. 
Enrolled 
NS1 
Summary of Number of Subjects 
Enrolled by Country and Site ID 
Only include “no treatment” if there is any enrolled but not 
randomized. Column Header style 2. 
M6, M12 
1.3. 
mITT-E 
Shell POP_T1 
Summary of Subject Accountability: 
Study and Phase Conclusion Record 
See 207966/primary_15/T1.3 
Include the sections: 
“Outcome of Adverse Events Which Led to Study 
Withdrawal” (Fatal and Non-Fatal); 
“Type of Adverse Events Which Led to Study Withdrawal” 
(COVID-19 and Non-COVID-19) 
HL, M6, 
M12, EOS 
1.4. 
mITT-E 
Shell POP_T4 
By Phase Summary of Subject 
Disposition 
201584/primary_07/T1.14 
 
M12, EOS 
1.5. 
mITT-E 
HIV_ES1 
Summary of Reasons for Withdrawals 
by Visit (Maintenance Phase) 
201584/ primary_07/T1.9 
 
M6, M12 
1.6. 
mITT-E 
ES1 
Summary of Study Drug 
Discontinuation 
mid207966/primary_15/T1.10. Include the sections for 
fatal/non-fatal, COVID/Non-COVID 
M6, M12, 
EOS 


 
CONFIDENTIAL 
 
 
213500 
 
167 
 
Study Population Tables 
No. 
Population 
GSK Standard  / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Protocol Deviation 
1.7. 
mITT-E 
Shell POP_T2 
Summary of Important Protocol 
Deviations  
ICH E3 
M6, M12, 
EOS 
1.8. 
mITT-E 
IE1 
Summary of Inclusion/Exclusion 
Criteria Deviations 
Header Style 1 
M6, M12 
Population Analysed 
1.9. 
Screened 
Shell POP_T3 
Summary of Study Populations  
 
HL, M6, 
M12, EOS 
1.10. 
mITT-E 
Shell POP_T2 
Summary of Protocol Deviations 
Leading to Exclusion from the Per-
Protocol Population - (Month X 
Analysis) 
[X =12 or 6] 
Add footnote:  
Month 6 Analysis: Month 6 (OLI and BIK)/Month 5 (D2I) or  
Month 12 Analysis: Month 12 (OLI and BIK)/Month 11 (D2I) 
M6, M12 
Demographic and Baseline Characteristics 
1.11. 
mITT-E 
mid207966/primary_15/T1.16  
 
Summary of Demographic 
Characteristics  
 
HL, M6, 
M12 
1.12. Screened 
mid207966/primary_15/T1.17 
 
Summary of Age Ranges 
Including a column for No treatment 
M6, M12 
1.13. 
mITT-E 
DM6 
Summary of Race and Racial 
Combinations Details 
 
M6, M12 
1.14. 
mITT-E 
mid207966/primary_15/T1.20 Summary of Hepatitis Status at Entry 
 
M6, M12 
1.15. 
mITT-E 
CDC1 
Summary of CDC Stages of HIV 
Infection at Maintenance Baseline 
 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
168 
 
Study Population Tables 
No. 
Population 
GSK Standard  / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.16. 
mITT-E 
mid207966/primary_15/T1.23 
Distribution of CD4+ Cell Count 
Results at Screening and 
Maintenance Baseline 
 
M6, M12 
1.17. 
mITT-E 
mid207966/primary_15/T1.25 Summary of HIV Risk Factors 
 
M6, M12 
Prior and Concomitant Medications 
1.18. 
mITT-E 
MH1 
Summary of Current and Past Medical 
Conditions 
Combine the current and past displays, by adding 
section headers: “Current”, “Past” 
M6, M12 
1.19. 
mITT-E 
MH4 
Summary of Current and Past 
Cardiac, Gastrointestinal, Metabolism 
and Nutrition, Psychiatric, Renal and 
Urinary, Nervous System Conditions, 
and Hepatobiliary Disorders 
Combine the two displays, by adding section headers: 
“Current”, “Past” 
M6, M12 
1.20. 
mITT-E 
CA3 
Summary of Prior ART Medications 
 
M6, M12 
1.21. 
mITT-E 
CM8 
Summary of Concomitant Non-ART 
Medication Ingredient Combinations - 
Maintenance Phase 
 
M6, M12 
1.22. 
mITT-E 
mid207966/primary_15/T1.33 
Summary of Lipid Modifying Agent 
Use at Baseline and During 
Maintenance Phase 
Combine the two displays, by adding a section 
header: “Maintenance Baseline”, “Started During 
Maintenance Phase” 
M6, M12 
1.23. 
mITT-E 
mid207966/primary_15/T1.35 Summary of Substance and Illicit Drug 
Use at Entry 
 
M6, M12 
COVID-19 Pandemic Impact 
1.24. 
mITT-E 
PAN4 
Summary of Visits impacted by 
COVID-19 Pandemic 
 
M6, M12, 
EOS 
 
 


 
CONFIDENTIAL 
 
 
213500 
 
169 
 
16.15.5. 
Efficacy Tables 
Note: For subgroup analyses, include randomization strata, all demographic and baseline characteristic subgroups as mentioned in EMA 
Subgroup Category 2 in Section 5.4.2 if applicable, unless otherwise specified. 
Note analysis population below has been updated to reflect the M12 analysis plan. In the Month 6 analysis, ITT-E and CVF were used 
prior to this amendment.  
Efficacy: Tables 
No. 
Population 
GSK Standard 
 /  Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Primary Efficacy Analyses 
2.1.  
mITT-E 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA >=50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis - mITT-E 
Q2M vs BIK. 
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
HL, M6, M12 
2.2.  
PP 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA >=50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis – Per Protocol 
Q2M vs BIK.  
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
HL, M6, M12 
2.3.  
ITT-E 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA >=50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis – ITT-E (Efficacy 
Sensitivity) 
 
M12 


 
CONFIDENTIAL 
 
 
213500 
 
170 
 
Efficacy: Tables 
No. 
Population 
GSK Standard 
 /  Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.4.  
mITT-E 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA >=50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis - mITT-E (All Data 
as Observed) 
Only required if there is any confirmed pregnancy on the 
Q2M arm. 
 
M6, M12 
2.5.  
mITT-E 
Shell EFF_T1 
Summary of Study Outcomes (50 c/mL 
Threshold) at Month 12 (OLI and 
BIK)/Month 11 (D2I) - Maintenance 
Phase - Snapshot Analysis – Overall 
and by subgroup 
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
Add section header for “Overall” and “Subgroup:xx:xx” 
HL (overall 
only), M6, 
M12 
2.6.  
ITT-E 
Shell EFF_T1 
Summary of Study Outcomes (50 c/mL 
Threshold) at Month 12 (OLI and 
BIK)/Month 11 (D2I) - Maintenance 
Phase - Snapshot Analysis – ITT-E 
(Efficacy Sensitivity) 
Overall only 
M12 
2.7.  
mITT-E 
Shell EFF_T1 
Summary of Study Outcomes (50 c/mL 
Threshold) at Month 12 (OLI and 
BIK)/Month 11 (D2I) - Maintenance 
Phase - Snapshot Analysis (All Data 
as Observed) 
Only required if there is any confirmed pregnancy on the 
Q2M arm. 
 
M6, M12 
2.8.  
mITT-E 
SNAPSHOT3A 
Treatment by Strata Tests of 
Homogeneity for Proportion of 
Subjects with Plasma HIV-1 RNA >=50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis 
Q2M vs BIK.  
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
For code refer to mid207966/primary_15/T2.10 
M12 


 
CONFIDENTIAL 
 
 
213500 
 
171 
 
Efficacy: Tables 
No. 
Population 
GSK Standard 
 /  Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.9.  
mITT-E 
SNAPSHOT5 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA >=50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) by Subgroup - Maintenance 
Phase - Snapshot Analysis 
Q2M vs BIK.  
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
For code refer to mid207966/primary_15/T2.5 
M12 
Secondary Efficacy Analyses 
2.10. 
mITT-E 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA < 50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis - mITT-E 
Q2M vs BIK. 
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
 
HL, M6, M12 
2.11. 
PP 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA < 50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis – Per Protocol 
Q2M vs BIK. 
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
 
HL, M6, M12 
2.12. 
ITT-E 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA < 50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis – ITT-E (Efficacy 
Sensitivity) 
 
M12 
2.13. 
mITT-E 
Shell EFF_T3 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA <50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis - mITT-E (All Data 
as Observed) 
Only required if there is any confirmed pregnancy on the 
Q2M arm. 
 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
172 
 
Efficacy: Tables 
No. 
Population 
GSK Standard 
 /  Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.14. 
mITT-E 
SNAPSHOT3A 
Treatment by Strata Tests of 
Homogeneity for Proportion of 
Subjects with Plasma HIV-1 RNA < 50 
c/mL at Month 12 (OLI and BIK)/Month 
11 (D2I) - Maintenance Phase - 
Snapshot Analysis 
Q2M vs BIK.  
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
 
M12 
2.15. 
mITT-E 
SNAPSHOT5 
Summary of Analysis for Proportion of 
Subjects with Plasma HIV-1 RNA < 50 
c/mL at Month 12 (OLI and BIK) and 
Month 11 (D2I) by Subgroup - 
Maintenance Phase - Snapshot 
Analysis 
Q2M vs BIK.  
For Month 6/5 deliverable: replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”.  
 
