Clinical trial NCT03639311
Conditions: HIV Infections
Keywords: HIV Antiretroviral therapy Maintenance Long acting LATTE
Sponsor: ViiV Healthcare
Start date: 2018-09-24; Completion date: 2023-01-30
Enrollment: 97 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study (POLAR), is designed to assess the antiviral activity and safety of CAB LA plus RPV LA, administered Q2M, in approximately 100 adult HIV-1 infected, antiretroviral therapy (ART) experienced participants. Participants will rollover from the NCT01641809 (LATTE) study, who have completed minimum duration of Week 312 and with demonstrated HIV-1 ribonucleic acid (RNA) suppression (less than \[\<\]50 copies (c) per milliliter \[mL\]), while receiving a two-drug regimen consisting of once-daily oral CAB at 30 milligram (mg) plus RPV at 25 mg. The participants will be offered the option to switch to the LA, intramuscular injections of CAB LA plus RPV LA, Q2M or the oral fixed dose combination (FDC) of dolutegravir (DTG) plus RPV, for the continued maintenance of HIV-1 RNA suppression, known as the Maintenance Phase (From Day 1 to Commercial Approval). Duration of study will vary from country to country, until regimen receives regulatory approval and becomes commercially available. The study plans to enroll approximately 100 participants. Any participant who receives at least one dose of CAB LA and/or RPV LA and discontinues the CAB LA plus RPV LA regimen for any reason will enter a 52-week Long-Term Follow-Up (LTFU) phase. Those participants must remain on suppressive highly active antiretroviral therapy (HAART) for at least 52 weeks after the last dose of CAB LA and or RPV LA.

Detailed description:

Arms: arm 1: Eligible participants from LAI116482 (NCT01641809 \[LATTE\]) study who were administered oral CAB 30 milligrams (mg) plus RPV 25 mg and who successfully completed Week 300 received their first dose CAB LA (600 mg) plus RPV LA (900 mg) injections within 2 hours of the final oral dose of LATTE given on the same day. The second loading injections were administered 1 month after initial loading dose, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring Q2M thereafter. Participants continued to receive the treatment until the study intervention was locally approved and commercially available. Participants who received at least one dose of CAB LA and/or RPV LA and discontinued the CAB LA + RPV LA regimen for any reason entered a 52-week long-term follow-up (LTFU) Phase. arm 2: Eligible participants from LAI116482 (NCT01641809 \[LATTE\]) study who were administered oral CAB 30 mg plus RPV 25 mg and who successfully completed Week 300 received their first dose of the Dolutegravir (DTG) 50 mg plus RPV 25 mg, once daily as oral regimen on Day 1 until Month 12 in the current study. These participants were not eligible for the LTFU phase. arm 3: This group included the participants who received at least one dose of CAB LA and/or RPV LA and discontinued the CAB LA + RPV LA regimen for any reason before end of Maintenance Period. The participants entered a 52-week LTFU period.
Interventions: intervention 1: CAB LA intervention 2: RPV LA intervention 3: RPV intervention 4: DTG
Intervention descriptions: intervention 1: Administered CAB LA (600 mg) Q2M, as intramuscular injection. intervention 2: Administered RPV LA (900 mg), Q2M, as intramuscular injection. intervention 3: Oral dose of RPV 25 mg, administered once daily from Day 1 up to Month 12 intervention 4: Oral dose of DTG 50 mg administered once daily from Day 1 up to Month 12.

Protocol documents:
Prot_000.pdf: 
2018N356280_02
CONFIDENTIAL
ViiV Healthcare and the GlaxoSmithKline group of companies
209035
1
TITLE PAGE
Protocol Title: A Phase IIb, Multicenter, Open-label, Rollover Study Evaluating the 
Efficacy, Safety and Tolerability of Long-acting Cabotegravir Plus Long-acting 
Rilpivirine Administered Every Two Months in HIV-1 infected Adults who are 
Virologically Suppressed and Participated in Study LAI116482 
Protocol Number: 209035/02
Compound Number:
GSK1265744
Study Phase: Phase 2b
Short Title: Phase 2b, open-label, multicenter, rollover study to assess antiviral activity 
and safety of CAB LA + RPV LA, administered every 2 months, in HIV positive 
participants from the LATTE study.
Sponsor Name and Legal Registered Address: 
This study is sponsored by ViiV Healthcare.  GlaxoSmithKline is implementing and 
managing all aspects of this study on behalf of ViiV Healthcare. 
US IND Sponsor Legal Registered Address:
ViiV Healthcare 
Five Moore Drive
P.O. 13398
Research Triangle Park, NC 27709-3398, USA
Telephone:  
Sponsor Legal Registered Address (excluding US): 
ViiV Healthcare
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
In some countries, local law requires that the Clinical Trial sponsor is a local 
company legal entity.  In these instances, the appropriate company to be identified 
as Sponsor must be agreed with the global ViiV Healthcare clinical team and signed 
off by the Vice President, Global Research and Medical Strategy
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual
Copyright 2020 ViiV Healthcare and the GlaxoSmithKline group of companies.  All 
rights reserved.  Unauthorised copying or use of this information is prohibited.
PPD


2018N356280_02
CONFIDENTIAL
ViiV Healthcare and the GlaxoSmithKline group of companies
209035
2
Regulatory Agency Identifying Number(s):
IND: 109, 678
EudraCT:  2017-002946-62
Approval Date: 19-MAY-2020


PPD
PPD


2018N356280_02
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4
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
DNG Number
Amendment 2
19-May-2020
2018N356280_02
Amendment 1
22-Jun-2018
2018N356280_01
Original Protocol
16-May-2018
2018N356280_00
Amendment 2, 19-MAY-2020
Overall Rationale for the Amendment: This amendment is to include information on 
COVID-19 specific guidance for clinical trial continuity (participant and study 
management) during the pandemic.
Section # and Name
Description of Change
Brief Rationale
Section 6.7 Dose 
Modifications
Section 6.7.1.1. Oral 
Bridging
Section 8.5. Adverse 
Events and Serious 
Adverse Events
Section 9 Data 
Management
Added reference to 
COVID-19 Section 12.10, 
Appendix 10
To link Appendix 10 to the main 
body of the protocol 
Section 12.10
Appendix 10: COVID-
19 Pandemic and 
Clinical Trial 
Continuity
Added Appendix 10
To summarize COVID-19 related 
patient management updates that 
were previously communicated in 
a memo to investigators 


2018N356280_02
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TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................4
1.
PROTOCOL SUMMARY........................................................................................10
1.1.
Synopsis.....................................................................................................10
1.2.
Schema ......................................................................................................16
1.3.
Schedule of Activities (SoA)........................................................................18
2.
INTRODUCTION....................................................................................................26
2.1.
Study Rationale ..........................................................................................26
2.2.
Background ................................................................................................26
2.3.
Benefit/Risk Assessment ............................................................................28
2.3.1.
Risk Assessment .........................................................................28
2.3.1.1.
Other Clinically Relevant Information..........................42
2.3.2.
Benefit Assessment.....................................................................43
2.3.3.
Overall Benefit: Risk Conclusion..................................................43
3.
OBJECTIVES AND ENDPOINTS...........................................................................43
4.
STUDY DESIGN ....................................................................................................45
4.1.
Overall Design ............................................................................................45
4.1.1.
Evaluable Participants .................................................................46
4.1.2.
Study Schematic..........................................................................46
4.2.
Treatment Groups and Duration .................................................................47
4.2.1.
Eligibility for the POLAR Study for Participants Entering 
from the LATTE Study .................................................................47
4.2.2.
Maintenance Phase (Day 1 up to Commercial Approval).............47
4.2.2.1.
Participants electing to receive oral DTG + 
RPV once daily...........................................................48
4.2.3.
LTFU Phase – IM Regimen Only .................................................48
4.3.
Scientific Rationale for Study Design ..........................................................49
4.4.
Justification for Dose ..................................................................................51
4.4.1.
Long Acting Injectable for Maintenance Phase ............................51
4.4.1.1.
CAB LA Q2M..............................................................52
4.4.1.2.
RPV LA Q2M..............................................................53
4.4.1.3.
DTG + RPV ................................................................54
4.5.
End of Study Definition ...............................................................................55
5.
STUDY POPULATION...........................................................................................55
5.1.
Inclusion Criteria.........................................................................................56
5.2.
Exclusion Criteria........................................................................................58
5.2.1.
Additional Eligibility Criteria..........................................................61
5.3.
Lifestyle Considerations..............................................................................61
6.
STUDY INTERVENTION........................................................................................62
6.1.
Study Intervention(s) Administered .............................................................62
6.1.1.
Formulations of CAB + RPV ........................................................62
6.1.1.1.
Cabotegravir Tablets (CAB)........................................62
6.1.1.2.
Rilpivirine Tablets (RPV).............................................62
6.1.1.3.
Cabotegravir Injectable Suspension (CAB LA) ...........63


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6.1.1.4.
Rilpivirine Injectable Suspension (RPV LA) ................63
6.1.2.
Tablet Formulation of DTG + RPV (Juluca)..................................63
6.2.
Treatment Assignment................................................................................63
6.3.
Blinding.......................................................................................................64
6.4.
Packaging and Labeling..............................................................................64
6.5.
Preparation/Handling/Storage/Accountability..............................................65
6.5.1.
Dosing Considerations for CAB LA + RPV LA..............................65
6.6.
Compliance with Study Intervention Administration.....................................66
6.7.
Dose Modifications .....................................................................................67
6.7.1.
Protocol Permitted Substitutions..................................................67
6.7.1.1.
Oral Bridging ..............................................................67
6.8.
Interruption of Study Intervention and Visit/Dosing Windows ......................68
6.8.1.
IM Dosing ....................................................................................68
6.8.1.1.
IM injections every 2 months (Q2M): ..........................69
6.8.2.
Oral Dosing..................................................................................69
6.9.
Treatment of Study Intervention Overdose..................................................69
6.10.
Intervention after the End of the Study........................................................70
6.11.
Concomitant Medications and Non-Drug Therapies....................................70
6.11.1.
Permitted Medications and Non-Drug Therapies..........................71
6.11.2.
Prohibited Medications and Non-Drug Therapies.........................72
6.11.2.1.
Concurrent with CAB and/or RPV and DTG + 
RPV............................................................................72
6.11.2.2.
Concurrent with oral RPV ...........................................73
6.11.2.3.
Concurrent with either CAB LA or RPV LA .................73
6.11.2.4.
Concurrent with DTG + RPV.......................................73
6.11.2.5.
Prohibited Medications for Participants 
Receiving HAART during the Long-Term 
Follow-Up Phase ........................................................74
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL.....................................................................74
7.1.
Discontinuation of Study Intervention..........................................................76
7.1.1.
Liver Chemistry Stopping Criteria ................................................76
7.1.1.1.
Liver Chemistry Stopping Criteria, Participant 
Management and Follow-up .......................................77
7.1.1.2.
Liver Event Adjudication Committee...........................78
7.1.1.3.
Liver Chemistry Stopping Criteria – Restart / 
Rechallenge ...............................................................78
7.1.1.3.1.
Drug Restart / Rechallenge.  
Following Liver Events that are 
Possibly Related and not related 
to Study intervention...............................79
7.1.1.3.2.
Drug Restart Following Transient 
Resolving Liver Events Not 
Related to Study intervention..................80
7.1.2.
QTc Stopping Criteria ..................................................................81
7.1.3.
Virologic Failure...........................................................................81
7.1.4.
Definition of Protocol-Defined Confirmed Virologic Failure...........81
7.1.5.
Managing Virologic Failure ..........................................................82
7.1.5.1.
HIV-1 RNA Blips.........................................................82
7.1.5.2.
Suspected Virologic Failure........................................82
7.1.5.3.
Confirmed Virologic Failure ........................................83


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7
8.
STUDY ASSESSMENTS AND PROCEDURES .....................................................84
8.1.
Time and Events Table...............................................................................85
8.1.1.
Time and Events Table for CAB LA + RPV LA Q2M 
Administration..............................................................................85
8.1.2.
Time and Events Table for DTG + RPV Administration................89
8.1.3.
Time and Events Table for Long Term Follow Up ........................91
8.2.
Baseline Assessments................................................................................92
8.3.
Efficacy Assessments.................................................................................93
8.3.1.
Plasma HIV-1 RNA......................................................................93
8.3.2.
Lymphocyte Subsets, CD4+ and CD8+ .......................................93
8.3.3.
HIV Associated Conditions ..........................................................93
8.4.
Safety Assessments ...................................................................................93
8.4.1.
Clinical Evaluations......................................................................93
8.4.2.
Laboratory Assessments .............................................................94
8.4.3.
Physical Examinations.................................................................96
8.4.4.
Vital Signs....................................................................................97
8.4.5.
Electrocardiograms......................................................................97
8.4.6.
Suicidal Ideation and Behaviour Risk Monitoring .........................97
8.4.7.
Pregnancy ...................................................................................98
8.4.7.1.
Pregnancy testing.......................................................98
8.4.7.2.
Time Period for Collecting Pregnancy 
Information .................................................................98
8.4.7.3.
Action to be Taken if Pregnancy Occurs.....................98
8.5.
Adverse Events and Serious Adverse Events.............................................99
8.5.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................99
8.5.2.
Method of Detecting AEs and SAEs...........................................100
8.5.3.
Follow-up of AEs and SAEs.......................................................100
8.5.4.
Prompt Reporting of Serious Adverse Events and Other 
Events .......................................................................................100
8.5.5.
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs.............................................103
8.5.6.
Regulatory Reporting Requirements for SAEs ...........................103
8.5.7.
Cardiovascular and Death Events..............................................104
8.5.8.
Death Events.............................................................................104
8.6.
Toxicity Management................................................................................105
8.6.1.
Treatment Interruption Due to an Adverse Event .......................105
8.6.2.
Grade 1 or Grade 2 Toxicity/Adverse Event...............................106
8.6.3.
Grade 3 Toxicity/Adverse Event.................................................106
8.6.4.
Grade 4 Toxicity/Adverse Event.................................................106
8.7.
Specific Toxicities/Adverse Event Management........................................107
8.7.1.
Liver Chemistry Stopping and Follow-up Criteria .......................107
8.7.2.
Diarrhea.....................................................................................107
8.7.3.
Hypertriglyceridemia/ Hypercholesterolemia..............................108
8.7.4.
Seizures ....................................................................................108
8.7.5.
Creatine Phosphokinase (CPK) Elevation..................................109
8.7.6.
Lipase Elevations and Pancreatitis ............................................109
8.7.7.
Decline in Renal Function..........................................................110
8.7.7.1.
Proximal Renal Tubule Dysfunctions (PRTD) ...........110
8.7.7.2.
Proteinuria................................................................111
8.7.8.
QTc Prolongation.......................................................................111
8.7.9.
Injection Site Reactions (ISRs) ..................................................111