M12 
2.16. 
mITT-E 
SNAPSHOT4 
Proportion of Subjects with Plasma 
HIV-1 RNA ≥50 c/mL by Visit 
(Maintenance Phase) – Snapshot 
Analysis 
For code refer to mid207966/primary_15/T2.13 
M6, M12 
2.17. 
mITT-E 
SNAPSHOT4 
Proportion of Subjects with Plasma 
HIV-1 RNA ≥50 c/mL by Visit 
Only required if there is any confirmed pregnancy on the 
Q2M arm. 
 
M6, M12, 
EOS 
2.18. 
mITT-E 
SNAPSHOT6 
Proportion of Subjects with Plasma 
HIV-1 RNA >=50 c/mL by Subgroup 
and Visit (Maintenance Phase) – 
Snapshot Analysis 
For code refer to mid207966/primary_15/T2.14 
M12 
2.19. 
mITT-E 
SNAPSHOT4 
Proportion of Subjects with Plasma 
HIV-1 RNA <50 c/mL by Visit 
(Maintenance Phase) – Snapshot 
Analysis 
 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
173 
 
Efficacy: Tables 
No. 
Population 
GSK Standard 
 /  Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.20. 
mITT-E 
SNAPSHOT4 
Proportion of Subjects with Plasma 
HIV-1 RNA <50 c/mL by Visit  
 
M6, M12, 
EOS 
2.21. 
mITT-E 
SNAPSHOT6 
Proportion of Subjects with Plasma 
HIV-1 RNA <50 c/mL by Subgroup and 
Visit (Maintenance Phase) – Snapshot 
Analysis 
 
M12 
2.22. 
mITT-E 
SNAPSHOT4 
Proportion of Subjects with Plasma 
HIV-1 RNA <200 c/mL by Visit 
(Maintenance Phase) – Snapshot 
Analysis 
 
M6, M12 
2.23. 
mITT-E 
SNAPSHOT4 
Proportion of Subjects with Plasma 
HIV-1 RNA >=200 c/mL by Visit 
(Maintenance Phase) – Snapshot 
Analysis 
 
M6, M12 
2.24. 
mITT-E 
Shell EFF_T1 
Summary of Study Outcomes (200 
c/mL Threshold) at Month 12 (OLI and 
BIK)/Month 11 (D2I) (Maintenance 
Phase) – Snapshot Analysis 
For Month 6/5 deliverable, replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)” 
No subgroup needed 
M6, M12 
2.25. 
mITT-E 
mid207966/primary_15/2.19 
Summary of Kaplan-Meier Estimates 
of Proportion of Subjects Without 
Confirmed Virologic Failure at Month 
12 (OLI and BIK) /Month 11 (D2I) - 
Treatment Related Discontinuation = 
Failure 
For Month 6/5 deliverable, replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)”  
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
174 
 
Efficacy: Tables 
No. 
Population 
GSK Standard 
 /  Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.26. 
mITT-E 
mid207966/primary_15/T 
2.20 
Summary of Kaplan-Meier Estimates 
of Proportion of Subjects Without 
Confirmed Virologic Failure at Month 
12 (OLI and BIK) /Month 11 (D2I) - 
Efficacy Related Discontinuation = 
Failure 
For Month 6/5 deliverable, replace “Month 12 (OLI and BIK) 
and Month 11 (D2I)” with “Month 6 (OLI and BIK) and 
Month 5 (D2I)” 
M6, M12 
2.27. 
mITT-E 
mid207966/primary_15/T2.21 
Proportion of Subjects with HIV-1 RNA 
>=50 c/mL at Month 12 (OLI and 
BIK)/Month 11 (D2I) (Snapshot) by 
Last Delay in IP Injection (Maintenance 
Phase) 
 
M6, M12 
2.28. 
mITT-E 
mid207966/primary_15/T2.38 
Summary of Change from 
Maintenance Baseline (Day 1) in 
Plasma HIV-1 RNA (log10 c/mL) by 
Visit  
 
M6, M12, 
EOS 
2.29. 
mITT-E 
mid207966/primary_15/T2.23 
Cumulative Proportion of Subjects 
Meeting Confirmed Virologic Failure 
Criteria by Visit During 
Up to Month 13/14 
HL, M6, M12, 
EOS 
2.30. 
mCVF 
mid207966/primary_15/T2.25 
By Phase Distribution of Quantitative 
Plasma HIV-1 RNA Results at 
Suspected and Confirmation of 
Confirmed Virologic Failure  
 
M6, M12, 
EOS 
2.31. 
mITT-E 
mid207966/primary_15/T2.28 Summary of Viral Load Category by 
Visit (Maintenance Phase) 
Q2M and BIK only 
M12 


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 7 5  
 
Effi c a c y: T a bl es  
N o.  
P o p ul ati o n  
G S K St a n d ar d  
 /  E x a m pl e S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
2. 3 2.  
 mI T T -E  
S h ell E F F _ T 2  
S u m m ary of C h a n ge fr o m 
M ai nt en a nce B as eli n e ( D ay 1) i n C D 4 + 
C ell C o u nt (c ells/ m m^ 3) by Visit - 
Ov er all  
 
M 6, M 12 , 
E O S  
2. 3 3.  
 mI T T -E  
S h ell E F F _ T 2  
S u m m ary of C h a n ge fr o m 
M ai nt en a nce B as eli n e ( D ay 1) i n C D 8 + 
C ell C o u nt (c ells/ m m^ 3) by Visit - 
M ai nt en a nce P h as e  
Bas eli n e, M 5/ 6, M 1 1/ 1 2  
N o s u b gr o u p  
M 6, M 12  
2. 3 4.  
 mI T T -E  
S h ell E F F _ T 2  
S u m m ary of C D 4 +/ C D 8 + C ell C o u nt 
R ati o by Visit –  M ai nt e n anc e P h as e  
Bas eli n e, M 5/ 6, M 1 1/ 1 2  
N o s u b gr o u p  
M 6, M 12  
2. 3 5.  
 mI T T -E  
C D C 2  
By P h as e S u m m ary of St ag e -3 HI V -1 
Ass oci at e d C o nditio ns  
Ad d s ecti o n h e a d er f or “I ncl u di n g R ec urr e nc es” a n d 
“ Excl u di n g R ec urr e nc es” 
M 6, M 12 . 
E O S  
 
 
C CI


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 7 6  
 
1 6. 1 5. 6.  
Effi c a c y Fi g ur e s  
N ote a nal ysis p o p ulati o n bel o w has bee n u p date d t o reflect t he M 1 2 a nal ysis pla n. I n t h e M o nt h 6 a n al ysis, I T T -E w as us e d pri or t o t his 
a me n d me nt.  
Effi c a c y: Fi g ur e s  
N o.  
P o p ul ati o n  G S K St a n d ar d  
 / E x a m pl e S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
Pri m ar y Effi c a c y A n al y se s  
1.   
m I T T-E  
mi d 2 0 7 9 6 6/ pri m ary _ 1 5/ F 2. 1  
Pr o p orti o n ( 95 % CI) of S u bj ects wit h 
HI V -1 R N A ≥5 0 c/ mL by Visit 
( M ai nt en a nc e P h as e) –  S n a psh ot 
A n alysis  
 
M 6, M 12  
2.   
m I T T-E  
mi d 2 0 7 9 6 6/ pri m ary _ 1 5/ F 2. 2 
U n a dj uste d Tr e at m e nt Diff er enc e i n 
Pr o p orti o n ( 95 % CI) of S u bj ects wit h 
HI V -1 R N A ≥5 0 c/ mL at M o nth 1 2 ( O LI 
a n d BI K) /M o nth 1 1 ( D 2I) by Su b gr o u p – 
S n a ps h ot A nalysis  
 
M 1 2  
S e c o n d ary 
 Effi c a c y A n al y s es 
3.   
m I T T-E  
mi d 2 0 7 9 6 6/ pri m ary _ 1 5/ F 2. 3  
Pr o p orti o n ( 95 % CI) of S u bj ects wit h 
HI V -1 R N A < 5 0 c/ m L by Visit 
( M ai nt en a nc e P h as e) –  S n a psh ot 
A n alysis  
 
M 6, M 12  
4.   
m I T T-E  
mi d 2 0 7 9 6 6/ pri m ary _ 1 5/ F 2. 4  U n a dj uste d Tr e at m e nt Diff er enc e i n 
Pr o p orti o n ( 95 % CI) of S u bj ects wit h 
HI V -1 R N A < 5 0 c/ m L at M o nth 1 2 ( O LI 
a n d BI K) /M o nth 1 1 ( D 2I) by Su b gr o u p – 
S n a ps h ot A nalysis  
 
M 1 2  
5.   
C V F  
mi d 2 0 7 9 6 6/ pri m ary _ 1 5/ F 2. 7  
(l o g 1 0 
c/ m L) Pr ofil es by Visit for C V F S u bj ects 
 
M 6, M 12 , 
E O S  
C CI
C CI


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 7 7  
 
Effi c a c y: Fi g ur e s  
N o.  
P o p ul ati o n  G S K St a n d ar d  
 / E x a m pl e S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
6.   
I T T-E  
mi d 2 0 7 9 6 6/ pri m ary _ 1 5/ F 2. 8  
I n divid u al
(l o g 1 0 
c/ m L) Pr ofil es by Visit for s u bjects W ho 
ar e i n t he C at e g ory of ‘ HI V -1 R N A > = 5 0 
c/ m L’ at M ont h 1 2 ( O LI a n d BI K) /M o nt h 
1 1  ( D2I) p er S n a ps h ot Al g orith m  
F or M o nt h 6/ 5 d eliv er a bl e, r e pl ac e “ M o nt h 1 2 ( O LI a n d 
BI K) a n d M o nt h 1 1 ( D 2I)” wit h “ M o nt h 6 ( O LI a n d BI K) a n d 
M o nt h 5 ( D 2I)”  
M 6, M 12  
 
1 6. 1 5. 7.  
S af et y  T a bl e s  
Not e: F or t h e M o nt h 6 a n alysis, r e m ov e “ By P has e” i n t h e titl e  if a pplic a ble a n d a d d t o th e e n d “( M aint e n anc e P h as e)” , unl ess ot h er wis e n ote d.  
S af et y : T a bl e s 
N o.  
P o p ul ati o n  G S K St a n d ar d / E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
E x p o s ure  
3. 1.  
S af ety  
S h ell S A F _ T 2 a a n d 
S A F _ T 2 b  
B y P h a s e  S u m mary of Ext e nt of Ex p osur e 
t o St u dy Tr eat m ent i ncl u di n g S O C Or al 
Bri d gi n g  
I C H E3 
M 6, M 12 , 
E O S  
3. 2.  
S af ety  
S h ell S A F _ T 3  
S u m m ary of N e e dle L e ngt h a nd G a u ge f or 
C A B a n d  R P V I nj ectio n s ( M aint e n a nc e 
P h as e)  
 
M 6, M 12  
3. 3.  
S af ety  
mi d 2 0 7 9 6 6/ pri m ary _ 1 5/ T 3. 5  
S u m m ary of A d h er enc e to C A B/ R P V 
I nj ecti o n D osi n g Sch e d ul e ( M ai nt e n a nc e 
P h as e)  
 
M 6, M 12  
C CI


 
CONFIDENTIAL 
 
 
213500 
 
178 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events 
3.4.  
Safety 
Shell SAF_T1a and 
SAF_T1b 
By Phase Summary of All Adverse Events 
by System Organ Class and Preferred 
Term 
ICH E3 
 
M6, M12 
3.5.  
Safety 
Shell SAF_T4a and Shell 
SAF_T4b 
By Phase Summary of All Adverse Events 
by System Organ Class, Preferred Term 
and Maximum Toxicity  
ICH E3 
Include Unknown column if at last 1 AE exists with a 
missing/unknown toxicity grade 
mid207966/primary_15/T3.7 
HL, M6, M12, 
EOS 
3.6.  
Safety 
Shell SAF_T4a and Shell 
SAF_T4b 
By Phase Summary of All Adverse Events 
Excluding Injection Site Reactions by 
System Organ Class, Preferred Term and 
Maximum Grade Toxicity 
 
HL, M6, M12, 
EOS 
3.7.  
Safety 
AE3 
By Phase Summary of Common Adverse 
Events (>=5%) by Overall Frequency  
ICH E3 
mid207966/primary_15/T3.11 
M6, M12, 
EOS 
3.8.  
Safety 
AE3 
By Phase Summary of Common Grade 2-5 
Adverse Events (>=1%) by Overall 
Frequency  
ICH E3 
mid207966/primary_15/T3.12 
M6, M12, 
EOS 
3.9.  
Safety 
Shell SAF_T1a and 
SAF_T1b 
By Phase Summary of All Drug-Related 
Adverse Events by System Organ Class 
and Preferred Term  
ICH E3 
 
M6, M12 
3.10. 
Safety 
Shell SAF_T4a and Shell 
SAF_T4b 
By Phase Summary of All Drug-Related 
Adverse Events by System Organ Class, 
Preferred Term and Maximum Toxicity  
ICH E3 
 
HL, M6, M12, 
EOS 
3.11. 
Safety 
Shell SAF_T4a and Shell 
SAF_T4b 
By Phase Summary of All Drug-Related 
Adverse Events Excluding Injection Site 
Reactions by System Organ Class, 
Preferred Term and Maximum Toxicity  
ICH E3 
For Month 6: remove “By Phase” and add 
“(Maintenance Phase)” to the end  
 
HL, M6, M12, 
EOS 


 
CONFIDENTIAL 
 
 
213500 
 
179 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.12. 
Safety 
AE3 
By Phase Summary of All Drug-Related 
Grade 2-5 Adverse Events by Overall 
Frequency 
mid207966/primary_15/T3.17 
M6, M12, 
EOS 
Serious and Other Significant Adverse Events 
3.13. 
Safety 
Shell SAF_T1a and 
SAF_T1b 
By Phase Summary of Serious Adverse 
Events by System Organ Class and 
Preferred Term  
ICH E3 
HL, M6, M12, 
EOS 
3.14. 
Safety 
Shell SAF_T1a and 
SAF_T1b 
By Phase Summary of Drug-Related 
Serious Adverse Events by System Organ 
Class and Preferred Term 
 
M6, M12, 
EOS 
3.15. 
Safety 
AE3 
By Phase Summary of Non-Fatal Serious 
Adverse Events by Overall Frequency 
mid207966/primary_15/T3.23 
M6, M12 
3.16. 
Safety 
AE3 
By Phase Summary of Drug-Related Non-
Fatal Serious Adverse Events by Overall 
Frequency 
mid207966/primary_15/T3.24 
M6, M12, 
EOS 
3.17. 
Safety 
Shell SAF_T1a and 
SAF_T1b 
By Phase Summary of Adverse Events 
Leading to Withdrawal/Permanent 
Discontinuation of Investigational Product 
by System Organ Class and Preferred 
Term  
 
HL, M6, M12, 
EOS 
3.18. 
Safety 
AE3 
Summary of Common (>=5%) Non-Serious 
Adverse Events by System Organ Class 
and Preferred Term (Maintenance Phase) 
 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
180 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.19. 
Safety 
AE15 
Summary of Subjects and Number of 
Occurrences of Common (>=5%) Non-
Serious Adverse Events by System Organ 
Class and Preferred Term (Maintenance 
Phase)  
mid207966/primary_15/T3.28 
M6, M12 
3.20. 
Safety 
AE16 
By Phase Summary of Subjects and 
Number of Occurrences of SAEs, Fatal 
SAEs, and Drug-related SAEs by System 
Organ Class and Preferred Term 
mid207966/primary_15/T3.29 
M6, M12, 
EOS 
3.21. 
Safety 
Shell SAF_T5 
Summary of Cumulative Adverse Events by 
Preferred Term and Visit (Maintenance 
Phase) 
mid207966/primary_15/T3.30 
M6, M12 
Injection Site Reaction Adverse Events 
3.22. 
Safety 
207966/primary_15/T3.31 
By Phase Event-level Summary of Injection 
Site Reaction Adverse Events by Preferred 
Term  
Include Overall ISR as a Preferred Term 
D2I, OLI and Q2M  
 
HL, M6, M12. 
EOS 
3.23. 
Safety 
207966/primary_15/T3.33 
Summary of Overall and Common Subject-
level Characteristics of Injection Site 
Reaction Adverse Events by Preferred 
Term (Maintenance Phase) 
Include Overall ISR as a Preferred Term 
D2I, OLI and Q2M  
Common ISR includes pain, induration, nodules and 
any other ISR with ≥5% subjects among randomized 
Q2M arm  
 
M6, M12 
3.24. 
Safety 
207966/primary_15/T3.36 
and T3.40 
Event-level Summary of Drug-Related 
Injection Site Reaction Adverse Events by 
Investigational Product and Preferred 
Term (Maintenance Phase) 
Include Overall ISR as a Preferred Term 
D2I, OLI and Q2M  
Investigational Product: “CAB LA” or “RPV LA”, 
“CAB/RPV LA” 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
181 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.25. 
Safety 
207966/primary_15/T3.37 
and T3.41 
Summary of Overall and Common Subject-
level Characteristics of Drug-Related 
Injection Site Reaction Adverse Events by 
Investigational Product and Preferred 
Term (Maintenance Phase) 
Include Overall ISR as a Preferred Term 
D2I, OLI and Q2M  
Investigational Product:“CAB LA” or “RPV LA”, 
“CAB/RPV LA” 
M6, M12 
3.26. 
Safety 
207966/primary_15/T3.35 
Summary of Overall and Common Injection 
Site Reaction Adverse Events by Preferred 
Term, Visit, and Maximum Severity 
(Maintenance Phase) 
Include Overall ISR as a Preferred Term 
D2I, OLI and Q2M  
 