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8.7.10.
Allergic reaction .........................................................................112
8.7.11.
Abacavir Hypersensitivity Reaction (ABC HSR).........................112
8.7.11.1.
Essential Participant Information ..............................113
8.7.11.2.
Reporting of Hypersensitivity Reactions ...................113
8.7.12.
Rash Without ABC HSR Symptoms...........................................114
8.8.
Pharmacokinetics .....................................................................................115
8.8.1.
PK Sample Collection ................................................................116
8.8.2.
Rationale for PK Sampling Strategy...........................................117
8.8.3.
Sample Analysis ........................................................................117
8.8.3.1.
CAB and DTG Sample Analysis ...............................117
8.8.3.2.
RPV Sample Analysis...............................................117
8.9.
Genetics ...................................................................................................117
8.10.
Viral Genotyping and Phenotyping............................................................117
8.10.1.
HIV-1 Polymerase Viral Genotyping and Phenotyping ...............118
8.10.2.
HIV-1 Exploratory Analysis ........................................................118
8.11.
Value Evidence and Outcomes.................................................................118
8.11.1.
Value Evidence and Outcomes Endpoints (Secondary).............119
8.11.2.
Value Evidence and Outcomes Endpoints (Exploratory)............119
8.12.
Digital Reminder .......................................................................................119
9.
DATA MANAGEMENT .........................................................................................120
10. STATISTICAL CONSIDERATIONS......................................................................120
10.1.
Statistical Hypotheses...............................................................................120
10.2.
Sample Size Determination ......................................................................120
10.2.1.
Sample Size Sensitivity..............................................................120
10.3.
Populations for Analyses ..........................................................................121
10.4.
Statistical Analyses...................................................................................121
10.4.1.
Safety Analyses.........................................................................122
10.4.2.
Other Analyses ..........................................................................122
10.5.
Interim Analyses .......................................................................................122
11. REFERENCES.....................................................................................................123
12. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS.............................................................................................126
12.1.
Appendix 1:  Abbreviations and Trademarks.............................................126
12.2.
Appendix 2: Regulatory, Ethical, and Study Oversight 
Considerations..........................................................................................131
12.2.1.
Regulatory and Ethical Considerations ......................................131
12.2.2.
Financial Disclosure...................................................................131
12.2.3.
Informed Consent Process ........................................................132
12.2.4.
Data Protection..........................................................................132
12.2.5.
Dissemination of Clinical Study Data .........................................133
12.2.6.
Data Quality Assurance .............................................................133
12.2.7.
Source Documents ....................................................................134
12.2.8.
Study and Site Closure ..............................................................134
12.2.9.
Publication Policy.......................................................................135
12.3.
Appendix 3: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Version 2.1, March 2017............................136
12.3.1.
Estimating Severity Grade for Parameters Not Identified in 
the Grading Table......................................................................136


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12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .....................................160
12.4.1.
Definition of AE..........................................................................160
12.4.2.
Definition of SAE........................................................................161
12.4.3.
Definition of Cardiovascular Events ...........................................162
12.4.4.
Recording and Follow-Up of AE and SAE..................................163
12.4.5.
Reporting of SAE to GSK...........................................................165
12.5.
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information................................................................................................166
12.5.1.
Definitions..................................................................................166
12.5.1.1.
Woman of Childbearing Potential (WOCBP).............166
12.5.1.1.1.
Women in the following categories 
are not considered WOCBP..................166
12.5.2.
Contraception Guidance: ...........................................................167
12.5.3.
Collection of Pregnancy Information: .........................................168
12.6.
Appendix 6: Genetics Research................................................................169
12.7.
Appendix 7: Liver Safety: Study intervention Restart or Rechallenge 
Guidelines.................................................................................................172
12.7.1.
VSLC Guidelines for Drug Restart or Rechallenge after 
stop for Liver criteria ..................................................................172
12.7.2.
VSLC Decision Process for Drug Rechallenge Approval or 
Disapproval................................................................................173
12.7.3.
VSLC Decision Process for Drug Restart Approval or 
Disapproval................................................................................176
12.7.4.
Medical monitor, GCSP Physician and PI actions for 
Restart or Rechallenge following VSLC decision .......................177
12.7.4.1.
Medical Monitor and GCSP Physician Actions..........177
12.7.4.2.
PI Actions:................................................................178
12.8.
Appendix 8: CDC Classification for HIV-1 Infection (2014)........................179
12.9.
Appendix 9: Country-specific requirements...............................................181
12.9.1.
Study Duration...........................................................................181
12.10. Appendix 10:  COVID-19 Pandemic and Clinical Trial Continuity..............182
12.10.1. Changes to Study Visits and Study Procedures.........................182
12.10.2. Changes to Informed Consent ...................................................183
12.10.3. Permissible Use of Antiretroviral Therapy ..................................183
12.10.4. Direct-To-Patient (DTP) Shipment of Oral Study IP ...................185
12.10.5. COVID-19 Experimental Agents ................................................186
12.10.6. COVID-19 Specific Data Capture...............................................186
12.10.6.1. Capturing COVID-19 Specific Protocol 
Deviations ................................................................186
12.10.6.2. Capturing COVID-19 Specific AEs and SAEs...........186
12.11. Appendix 11: Protocol Amendment History...............................................189


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1.
PROTOCOL SUMMARY
1.1.
Synopsis
Protocol Title: A Phase IIb, Multicenter, Open-label, Rollover Study Evaluating the 
Efficacy, Safety and Tolerability of Long-acting Cabotegravir Plus Long-acting 
Rilpivirine Administered Every Two Months in HIV-1 infected Adults who are 
Virologically Suppressed and Participated in Study LAI116482
Short Title: Phase 2b, open-label, multicenter, rollover study to assess antiviral activity 
and safety of CAB LA + RPV LA, administered every 2 months, in HIV positive 
participants from the LATTE study.
Rationale:
While advances in the development of new anti-retroviral therapies (ART) provide 
extensive insights into the management of HIV-infected individuals, chronic HIV 
infection in adults continues to be characterized by increased development of resistant 
virus, increasing transmission of resistant virus and issues associated with the long-term 
toxicity of ART. The current paradigm in the treatment of HIV involves life-long 
therapy with multiple antiretrovirals. There is an enduring need to develop new agents 
with improved safety and resistance profiles with convenient dosing for both 
antiretroviral treatment-naive and treatment-experienced participants. 
This clinical trial, 209035 (Oral (PO) to Long Acting (LA) Rollover-POLAR), will 
evaluate an antiretroviral treatment approach that is potentially more convenient for the 
participant.  Participants will rollover from the LAI116482 (LATTE) study with 
demonstrated HIV-1 ribonucleic acid (RNA) suppression while receiving a two-drug 
regimen consisting of once-daily oral CAB 30 mg + RPV 25 mg.  The participants will 
be offered the option to switch to the LA formulations of the regimen consisting of CAB
LA + RPV LA for the continued maintenance of HIV-1 RNA suppression, being dosed 
by intramuscular injection every 2 months (Q2M) or the oral fixed dose combination 
(FDC) of DTG + RPV for the continued maintenance of HIV-1 RNA suppression.
Those entering this study who do not wish to receive injectable CAB LA + RPV LA are 
eligible to elect to transition to once-daily oral therapy with a single tablet regimen (STR)
of DTG + RPV for a period of at least 12 months, or until commercial availability.  The 
efficacy of DTG + RPV, or Juluca, is supported by data from 2 open label, controlled 
trials (SWORD-1 and SWORD-2) in virologically suppressed participants switching 
from their current antiretroviral regimen.  
The overall objective of this study is to demonstrate the antiviral activity of CAB LA + 
RPV LA every 2 months in virally-suppressed HIV-1 infected antiretroviral therapy 
ART-experienced participants.  An evaluation of the antiviral activity, tolerability, 
durability and safety of the IM dosing regimen will be performed.  
This study consists of a Maintenance Period and a Long-Term Follow Up Period for 
participants who withdraw and have received at least one dose of CAB LA and / or RPV
LA.


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Objectives and Endpoints:
Objectives
Endpoints
Primary
To demonstrate the antiviral activity of 
CAB LA + RPV LA every 2 months in 
suppressed HIV-1 infected antiretroviral 
therapy ART-experienced participants
Proportion of participants with HIV-RNA 
50 c/mL as per food and drug 
administration (FDA) Snapshot algorithm 
at Month 12
Secondary
To demonstrate the antiviral and 
immunologic activity of CAB LA + RPV 
LA every 2 months and oral DTG +RPV 
once daily.
Proportion of participants with plasma 
HIV-1 RNA <50 c/mL (c/mL) at Month 12
using the FDA Snapshot algorithm 
Proportion of participants with protocol-
defined confirmed virologic failure (CVF) 
over time
Proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL as per 
FDA Snapshot algorithm over time
Absolute values and changes from Baseline 
in viral load and cluster of differentiation 4
(CD4+) cell counts over time 
To demonstrate the safety and tolerability 
of CAB LA + RPV LA every 2 months and 
oral DTG +RPV once daily.
Incidence and severity of adverse events 
(AEs) and laboratory abnormalities over 
time 
Proportion of participants who discontinue
treatment due to AEs over time
Change from Baseline in laboratory 
parameters over time 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure 
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV, 
DTG + RPV
To characterize CAB and RPV 
concentrations and population 
pharmacokinetics and identify important 
determinants of variability
Plasma pharmacokinetic (PK) parameters 
for CAB LA and RPV LA (when 
evaluable, trough concentrations [Ctrough])


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Objectives
Endpoints
To assess participant reported health-
related quality of life, injection 
tolerability/acceptability, and treatment 
satisfaction.  
Change from Baseline (Day 1) in HIV 
dependent quality of life (HIVDQoL) at 
Months 6 and 12 (or Withdrawal)
Change from baseline (Day 1) in total 
“treatment satisfaction” score, and 
individual item scores of the HIV 
Treatment Satisfaction Status 
Questionnaire (HIVTSQs) at Months 6 and 
12 (or Withdrawal)
Change in treatment satisfaction over time 
using the HIV Treatment Satisfaction 
Change Questionnaire (HIVTSQc) at 
Month 12 (or Withdrawal).
Exploratory
Explore the concept of a digital assistance 
program and the effect on participant
participation and adherence to timeliness of 
injections given every 2 months
The number of participants who utilize the 
program
Adherence to scheduled date of injection
To assess reason for switching using a 
single question. 
To assess preference using a single 
question
The ‘Preference” question will be used to 
assess preference for CAB LA + RPV LA 
every 2 months compared to prior oral 
CAB + RPV regimen, at Month 12 using a 
single dichotomous preference question.
The “Reason for Switch” question will be 
administered at Day 1 (Baseline) to assess 
the reasons for willingness to switch to LA 
injectable ART.
Overall Design:
Study 209035 (POLAR) is a Phase IIb, open-label, multicenter rollover study designed to 
assess the antiviral activity and safety of CAB LA + RPV LA administered every 2 
months in approximately 100 adult HIV-1 infected participants from the LATTE study.
Participants who fulfill eligibility requirements will be entered into the study to receive 
either CAB LA + RPV LA Q2M or the oral DTG + RPV regimen for at least 12 months, 
until commercially available.
Participants currently receiving oral CAB + RPV within LATTE will enter POLAR at 
Day 1 and choose to either transition to Q2M administration of injectable CAB LA + 


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RPV LA or take oral DTG + RPV daily for 12 months.  Eligible participants include 
those originally randomized to oral CAB + RPV in the Maintenance phase and 
transitioned to the Extension Phase of LATTE.  The first injection visit for POLAR can 
be performed once the most recent central lab results from LATTE are available and 
safety parameters have been reviewed, and the LATTE Week 312 visit (close-out visit) 
has been completed (or Week 324 in the event of unavoidable delays).  Participants will 
continue to receive oral CAB + RPV as scheduled within the LATTE trial until their 
eligibility for POLAR can be fully evaluated and the participant has chosen the new 
regimen.  If determined to be ineligible for POLAR or participant elects to not participate 
in the study those participants will be withdrawn from the LATTE study.
Participants in POLAR who successfully complete Week 300 in the LATTE study 
(without meeting study defined withdrawal criteria) will be given the option to receive 
either CAB LA + RPV LA (administered Q2M) or oral DTG + RPV daily until study 
intervention is either locally approved and commercially available within the local sector 
(including through local public/government health sectors), the participant no longer 
derives clinical benefit, the participant meets a protocol-defined reason for 
discontinuation or until development of either CAB LA + RPV LA Q2M is terminated.
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 will enter a 52-week Long-
Term Follow-Up (LTFU) Phase.  Those participants must remain on suppressive highly 
active antiretroviral therapy (HAART) for at least 52 weeks after the last dose of CAB 
LA and/or RPV LA.
The primary endpoint for the study is the proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL at Month 12 as per Food and Drug Administration 
(FDA) Snapshot algorithm using the Intent-to-Treat Exposed (ITT-E) population.
Disclosure Statement: 
This is an Intervention Model (Parallel) Primary Purpose (Treatment) study with Number 
Arms (2) No masking.
Number of Participants:
The target population to be enrolled is HIV-1 infected virologically suppressed (HIV-1 
RNA <50 c/mL) participants on stable antiretroviral therapy (ART) who have completed, 
at minimum, Week 312 (or Week 324 in the event of unavoidable delays) of the LATTE
study.  It is anticipated that approximately 100 participants will be enrolled into POLAR.
Intervention Groups and Duration:
Informed consent must be obtained prior to any study procedures, including any Day 1
assessment.
All participants with an undetectable HIV-1 RNA (<50 c/mL) at Week 300 in the LATTE 
study are eligible to enter this study. A single repeat to determine eligibility may be 
allowed ONLY after consultation with the medical monitor.  Participants with HIV-1 


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RNA 200 c/mL at Week 300 are not eligible to enter the study and will not be allowed a 
repeat to determine eligibility.  The Day 1 visit of the POLAR study will be performed in 
parallel with the final closeout visit for the LATTE study, Week 312 or (if contracts have 
not been finalized and/or institutional review board (IRB) approval has not been obtained 
by Week 312 in the LATTE study) Week 324.
Result of HIV-1 RNA at Week 300
Action
<50 c/mL
Begin POLAR study at Day 1 
50 c/mL but <200 c/mL
Single repeat allowed only after consultation 
and approval from medical monitor
Single repeat <50 c/mL
Begin POLAR study at Day 1
Single repeat 50 c/mL
Cannot begin POLAR and must be withdrawn 
from the LATTE study; Complete withdrawal 
visit.  
200 c/mL
Cannot begin POLAR and must be withdrawn 
from LATTE; Complete withdrawal visit.
Should a participant be allowed a repeat, results of this repeat must be available prior to 
Day 1 of this study, therefore the time needed for scheduling the Day 1 visit, lab draws 
and lab analysis should be considered.  
In addition to the viral load criteria above, if in the opinion of the Investigator, a 
participant experiences a significant safety event while taking either CAB or RPV, study 
eligibility will be determined ONLY in consultation with the medical monitor.  
Participants ineligible for this study will be withdrawn from LATTE.  
Maintenance Phase (Day 1 up to Commercial Approval)
At the Day 1 visit (the start of the first month of the study), 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 second loading injections will be administered 1 month (Month 2 
visit, the start of the second month of the study) after initial loading dose (CAB LA 
600 mg + RPV LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 
900 mg) occurring every 2 months thereafter.  The dosing window for the second 
injection will be -7 days from the projected dosing visit.
After Month 2, a dosing window (7 days) for injections is stipulated.  Doses outside of 
the window may be allowed with Medical Monitor approval.
Participants will continue CAB LA + RPV LA until:


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
study intervention is locally approved and commercially available, 

the participant no longer derives clinical benefit, 

the participant meets a protocol-defined reason for discontinuation  

the development of either CAB LA or RPV LA is terminated.
Safety and efficacy assessments will be conducted as per the Time and Events schedule.  
Dosing will occur according to the selected regimen. 
If the intramuscular (IM) dosing regimen (Q2M) is discontinued as a result of an 
independent data monitoring committee (IDMC) review any subsequent analysis, or any 
other programmatic analysis, those participants who have not met any clinical 
management criteria for discontinuation will be discontinued permanently from the study 
and will enter into the LTFU Phase of the study.
Participants electing to receive oral DTG + RPV once daily
The DTG + RPV oral regimen will be administered in an open-label fashion starting on 
Day 1 until Month 12.  Participants will continue study intervention until:

study intervention is locally approved and commercially available, 

the participant no longer derives clinical benefit, 

the participant meets a protocol-defined reason for discontinuation  
Safety and efficacy assessments will be conducted as per the Time and Events schedule.  
Dosing will occur according to the selected regimen.
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 after the last Q2M injection, however if 
withdrawn due to virologic failure, HAART should be initiated as soon as virologic 
failure is confirmed.  Discuss with medical monitor.  The LTFU will begin the day of 
the last CAB LA and/or RPV LA dose and continue for 52 weeks.  These participants 
will not complete a Withdrawal visit, but will instead move directly into the LTFU 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. 
Participants will be assessed with clinic visits at months 1, 3, 6, 9, and 12 during the 
LTFU Phase.  Female participants of child bearing potential must continue to use 
adequate contraception methods for the entire year of follow up.  
In order to assure that participants have access to HAART during the LTFU, ViiV
Healthcare 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 


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the study for various reasons, e.g., better understanding of risks of development of 
resistance as CAB and RPV exposures decline, end of study timings, etc.
This phase is considered study participation and participants will be followed on study 
during this time.  A withdrawal visit is not required for participants who do not complete 
the LTFU Phase.  The participants’ last on study visit will be considered as their 
withdrawal visit.
Dose Modifications
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 
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.  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.
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.
Data Monitoring Committee: No
1.2.
Schema
209035 (POLAR) Study Design Schematic
§ All participants in LATTE administered oral CAB 30 mg + RPV 25 mg


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† Access commercially once Q8W is approved
# Access longer term via commercial route.  Participants will continue to receive DTG + RPV if located in a region 
where not commercially available.
Participants transitioning from the LATTE study on oral CAB + RPV treatment will 
transition to their elected treatment regimen, either Q2M administration of CAB LA + 
RPV LA or oral DTG + RPV single tablet regimen.  Regardless of treatment arm, the 
investigator should instruct all participants on the importance of treatment adherence.  
This study has an open-label design.  Dosing is outlined below.
Dosage and Administration
Maintenance Phase (Day 1 to End of Study+)
Q2M Arm- Transitioning from LATTE
First Injections (Loading Doses) – Day 1 and Month 2
Day 1

Receive last dose of oral CAB + RPV regimen

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 
Month 2

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 2
Month 4 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
Oral DTG + RPV Arm – Transitioning from LATTE
Day 1 to Month 12
(once daily FDC tablet taken 
with food)

Take one tablet of DTG 50 mg + RPV 25 mg once daily
+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


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1.3.
Schedule of Activities (SoA)
Time and Events Table for CAB LA + RPV LA Q2M Administration
Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Written Informed Consent 
X
Demography
X
Eligibility Verification
X
Physical Exam
X
Medical History
X
Center for Disease Control 
and Prevention (CDC)
Classification
X
Rapid Plasma Reagin (RPR)
X
Symptom Directed Physical 
Exam, injection site reaction 
(ISR) and Medical 
Assessment c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs
(blood pressure [BP], heart 
rate [HR]) d
X
X
X
X
X
X
X
X
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Weight, Height & body mass 
index (BMI)e
X
X
X
X
X
X
X
X
X
HIV Associated Conditions, 
AE and serious adverse 
event (SAE) Assessments, 
Con Meds
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-Lead electrocardiogram 
(ECG) f
X
X
X
Clinical Chemistry and 
Hematology
X
X
X
X
X
X
X
X
X
Pregnancy Testing 
(U)rine or (S)erum g
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
HIV-1 RNA and sample for 
storage h
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
X
X
X
Urinalysis
X
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Fasting Glucose, 
Cholesterol (Total, high 
density lipoprotein [HDL]
and low density lipoprotein
[LDL]) and Triglycerides i
X
X
X
X
Prothrombin time (PT)/
partial thromboplastin time
(PTT)/international 
normalized ratio (INR)
X
X
PK Diary 
(D)ispensation and (R)eview
R
PK Sample 
(S)torage j
S
S
S
LA Study Intervention
Administration k
X 
X 
X
X
X
X
X
X
X
X
X
X
X
X
HIVTSQc
X
X
HIVTSQs
X
X
X
X
HIVDQoL
X
X
X
X
Preference
X
Reason for Switch
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Participant Visit Reminder 
Contact
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Participant Contact Detail 
Confirmation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
See footnote “b” for continuation of visit schedule after Month 26.  Continue until either locally approved and commercially available, the participant no longer derives clinical benefit or meets a 
protocol-defined reason for discontinuation or until development is terminated.
a.
The Day 1 visit will take place during Week 312 (or Week 324 in the event of unavoidable delays) of the LATTE study, the participant’s last week on study.  LATTE participants eligible for 
POLAR study dosing will take final dose of CAB 30 mg + RPV 25 mg in the clinic within 2 hours of the Q2M IM regimen.  For IM dosing administration loading doses are required. (Day 
1=1st loading dose; Month 2=2nd loading dose)
b.
Continue this pattern for visits for the remainder of the study.  For example, Month 28 will be conducted just like Month 20, Month 30 will be conducted just like Month 22 and so on.
c.
Physical exams should be conducted as part of normal routine clinical care but data will not be collected in the electronic case report form (eCRF). Medical assessments include any 
decisions the study staff must make for participant management.
d.
Measure vital signs after about 5 minutes of rest in a semi-supine position.
e.
Height collected at Day 1 only.
f.
On Day 1, ECGs should be performed in triplicate at least 5 minutes apart and following 5 minutes of rest in a semi-supine position within 1 hour prior to first dose.  Also on Day 1, a 2-hour 
post dose ECG will be performed for all participants.  The 2-hour post dose ECG on Day 1 can also be used for the LATTE Week 312 (or Week 324, if needed) visit.  ECG evaluations at 
other visits should be obtained after dosing, preferably 2-4 hours post dosing.
g.
A (-) urine pregnancy test is required prior to any injection and as required by medical monitor after a treatment interruption. A (+) urine test should be confirmed with a stat serum test.  If 
(+), participant will need to be withdrawn.
h.
Plasma for storage samples are collected for possible future analyses, back-up in cases of loss/damage in transit and geno/pheno analyses for virologic failures.
i.
Fast overnight; however, a minimum of a 6 hour fast is acceptable.
j.
Take PK samples pre-dose.
k.
Q2M Injections are 1 x CAB LA 600 mg IM + 1 x RPV LA 900 mg IM.  If possible, injections should be spaced approximately 2 cm from one another and from the site of any previous 
injection and or any injection site reaction.  Bring RPV LA to approximately room temperature prior to injecting.   Time and location of injection (right or left) as well as needle length used 
will be collected in the eCRF.  IM dosing is expected to occur during the month in which the participant’s projected visit falls (as according to the Day 1 visit).  An additional (+ 
or -) 7 day window from date of projected visit is stipulated for IM dosing.  All decisions regarding dose interruption/ resumption must be discussed with the medical monitor 
in advance.


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l.
Or Long-Term Follow Up
m.
Follow Up Visit - Conduct ~4 weeks after the last dose of investigational product (IP) if not entering Long-Term Follow Up and only if the participant has ongoing AEs or lab abnormalities at 
the last on-study visit.  May be conducted by telephone.
Time and Events Table for DTG + RPV Administration
Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j
Notes
Written Informed Consent 
X
a.
The Day 1 visit will take place during Week 312 (or Week 324 in 
the event of unavoidable delays) of the LATTE study, the 
participant’s last week on study.  LATTE participants eligible for 
POLAR study dosing will take final dose of CAB 30 mg + RPV 25 
mg in the clinic.  See Section 6.2 for dosing administration.
b.
Physical exams should be conducted as part of normal routine 
clinical care but data will not be collected in the eCRF. Medical 
assessments include any decisions the study staff must make for 
participant management.
c.
Measure vital signs after about 5 minutes of rest in a semi-supine 
position.
d.
Height collected at Day 1 only.
e.
On Day 1, ECGs should be performed in triplicate at least 5 
minutes apart and following 5 minutes of rest in a semi-supine 
position within 1 hour prior to first dose.  Also on Day 1, a 2-hour 
post dose ECG will be performed for all participants.  The 2-hour 
post dose ECG on Day 1 can also be used for the LATTE Week 
312 (or Week 324, if needed) visit.  ECG evaluations at other 
visits should be obtained after dosing, preferably 2-4 hours post 
dosing.
f.
Plasma for storage samples are collected for possible future 
analyses, back-up in cases of loss/damage in transit and 
geno/pheno analyses for virologic failures.
g.
A (-) urine pregnancy test is required prior to any administration 
of drug and as required by medical monitor after a treatment 
interruption. A (+) urine test should be confirmed with a stat 
serum test.  If (+), participant will need to be WD.
Demography
X
Eligibility Verification
X
Physical Exam
X
Medical History
X
CDC Classification
X
RPR
X
Symptom Directed Physical Exam and 
Medical Assessment b
X
X
X
X
X
Vital Signs(BP, HR) c
X
X
X
X
X
X
Weight, Height & BMI d
X
X
X
X
X
X
HIV Associated Conditions, AE and 
SAE Assessments, Con Meds
X
X
X
X
X
X


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Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j
Notes
12-Lead ECG e
X
X
X
h.
Fast overnight; however, a minimum of a 6 hour fast is 
acceptable.
i.
DTG 50 mg + RPV 25 mg.  Administer daily with food
j.
Follow Up Visit - Conduct ~4 weeks after the last dose of IP and 
only if the participant has ongoing AEs or lab abnormalities at the 
last on-study visit.  May be conducted by telephone.
HIV-1 RNA
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
Plasma for Storage f
X
X
X
X
X
X
PK Sample for Storage
S
Clinical Chemistry and Hematology
X
X
X
X
X
X
Pregnancy Testing g
U
U
U
U
U
U
Urinalysis
X
X
Fasting:  Glucose, Cholesterol (Total, 
HDL and LDL) and Triglycerides h
X
X
PT/PTT/INR
X
X
HIVTSQc
X
X
HIVTSQs
X
X
X
X
HIVDQoL
X
X
X
X
Participant Visit Reminder Contact
X
X
X
X
X
Participant Contact Detail Confirmation
X
X
X
X
X


2018N356280_02
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Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j
Notes
Study Treatment Dispensation i
X
X
X
X
X
Time and Events Table for Long Term Follow Up
Procedures for Long-Term Follow Up
Month 1 a
Month 
3
Month 
6
Month 
9
Month 12
WD
Notes
HIV Associated Conditions, AE and SAE 
Assessments, Con Meds
X
X
X
X
X
X
Every effort should be made to enter participants into the Long-
Term Follow Up if they withdraw from or discontinue the study after 
receiving at least one dose of CAB LA and / or RPV LA.
a.
The start of the 52-week follow up period begins the day of the 
last CAB LA and/or RPV LA dose.
b.
Women of childbearing potential only.  S = Serum
c.
Fast overnight; however, a minimum of a 6 hour fast is 
acceptable.
d.
Women of childbearing potential should continue to receive 
counselling on the need to use adequate contraception for the 
entirety of the Long-Term Follow-Up Period. 
e.
Investigators must discuss choice of HAART regimen and 
timing of initiation with the medical monitor before initiating.  
This regimen may be supplied regionally by GlaxoSmithKline 
(GSK) or reimbursement will be provided.
HIV-1 RNA
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
Plasma for Storage
X
X
X
X
X
X
PK Sample for Storage
S
S
S
S
S
S
Clinical Chemistry and Hematology
X
X
X
X
X
X
Pregnancy Testing b
S
S
S
S
S
S
Urinalysis
X
X
X
Fasting:  Glucose, Cholesterol (Total, 
HDL and LDL) and Triglycerides c
X
X
PT/PTT/INR
X
X


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Procedures for Long-Term Follow Up
Month 1 a
Month 
3
Month 
6
Month 
9
Month 12
WD
Notes
Contraception Counselling d
X
X
X
X
X
X
HAART Dispensation e
X
X
X
X
X
X


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2.
INTRODUCTION
2.1.
Study Rationale
While advances in the development of new anti-retroviral therapies (ART) provide 
extensive insights into the management of human immunodeficiency virus (HIV)-
infected individuals, chronic HIV infection in adults continues to be characterized by 
increased development of resistant virus, increasing transmission of resistant virus and 
issues associated with the long-term toxicity of ART. The current paradigm in the 
treatment of HIV involves life-long therapy with multiple antiretrovirals. There is an 
enduring need to develop new agents with improved safety and resistance profiles with 
convenient dosing for both antiretroviral treatment-naive and treatment-experienced 
participants. 
This clinical trial, 209035 (Oral (PO) to Long Acting (LA) Rollover-POLAR), will 
evaluate an antiretroviral treatment approach that may be more convenient for the 
participant (see Section 4.1 for study schematic).  Participants will rollover from the 
LAI116482 (LATTE) study with demonstrated HIV-1 ribonucleic acid (RNA)
suppression while receiving a two-drug regimen consisting of once-daily oral 
cabotegravir (CAB) 30 mg + rilpivirine (RPV) 25 mg.  The participants will be offered 
the option to switch to the LA intramuscular injections of CAB LA + RPV LA every 
2 months (Q2M) or the oral fixed dose combination (FDC) of dolutegravir (DTG) + RPV
for the continued maintenance of HIV-1 RNA suppression.
Those entering this study who do not wish to receive injectable CAB LA + RPV LA are 
eligible to elect to transition to once-daily oral therapy with a single tablet regimen of 
DTG + RPV for a period of at least 12 months, or until commercial availability. The 
efficacy of DTG + RPV, or Juluca, is supported by data from 2 open label, controlled 
trials (GlaxoSmithKline Document Number 2016N287382_03 [SWORD-1] and 
GlaxoSmithKline Document Number 2016N287539_02 [SWORD-2]) in virologically 
suppressed participants switching from their current antiretroviral regimen.
The overall objective of this study is to demonstrate the antiviral activity of CAB LA + 
RPV LA every 2 months in virally-suppressed HIV-1 infected antiretroviral therapy 
ART-experienced participants.  An evaluation of the antiviral activity, tolerability,
durability and safety of the intramuscular (IM) dosing regimen will be performed.  
This study consists of a Maintenance Period and a Long-Term Follow Up Period for 
participants who withdraw and have received at least one dose of CAB LA and / or RPV
LA.
2.2.
Background
It is estimated that 36.7 million people are currently living with HIV/Acquired 
Immunodeficiency Syndrome (AIDS) and that the worldwide epidemic continues to grow 
at a rate of two million new infections and cause 1.1 million deaths per year [UNAIDS, 
2016]. Chronic HIV infection in adults continues to be characterized by increased 
development of resistant virus, increasing transmission of resistant virus and issues 