M6, M12 
3.27. 
Safety 
207966/primary_15/T3.38 
and T3.42 
Summary of Overall and Common Drug-
Related Injection Site Reaction Adverse 
Events by Investigational Product, 
Preferred Term, Visit and Maximum 
Severity(Maintenance Phase) 
Include Overall ISR as a Preferred Term 
D2I, OLI and Q2M  
Investigational Product: “CAB LA” or “RPV LA”, 
“CAB/RPV LA” 
 
M6, M12 
3.28. 
Safety 
207966/primary_15/T3.39 
and T3.43 
Summary of Maximum Drug-Related 
Injection Site Reaction Adverse Event 
Grade by Investigational Product, 
Preferred Term and Needle Length 
(Maintenance Phase) - Common ISRs 
Do not include Overall ISR as a Preferred Term 
D2I, OLI and Q2M  
Investigational Product: “CAB LA” or “RPV LA” 
 
M6, M12 
Laboratory: Chemistry and Hematology 
3.29. 
Safety 
Shell SAF_T6 
Summary of Chemistry Changes from 
Baseline by Visit  
ICH E3 
 
 
M6, M12, 
EOS 
3.30. 
Safety 
Shell SAF_T7 
By Phase Summary of Maximum Emergent 
Chemistry Toxicities  
207966/primary_15/T3.48 
M6, M12, 
EOS 
3.31. 
Safety 
Shell SAF_T6 
Summary of Hematology Changes from 
Baseline by Visit 
ICH E3 
M6, M12, 
EOS 


 
CONFIDENTIAL 
 
 
213500 
 
182 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.32. 
Safety 
Shell SAF_T7 
By Phase Summary of Maximum Emergent 
Hematology Toxicities  
207966/primary_15/T3.50 
M6, M12, 
EOS 
Laboratory: Urinalysis 
3.33. 
Safety 
207966/primary_15/T3.39 
and T3.52 
Summary of Urinalysis Dipstick Results by 
Visit (Maintenance Phase) 
 
 
M6, M12 
3.34. 
Safety 
Shell SAF_T6 
Summary of Urine Concentrations 
Changes from Baseline by Visit 
(Maintenance Phase) 
207966/primary_15/ T3.53 
M6, M12 
3.35. 
Safety 
207966/primary_15/ T3.53 
Summary of Changes in Proteinuria 
Baseline Laboratory Result to Maximum 
Post-Baseline Laboratory Result 
(Maintenance Phase) 
 
M6, M12 
Laboratory: Lipids 
3.36. 
Safety 
207966/primary_15/ T3.55 
Summary of Changes from Maintenance 
Baseline (Day 1) NCEP Fasting Lipid 
Category to Maximum Maintenance Phase 
Category – Triglycerides 
 
M6, M12 
3.37. 
Safety 
207966/primary_15/ T3.56 
Summary of Changes from Maintenance 
Baseline (Day 1) NCEP Fasting Lipid 
Category to Maximum Maintenance Phase 
Category – Total Cholesterol 
 
M6, M12 
3.38. 
Safety 
207966/primary_15/ T3.57 
Summary of Changes from Maintenance 
Baseline (Day 1) NCEP Fasting Lipid 
Category to Minimum Maintenance Phase 
Category – HDL Cholesterol   
 
M6, M12 


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 8 3  
 
S af et y : T a bl e s 
N o.  
P o p ul ati o n  G S K St a n d ar d / E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
3. 3 9.  
 S af ety  
2 0 7 9 6 6 /pri m ary _ 1 5/  T 3. 5 8  
S u m m ary of C h a n ges fr o m Mai nt e n anc e 
B as eli ne ( Day 1) N C E P F asti ng Li pi d 
C at e g ory t o M axi m u m M ai nt en a nc e P has e 
C at e g ory –  L D L C h ol est er ol  
 
M 6, M 12  
3. 4 0.  
 S af ety  
2 0 7 9 6 6 /pri m ary _ 1 5/  T 3. 5 9  
S u m m ary of F asti n g Li pids P erc e nt a g e 
C h a n g es fr o m B aseli ne by Visit ( Li pi d 
Ev al u a bl e ) - Mai nt en a nc e P h as e  
 
M 6, M 12  
3. 4 1.  
 S af ety  
2 0 7 9 6 6 /pri m ary _ 1 5/  T 3. 6 0  
S u m m ary of F asti n g T C/ H D L R ati o 
C h a n g es fr o m Mai nt e na nc e B as elin e ( D ay 
1)  ( M ai nte n a nc e P h as e) –  Li pid Ev al u abl e  
 
M 6, M 12  
L a b orat ory: He p at o bili ar y ( Li v er)  
3. 4 2.  
 S af ety  
LI V E R 1  
By P h as e S u m m ary of Liv er 
M o nit ori n g/ St o ppi n g Ev e nt R ep orti n g  
G S K St atistic al Dis pl ay St a n d ar d  
2 0 7 9 6 6/ pri m ary _ 1 5/ T 3 . 6 1 
M 6, M 12 , 
E O S  
3. 4 3.  
 S af ety  
2 0 7 9 6 6 /pri m ary _ 1 5/  T 3. 6 2  
By P h as e S u m m ary of S u bj ects M e eti n g 
H e p at o bili ary A bn or m ality Criteri a   
G S K St atistic al Dis pl ay St a n d ar d  
I ncl u d e 2  s ecti o ns: O LI, M ai nt e n a nc e( S e e S A F _ T 7 f or 
s ecti o n h e a d ers) 
M 6, M 12 , 
E O S  
B o n e, Re n al, I nfl a m m ati o n, I n s uli n Re si st a nc e M ar ker s  a n d 
 
3. 4 4.  
 S af ety  
S A F _ T 8  
S u m m ary of C h a n ges fr o m Mai nt e n anc e 
B as eli ne ( Day  1) - Bo n e, R e n al, 
I nfl a m m ati on a n d Ins uli n R esist a nc e 
M ark ers ( M aint e n anc e P h as e)  
Ass s ecti o n h e a d er: B o n e M ark ers/ R e n al M ark ers/ 
/I ns uli n R esist a nc e M ark ers 
H O M A -I R f or i ns uli n r esist a nc e m ark er 
Q 2 M vs. BI K  
M 1 2  
3. 4 5.  
 S af ety  
S A F _ T 1 1  
S u m m ary of S hift i n H O M A -I ns uli n 
R esist anc e C at eg ori es fr o m B as elin e by 
Visit  ( Mai nt en a nce P h as e) 
 
M 1 2  
C CI
C CI


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 8 4  
 
S af et y : T a bl e s 
N o.  
P o p ul ati o n  G S K St a n d ar d / E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
3. 4 6.  
 S af ety  
S A F _ T 9  
St atistic al A nalysis of L o g -Tr ansf or m ed 
R ati o t o B aseli ne i n H O M A -I nsuli n 
R esist anc e - M M R M  
 
 
2 0 1 5 8 4 pri m ary _ 1 6/ T 6. 0 8  
M 1 2  
3. 4 7.  
 S af ety  
S A F _ T 1 0  
St atistic al A nalysis of Pr o p ortio n of 
S u bj ect s wit h  H O M A -I R ≥2, > = 3 a n d > = 4 
at M 1 2 ( O LI a nd BI K) / M 11( D2I) –  L o gistic 
R e gr essio n  
Se e S ecti o n 8. 5. 4  f or d et ails. 
N ot e: S u bj ects wit h evi d e nc e of pr e -st u dy di a b et es (vi a 
m e dic al hist ory or pri or m e dic ati o ns) ar e excl u d e d.  
M 1 2  
3. 4 8.  
 S af ety  
S A F _ T 9  
St atistic al A nalysis of L o g -Tr ansf or m ed 
R ati o t o B aseli ne i n B on e M ark ers  - M M R M  
 
 
2 0 1 5 8 4 pri m ary _ 1 6/ T 6. 0 8  
M 1 2  
3. 4 9.  
 S af ety  
S A F _ T 9  
St atistic al A nalysis of L o g -Tr ansf or m ed 
R ati o t o B aseli ne i n R e nal Mark ers - M M R M  
 
 
2 0 1 5 8 4 pri m ary _ 1 6/ T 6. 0 8  
M 1 2  
3. 5 0.  
 S af ety  
S A F _ T 9  
St atistic al A nalysis of L o g -Tr ansf or m ed 
R ati o t o B aseli ne i n 
- 
M M R M  
 
 
2 0 1 5 8 4 pri m ary _ 1 6/ T 6. 0 8  
M 1 2  
3. 5 1.  
 S af ety  
S A F _ T 8  
S u m m ary of C h a n ge fr o m B aseli n e i n 
 by Visit 
I ncl u de b aseli ne 
M 1 2  
E C G  
3. 5 2.  
 S af ety  
E G 1  
S u m m ary of E C G Fin di ngs ( Mai nt e n anc e 
P h as e)  
2 0 7 9 6 6/ pri m ary _ 1 5 / T 3.6 4  
M 1 2  
3. 5 3.  
 S af ety  
E G 2  
S u m m ary of C h a n ge fr o m B aseli n e i n E C G 
V al u es by Visit ( Mai nt en a nc e P h as e) 
 