2018N356280_02
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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.
One approach is simplifying from an oral 3-drug regimen to a long-acting 2-drug 
injectable regimen. The 200056 study (GlaxoSmithKline Document Number 
2013N168152_09, Study [LATTE-2]) is an ongoing Phase 2b study designed to assess 
the induction of virologic suppression with CAB 30 mg daily + two NRTIs, followed by 
a maintenance period where participants are randomized (1:2:2) to continue on oral CAB 
30 mg + two nucleoside reverse transcriptase inhibitor (NRTIs) or switch to an IM 
injection of CAB LA + RPV LA administered every 4 weeks (Q4W) or once every 
8 weeks (Q8W).  A total of 309 participants were enrolled and treated.
During the Induction Phase, there was a rapid and sustained decline in HIV-1 RNA, with 
91% of participants (282/309) achieving HIV-1 RNA <50 c/mL through 20 weeks of 
therapy.  There was a single participant (with known compliance issues) with confirmed 
virologic failure during the Induction period.  Virologic testing revealed no treatment 
emergent phenotypic or genotypic resistance in this participant.
The primary endpoint for 200056 was the Week 32 proportion of participants with HIV-1 
RNA <50 c/mL (Snapshot, Intent-to-Treat Maintenance Exposed population [ITT-ME]). 
Following virologic suppression on three drug oral therapy in the Induction Phase, 
286 participants qualified to enter randomization at the Day 1 visit, and were 
subsequently randomized 2:2:1 onto once Q4W IM injections with CAB LA + RPV LA 
Q4W, Q8W IM injections with CAB LA + RPV LA or continuation of oral CAB +
NRTIs, respectively.  Through 32 weeks of two-drug maintenance therapy, 95% (Q8W) 
and 94% (Q4W) of participants on injectable dosing were virologic successes, compared 
to 91% of participants continuing three drug oral CAB + NRTIs, meeting pre-specified 
criteria for comparability between the dosing arms.
At Week 96, 94% (Q8W IM) and 87% (Q4W) of participants receiving injectable dosing 
maintained virologic suppression (HIV-1 RNA <50 c/mL) compared to 84% of 
participants receiving oral CAB plus ABC/ lamivudine (3TC).  Of the participants 
receiving Q8W IM dosing, 4% failed snapshot for virologic reasons (n=2, HIV-1 
RNA >50 c/mL; n=1, lack of efficacy; n=2, withdrawal for other reasons with HIV-1 
RNA >50 c/mL).  No participants on Q4W IM dosing failed snapshot due to virologic 
reasons.  There were 2 protocol-defined virologic failure (PDVFs) on Q8W dosing, and 
1 PDVF on the oral dosing arm, with evolution of resistance (treatment-emergent reverse 
transcriptase mutations K103N, E138G, and K238T; integrase mutation Q148R).  A good 
response was observed across all arms with no significant differences between arms with 
regard to increases in mean Cluster of Differentiation 4 (CD4+) cell count from Baseline.  
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 adverse events 
(AEs), including injection site reaction (ISR) related AEs in either dosing arm, with no 
significant dose-dependent trends in safety parameters.  Through Week 96, the proportion 
of AEs leading to withdrawal during the study Maintenance Period was low across all 


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arms (Q8W IM: n=2, 2%; Q4W IM: n=8, 7%; Oral CAB; n=1, 2%), with only one 
additional AE leading to withdrawal since the Week 48 analysis.  
Long-acting two class therapy consisting of CAB LA + RPV LA as an IM regimen has 
the benefit of being a NRTI-sparing regimen for long-term treatment of HIV infection 
which will avoid known NRTI-associated adverse drug reactions and long-term 
toxicities.  Additionally, a two-drug combination therapy with CAB LA plus RPV LA 
may offer a better tolerability and resistance profile, as well as improved adherence and 
treatment satisfaction in virologically suppressed participants improving the quality of 
life for participants with living with HIV.  Two Phase 3 studies FLAIR and ATLAS are 
currently ongoing.
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 (2017 CAB IB:  
GlaxoSmithKline Document Number RH2009/00003/07; RPV IB, 2017).
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 is in clinical development and 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 investigator’s 
brochure (IB).


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Drug Induced Liver Injury 
(DILI)
A small proportion of participants in the CAB program to date (total exposure 
approximately 2376 to 17 Dec 2017) have developed transaminitis (elevated 
liver transaminases characterised by predominant alanine aminotransferase 
(ALT) elevation).  In most participants, transient transaminitis was explained by 
acute hepatitis C infection (majority) and other systemic infections.  In a small 
number of participants, there was not an alternative explanation, suggesting a 
mild form of drug induced liver injury (DILI) without hepatic dysfunction, which 
resolved upon withdrawal of treatment with CAB. 
All four participants with suspected DILI identified in Phase 2 HIV treatment 
studies, were receiving oral CAB. 

Exclusion criteria as described in Section 5.2 will prohibit 
participants with significant liver impairment based on 
screening liver chemistry including transaminases (ALT 
and Aspartate aminotransferase [AST]) as well on prior 
medical history.  Participants with a history of chronic liver 
disease with ongoing inflammation and/or fibrosis will 
have additional confirmatory assessments to confirm 
suitability for entry into the study. 

Liver transaminases (ALT and AST) will be monitored 
throughout this study (refer to Time & Events Table) and 
the liver chemistry stopping criteria will be adopted as 
described in Section 7.1.1.1 of this protocol. Participants 
will be withdrawn from CAB treatment where no
compelling alternative cause is identified and DILI is 
suspected.

Participants who develop ALT ≥5 times the upper limit of 
normal (ULN) while on study must consult with Medical 
Monitor prior to initiation or continuation of CAB LA + RPV 
LA.  
Injection Site Reactions 
(ISRs)
Clinical, experience to date has demonstrated ISRs occur in the majority of 
exposed participants treated with CAB LA but are generally mild (Grade 1) or 
moderate (Grade 2) and include events of pain, tenderness, erythema, or 
nodule formation of several days duration (median duration for individual events 
<1 week).
ISRs may occur more than once in an individual participant receiving multiple 
injections.  Although some Grade 3 ISRs were reported, overall ISRs have been 
well tolerated and have not to date been associated with an excess of 

Administration advice will be given to minimize risk of 
poor administration technique giving rise to injection site 
reactions.  Advice on care, monitoring, natural course, 
and 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.


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participants’ withdrawal. 
None of the ISRs reported to date have been serious.  

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 

Significant ISRs may be photographed and referred to a 
dermatologist for specialist advice.
Hypersensitivity Reactions 
(HSR)
Hypersensitivity reactions have been reported as uncommon occurrences with 
integrase inhibitors (INI), 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 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.

The risk of developing a hypersensitivity reaction post 
administration of IM CAB is minimized since the 
participants in this study have been administered oral 
CAB 30 mg + oral RPV 25 mg within the LATTE study for 
at least 192 weeks. 

Clinical assessments, laboratory tests (including liver 
transaminases) and vital signs will be performed 
throughout this study (refer to Time & Events Table, 
Section 8.1). Results from these assessments may aid 
early detection of HSR. 

Participants receiving the injection would not receive 
further injections.  During oral (oral bridge) and IM CAB 


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treatment, any HSR reactions that occur would be 
managed supportively.
Effects in late stage 
pregnancy seen in non-
clinical studies
Non-clinical data from rat pre- and postnatal (PPN) studies have indicated 
reduced survival and viability rates amongst rat pups during the first 4 days of 
life at the maximum tested dose of 1000 mg/kg/day (maternal exposure).  no-
observed-adverse-effect-level (NOAEL) was
established at the mid dose 5 mg/kg/day, the maternal exposure at this dose 
calculated using systemic exposure from non-pregnant rats is >20 fold predicted 
maximum concentration (Cmax) and area under curve (AUC) exposures for 
anticipated clinical CAB LA exposures for HIV treatment
The clinical significance in humans of these findings is unknown.

As a routine precaution, pregnant women are excluded 
from participation in this study at this time and females of 
reproductive potential (FRP) 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.

FRP are also required to undergo regular pregnancy 
testing throughout study conduct to enable early 
discontinuation of CAB LA once pregnancy is identified.
Development of 
Resistance following 
discontinuation of CAB LA
Residual concentrations of CAB would remain in the systemic circulation of 
participants who stop CAB LA treatment for prolonged periods (more than 1 
year, in some participants, GlaxoSmithKline Document Number 
2016N269422_00) after last injection (e.g., for tolerability issues or treatment 
failure).  Participants discontinuing CAB LA regimen may be at risk for 
developing HIV-1 resistance to CAB many weeks after discontinuing injectable 
therapy. 

After participants stop CAB LA, Oral highly active 
antiretroviral therapy (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 minimum of 52 weeks 
from the time of the last IM CAB injection.


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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 UDP-glucuronosyltransferase (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 drug-drug 
interactions (DDIs) many weeks after discontinuing injectable therapy.  

All participants will be informed of prohibited medications 
throughout the study and updates provided as needed via 
the informed consent.
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.  


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
Laboratory samples for safety parameters and HIV-1 RNA 
will be closely monitored in all participants.  Additionally, 
2 hour post dose PK samples will be obtained at a few 
early timepoints for determination of CAB concentration 
and possible pharmacokinetic correlation with safety 
parameters such as ECG changes and virologic 
response.  Additionally, an unscheduled PK sample may 
be drawn approximately 2 hours post dosing for future 
evaluation of CAB concentrations.
ORAL RPV
For safety and risk mitigation for oral RPV refer to the RPV local prescribing information [Edurant Prescribing Information, 2018].  
RPV LA
Information about the clinical experience to date and possible risks associated with treatment using RPV LA can be found in the Summary 
of Data and Guidance for the Investigator section of the IB.  Beyond what has already been identified with oral RPV, no new systemic 
adverse reactions to RPV LA (same active moiety) have been observed.  The following risks are considered to be of specific clinical 
relevance in the context of IM use.


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Injection Site Reactions
Clinical, experience to date has demonstrated ISRs occur in the majority of 
exposed participants treated with RPV LA but are generally mild (Grade 1) or 
moderate (Grade 2) and include events of pain, tenderness, erythema, or 
nodule formation of several days duration (median duration for individual 
events <1 week).  ISRs may occur more than once in an individual participant
receiving multiple injections.  Although some Grade 3 ISRs were reported, 
overall ISRs have been well tolerated and have not to date been associated 
with an excess of participants’ withdrawal due to ISRs.
None of the ISRs was serious and no clinical significant complications were 
reported

Administration advice to minimize risk of poor 
administration technique giving rise to injection site 
reactions.  Advice on care, monitoring, natural course, and 
treatment of ISRs given in study documentation 

Advice to participants on care of injection site on day/days 
immediately post administration, use of analgesia, 
compresses where appropriate.

Participants will be closely monitored for ISRs particularly 
for signs of pain, tenderness, infections, erythema, 
swelling, 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 

Significant ISRs may be photographed and referred to a 
dermatologist for specialist advice.
Rash
Some observations of rash with oral RPV have been reported in clinical 
studies executed to date (the majority are Grade 1 or 2). 
Severe skin and hypersensitivity reactions have been reported during the 
postmarketing experience, including cases of Drug Reaction with Eosinophilia 
and Systemic Symptoms (DRESS), with oral RPV containing regimens.  While 
some skin reactions were accompanied by constitutional symptoms such as 
fever, other skin reactions were associated with organ dysfunctions, including 
elevations in hepatic serum biochemistries.

Participants with a Grade 1 or 2 rash will be allowed to 
continue treatment or to be rechallenged, depending on 
the clinical judgment of the investigator.

All participants experiencing a Grade 3 or 4 rash should 
discontinue their antiretroviral (ARV) medication (study 
medication and background regimen) 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 


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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 
8.7.12 for additional guidance on management of rash 
events.
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, rifabutin

All participants will be informed of prohibited medications 
throughout the study and updates provided as needed via 
informed consent.


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-
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 discontinuing injectable therapy.  


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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
intravenous [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, 2-
hour post dose PK samples will be obtained at a few early 
timepoints for determination of RPV concentration and 
possible pharmacokinetic correlation with safety 
parameters such as ECG changes and virologic response. 
Additionally, an unscheduled PK sample may be drawn 
approximately 2 hours post dosing for future evaluation of 
RPV concentrations.
Overall 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
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 and 200056, however the efficacy of Q8W v Q4W dosing remains 

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 


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under evaluation.   
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 could lead to virologic failure and possibly the 
development of viral resistance.  
HAART regimen.

Plasma samples will be collected throughout the 
Maintenance Phase for determination of CAB and RPV 
concentration and possible pharmacokinetic correlation 
with virologic response.  
DTG + RPV
For safety and risk mitigation for DTG +RPV, you may also refer to the Juluca prescribing information [Juluca Prescribing Information, 
2017].
Potential Risk of 
Clinical Significance
Data/Rationale for Risk
Mitigation Strategy a
Commercial Juluca [DTG and RPV]
Refer to IBs for additional information
DTG: Hypersensitivity 
reaction (HSR) and rash
RPV: Rash 
DTG: HSR has been observed uncommonly with DTG.  Rash was commonly 
reported in DTG Phase IIb/III clinical trials; episodes were generally mild to 
moderate in intensity; no episodes of severe rash, such as Stevens-Johnson 
Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and erythema multiforme 
were reported. 
RPV: Rash is a recognized risk for the non-nucleoside reverse transcriptase 
inhibitors (NNRTI) class; however, the severe rashes defined above that are 
labeled for efavirenz (EFV) and nevirapine (NVP) were not seen with RPV in 
Specific/detailed toxicity management guidance is provided for HSR 
(Section 8.7.11) and rash (Section 8.7.12).
The subject informed consent form includes information on this risk 
and the actions subjects should take in the event of: 1) a HSR or 
associated signs and symptoms; or 2) developing any type of rash 
or skin abnormality. For Grade 3/4 rash, except where the etiology 
is clear and not associated with study drug or where there is a 
definitive diagnosis clearly attributable to a concomitant medication 


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Commercial Juluca [DTG and RPV]
Refer to IBs for additional information
clinical trials.  In Phase III clinical trials, skin events of interest were reported at 
a lower incidence and grades, and resulted in fewer subject withdrawals, in the 
RPV group than in the EFV group and were mostly driven by the individual 
preferred term Rash. 
(and not to study drug) or to a concomitant infection, subjects must 
permanently discontinue study drug and be withdrawn from the 
study.
DTG & RPV: Drug induced 
liver injury (DILI) and other 
clinically significant liver 
chemistry elevations
DTG: Non-clinical data suggested a possible, albeit low, risk for hepatobiliary 
toxicity with DTG.  Drug-related hepatitis is considered an uncommon risk for 
ART containing DTG regardless of dose or treatment population.  For subjects 
with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, 
improvements in immunosuppression as a result of HIV virologic and 
immunologic responses to DTG- containing ART, along with inadequate 
therapy for HBV co-infected subjects, likely contributed to significant 
elevations in liver chemistries.  
RPV: Hepatic events have been reported in patients receiving a RPV 
containing regimen.  Patients with underlying HBV or HCV, or marked 
elevations in transaminases prior to treatment may be at increased risk for 
worsening or development of transaminase elevations with use of RPV. A few 
cases of hepatic toxicity have been reported in patients receiving a RPV 
containing regimen who had no pre-existing hepatic disease or other 
identifiable risk factors.
Specific/detailed liver stopping criteria and toxicity management 
guidance is provided for suspected DILI or other clinically significant 
liver chemistry elevations (Section 7.1.1).  
DTG & RPV: Psychiatric 
disorders
DTG: Psychiatric disorders including suicidal ideation and behaviors are 
common in HIV-infected patients. The psychiatric profile for DTG (including 
suicidality, depression, bipolar and hypomania, anxiety and abnormal dreams) 
was similar to RAL- or favorable compared with EFV- based regimens. 
The reporting rate for insomnia was statistically higher for blinded DTG+ 
abacavir/lamivudine (ABC/3TC) compared to efavirenz/tenofovir disoproxil 
fumarate/emtricitabine (EFV/TDF/FTC) in ING114467; however, this was not 
duplicated in any other Phase IIb/III study conducted with DTG.  
RPV: In Phase 3 clinical trials the incidence and grading of depressive 
disorders (regardless of causality), and the incidence of episodes resulting in 
subject withdrawal, were comparable between the RPV and EFV treatment 
Subjects who in the investigator’s judgment, pose a significant 
suicidality risk, are excluded from participating (Section 5.2).
Because of the elevated risk in the HIV- infected population, 
treatment emergent assessment of suicidality will be monitored 
during this study through the end of the study participation.  
Investigators are advised to consider mental health consultation or 
referral for subjects who experience signs of suicidal ideation or 
behavior (Section 8.4.6).


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Commercial Juluca [DTG and RPV]
Refer to IBs for additional information
groups.  Most depressive disorder events in either treatment group were of 
Grade 1 or 2 intensity. Suicidal ideation was reported in 4 subjects in each arm 
while suicide attempt was reported in 2 subjects in the RPV arm.
DTG & RPV: Increased rates 
of virologic failure/ Observed 
Resistance
Virologically suppressed subjects switching from oral CAB + RPV to DTG + 
RPV may experience virologic failure/breakthrough and development of 
resistance.
DTG: Week 96 and Week 144 analyses for the Phase III/IIIb clinical studies 
supported the efficacy findings from earlier analyses, and demonstrated robust 
maintenance of viral suppression with no finding of HIV-1 resistance in 
treatment-naïve subjects.
RPV: In Phase III clinical trials (pooled Week 96 analyses), 3.2% of patients in 
the RPV arm experienced virologic failure between Week 48 and Week 96 
(2.3 % on EFV).
Subjects will have HIV-1 RNA measured at each study visit. 
Management of subjects experiencing increase in viral load is 
described in Section 7.1.5.  
DTG: Theoretical serious 
drug interaction with 
dofetilide and pilsicainide
Co-administration of DTG may increase dofetilide/pilsicainide plasma 
concentration via inhibition of organic cation transporter (OCT-2), resulting in 
potentially life-threatening toxicity. 
The co-administration of DTG with dofetilide or pilsicainide is 
prohibited in the study (Section 6.11.2.4).
DTG: Renal function
Mild elevations of creatinine have been observed with DTG which are related 
to a likely benign effect on creatinine secretion with blockade of OCT-2.  DTG 
has been shown to have no significant effect on glomerular filtration rate 
(GFR) or effective renal plasma flow.
Specific/detailed toxicity management guidance is provided for 
subjects who develop a decline in renal function (Section 8.7.7). 
DTG: Creatine 
Phosphokinase (CPK) 
elevations
Asymptomatic CPK elevations mainly in association with exercise have been 
reported with DTG therapy.
Specific detailed toxicity management guidance is provided for 
subjects who develop Grade 3 to 4 CPK elevations (Section 8.7.5).


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Commercial Juluca [DTG and RPV]
Refer to IBs for additional information
RPV: Corrected QT interval 
(QTc) prolongation
In healthy subjects, supratherapeutic doses of RPV (75 mg once daily and 
300 mg once daily) have been shown to prolong the QTc interval of the 
electrocardiogram (ECG). RPV at the recommended dose of 25 mg 
administered once daily is not associated with a clinically relevant effect on 
QTc.
Subjects who use medications which are associated with Torsades 
de Pointes are excluded.
Day 1 ECG to identify those with pre-existing prolonged QT interval.
Per sentinel event management, study drug will be discontinued 
when a prolonged QT is identified.
RPV: Fat Redistribution
Redistribution/accumulation of body fat, including central obesity, 
dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial 
wasting, breast enlargement, and “cushingoid appearance” have been 
observed in patients receiving ART. The mechanism and long-term 
consequences of these events are currently unknown. A causal relationship 
has not been established.
Routine monitoring of adverse reactions will be performed.
a.
Careful monitoring of events will be conducted using serious adverse event (SAE) reports and alerts for Grade 3/4 laboratory toxicities (per Division of Acquired Immune 
Deficiency Syndrome [DAIDS] toxicity gradings for HIV-infected patients). Serious/severe events will be managed appropriately including, but not limited to, withdrawal of study 
drug, and will be followed to resolution as per Sponsor’s standard medical monitoring practices.  
Clinical Safety Data will be routinely reviewed in GlaxoSmithKline (GSK) Safety Review Team meetings. This will include in-stream review of data from this clinical trial on a 
routine basis, review of aggregate data on a protocol and program basis when available, and review of competitor data from the literature.


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2.3.1.1.
Other Clinically Relevant Information
Additional details concerning safety observations from clinical studies and for which a 
causal association has not been established or which are of minimal clinical significance 
may be found in the Investigator’s Brochures (GlaxoSmithKline Document Number 
RH2009/00003/07 [CAB IB, 2017], RPV IB, 2017, GlaxoSmithKline Document Number 
RM2007/00683/11 [DTG IB, 2017]).  
Adverse Events of Special Interest:
Seizure
Four cases of seizures have occurred in the cabotegravir programme cumulatively 
through 04 May 2018 (update Date). Two of the cases occurred in HIV uninfected 
subjects with a prior history of seizure, of which one had CAB drug levels below the 
level of quantification 6 months prior to the event and one case involved a subject in 
study 200056 with circumstantial and anecdotal evidence of illicit drug use. Another case 
occurred in FLAIR in the context of influenza A meningoencephalitis. Overall, there is 
not convincing evidence that cabotegravir exposure may be causally associated with 
seizure or with reduction of seizure threshold, due to the low frequency of reports, the 
confounders present in the cases received to date and lack of any pre-clinical signal or 
identified plausible mechanism. However, seizure and seizure-like events are considered 
as AEs of special interest for close monitoring in studies. Subjects with an unstable or 
poorly controlled seizure disorder will be excluded from study participation.


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2.3.2.
Benefit Assessment
The antiviral activity against HIV-1 of CAB has been well established through Phase 2a 
and Phase 2b studies. RPV is an established antiviral agent against HIV-1 in treatment 
naive participants, with long term durability (>96 weeks in Phase 3 and >240 weeks in 
Phase IIb).
Participants receiving CAB LA + RPV LA are anticipated to benefit from maintenance of 
virological suppression using LA agents. Participants who 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 this two-drug regimen, as IM agents, has been demonstrated 
through Week 96 of the ongoing 200056 study. This regimen may continue to offer long 
term safety and tolerability benefits in these participants.
Participants who will receive PO DTG and RPV are anticipated to benefit from the fact 
that both are conveniently dosed as a single tablet once daily, without need for a 
pharmacokinetic (PK) booster, and with limited safety implications resulting from 
theoretical or actual drug:drug interactions compared to other ART agents (including 
efavirenz (EFV) and those requiring a PK booster).  In addition, the high barrier to 
resistance observed with DTG should help protect against the development of resistance 
to both components of the DTG + RPV regimen.  Juluca was recently approved as single 
dose maintenance.  Individually, DTG and RPV in combination with other ARVs have 
demonstrated durable virologic and immunologic response.
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 the CAB LA and RPV LA 
Q2M and DTG + RPV regimens and the study as a whole are justified by the anticipated 
benefits that may be afforded to virologically suppressed, treatment-experienced 
participants with HIV-1 infection.
3.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To demonstrate the antiviral activity of 
CAB LA + RPV LA every 2 months in 
suppressed HIV-1 infected antiretroviral 
therapy ART-experienced participants
Proportion of participants with HIV-RNA 
50 c/mL as per food and drug 
administration (FDA) Snapshot algorithm 
at Month 12
Secondary
To demonstrate the antiviral and 
immunologic activity of CAB LA + RPV 
LA every 2 months and oral DTG +RPV 
Proportion of participants with plasma 
HIV-1 RNA <50 c/mL (c/mL) at Month 12


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Objectives
Endpoints
once daily
using the FDA Snapshot algorithm 
Proportion of participants with protocol-
defined confirmed virologic failure (CVF) 
over time
Proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL as per 
FDA Snapshot algorithm over time
Absolute values and changes from Baseline 
in viral load and CD4+ cell counts over 
time 
To demonstrate the safety and tolerability 
of CAB LA + RPV LA every 2 months and 
oral DTG + RPV once daily
Incidence and severity of AEs and 
laboratory abnormalities over time 
Proportion of participants who discontinue
treatment due to AEs over time
Change from Baseline in laboratory 
parameters over time 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure 
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV, 
and DTG + RPV
To characterize CAB and RPV 
concentrations and population 
pharmacokinetics and identify important 
determinants of variability
Plasma PK parameters for CAB LA and 
RPV LA (when evaluable, trough 
concentrations [Ctrough])
To assess participant reported health-
related quality of life, injection 
tolerability/acceptability, and treatment 
satisfaction.
Change from Baseline (Day 1) in 
HIVDQoL at Months 6 and 12 (or 
Withdrawal)
Change from baseline (Day 1) in total 
“treatment satisfaction” score, and 
individual item scores of the HIV 
Treatment Satisfaction Status 
Questionnaire (HIVTSQs) at Months 6 and 
12 (or Withdrawal)
Change in treatment satisfaction over time 
using the HIV Treatment Satisfaction 
Change Questionnaire HIVTSQc at Month 


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Objectives
Endpoints
12 (or Withdrawal).
Exploratory
Explore the concept of a digital assistance 
program and the effect on participant
participation and adherence to timeliness of
injections given every 2 months
The number of participants who utilize the 
program
Adherence to scheduled date of injection
To assess reason for switching using a 
single question. 
To assess preference using a single 
question
The ‘Preference” question will be used to 
assess preference for CAB LA + RPV LA 
every 2 months compared to prior oral 
CAB + RPV regimen, at Month 12 using a 
single dichotomous preference question.
The “Reason for Switch” question will be 
administered at Day 1 (Baseline) to assess 
the reasons for willingness to switch to LA 
injectable ART.
4.
STUDY DESIGN
4.1.
Overall Design
Study 209035 (POLAR) is a Phase IIb, open-label, multicenter rollover study designed to 
assess the antiviral activity and safety of CAB LA + RPV LA administered every 2 
months in approximately 100 adult HIV-1 infected participants from the LATTE study.
Participants who fulfill eligibility requirements will be entered into the study to receive 
CAB LA + RPV LA Q2M or the oral DTG + RPV regimen for at least 12 months, until 
commercially available.
Participants currently receiving oral CAB + RPV within LATTE will enter POLAR at 
Day 1 and choose to either transition to Q2M administration of injectable CAB LA + 
RPV LA or take oral DTG + RPV daily for 12 months.  Eligible participants include 
those originally randomized to oral CAB + RPV in the Maintenance phase and 
transitioned to the Extension Phase of LATTE.  The first injection visit for POLAR can 
be performed once the most recent central lab results from LATTE are available and 
safety parameters have been reviewed, and the LATTE Week 312 visit (close-out visit) 
has been completed (or Week 324 in the event of unavoidable delays).  Participants will 
continue to receive oral CAB + RPV as scheduled within the LATTE trial until their 
eligibility for POLAR can be fully evaluated and the participant has chosen the new 
regimen.  If determined to be ineligible for POLAR or participant elects to not participate 
in the study those participants will be withdrawn from the LATTE study.


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Participants in POLAR who successfully complete Week 300 in the LATTE study 
(without meeting study defined withdrawal criteria) will be given the option to receive 
either CAB LA + RPV LA (administered Q2M) or oral DTG + RPV daily until study 
intervention is either locally approved and commercially available within the local sector 
(including through local public/government health sectors), the participant no longer 
derives clinical benefit, the participant meets a protocol-defined reason for 
discontinuation or until development of either CAB LA + RPV LA Q2M is terminated.  
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 will enter a 52-week LTFU 
Phase.  Those participants must remain on suppressive HAART for at least 52 weeks 
after the last dose of CAB LA and/or RPV LA.
The primary endpoint for the study is the proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL at Month 12 as per Food and Drug Administration 
(FDA) Snapshot algorithm using the Intent-to-Treat Exposed (ITT-E) population.  
4.1.1.
Evaluable Participants
The target population to be enrolled is HIV-1 infected virologically suppressed (HIV-1 
RNA <50 c/mL) participants on stable ART who have completed, at minimum, Week 
312 (or Week 324 in the event of unavoidable delays) of the LATTE study.  It is 
anticipated that approximately 100 participants will be enrolled into POLAR (see Section 
10.2).
4.1.2.
Study Schematic
Figure 1
209035 (POLAR) Study Design Schematic
§ All participants in LATTE administered oral CAB 30 mg + RPV 25 mg
† Access commercially once Q8W is approved
# Access longer term via commercial route.  Participants will continue to receive DTG + RPV if located in a region 
where not commercially available.


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4.2.
Treatment Groups and Duration
4.2.1.
Eligibility for the POLAR Study for Participants Entering from the 
LATTE Study
Informed consent must be obtained prior to any study procedures, including any Day 1
assessment.
All participants with an undetectable HIV-1 RNA (<50 c/mL) at Week 300 in the LATTE 
study are eligible to enter this study. A single repeat to determine eligibility may be 
allowed ONLY after consultation with the medical monitor.  Participants with HIV-1 
RNA 200 c/mL at Week 300 are not eligible to enter the study and will not be allowed a 
repeat to determine eligibility.  The Day 1 visit of the POLAR study will be performed in 
parallel with the final closeout visit for the LATTE study, Week 312 or (if contracts have 
not been finalized and/or institutional review board (IRB) approval has not been obtained 
by Week 312 in the LATTE study) Week 324.
Result of HIV-1 RNA at Week 300
Action
<50 c/mL
Begin POLAR study at Day 1 
50 c/mL but <200 c/mL
Single repeat allowed only after consultation 
and approval from medical monitor
Single repeat <50 c/mL
Begin POLAR study at Day 1
Single repeat 50 c/mL
Cannot begin POLAR and must be withdrawn 
from the LATTE study; Complete withdrawal 
visit.  
200 c/mL
Cannot begin POLAR and must be withdrawn 
from LATTE; Complete withdrawal visit.
Should a participant be allowed a repeat, results of this repeat must be available prior to 
Day 1 of this study, therefore the time needed for scheduling the Day 1 visit, lab draws 
and lab analysis should be considered.  
In addition to the viral load criteria above, if in the opinion of the Investigator, a 
participant experiences a significant safety event while taking either CAB or RPV, study
eligibility will be determined ONLY in consultation with the medical monitor.  
Participants ineligible for this study will be withdrawn from LATTE.  
4.2.2.
Maintenance Phase (Day 1 up to Commercial Approval)
At the Day 1 visit (the start of the first month of the study), participants will return to the 
clinic, take the last dose of their oral (CAB 30 mg + RPV 25 mg), and receive the first 