M 1 2  
C CI
C CI


 
CONFIDENTIAL 
 
 
213500 
 
185 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.54. 
Safety 
EG10 
Summary of QTc Values by Category 
(Maintenance Phase)  
207966/primary_15/T3.66 
M12 
3.55. 
Safety 
EG10 
Summary of Change from Baseline QTc 
Values by Category (Maintenance Phase)  
207966/primary_15/T3.67 
M12 
Vital Signs and Anthropometric Profile 
3.56. 
Safety 
VS1 
By Phase Summary of Change from 
Baseline in Vital Signs by Visit  
Q2M and BIK only 
M6, M12, 
EOS 
3.57. 
Safety 
SAF_T12 
Summary of Shift in BMI Categories from 
Baseline by Visit (Overall and By Strata) – 
Maintenance Phase 
Q2M and BIK only 
207966/primary_15/T3.70 
Month 5/6 and Month 11/12  
For month 6 remove “ by visit” 
Only include Gender, as BMI is already one of the 
stratification factors (M12) 
M6, M12 
3.58. 
Safety 
SAF_T13 
Summary of Change from Baseline in 
Weight and BMI by Gender, Baseline BMI, 
Race and by Visit (Maintenance Phase) 
Q2M and BIK only 
207966/primary_15/T3.71 
Month 5/6 and Month 11/12 
For month 6 remove “ by visit”.  
Do not need overall 
M6, M12 


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 8 6  
 
S af et y : T a bl e s 
N o.  
P o p ul ati o n  G S K St a n d ar d / E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
3. 5 9.  
 S af ety  
S A F _ T 1 4  
S u m m ary of P erc ent C h a n ge fr o m B as eli n e 
i n W ei ght ( M ai nt e n anc e P hase) 
Q 2 M an d BI K o nly  
M 6. M 12  
3. 6 0.  
 S af ety  
V S 1  
S u m m ary of A nt hr op o m etric Par a m et ers by 
Visit  ( Li pi d Ev al u abl e) 
Q 2 M an d BI K o nly . I ncl u de all pl a n n e d visits 
I ncl u de: w ei g ht, h eig ht, B MI, w aist a nd hi p 
circ u mf er e nc e, 
 a n d 
T a nit a sc ale m e as ur e m e nts ( tot al b o dy F at  % , 
b o n e m ass, m usl m ass, T B W % ) 
 
M 6  
3. 6 1.  
 S af ety  
V S 1  
S u m m ary of A nt hr op o m etric Par a m et ers by 
Visit Excl u di n g S u bj ects wit h C os m etic 
pr oc e d ures  ( Lipi d Ev al u abl e) 
Q 2 M an d BI K o nly  
a d d f o ot not e:  
C os m etic pr oc e d ur es i ncl u de pr oc e d ures of th e 
t ors o/t hi g hs (excl u d e fac e/n eck) i ncl u din g b ut n ot 
li mite d t o li p os ucti o n/li p osc ulptur e/i m pl a nts. 
M 1 2  
3. 6 2.  
 S af ety  
V S 1  
S u m m ary of C h a n ge fr o m B aseli n e i n 
A nt hr o p o m etric P ara m et ers by Visit  ( Li pi d 
Ev al u a bl e)  
Q 2 M an d BI K o nly  
S a m e p ar a m et ers as 3. 6 0 
 
M 6  
C CI


 
CONFIDENTIAL 
 
 
213500 
 
187 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.63. 
Safety 
VS1 
Summary of Change from Baseline in 
Anthropometric Parameters by Visit 
Excluding Subjects with Cosmetic 
Procedures (Lipid Evaluable) 
Q2M and BIK only  
 
add footnote: 
Cosmetic procedures include procedures of the 
torso/thighs (exclude face/neck) including but not 
limited to liposuction/liposculpture/implants. 
M12 


 
CONFIDENTIAL 
 
 
213500 
 
188 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Metabolic Syndrome 
3.64. 
Safety 
SAF_T15 
Summary of Percent of Subjects with 
Metabolic Syndrome and Risk Factors 
(Maintenance Phase) 
Q2M and BIK only 
In addition to Metabolic syndrome, also include 
percentage for each of the 5 factors: 
Elevated waist circumference; Elevated triglycerides; 
Reduced HDL-C; Elevated blood pressure; Elevated 
fasting glucose  
 
M6, M12 
3.65. 
Safety 
SAF_T12 
Summary of Shift in Metabolic Syndrome 
and Risk Factors at M12 (OLI and BIK) 
/M11(D2I) from Baseline 
Update to M5/6 for M6 RE. Q2M and BIK only. 
Shift table from baseline to M5/6 or M11/12, 
Yes/No/Missing 
M6, M12 
3.66. 
Safety 
SAF_T10 
Statistical Analysis of Proportion of 
Subjects with Metabolic Syndrome at M12 
(OLI and BIK) /M11(D2I) – Logistic 
Regression 
 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
189 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Cardiovascular Risk and Substance Use 
3.67. 
Safety 
207966/primary_15/T1.22 Summary of Cardiovascular Risk 
Assessments by Visit (Maintenance Phase) 
Add section header for each visit. 
For month 6, only calculate Framingham equation 
For month 12, also include smoking status 
Q2M vs. BIK 
M6, M12 
3.68. 
Safety 
SAF_T17 
Summary of Substance and Illicit Drug Use 
(Maintenance Phase) 
Q2M vs. BIK 
M12 
eC-SSRS 
3.69. 
Safety 
CSSRS1 
By Phase Summary of Subjects with eC-
SSRS Suicidal Ideation or Behaviour  
207966/primary_15/T3.72 
Q2M and BIK 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
190 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
AEs of Special Interest (AESI) 
3.70. 
Safety 
207966/primary_15/T3.73 
By Phase Summary of Depression, Anxiety 
and Suicidal Ideation/Behaviour Adverse 
Events by System Organ Class, Preferred 
Term, Maximum DAIDS Toxicity Grade, 
and Prior History (Depression, Anxiety or 
Suicidal Ideation) at Screening  
3 Layers of section headers: 
 
Phase: Oral Lead-In 
Period(Maintenance)/Maintenance 
Treatment: Q2M, OLI(Q2M), D2I(Q2M), BIK 
Subjects has:  yes/no prior history of depression, 
yes/or prior history of anxiety, yes/or prior history of 
suicidal ideation 
 
For Oral Lead-In period, only need to present the 
OLI(Q2M) groups 
M6, M12, 
EOS 
3.71. 
Safety 
SAF_T16a and 
SAF_T16b 
 
By Phase Summary of Adverse Events of 
Special Interest by AESI Category, 
System Organ Class and Preferred Term 
(Number of Subjects and Occurrence)  
207966/primary_15/T3.75 
 
M6, M12, 
EOS 
3.72. 
Safety 
207966/primary_15/T3.109 
By Phase Summary of Characteristics of 
Adverse Events of Special Interest  
 
Add footnote: AESIs with at least 1 event are included 
in the summary. 
M6, M12, 
EOS 
3.73. 
Safety 
207966/primary_15/T3.111 
and T3.112 
By Phase Summary of Syncope and 
Presyncope Adverse Events  
 
M6, M12, 
EOS 
COVID-19 Assessments 
3.74. 
Safety 
207966 primary 15/Table 
3.113 
Summary of COVID-19 Adverse Events by 
System Organ Class, Preferred Term and 
Maximum Toxicity (Maintenance Phase) 
Q2M and BIK only  
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
191 
 
Safety: Tables 
No. 
Population GSK Standard/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.75. 
Safety 
PAN1 / PAN1A 
Summary of COVID-19 Assessments for 
Subjects with COVID-19 Adverse Events 
Q2M and BIK only  
M6, M12 
3.76. 
Safety 
PAN3 / PAN3A 
Summary of COVID-19 Symptoms for 
Subjects with COVID-19 Adverse Events 
Q2M and BIK only  
M6, M12 
Additional Analysis 
3.77. 
Safety 
Shell SAF_T6 
Summary of Absolute and Change from 
Baseline Values by Visit (Maintenance 
Phase) – Creatinine and GFR (Excluding 
Samples Impacted by Possible Faulty 
Reagents) 
Q2M and BIK only. Note: Samples impacted by 
possible faulty reagents are those collected from 
Australia, Japan, USA and  Canada between 21Dec 
212020 and 30Mar2021, and those collected from all 
other European countries between 02Jan2021 to 
28Feb2021. 
M12 
3.78. 
Safety 
Shell SAF_T7 
Summary of Maximum Maintenance Phase 
Emergent Chemistry Toxicities – Creatinine 
and GFR (Excluding Samples Impacted by 
Possible Faulty Reagents) 
Q2M and BIK only. Note: Samples impacted by 
possible faulty reagents are those collected from 
Australia, Japan, USA and Canada between 
21Dec2020 and 30Mar2021, and those collected from 
all other European countries between 02Jan2021 to 
28Feb2021. 
M12 
3.81. 
Safety 
Shell SAF_T6 
Summary of Change from Baseline in 
Weight and BMI by Visit 
 