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CAB LA (600 mg) + RPV LA (900 mg) injections (within 2 hours of the final oral dose 
of CAB + RPV).  The second loading injections will be administered 1 month (Month 2 
visit, start of the second month of the study) after initial loading dose (CAB LA 600 mg + 
RPV LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) 
occurring every 2 months thereafter.  The dosing window for the second injection will be 
-7 days from the projected dosing visit.
After Month 2, a dosing window (7 days) for injections is stipulated.  Doses outside of 
the window may be allowed with Medical Monitor approval.
Participants will continue CAB LA + RPV LA until:

study intervention is locally approved and commercially available, 

the participant no longer derives clinical benefit, 

the participant meets a protocol-defined reason for discontinuation  

the development of either CAB LA or RPV LA is terminated.
Safety and efficacy assessments will be conducted as per the Time and Events schedule 
(Section 8.1 for more information).  Dosing will occur according to the selected regimen. 
If the IM dosing regimen (Q2M) is discontinued as a result of an independent data 
monitoring committee (IDMC) from another study evaluating the same regimen, review
any subsequent analysis, or any other programmatic analysis, those participants who have 
not met any clinical management criteria for discontinuation will be discontinued
permanently from the study and will enter into the long-term follow-up (LTFU) Phase of 
the study.
4.2.2.1.
Participants electing to receive oral DTG + RPV once daily
The DTG + RPV oral regimen will be administered in an open-label fashion starting on 
Day 1 until Month 12.  Participants will continue study intervention until:

study intervention is locally approved and commercially available, 

the participant no longer derives clinical benefit, 

the participant meets a protocol-defined reason for discontinuation  
Safety and efficacy assessments will be conducted as per the Time and Events schedule 
(Section 8.1 for more information).  Dosing will occur according to the selected regimen.
4.2.3.
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 after the last Q2M injection, however if 
withdrawn due to virologic failure, HAART should be initiated as soon as virologic 


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failure is confirmed.  Discuss with medical monitor.  The LTFU will begin the day of 
the last CAB LA and/or RPV LA dose and continue for 52 weeks.  These participants 
will not complete a Withdrawal visit, but will instead move directly into the LTFU 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. 
Participants will be assessed with clinic visits at months 1, 3, 6, 9, and 12 during the 
LTFU Phase.  Female participants of child bearing potential must continue to use 
adequate 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, end of study timings, etc.
This phase is considered study participation and participants will be followed on study 
during this time.  A withdrawal visit is not required for participants who do not complete 
the LTFU Phase.  The participants’ last on study visit will be considered as their 
withdrawal visit.
4.3.
Scientific Rationale for Study Design
The design of this study (open-label, multicenter rollover study) will allow for the 
collection of longer term efficacy, safety and tolerability data for the CAB LA + RPV LA 
Q2M regimen. This study will also allow participants in the LATTE study who are on the 
oral CAB 30 mg + RPV 25 mg regimen, which will not be submitted to the regulatory 
agencies as a maintenance regimen for the treatment of HIV-1 infection, to be placed on a 
regimen currently being studied for those purposes (CAB LA +RPV LA).  Those 
participants who want to remain on oral 2 drug therapy will be administered the 
regulatory-approved regimen of oral DTG + RPV for at least a year, until commercial 
approval of said regimen is met.  The primary endpoint, proportion of participants 
defined as virologic failures by the FDA Snapshot algorithm is recommended in the 
FDA’s 2015 guidance document (FDA, 2015) for assessing efficacy in Switch Trials.  
The key secondary endpoints, proportion with plasma HIV-1 RNA <50 c/mL at Month 
12, is also a well-established surrogate endpoint for prognosis of HIV-1 infection and 
disease progression. 
Various approaches to simplify a participant's 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 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. 


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The 200056 (LATTE-2) (GlaxoSmithKline Document Number 2013N168152_05) 
clinical trial evaluated a different simplification approach and served as proof of concept 
for POLAR.  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.  The CAB LA + 
RPV LA Q8W regimen is currently under evaluation in the ongoing Phase IIIb ATLAS-
2M study.
Participants electing to receive CAB LA + RPV LA Q2M IM administration will be 
required to participate in clinic visits approximately every 2 months while participants 
electing to receive oral DTG + RPV administration will be required to participate in 
clinic visits approximately every 3 months.  Importantly, secondary objectives of this 
study are to understand the acceptability, tolerability, and patient reported preferences to 
the novel injectable regimen.  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. If the Q2M arm were required to receive blinded 
placebo tablets every day, the value of comparing safety, tolerability, and convenience of 
Q2M compared to oral administrations would be limited and include overly burdensome 
visit requirements for those randomized to Q2M administration.  Additionally, the 
perceived value for participants to transition from the LATTE study to POLAR to receive 
the Q2M regimen would also be limited and may result in loss of patients with prior oral 
2 drug regimen experience, thereby limiting the ability to compare and evaluate the 
experience gained after 6 years of treatment on an oral 2 drug regimen plus Q2M regimen
administration within individual participants.  
Due to the complexities, lack of feasibility and limitations of blinding CAB LA and RPV 
LA injections for Q2M compared to oral DTG + RPV administration, this Phase 2b study 
is planned as open label.  
To maintain the integrity of the trial, data aggregated by actual treatment group will not 
be made available to members of the Study Team nor Investigators in advance of the 
primary analysis.  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.


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4.4.
Justification for Dose
4.4.1.
Long Acting Injectable for Maintenance Phase
LATTE demonstrated that a 2-drug, 2-class regimen could safely maintain virologic 
suppression with oral CAB and RPV, which informed CAB LA and RPV LA dose 
selection for the Phase 2b study 200056 (LATTE-2).  LATTE-2 is currently ongoing with 
two dosing regimens of CAB LA + RPV LA given Q4W or Q8W. Following a 20-week 
Induction Phase (16 weeks of oral CAB + 2 NRTIs, 4 weeks of CAB + 2 NRTIs + oral 
RPV), participants who were eligible to continue into the Maintenance Phase were then 
randomized (2:2:1) to receive IM injections of CAB LA Q4W (800 mg Day 1 then 
400 mg Q4W)) or Q8W (800 mg Day 1, 600 mg Week 4, 600 mg Week 8, then 600 mg 
Q8W) in combination with IM RPV LA Q4W (600 mg Day 1 then 600 mg Q4W) or 
Q8W (900 mg Day 1, 900 mg Week 8, then 900 mg Q8W), respectively, or to continue 
on their triple ART regimen.
The Q4W dosing strategy was selected for further investigation in Phase 3 based on 
observed viral suppression, safety, and tolerability at Week 48.  Both Q4W and Q8W 
regimens were continued throughout the Maintenance Phase of LATTE-2 as planned, and 
Week 96 results (Table 1) were supportive of further evaluation of the Q2M regimen in 
the present study.  Moreover, LATTE-2 was amended to permit participants to remain on 
their randomized LA regimen (either Q4W or Q8W) during the Extension Phase (post 
Week 96), and those participants randomized to the oral comparator arm were allowed 
transition to either LA regimen at Week 96.  Forty-four participants were transitioned 
from the oral comparator arm to LA treatments in the Extension Phase; 34 (77%) opted 
for the Q8W regimen and 10 (23%) for the Q4W regimen.  Initial LA injections for these 
subjects were administered at Week 100.
Table 1
Summary of Study Outcomes (<50 copies/mL) at Weeks 48 and 96 –
Snapshot (MSDF) Analysis (ITT-ME Population) in LATTE-2
Endpoint 
(Week)
Outcome
Q8W IM
N=115
n (%)
Q4W IM
N=115
n (%)
CAB 30 mg+ 
ABC/3TC
N=56
n (%)
Subtotal IM
N=230
n (%)
W48
Virologic Success, n (%)
106 (92) 
105 (91)
50 (89)
211 (92)
Virologic Failure, n (%)
8 (7) 
1 (<1)
1 (2)
9 (4)
W96
Virologic Success, n (%)
108 (94)
100 (87)
47 (84)
208 (90)
Virologic Failure, n (%)
5 (4)
0
1 (2)
5 (2)
The CAB LA population PK model was updated to include data from CAB LA pre-
exposure prophylaxis (PrEP) Study 201120 (ÉCLAIR; GlaxoSmithKline Document 
Number 2016N269422_00) and Study 200056 (LATTE-2), increasing the original model 
from 93 participants to 416 participants receiving CAB LA single or repeat IM injections.  
Modeling and simulation was used to enable simplification and alignment of loading dose 
strategy used in LATTE-2 for both Q4W and Q8W CAB LA and RPV LA dosing 
regimens, resulting in selection of optimized loading dosing strategy for use in the 
Extension Phase of LATTE-2 and Phase 3 studies.  The Phase 3 studies FLAIR and 
ALTAS adopted a monthly (QM) dosing strategy with a regimen of CAB LA 600 mg IM 
and RPV LA 900 mg IM as initial loading doses followed by CAB LA 400 mg IM and 
RPV LA 600 mg IM QM.  Based on positive results from the Week 96 analysis of 


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LATTE-2, an additional Phase 3b study ATLAS 2M was initiated to further evaluate 
bimonthly (Q2M) dosing of CAB LA 600 mg IM and RPV LA 900 mg IM administered 
upon initiation of long-acting treatment and again one month after the initial injection 
then Q2M thereafter.  POLAR will transition subjects in LATTE receiving oral CAB 
30 mg and RPV 25 mg once daily to the Q2M regimen.
4.4.1.1.
CAB LA Q2M
The CAB LA 600 mg Q2M regimen is predicted to achieve concentrations above 
1.35 g/mL, the geometric mean trough concentration (C) following oral CAB 10 mg 
once daily, which was shown to be efficacious in the LATTE study.  The lower bound of 
the 90% prediction interval is approximately 0.166 g/mL, indicating that 95% of 
participants on this regimen should remain above the PA-IC90 throughout dosing (Figure 
2).  The CAB LA Q2M regimen consists of identical 600 mg doses administered at 
Day 1, Month 2, and Q2M thereafter.  Observed data for the optimized Q2M regimen in 
LATTE-2 Extension Phase were consistent with predictions, with a geometric mean CAB 
trough concentration of 1.58 g/mL 4 weeks following the reduced 600 mg IM loading 
dose and of 2.03 g/mL following the fourth injection.
Figure 2
Simulated* Median (90% Prediction Interval [PI]) CAB Plasma 
Concentrations versus Time for the Optimized CAB LA Q8W 
Regimen (600 mg IM Day 1, Week 4, Q8W Thereafter)
*Note: current simulations based on interim plasma concentration dataset
A one-week delay in CAB LA dosing for the Q2M regimen at steady state is predicted to 
result in ~92% rather than 95% of participants achieving trough concentrations above the 
PA-IC90, which is considered acceptable.


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4.4.1.2.
RPV LA Q2M
The RPV LA Q2M regimen for this study (POLAR) was selected based on safety and 
efficacy data from study 200056 (LATTE-2) and supported by modeling and simulation 
of pharmacokinetic data obtained following administration RPV LA administration in 
healthy participants (Phase 1 studies C158, and LAI115428 [GlaxoSmithKline Document 
Number 2011N112455_03]) and in HIV-infected participants (Phase 2 study LATTE-2), 
the majority of the data coming from 200056 (LATTE-2). 
The RPV LA 900 mg Q2M regimen is predicted to achieve median (90% PI) steady-state 
Cof 54 ng/mL (23 – 112 ng/mL) (Figure 3).  With this regimen, 100% of participants 
remain above the RPV protein-adjusted 90% inhibitory concentration (PA-IC90) during 
the whole dose interval at steady-state.  These data are similar to the observed Week 32 
median steady-state Cin LATTE-2 for Q8W which was also 54 ng/mL and the mean C
was 58 ng/mL.  The RPV LA Q2M regimen consists of identical 900 mg doses 
administered at Day 1, Month 2, and Q2M thereafter.  With the second RPV LA dose 
administered 1 month after the first dose, the anticipated median RPV Cat Week 4 
(prior to second injection) is 40 ng/mL (versus 30 ng/mL observed prior to second 
injection at Week 8 in LATTE-2, where the RPV LA dose at Week 4 was not included), 
with >92% of participants above the RPV PA-IC90 of 12 ng/mL.  Observed data for the 
optimized Q2M regimen in LATTE-2 Extension Phase were consistent with predictions, 
with a geometric mean RPV trough concentration of 49.9 ng/mL 4 weeks following the 
900 mg IM loading dose and of 57.5 ng/mL following the fourth injection.


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Figure 3
Simulated* Median (90% PI) RPV Plasma Concentrations versus 
Time Profile for the Optimized RPV LA Q8W regimen (900 mg IM 
Day)
* Note: current simulations based on interim plasma concentration dataset
At steady-state, a one-week delay in dosing for the RPV LA Q2M regimen is predicted to 
result in a median steady-state Cthat is approximately 11% lower (48 ng/mL) than for 
dosing that is administered on schedule, with >99% of subjects still remaining above the 
RPV PA-IC90.  This supports allowance of some flexibility in the dosing regimen similar 
to what is currently practiced in ongoing LATTE-2 and ATLAS 2M studies.
4.4.1.3.
DTG + RPV
To date, the efficacy, PK, safety, and drug interaction potential of DTG and RPV as 
individual agents have been evaluated in two extensive clinical development programs of 
Phase I to III clinical trials. As individual agents, DTG and RPV are both approved and 
marketed as TIVICAY 50 mg once daily and Edurant 25 mg once daily, respectively, the 
doses used in the current study.  
Clinical data showed the absence of a drug:drug interaction between DTG and RPV.  
Study ING116181 was a Phase I, open-label, crossover study to evaluate the 
pharmacokinetics and safety of GSK1265744 and RPV and DTG and RPV in healthy
adult participants.  The study showed that co-administration of RPV with DTG had no 
clinically meaningful effect on DTG or RPV pharmacokinetics [Ford, 2013].  


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Co-administration of RPV with DTG had no effect on DTG area under the concentration 
curve from 0 hours to the time of next dosing (AUC[0-]) or maximum concentration 
(Cmax), and increased DTG Cby 22%, while co-administration of DTG with RPV had 
no effect on RPV AUC(0-) or Cmax and increased RPV Cby 21%.  Hence, based on 
this data there is no need for a dose adjustment from approved doses when both products 
are used in combination.
A summary of the overall clinical development for both products is available in the IBs 
for the respective products [see DTG IB: GlaxoSmithKline Document Number 
RM2007/00683/11, 2017 and RPV IB, 2017] as well as the Juluca Prescribing 
Information, 2017.
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 study intervention) and satisfy one of the following:

Assigned to either treatment group, completed the Maintenance Phase (Month 12 for 
DTG +RPV participants only), remaining on study until commercial supplies of 
CAB LA + RPV LA Q2M or DTG + RPV regimens become locally available or 
development of CAB LA + RPV LA is terminated;
Additionally, participants will continue this study until:

the participant no longer derives clinical benefit, 

the participant meets a protocol-defined reason for discontinuation  
Participants who withdraw from CAB LA + RPV LA and go into the LTFU Phase will be 
considered to have prematurely withdrawn from the study intervention.
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 from the DTG + RPV regimen 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 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.
5.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.