M12, EOS 
 


 
CONFIDENTIAL 
 
 
213500 
 
192 
 
16.15.8. 
Safety Figures 
Safety: Figures 
No. 
Popul
ation 
GSK Standard / 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) – Q2M vs. BIK  
207966/primary_15/F3.1 
M6, M12 
3.2.  
Safety 
mid201584/primary_07/T3.
14 
Plot of Incidence of Maintenance Phase Drug-Related 
Injection Site Reaction Adverse Events by Visit (Overall 
and Common)  
Q2M only. 
3 Sections: 
CAB and or RPV 
CAB 
RPV 
 
M6, M12 
3.3.  
Safety 
201584/primary_07/F3.17 
Plot of Incidence of Grade 3-5 Maintenance Phase Drug-
Related Injection Site Reaction Adverse Events by Visit 
(Overall and Common)  
Q2M only. 
3 Sections: 
CAB and or RPV 
CAB 
RPV 
 
M6, M12 
Laboratory 
3.4.  
Safety 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT and BILT – 
Maintenance Phase 
GSK Statistical Display Standard  
Q2M and BIK 
M6, M12 
3.5.  
Safety 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin– 
Maintenance Phase 
GSK Statistical Display Standard  
Q2M and BIK. Remove the 
reference lines where ULN = 1X 
(only keep the 2X for BILT and 3X 
for ALT).  
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
193 
 
Safety: Figures 
No. 
Popul
ation 
GSK Standard / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.6.  
Safety 
mid207966/primary_15/F3.
18 
Bar Chart of Fasting Lipid NCEP Categories  
 
Baseline, M5/6 and M11/12. 
Include all 4 parameters: 
Triglycerides, Total Cholesterol, 
LDL, HDL 
M6, M12 
3.7.  
Safety 
mid215307/iss_01/F3.5 
Bar Chart of Total Cholesterol/HDL Ratio Categories 
Q2M and BIK . 
Baseline, M5/6 and M11/12. 
Keep big N as denominator 
M6, M12 
3.8.  
Safety 
mid215307/iss_01/F3.6 
Bar Chart of Fasting Blood Glucose 
Q2M and BIK . 
Baseline, M5/6 and M11/12 
Keep big N as denominator 
M6, M12 
3.9.  
Safety 
207966/primary_15/F3.21 
Plot of Incidence of Maintenance Phase Drug-Related 
Injection Site Reaction Adverse Events by Strata and Visit 
(Overall and Common) - CAB and/or RPV  
Q2M only. Color-code Severity 
grade within each bar 
M6, M12 
3.10. 
 
Safety 
SAF_F1 
Line Plot of Mean Change from Baseline by Visit for  Bone, 
Renal, Inflammation and Insulin Resistance Markers 
 
M12 
3.11. 
 
Safety 
SAF_F2 
Patient Profile Plot of Clinical Diagnosis Factors for 
Patients with Metabolic Syndrome at Any Time Point 
(Treatment Q2M (OLI)) 
Five parameters for each 
patient, see Section 16.6.4 waist 
circumference, triglycerides, 
HDL, BP, fasting glucose. Note 
for M12 analysis, due to space 
limit, only those with metabolic 
syndrome at M11/12 will be 
plotted. Full plot including all 
subjects will be produced post 
hoc. 
 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
194 
 
Safety: Figures 
No. 
Popul
ation 
GSK Standard / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.12. 
 
Safety 
SAF_F2 
Patient Profile Plot of Clinical Diagnosis Factors for 
Patients with Metabolic Syndrome at Any Time Point 
(Treatment Q2M (D2I))  
Same as 3.11 
M6, M12 
3.13. 
 
Safety 
SAF_F2 
Patient Profile Plot of Clinical Diagnosis Factors for 
Patients with Metabolic Syndrome at Any Time Point 
(Treatment BIK)  
Same as 3.11 
M6, M12 
 
 


 
CONFIDENTIAL 
 
 
213500 
 
195 
 
16.15.9. 
Health Outcome Tables 
Note analysis population below has been updated to reflect the M12 analysis plan. In the Month 6 analysis, ITT-E as used instead of 
mITT-E prior to this amendment. 
 
Health Outcome: Tables 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Perception of INjection Questionnaire (PIN)  
6.1.  
mITT-E 
201584/primary_07/T6.1 
Proportion of Subjects with each individual Questionnaire 
item score in PIN by Visit (Maintenance Phase) 
No BIK 
M12 
6.2.  
mITT-E 
201584/primary_07/T6.3 
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 
(Maintenance Phase) 
No BIK 
Wilcoxon Signed -rank test for 
analysis (acceptance score only) 
M12 
6.3.  
mITT-E 
201584/primary_07/T6.4 
Summary of PIN Change from Month 2(OLI)/Month 1(D2I) 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) 
No BIK 
M12 
Treatment Satisfaction (HIVTSQs) 
6.4.  
mITT-E 
201584/primary_07/T6.18 Proportion of Subjects with HIVTSQs – Treatment 
Satisfaction Individual Item Scores (Maintenance Phase) 
 
M6, M12 
6.5.  
mITT-E 
201584/primary_07/T6.18 
Proportion of Subjects with HIVTSQs – Change from 
baseline in Treatment Satisfaction Individual Item Scores 
(Maintenance Phase) 
Include all possible categories for 
CFB 
M6, M12 


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 9 6  
 
He alt h O ut c o me : T a bl e s 
N o.  
P o p ul ati o n  
G S K St a n d ar d / 
E x a m pl e S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
6. 6.  
m I T T-E  
2 0 1 5 8 4/ pri m ary _ 0 7/ T6. 2 1  
S u m m ary of HI V T S Qs - A bs olut e a n d C h an g e fr o m b as elin e 
i n Tr e at me nt S atisf acti o n Sc ore by Visit ( Mai nt en a nce 
P h as e)  - T otal a nd I n divi d ual  
O bs erv e d, us e s ecti o n h e a d ers 
“ A bs ol ut e V al u e”, “ C h a n g e fr o m 
B as eli n e”  
M 6, M 12  
6. 7.  
m I T T-E  
H O _ T 1  
St atistic al A nalysis of  HI V T S Qs - C h a n g e fro m Mai nt en a nce 
B as eli ne ( Day 1) i n T otal Tr e at m e nt S atisf acti o n Sc or e a nd 
i n divi d u al it e ms 5 (c o nv e ni ent), 6 (fl exi bl e) a n d 10 (c o nti n u e) 
( M ai nt en a nc e P h as e) 
A N C O V A f or M 6, M M R M f or M 1 2  
2 0 1 5 8 4/ pri m ary _ 0 7/ T6. 2 4  
2 0 1 5 8 4/ pri m ary _ 1 6/ T6. 0 8  
M 6 , M 12 
6. 8.  
m I T T-E  
H O _ T 4 
St atistic al A nalysis of HI V T S Qs - C h a n g e fro m Mai nt en a nce  
B as eli ne ( Day 1) i n T otal Tr e at m e nt S atisf acti o n Sc or e a nd 
i n divi d u al it e ms 5 (c o nv e ni ent), 6 (fl exi bl e) a n d 10 (c o nti n u e) 
by B as eli n e Sc or e G r o u p ( M aint e n a nc e P h ase) 
M M R M . S e e m ock s h ell f or d et ails.  
2 0 1 5 8 4/ pri m ary _ 1 6/ T6. 0 9  
M 1 2  
Tre at m e nt Sati sf a cti o n  ( HI V T S Q c) 
6. 9.  
m I T T-E  
2 0 1 5 8 4/ pri m ary _ 0 1/ T6. 2 5  
Pr o p orti o n of S u bj ects wit h HI V -Tr e at m e nt S atisf acti on 
Q u esti o n n air e I n divid u al It e m Sc or e c ha n g e ( HI V T S Qc) at 
M o nt h 12( O LI a n d BI K)/ Mo nt h 1 1( D 2I)  ( M aint e n a nc e P h as e) 
 
M 1 2  
6. 1 0.  
 m I T T-E  
2 0 1 5 8 4/ pri m ary _ 0 1/ T6. 2 6  
S u m m ary of HI V -Tr e at me nt Satisf acti o n Q u esti on n air e i n 
Tr e at m e nt Satisfactio n Sc ore C h a n g e ( HI V T S Qc) at M ont h 
1 2( O LI an d BI K)/ M ont h 1 1( D 2I) ( M ai nt en a nce P h ase) - T ot al 
a n d I n divi du al 
 
M 1 2  
6. 1 1.  
 m I T T-E  
2 0 1 5 8 4/ pri m ary _ 0 1/ T6. 2 7  
St atistic al A nalysis of HI V -Tr eat m e nt S atisf acti on 
Q u esti o n n air e in Tr e at m e nt Satisf acti o n Sc or e C h an g e 
( HI V T S Qc) at Mo nt h 12 ( O LI an d BI K)/ M o nt h 1 1( D 2I) 
(M ai nt en a nc e P h as e)  
 
M 1 2  
C CI


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 9 7  
 
He alt h O ut c o me : T a bl e s 
N o.  
P o p ul ati o n  
G S K St a n d ar d / 
E x a m pl e S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
C CI


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 9 8  
 
He alt h O ut c o me : T a bl e s 
N o.  
P o p ul ati o n  
G S K St a n d ar d / 
E x a m pl e S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
Tre at m e nt Pr ef er e n c e f or Q 2 M v s. BI K  
6. 1 4.  
 m I T T-E  
H O _ T 2  
S u m m ary of Tr e at m e nt Pr efere nc e a nd R e as on f or 
Pr ef er e nc e  
 
M 1 2  
 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
2 1 3 5 0 0  
 
1 9 9  
 
1 6. 1 5. 1 0.  Vir ol o g y T a bl e s  
Q 2 M vs. BI K o nl y f or vir ol o g y ta bles  i n t his secti o n. N ote  n o s u m mar y ta bles will be pr o d uce d if less t ha n 5 C V Fs i n t otal are o bser ve d  
(e x cl u di n g s u bjects fr o m site  
). A ll pla n ne d  listi n gs will be pr o d uce d re gar dl ess. 
N ote a nal ysis p o p ulati o n bel o w has bee n u p date d t o reflect t he M 1 2 a nal ysis pla n. N o ta bles were pr o d uce d at t he M 6 a n al ysis (t otal 
n u m ber  of C V Fs  < 5).  
Vir ol o g y: T a bl e s  
N o.  
P o p ul ati o n  
G S K St a n d ar d  
 /  E x a m pl e S h ell 
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
G e n ot y pi c  
7. 1.  
m C V F  
2 0 7 9 6 6/ pri m ary _ 1 5/ T7. 1  
S u m m ary of t h e Pr ev ale nc e of K n o w n 
I NI R esist anc e M ut atio ns at ti m e of C V F 
( M ai nt en a nc e P h as e) –  Pl as ma S a m pl e  
 
M 6 , M 12  
7. 2.  
m C V F  
2 0 7 9 6 6/ pri m ary _ 1 5/ T7. 2  
S u m m ary of t h e Pr ev ale nc e of M aj or 
R esist anc e M ut atio ns of N R TI, N N R TI 
a n d PI Cl ass at ti m e of C V F 
( M ai nt en a nc e P h as e) - Pl as ma S a m pl e  
 
M 6 , M 12  
7. 3.  
m C V F  
2 0 7 9 6 6/ pri m ary _ 1 5/ T7. 3  
S u m m ary of Ge n otypic S usc epti bility at 
ti m e of C V F ( M ai nte n a nc e P has e) - 
Pl as m a S a m ple  
 
M 6 , M 12  
P h e n ot y pi c  
7. 4.  
m C V F  
2 0 7 9 6 6/ pri m ary _ 1 5/ T7. 4  
S u m m ary of P h e n oty p e Suscepti bility at 
Ti m e of C V F ( M ai nte n a nc e P has e) - 
Pl as m a S a m ple  
 
M 6 , M 12  
P P D


 
CONFIDENTIAL 
 
 
213500 
 
200 
 
Virology: Tables 
No. 
Population 
GSK Standard 
 /  Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
7.5.  
mCVF 
207966/primary_15/T7.5 
Summary of Phenotype: Number of 
Drugs to Which Subject is Phenotypic 
Resistant, Partially Sensitive or 
Sensitive at Time of CVF (Maintenance 
Phase) - Plasma Sample 
 
M6, M12 
7.6.  
mCVF 
207966/primary_15/T7.6 
Summary of Fold Change to CAB, RPV 
and BIC at Time of CVF (Maintenance 
Phase) - Plasma Sample 
 
M6, M12 
Other 
7.7.  
mCVF 
207966/primary_15/T7.7 
Summary of Net Assessment at Time of 
CVF (Maintenance Phase) - Plasma 
Sample  
 
M6, M12 
 
 
 


 
CONFIDENTIAL 
 
 
213500 
 
201 
 
16.15.11. ICH Listings 
ICH: Listings 
No. 
Population 
GSK Standard / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Study Population 
1.  Randomized 
mid207966/primary_15/Listing 1 
Listing of Subjects Randomized but Not Treated 
ICH E3 
M6, M12 
2.  
ITT-E 
Shell POP_L1 
Listing of Reasons for Study Withdrawal  
ICH E3 
Start from mid201584/primary_40 
listing 40. Also see mock up. 
HL, M6, 
M12, EOS 
3.  
ITT-E 
ES2 
Listing of Reasons for Study Drug Discontinuation 
ICH E3 
 
M6, M12, 
EOS 
4.  
ITT-E 
DV2 
Listing of Important Protocol Deviations 
ICH E3 
mid201584/primary_07 listing 6. 
Note: add if related to COVID-19 
Column 
M6, M12, 
EOS 
5.  
ITT-E 
DV2 
Listing of Protocol Deviations Leading to Exclusion from 
the Per-Protocol Population 
 
HL, M6, 
M12 
6.  
ITT-E 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations 
ICH E3 
 
M6, M12, 
EOS 
7.  
ITT-E 
DM2 
Listing of Demographic Characteristics including Race 
ICH E3 
mid201584/primary_07 listing 9 
and 10 
M6, M12, 
EOS 


 
CONFIDENTIAL 
 
 
213500 
 
202 
 
ICH: Listings 
No. 
Population 
GSK Standard / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Efficacy 
8.  
ITT-E 
207966/primary_15/Listing 11 
Listing of Study Outcome (50 c/mL Threshold) at Month 
12(OLI and BIK)/Month 11(D2I) – Snapshot Analysis 
For Month 6/5 deliverable, 
replace “Month 12 (OLI and 
BIK) and Month 11 (D2I)” with 
“Month 6 (OLI and BIK) and 
Month 5 (D2I)” 
HL, M6, 
M12 
9.  
ITT-E 
207966/primary_15/Listing 11 
Listing of Study Outcome (50 c/mL Threshold) at Month 
12(OLI and BIK)/Month 11(D2I) – Snapshot Analysis 
(All Data as Observed) 
For Month 6/5 deliverable, 
replace “Month 12 (OLI and 
BIK) and Month 11 (D2I)” with 
“Month 6 (OLI and BIK) and 
Month 5 (D2I)” 
M6, M12 
10.  Randomized 
Shell EFF_L1 
Listing of All Plasma HIV-1 RNA Data 
 
 
M6, M12, 
EOS 
Safety: Exposure  
11.  
Safety 
207966 primary_02, L14 / EX3 
Listing of Investigational Product Exposure Data 
ICH E3 
 
M6, M12 
Safety: Adverse Events 
12.  Randomized 
AE8 
Listing of All Adverse Events 
ICH E3 
M6,M12, 
EOS 
13.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse 
Events 
ICH E3 
M6,M12 
Safety: Serious and Other Significant Adverse Events 
14.  
Safety 
AE8 
 
Listing of Fatal Serious Adverse Events 
ICH E3 
M6,M12 


 
CONFIDENTIAL 
 
 
213500 
 
203 
 
ICH: Listings 
No. 
Population 
GSK Standard / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
15.  
Safety 
AE8 
Listing of Non-Fatal Serious Adverse Events 
ICH E3 
 
M6,M12 
16.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious 
Adverse Event 
ICH E3 
M6,M12, 
EOS 
17.  
Safety 
AE8 
Listing of Adverse Events Leading to Withdrawal from 
Study/Permanent Discontinuation of Study Treatment 
ICH E3 
HL, 
M6,M12, 
EOS 
18.  
Safety 
PSRAE1 
Listing of Possible Suicidality-Related Adverse Event 
Data: Event and Description (Section 1-Section 2) 
 
M6, M12 
19.  
Safety 
PSRAE3 
Listing of Possible Suicidality-Related Adverse Event 
Data: Possible Cause(s) (Section 3) 
 
M6, M12 
20.  
Safety 
PSRAE4 
Listing of Possible Suicidality-Related Adverse Event 
Data (Section 4) 
 
M6, M12 
21.  
Safety 
PSRAE5 
Listing of Possible Suicidality-Related Adverse Event 
Data (Section 5-Section 8) 
 
M6, M12 
 
 
 


 
CONFIDENTIAL 
 
 
213500 
 
204 
 
16.15.12. Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
GSK Standard GSK 
Statistical Display Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Study Population 
22.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
Journal Guidelines 
M6, M12, 
EOS 
23.  
Randomized 
TA1 
Listing of Randomized and Actual Strata and 
Treatment Assignment 
GSK Statistical Display Standard 
Add “Choice of OLI/D2I” 
M6, M12, 
EOS 
24.  
ITT-E 
CA3 
Listing of Prior ART Medications 
 
  M6, M12 
25.  
ITT-E 
mid207966/primary_15/listing37 Listing of Concomitant ART Medications during the 
Maintenance Phase 
 
M6, M12, 
EOS 
26.  
ITT-E 
CA3 
Listing of ART Medications Received during LTFU 
Phase 
 
M6, M12 
27.  
ITT-E 
mid207966/primary_15/listing39 Listing of Investigational Product Accountability - Oral 
Regimens 
 
M6, M12 
28.  
ITT-E 
mid207966/primary_15/listing40 Listing of Medical History of Seizure 
 
M6, M12 
29.  
ITT-E 
PAN 7 
Listing of All Subjects with Visits and Assessments 
Impacted by COVID-19 Pandemic 
 