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Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the investigational regimen or other study intervention
that may impact participant eligibility is provided in the current Investigator’s Brochures 
(IB) for CAB (GlaxoSmithKline Document Number RH2009/00003/07) and RPV IB, 
2017, Edurant Prescribing Information, 2018 and Juluca Prescribing Information, 2017.
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 lab results can be reviewed and approved 
by the Medical Monitor for consideration of participant eligibility.  A repeat sample to 
the central lab will be submitted concurrently or at the next planned visit.
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 
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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 urine human chorionic gonadotrophin [hCG] test at Day 1), 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. 
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 


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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 Inclusion Criteria:
4. Must have been on oral CAB 30 mg + RPV 25 mg regimen through at minimum 
Week 300 of the LATTE study as per LATTE protocol dosing requirements and 
until Day 1 of the POLAR study.  Any disruptions in dosing during LATTE must 
be discussed with the Medical Monitor for a final determination of eligibility.
5. Plasma HIV-1 RNA <50 c/mL at Week 300.  If participant has plasma HIV-1 
RNA 50 c/mL at Week 300 in LATTE, a single repeat to determine eligibility 
may be allowed ONLY after consultation with the medical monitor.
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:
Participants transitioning from LAI116482 (LATTE)
1. During the last 6 months of participation in LATTE, consecutive (2 or more 
sequential) plasma HIV-1 RNA measurements 50 c/mL
2. During the last 6 months of participation in LATTE, any HIV-1 RNA 
measurement 200 c/mL
Exclusionary medical conditions
3. Any evidence of a current Center for Disease Control and Prevention (CDC) 
Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring 
systemic therapy.
4. Participants with moderate to severe hepatic impairment determined by Child-
Pugh classification.
5. Any pre-existing physical or mental condition (including substance use disorder) 
which, in the opinion of the Investigator, may interfere with the participant’s 


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ability to comply with the dosing schedule and/or protocol evaluations or which 
may compromise the safety of the participant
6. 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.
7. 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
8. The participant has a tattoo or other dermatological condition overlying the 
gluteus region which may interfere with interpretation of injection site reactions
9. Evidence of Hepatitis B virus (HBV) infection based on the results of testing 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) and positive for HBV DNA are excluded
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti-
HBs (past and/or current evidence) are immune to HBV and are not excluded.
10. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not 
be excluded, however Investigators must carefully assess if therapy specific for 
HCV infection is required; participants who are anticipated to require HCV 
treatment within 12 months must be excluded.  (HCV treatment on study may be 
permitted, following consultation with the medical monitor)
11. 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.  
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 ])
12. 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), known biliary abnormalities (with the 


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exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable 
chronic liver disease per investigator assessment)
13. History of liver cirrhosis with or without hepatitis viral co-infection.
14. Ongoing or clinically relevant pancreatitis
15. 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
16. 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
17. 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
18. 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
19. 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.
20. Corrected QT interval (QTc (Bazett)) >450 msec or QTc (Bazett) >480 msec for 
subjects with bundle branch block.
Exclusionary Laboratory Values or Clinical Assessments (a single repeat to determine 
eligibility is allowed)
21. Any verified Grade 4 laboratory abnormality over the last 6 months in LATTE. A 
single repeat test is allowed to verify a result 
22. Any acute laboratory abnormality over the last 6 months in LATTE, which, in the 
opinion of the investigator, would preclude the participant’s participation in the 
study of an investigational compound
23. Alanine aminotransferase (ALT) 5 × ULN or ALT 3xULN and bilirubin 
1.5xULN (with >35% direct bilirubin) over the last 6 months in LATTE
Concomitant Medications
24. Exposure to an experimental drug (with the exception of those in the LATTE 
study including CAB and RPV) 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;
25. Treatment with any of the following agents within 28 days of Day 1:


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
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. 
26. Use of medications which are associated with Torsade de Pointes must be 
discussed with the Medical Monitor to determine eligibility.  (See SPM for a list 
of relevant medications)
27. 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 and/or DTG concentrations should be discontinued for a 
minimum of four weeks or a minimum of three half-lives (whichever is longer) 
prior to the first dose 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
5.2.1.
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.
5.3.
Lifestyle Considerations
No restrictions are required.


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6.
STUDY INTERVENTION
6.1.
Study Intervention(s) Administered
The term ‘study intervention’ is used throughout the protocol to describe any 
combination of products received by the participant as per the protocol design.  Study 
intervention 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 intervention may therefore refer to the individual 
study interventions or the combination of those study interventions.
Investigational product (IP) in this protocol refers to the investigational study drugs Oral 
Cabotegravir, Cabotegravir LA, Oral Rilpivirine and Rilpivirine LA.  These will be 
supplied by GlaxoSmithKline/ViiV Healthcare and Janssen Pharmaceuticals, 
respectively. Commercially available DTG + RPV (Juluca) will be supplied by 
GlaxoSmithKline/ViiV Healthcare as fixed dose combination tablets.
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.
6.1.1.
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.  The recommended storage conditions, and 
expiry date where required, are stated on the product label.
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.  The recommended storage conditions, and expiry 
date where required, are stated on the product label.


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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.  The recommended storage conditions, and expiry 
date where required, are stated on the product label.
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. The recommended storage conditions, and 
expiry date where required, are stated on the product label.
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.
Tablet Formulation of DTG + RPV (Juluca)
Each Juluca tablet contains 50 mg of dolutegravir and 25 mg of rilpivirine, and is a pink, 
oval, film-coated, biconvex tablet debossed with “SV J3T” on one side. Bottle of 
30 tablets with child-resistant closure (contains a desiccant) NDC 49702-242-13.
The recommended storage conditions, and expiry date where required, are stated on the 
product label.
6.2.
Treatment Assignment
Participants transitioning from the LATTE study on oral CAB + RPV treatment will 
transition to their elected treatment regimen, either Q2M administration of CAB LA + 
RPV LA or oral DTG + RPV single tablet regimen.  Regardless of treatment arm, the 


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investigator should instruct all participants on the importance of treatment adherence.  
This study has an open-label design.  Dosing is outlined in Table 2.
Table 2
Dosage and Administration
Maintenance Phase (Day 1 to End of Study+)
Q2M Arm- Transitioning from LATTE
First Injections (Loading Doses) – Day 1 and Month 2
Day 1

Receive last dose of oral CAB + RPV regimen

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 
Month 2

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 2
Month 4 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
Oral DTG + RPV Arm – Transitioning from LATTE
Day 1 to Month 12+
(once daily FDC tablet taken 
with food)

Take one tablet of DTG 50 mg + RPV 25 mg once daily
+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
6.3.
Blinding
This will be an open-label study and therefore no blinding is required. 
6.4.
Packaging and Labeling
The contents of the label will be in accordance with all applicable regulatory 
requirements.


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6.5.
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.

In accordance with local regulatory requirements, 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).  The amount of IP dispensed and/or 
administered to study participants, the amount returned by study participants, and the 
amount received from and returned to GSK must be documented.

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.

Product accountability records must be maintained throughout the course of the 
study.
IP accountability will be evaluated using pill counts of unused IP for participants 
receiving oral treatment (oral CAB and oral RPV).  This assessment will be conducted
each time the participant receives a new (refill) supply of IP through the withdrawal or 
study completion.
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.
No special preparation of study intervention is required for DTG + RPV.
6.5.1.
Dosing Considerations for CAB LA + RPV LA
Vials of CAB LA and RPV LA are each supplied as a suspension and need no further 
dilution or reconstitution.  Since RPV LA requires refrigeration, sites should allow the 


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vial to come to approximately room temperature prior to injecting. The vials should be 
gently inverted a few times to re-suspend sediments and allow bubbles to subside, and 
then use a syringe to withdraw the required volume of suspension for IM injection.  
All injections must be given intramuscularly in the gluteus medius.  Sites may use their 
discretion as to where in the gluteus muscle each injection is given according to 
individual participant circumstance.  If possible, injections should be spaced 
approximately 2 cm from one another, from the site of any previous injection or any 
injection site reaction.  The time and location of injection will be captured in the eCRF.  
Intermuscular injections should be administered at a 90-degree angle into the gluteus 
medius muscle using a needle of appropriate gauge and length (In most participants, a 
1.5” 23 gauge needle for CAB LA and a 1.5” 23 gauge needle for RPV LA is 
recommended).  The needle should be long enough to reach the muscle mass and prevent 
study drug from seeping into subcutaneous tissue, but not so long as to involve 
underlying nerves, blood vessels, or bone.  Variable needle lengths and/or needles with 
different gauge (CAB LA: 21 to 25 gauge; RPV LA: 21 to 23 gauge) are permitted if 
needed to accommodate individual body types.  Longer needle lengths may be required 
for participants with higher body mass indexes (BMIs, example > 30), to ensure that 
injections are administered intramuscularly as opposed to subcutaneously.  BMI, needle 
gauge and length used will be collected in the eCRF. Additional details of the injection 
device used by sites for IM administration including, but not limited to functional 
performance, may also be collected within the eCRF.
At the Day 1 visit, participants transitioning from oral CAB + RPV should be dosed with 
the IM regimen within 2 hours of taking the last oral regimen dose where possible. 
Should IM maladministration be suspected at any time (e.g., suspected under or overdose 
or inadvertent IV dosing), the investigator may consider requesting the participant stay 
onsite for approximately 2-3 hours post dose for safety monitoring and notifying the 
Medical Monitor.  An ECG or any other supportive testing may be obtained at the 
discretion of the investigator. Additionally, a PK sample may be drawn approximately 
2 hours post dosing for future evaluation of CAB and RPV plasma concentrations.
Additional dosing instructions and considerations can be found in the SPM.
6.6.
Compliance with Study Intervention Administration
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 participant’s eCRF.  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. 
When participants self-administer oral study interventions at home, compliance with 
CAB + RPV and DTG + RPV dosing will be assessed through querying the participant
during the site visits and documented in the source documents and CRF.  IP 
accountability will be evaluated using pill counts of unused IP (CAB, RPV and DTG + 
RPV tablets).  This assessment will be conducted each time the participant receives a new 


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(refill) supply of oral study medication or any oral bridging phase.  A record of the 
number of CAB, RPV and DTG + RPV tablets dispensed to and taken by each participant
must be maintained and reconciled with study intervention and compliance records.  
Treatment start and stop dates will also be recorded in the eCRF. 
Due to the long acting nature of the CAB LA and RPV LA it will be imperative that the 
participant is compliant with dosing instructions.  As part of the screening and participant
selection process, it is imperative that Investigators discuss with potential participants the 
long-term commitments for the trial, and the importance of adhering to treatment 
regimens.  Sites are to have plans in place for adherence counselling for both treatment 
arms of the study for the duration of the study including the LTFU Phase.  In addition, 
Investigators must have plans in place to perform visit reminders, utilizing participant
trackers provided by the study team as needed, and to verify the participant’s contact 
information at each visit.  Investigators should contact participants directly in the event 
that a participant misses any scheduled visit. 
6.7.
Dose Modifications
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 
exemptions are not allowed. Therefore, adherence to the study design requirements is 
essential and required for study conduct.  See Section 4.4 for the justification of dose.
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.
Please refer to Appendix 10 in Section 12.10 for study management information during 
the COVID-19 pandemic.
6.7.1.
Protocol Permitted Substitutions
6.7.1.1.
Oral Bridging
In exceptional circumstances, to address pre-planned missed CAB LA + RPV LA dosing 
visits, in consultation with 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 >4 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 10 in Section 12.10 for study management information during 
the COVID-19 pandemic.


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6.8.
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.  
Note: All decisions regarding dose interruption / resumption must be discussed with 
the medical monitor in advance.
6.8.1.
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 
from LATTE on oral CAB + RPV will occur at Day 1.
Since the first injection visit (Day 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, etc.).
CAB LA + RPV LA dosing for participants transitioning from oral CAB + RPV is 
as follows:
All injections should be planned as single injections per drug.


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6.8.1.1.
IM injections every 2 months (Q2M):
On Day 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 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.  The dosing window for the second injection allows 
administration between -7 days of the proposed Month 2 injection visit and the proposed 
Month 2 injection visit date, but preferably not later than the proposed Month 2 injection 
visit date.  After Month 2, a dosing window (7 days) for injections is stipulated. the
Medical Monitor must be contacted to discuss individual participant case management if 
a dose has to be administered outside of the window.  
6.8.2.
Oral Dosing
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 LTFU are expected to occur as projected according to the last 
injection.  
6.9.
Treatment of Study Intervention Overdose
For participants receiving Oral CAB, any tablet intake exceeding a total daily dose of 
30 mg will be considered an overdose.  For participants receiving oral RPV, any dose 
exceeding a total daily dose of 25 mg will be considered an overdose. For participants 
receiving DTG + RPV, any tablet intake exceeding the daily number of tablets 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 
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 the purposes of this study, an overdose is not an AE (refer to Section 12.4.1) unless it 
is accompanied by a clinical manifestation associated with the overdose.  If the clinical 
manifestation presents with serious criteria, the event is a SAE (see Section 12.4.2).


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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 DTG + RPV, 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 intervention 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.
6.10.
Intervention after the End of the Study
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition, whether or not GSK is providing 
specific post-study intervention.  Participants who have successfully completed IM 
dosing and 12 months of oral DTG + RPV will continue to have access to both CAB LA 
and RPV LA and oral DTG + RPV until study intervention 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.
6.11.
Concomitant Medications and Non-Drug Therapies
Participants must be advised to notify their Investigator of any current or proposed 
concomitant medication, whether prescribed or over-the-counter, because of the potential 
for interactions between such treatments and the study medications.  Concomitant 
medications (prescription and non-prescription) will be permitted during the course of the 
study at the investigator’s discretion (except for prohibited medications described in 
Section 6.11.2 and should be administered only as medically necessary during the study. 
All concomitant medication, 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.
For DTG + RPV, The investigator should evaluate any potential drug:drug interactions at 
every visit, including reviewing the most current version of the U.S and local prescribing 


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information for DTG and RPV, especially if any new concomitant medications are 
reported by participants.
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with:

reason for use

dates of administration including start and end dates

dosage information including dose and frequency
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy.
6.11.1.
Permitted Medications and Non-Drug Therapies
Chemoprophylaxis for HIV-associated conditions is encouraged, if appropriate, at the 
discretion of the participant and their physician.  All concomitant medications, blood 
products, and vaccines taken during the study will be recorded in the eCRF with dates of 
administration.
Because non-HIV vaccines may cause a temporary increase in the level of plasma HIV-1 
RNA, it is 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 (should be spaced 2 cm or more away from site of 
IP injection).
Antacid and H2 Antagonist Use:
The most restrictive dosing requirements must be taken into consideration to account for 
the co-administration of oral CAB and RPV. The marketed approved recommendation 
for administration of antacids and H2 antagonists with the FDC of DTG + RPV 
incorporates the most restrictive dosing requirements.
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.
RPV oral administration only: Antacid products 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-receptor antagonists should only be administered at least 12 hours before or at least 
4 hours after RPV.  RPV should not be co-administered with proton pump inhibitors, 
such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.


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RPV:  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.  Please refer to the local rilpivirine prescribing information for guidance 
regarding other drugs that are prohibited, should be used with caution, require dose 
adjustment, or increased clinical monitoring if taken with rilpivirine.
Drugs with a known risk of Torsade des Pointes (TdP) should be used with caution when 
on rilpivirine (see SPM for list of drugs associated with TdP).
6.11.2.
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 Exclusion Criteria: 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 their immunosuppressive effect; 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 (more than a 
single dose in a treatment course may cause significant decrease in RPV 
plasma concentration and is prohibited). Topical, inhaled or intranasal use of 
glucocorticoids will be allowed.  