M6, M12 
Efficacy 
30.  
ITT-E 
201584/primary_07/L54 
Listing of Stage-3 HIV-1 Associated Conditions  
 
M6, M12 
31.  
CVF 
Shell EFF_L1 
Listing of All Plasma HIV-1 RNA Data for Subjects with 
Confirmed Virologic Failure 
 
HL, M6, M12 
32.  
ITT-E 
Shell EFF_L1 
Listing of HIV-1 RNA Data for Subjects Who Became 
Pregnant During the Study 
Add: date of confirmed pregnancy. 
Only required if any subject 
becomes pregnant on Q2M. 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
205 
 
Non-ICH: Listings 
No. 
Population 
GSK Standard GSK 
Statistical Display Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Safety: Exposure 
33.  
Safety 
201584/primary_07/L72 
Listing of Investigational Product Exposure Data 
during Oral Bridging 
 
M6, M12 
34.  
Safety 
201584/primary_07/L73 
Listing of Dosing Errors and IP Device Malfunctions   
 
M6, M12 
Safety: Adverse Events 
35.  
[Insert] 
AE2 
Listing of Relationship Between Adverse Event 
System Organ Classes, Preferred Terms, and 
Verbatim Text 
GSK Statistical Display Standard 
M6, M12 
36.  
Safety 
AE8 
Listing of Changes in Intensity/Grades of Injection Site 
Adverse Events  
2011584/primary_07/Listing 22 
M6, M12 
37.  
Safety 
PAN12 
Listing of COVID-19 Assessments and Symptom 
Assessments for Subjects with COVID-19 Adverse 
Events 
 
M6, M12 
38.  
Safety 
AE8 
Listing of Grade 3 to 5 Adverse Events 
 
M6, M12 
Safety: All Laboratory 
39.  
Safety 
207966/primary_15/L59 
Listing of Clinical Chemistry Data for Subjects with 
Any Grade 3 to 5 Lab Toxicity 
Remove PCI flag. Treatment as 
section header. Only include the 
parameters with G3-5. 
M6, M12, 
EOS 
40.  
Safety 
207966/primary_15/L59 
Listing of Selected Laboratory Data for Subjects Who 
Became Pregnant During the Study 
Remove PCI flag. Treatment as 
section header. Selected 
parameters only. Do not produce if 
no subject became pregnant on 
Q2M. 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
206 
 
Non-ICH: Listings 
No. 
Population 
GSK Standard GSK 
Statistical Display Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Safety: Hepatobiliary (Liver) 
41.  
Safety 
MH2 
Listing of Medical Conditions for Subjects with Liver 
Stopping Events 
GSK Statistical Display Standard 
M6, M12 
42.  
Safety 
SU2 
Listing of Substance Use for Subjects with Liver 
Stopping Events 
GSK Statistical Display Standard 
M6, M12 
43.  
Safety 
201584/primary_07/L63 
Listing of All Subjects Meeting Liver Stopping Criteria 
 
M6, M12 
44.  
Safety 
207966/primary_15/L52 
Listing of Liver Monitoring/Stopping Event Reporting 
 
M6, M12 
45.  
Safety 
207966/primary_15/L53 
Listing of Liver Event Information for RUCAM Score 
 
M6, M12 
46.  
Safety 
207966/primary_15/L54 
Listing of Liver Biopsy Details 
 
M6, M12 
47.  
Safety 
207966/primary_15/L55 
Listing of Liver Imaging Details 
 
M6, M12 
48.  
Safety 
207966/primary_15/L56 
Listing of Subjects Meeting Hepatobiliary Lab Criteria  
 
M6, M12 
49.  
Safety 
207966/primary_15/L59 
Listing of ALT, AST, Bilirubin (including Total and 
Direct Bilirubin), INR, and ALP for Subjects Meeting 
Hepatobiliary Lab Abnormality Criteria 
 
HL, M6, M12 
Safety: ECG 
50.  
Safety 
EG3 
Listing of All ECG Values for Subjects with Any Value 
of Potential Clinical Importance 
GSK Statistical Display Standard 
Check all 3: QTcB, QTcF, and 
Unspecified for PCI criteria 
M6, M12 
51.  
Safety 
EG5  
Listing of Abnormal ECG Findings 
GSK Statistical Display Standard 
 
M6, M12 
52.  
Safety 
207966/primary_15/L57 
Listing of Potential QTc Interval Prolonging Events of 
Interest  
 
M6, M12 
53.  
Safety 
207966/primary_15/L58 
Listing of ECG values for Subjects with Potential QTc 
Interval Prolonging Events of Interest 
 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
207 
 
Non-ICH: Listings 
No. 
Population 
GSK Standard GSK 
Statistical Display Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Safety: Vital Signs 
54.  
Safety 
VS4 
Listing of All Vital Signs and Anthropometric 
Parameters 
GSK Statistical Display Standard 
Include weight, height and BMI, 
waist and hip circumference, and 
Tanita scale measurements (body 
Fat, bone mass, musl mass, TBW)  
M6, M12 
55.  
Safety 
PREG1A  
Listing of Subjects Who Became Pregnant During the 
Study 
 
GSK Statistical Display 
Standard 
Required by GCSP 
Include Date of confirmed 
pregnancy 
M6, M12 
Safety: Metabolic Syndrome 
56.  
Safety 
SAF_L2 
Listing of Clinical Diagnosis Factor Data by Visit for 
Subjects Diagnosed with Metabolic Syndrome 
(Maintenance Phase) 
 
M6, M12 
Safety: Abacavir Hypersensitivity 
57.  
Safety 
ABC_HSR 
_EXPO2 
Listing of Abacavir Hypersensitivity Reaction Record - 
Exposure to Abacavir 
Produce empty listing if no data to 
report 
M6, M12 
58.  
Safety 
ABC_HSR 
_DRUG2 
Listing of Abacavir Hypersensitivity Reaction Record - 
Subject History of Drug Allergies 
Do not produce if no data to report 
M6, M12 
59.  
Safety 
ABC_HSR 
COND2 
Listing of Abacavir Hypersensitivity Reaction Record - 
Subject and Family Conditions 
Do not produce if no data to report 
M6, M12 
60.  
Safety 
ABC_HSR 
_RASH2 
Listing of Abacavir Hypersensitivity Reaction Record - 
Skin Rash Details 
Do not produce if no data to report 
M6, M12 


 
CONFIDENTIAL 
 
 
213500 
 
208 
 
Non-ICH: Listings 
No. 
Population 
GSK Standard GSK 
Statistical Display Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
61.  
Safety 
ABC_HSR 
_SYMP4 
Listing of Abacavir Hypersensitivity Reaction Record - 
Symptoms 
Do not produce if no data to report 
M6, M12 
62.  
Safety 
VS4 
Listing of Abacavir Hypersensitivity Reaction Record - 
Vital Signs 
Do not produce if no data to report 
M6, M12 
63.  
Safety 
ABC_HSR 
_SYMP6 
Listing of Abacavir Hypersensitivity Reaction Record - 
Individual Symptoms and Diagnostic Category 
Assignments 
Do not produce if no data to report 
M6, M12 
Virology 
64.  
CVF 
207966/primary_15/T7.8 
Listing of Viral load, Genotypic, Phenotypic data for 
Subjects Who Met Confirmed Virologic Failure Criteria  
 
HL, M6, 
M12, EOS 
65.  
Safety 
207966/primary_15/T7.10 
Listing of Viral load, Genotypic, Phenotypic data for 
Non-CVF Subjects with Genotypic and/or Phenotypic 
Data                                
 
M6, M12, 
EOS 
66.  
CVF 
207966/primary_15/Listing 62 
Listing of Replication Capacity in IN and PR/RT 
Region 
 
M6, M12, 
EOS 
67.  
Safety 
207966/primary_15/Listing 63 
Listing of Resistance Associated Mutations (Pre-
specified INSTI and IAS-USA NNRTI) 
 
M6, M12, 
EOS 
68.  
CVF 
 
Listing of Net Assessment data for Subjects Who Met 
Confirmed Virologic Failure Criteria  
 
M6, M12, 
EOS 
69.  
Safety 
 
Listing of Net Assessment data for Non-CVF Subjects 
with Genotypic and/or Phenotypic Data                             
M6, M12, 
EOS 


 
CONFIDENTIAL 
 
 
213500 
 
209 
 
Non-ICH: Listings 
No. 
Population 
GSK Standard GSK 
Statistical Display Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK 
70.  
PK 
207966/primary_15/L63 
Listing of Plasma PK Concentrations for Subjects Who 
Became Pregnant During the Study 
CAB and RPV With Section 
Headers. Do not produce if no 
subject became pregnant on Q2M 
and continued study 
M12 
71.  
ITT-E 
207966/primary_15/L63 
Listing of Plasma PK Concentrations at Withdrawal 
 
M12 
72.  
CVF 
207966/primary_15/L63 
Listing of All Plasma PK Concentrations for CVF 
Subjects 
 
M12 
 


 
CONFIDENTIAL 
 
 
213500 
 
210 
 
16.16. 
Appendix 16: Example Mock Shells for Data Displays 
Available upon request