Hepatitis C infection therapy is allowed, and interferon-based HCV therapy 
or use of any drugs that have a potential for adverse drug:drug interactions 
with study intervention is prohibited throughout the entire study. 
For information on concurrent therapies and interactions suspected to be relevant to other 
antiretroviral therapy in the regimen, please consult the local prescribing information.
6.11.2.1.
Concurrent with CAB and/or RPV and DTG + RPV
For participants receiving either formulation of CAB and RPV and DTG +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


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
Phenobarbital 

Phenytoin

Rifabutin

Rifampicin / Rifampin

Rifapentine

St. John’s wort (Hypericum perforatum)
6.11.2.2.
Concurrent with oral RPV
In addition to the medications listed in Section 6.11.2.1, participants must discontinue the 
following (or change to an allowable alternative) while receiving treatment with oral 
RPV:

proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, 
pantoprazole, rabeprazole;

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.
6.11.2.3.
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 deep vein thrombosis (DVT) prophylaxis (e.g., postoperative DVT 
prophylaxis) or the use of low dose acetylsalicylic acid (≤325 mg). Systemic 
anticoagulation (including prophylaxis doses) on the day of an IM injection should be 
avoided.
Note: Any prohibited medications that decrease cabotegravir or rilpivirine 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.
6.11.2.4.
Concurrent with DTG + RPV
In addition, for participants receiving DTG +RPV, the following is prohibited:

Dofetilide and pilsicainide (as DTG may inhibit renal tubular secretion resulting 
in increased dofetilide concentrations and potential for toxicity).
Note: Any prohibited medications that decrease dolutegravir or rilpivirine 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.
Refer to the Juluca prescribing information [Juluca Prescribing Information, 2017] for a 
full list of prohibited medications.


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6.11.2.5.
Prohibited Medications for Participants Receiving HAART during the 
Long-Term Follow-Up Phase
For participants taking HAART during the Long-Term Follow-Up Phase, refer to local 
prescribing information for details regarding concurrent therapies.
7.
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
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).  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. 
Participants may have a temporary interruption to their study intervention for 
management of toxicities.
Participants may be prematurely discontinued from the study intervention 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.


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Participants must be discontinued from study intervention for any of the following 
reasons:

Virologic withdrawal criteria as specified in Section 7.1.3 are met;

Participant requires substitution of ART; 

Participant requires substitution or dose reduction of CAB LA, RPV LA (oral 
bridging supply and potential for a second loading dose may be permissible 
following discussion with the Medical Monitor) and oral DTG + RPV.

Liver toxicity where stopping criteria are met and no compelling alternate cause is 
identified (see Section 7.1.1);

Renal toxicity is met and no compelling alternate cause is identified;

Corrected QT interval (QTc) >550 msec from three or more tracings separated by at 
least 5 minutes and considered causally related to IP.  Note:  ECGs are not routinely 
conducted in this study.

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. 

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.
If a participant is prematurely or permanently withdrawn from the study, the procedures 
described in the Time and Events Table for the in-clinic Withdrawal visit are to be 
performed.  An in-clinic Follow-Up visit will be conducted 4 weeks after the last dose of 
study medication for participants with ongoing AEs, and serious adverse events (SAEs) 
related & not related to study drug and also any laboratory abnormalities that are 
considered to be AEs or potentially harmful to the participant, at the last on-study visit. 
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. 


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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 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 intervention 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.
Discontinuation of Study Intervention
Participants unable to manage drug toxicity or tolerate investigational product (IP, either 
formulations of CAB or RPV, or DTG + RPV) must have IP discontinued.  Any 
participant receiving at least one dose of CAB LA and /or RPV LA who discontinue IP / 
Withdraw will initiate treatment with HAART enter the LTFU Phase for 52 weeks of 
follow up (see Section 4.2.3).
7.1.1.
Liver Chemistry Stopping Criteria
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology.
IP will be stopped if any of the following liver chemistry criteria are met:

ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin, bilirubin fractionation 
required).

NOTE: serum bilirubin fractionation should be performed if testing is available.  If 
testing is unavailable, sites should evaluate the presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver 
injury.  If testing is unavailable and a participant meets the criterion of total bilirubin 
2xULN, then the event meets liver stopping criteria.

ALT 8xULN.

ALT ≥3xULN (if Baseline ALT is <ULN) with symptoms or worsening of acute
hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant
pain or tenderness, fever, rash, or eosinophilia, OR;


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
ALT ≥3x Baseline ALT (if Baseline ALT is >ULN) with symptoms or worsening of 
acute hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, or eosinophilia;

ALT ≥5xULN and <8xULN that persists ≥2 weeks (with bilirubin <2 ULN & no 
signs or symptoms of acute hepatitis or hypersensitivity).
ALT ≥5xULN but <8xULN and cannot be monitored weekly for >2 weeks.
7.1.1.1.
Liver Chemistry Stopping Criteria, Participant Management and Follow-
up
Participants who develop ALT ≥5xULN must be followed weekly until resolution or 
stabilization (ALT <5xULN on 2 consecutive evaluations).
When any of the liver chemistry stopping 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:

Hepatitis A immunoglobulin M (IgM) antibody;

Hepatitis B surface antigen (HBsAg) and Hepatitis B Core Antibody 
(IgM);

Hepatitis C RNA;

Hepatitis E IgM antibody;

Cytomegalovirus IgM antibody;

Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing);


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
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.

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.
7.1.1.2.
Liver Event Adjudication Committee
A liver safety panel will be used to evaluate all participants who meet liver stopping 
criteria.  Uniform sets of data and standards for adjudication will be applied across cases 
to inform outcomes.  Full details of the analysis, timing, and the decision criteria will be 
pre-specified in an Adjudication Committee Charter. 
7.1.1.3.
Liver Chemistry Stopping Criteria – Restart / Rechallenge
If participant meets liver chemistry stopping criteria do not restart/rechallenge participant 
with study treatment unless:

ViiV Healthcare Safety and Labelling Committee (VSLC) approval is granted

Ethics and/or IRB approval is obtained, if required, and


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
Separate consent for treatment restart/rechallenge is signed by the participant
If VSLC approval to restart/rechallenge subject with study treatment is not granted, then 
subject must permanently discontinue study treatment and may continue in the study for 
protocol-specified follow up assessments.
7.1.1.3.1.
Drug Restart / Rechallenge.  Following Liver Events that are Possibly 
Related and not related to Study intervention
Following drug-induced liver injury, drug rechallenge is associated with a 13% 
mortality across all drugs in prospective studies [Andrade, 2009]. Clinical outcomes 
vary by drug, with nearly 50% fatality with halothane readministered within one month 
of initial injury. However, some drugs seldom result in recurrent liver injury or fatality.  
Risk factors for a fatal drug rechallenge outcome include:

Hypersensitivity [Andrade, 2009] with initial liver injury (e.g. fever, rash, 
eosinophilia) 

jaundice or bilirubin >2xULN with initial liver injury (direct bilirubin >35% of total)

subject currently exhibits severe liver injury defined by: ALT 3xULN, bilirubin 
2xULN (direct bilirubin >35% of total), or INR1.5

serious adverse event or fatality has earlier been observed with drug rechallenges
[Hunt, 2010; Papay, 2009]

evidence of drug-related preclinical liability (e.g. reactive metabolites; mitochondrial 
impairment [Hunt, 2010].
Rechallenge refers to resuming study treatment following drug induced liver injury 
(DILI). Because of the risks associated with rechallenge after DILI this should only be 
considered for a subject for whom there is compelling evidence of benefit from a critical 
or life-saving medicine, there is no alternative approved medicine available, and a 
benefit:risk assessment of rechallenge is considered to be favourable.
Approval by the VSLC for drug rechallenge can be considered where:

Principal Investigator (PI) requests consideration of rechallenge with study treatment 
for a subject is receiving compelling benefit, benefit of drug restart exceeds risk, and
no effective alternative therapy is available. Ethics Committee or Institutional
Review Board approval of drug restart/rechallenge must be obtained, as required.

If the restart/rechallenge is approved by the VSLC in writing, the subject must be
provided with a clear description of the possible benefits and risks of drug
administration, including the possibility of recurrent, more severe liver injury or
death.

The subject must also provide signed informed consent specifically for the IP
restart/rechallenge. Documentation of informed consent must be recorded in the
study chart.

Study drug must be administered at the dose specified by the VSLC.


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
Subjects approved by the VSLC for rechallenge of IP must return to the clinic twice 
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 after study treatment rechallenge, subject meets protocol defined liver chemistry 
stopping criteria, study drug must be permanently discontinued.

The Medical Monitor and the Ethics Committee or Institutional Review Board as 
required, must be informed of the subject’s outcome following study treatment 
rechallenge

Any adverse events should be recorded on the appropriate eCRF(s), and reported 
where applicable, as per Section 8.5.
7.1.1.3.2.
Drug Restart Following Transient Resolving Liver Events Not Related 
to Study intervention
Restart refers to resuming study treatment following liver stopping events 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 study treatment should not be 
associated with HLA markers of liver injury.
Approval by the VSLC for drug restart can be considered where:

Investigator requests consideration for study treatment restart if Liver 
chemistries have a clear underlying cause (e.g., biliary obstruction, hypotension 
and liver chemistries have improved to normal or are within 1.5 x baseline and 
ALT <5xULN). 

Furthermore, there should be no evidence of fever, rash, eosinophilia, 
hypersensitivity, alcoholic hepatitis or possible study treatment-induced liver, 
and the drug should not be associated with HLA markers of liver injury.  (If 
restart of TRIUMEQ or any other abacavir- containing product is being 
considered then the Subject must be HLA-B*5701 negative).

Ethics Committee or Institutional Review Board approval of drug 
restart/rechallenge must be obtained, as required.

If restart of drug is approved by the VSLC in writing, the subject must be 
provided with a clear description of the possible benefits and risks of drug 
administration, including the possibility of recurrent, more severe liver injury or 
death.

The subject 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.

Subjects approved by the VSLC for restarting IP must return to the clinic once a 
week for liver chemistry tests for a minimum of one month and thereafter for as 


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long as clinically indicated and then laboratory monitoring may resume as per 
protocol. 

If after study treatment re-start, subject meets protocol-defined liver chemistry 
stopping criteria, follow usual stopping criteria instructions..

The Medical Monitor and the Ethics Committee or Institutional Review Board 
as required, must be informed of the subject’s outcome following study 
treatment restart

Any adverse events should be recorded on the appropriate eCRF(s), and reported 
where applicable, as per Section 8.5.
7.1.2.
QTc Stopping Criteria
A participant who has a QTc interval >550 msec considered causally related to IP will be 
withdrawn from the study. The QTc should be based on averaged QTc values of 
triplicate electrocardiograms obtained over a brief (e.g., 5 to 10 minute) recording 
period.
If an alternative cause of the QT prolongation is determined (e.g., participant receiving 
drug known to cause prolonged QT or TdP), the IP may be restarted (or continued) after 
consultation and agreement with the Medical Monitor. RPV and RPV LA should not be 
administered to participants 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.
7.1.3.
Virologic Failure
Only plasma HIV-1 RNA values determined by the central laboratory will be used to 
assess virologic failure. 
7.1.4.
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 after 
prior suppression to <200 c/mL.


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7.1.5.
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. 
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 (SVF), the 
Investigator should query the participant regarding intercurrent illness, recent 
immunization, or interruption of oral therapy.
7.1.5.1.
HIV-1 RNA Blips
HIV-1 RNA “blips” are not usually associated with subsequent virologic failure [DHHS, 
2016].  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 12 and End of study must return to the clinic as soon as possible (but 
no later than 4 weeks after the date of the Month 12 and End of study visit, 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
7.1.5.2.
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:


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
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 study intervention.

Confirmatory testing should be scheduled at least 4 weeks following any 
immunization, during which time the participant should receive full dose of all study 
intervention.

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 study intervention.

The participant should have received full dose of study intervention 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.
7.1.5.3.
Confirmed Virologic Failure
Participants with CVF must be discontinued from study intervention.  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 intervention.
If a participant is prematurely discontinued from the study intervention, 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.


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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 Time and Events Table, are essential and required for study conduct.
This section lists the procedures and parameters of each planned study assessment.  The 
exact timing of each assessment is listed in the Time and Events Table (Section 8.1).
The following points must be noted: 

If assessments are scheduled for the same nominal time, THEN the assessments 
should occur in the following order:
1. 12-lead ECG
2. vital signs
3. blood draws  
Note: The timing of the assessments should allow the blood draw to occur at the 
exact nominal time.

The timing and number of planned study assessments, including safety, 
pharmacokinetic, pharmacodynamic/biomarker assessments may be altered 
during the course of the study based on newly available data (e.g., to obtain data 
closer to the time of peak plasma concentrations) to ensure appropriate 
monitoring. 

The IRB/independent ethics committee (IEC) will be informed of any safety 
issues that require alteration of the safety monitoring scheme or amendment of the 
Informed Consent Form.


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8.1.
Time and Events Table
8.1.1.
Time and Events Table for CAB LA + RPV LA Q2M Administration
Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Written Informed Consent 
X
Demography
X
Eligibility Verification
X
Physical Exam
X
Medical History
X
CDC Classification
X
Rapid Plasma Reagin (RPR)
X
Symptom Directed Physical 
Exam, ISR and Medical 
Assessment c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs
(blood pressure [BP], heart 
rate [HR]) d
X
X
X
X
X
X
X
X
X
Weight, Height & body mass 
index (BMI) e
X
X
X
X
X
X
X
X
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
HIV Associated Conditions, 
AE and SAE Assessments, 
Con Meds
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-Lead ECG f
X
X
X
Clinical Chemistry and 
Hematology
X
X
X
X
X
X
X
X
X
Pregnancy Testing 
(U)rine or (S)erum g
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
HIV-1 RNA and sample for 
storage h
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
Fasting Glucose, Cholesterol 
(Total, high density 
lipoprotein [HDL] and low 
density lipoprotein [LDL]) and 
Triglycerides i
X
X
X
X
Prothrombin time (PT)/
Partial Thromboplastin Time
(PTT)/international 
normalized ratio (INR)
X
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
PK Diary 
(D)ispensation and (R)eview
R
PK Sample 
(S)torage j
S
S
S
LA Study intervention
Administration k
X 
X 
X
X
X
X
X
X
X
X
X
X
X
X
HIVTSQc
X
X
HIVTSQs
X
X
X
X
HIVDQoL
X
X
X
X
Preference
X
Reason for Switch
X
Participant Visit Reminder 
Contact
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Participant Contact Detail 
Confirmation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
See footnote “b” for continuation of visit schedule after Month 26.  Continue until either locally approved and commercially available, the participant no longer derives clinical 
benefit or meets a protocol-defined reason for discontinuation or until development is terminated.


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a.
The Day 1 visit will take place during Week 312 (or Week 324 in the event of unavoidable delays) of the LATTE study, the participant’s last week on study.  LATTE participants eligible for 
POLAR study dosing will take final dose of CAB 30 mg + RPV 25 mg in the clinic within 2 hours of the Q2M IM regimen.  See Section 6.1 for IM dosing administration as loading doses are 
required. (Day 1=1st loading dose; Month 2=2nd loading dose)
b.
Continue this pattern for visits for the remainder of the study.  For example, Month 28 will be conducted just like Month 20, Month 30 will be conducted just like Month 22 and so on.
c.
Physical exams should be conducted as part of normal routine clinical care but data will not be collected in the eCRF. Medical assessments include any decisions the study staff must make 
for participant management.
d.
Measure vital signs after about 5 minutes of rest in a semi-supine position.
e.
Height collected at Day 1 only.
f.
On Day 1, ECGs should be performed in triplicate at least 5 minutes apart and following 5 minutes of rest in a semi-supine position within 1 hour prior to first dose.  Also on Day 1, a 2-hour 
post dose ECG will be performed for all participants.  The 2-hour post dose ECG on Day 1 can also be used for the LATTE Week 312 (or Week 324, if needed) visit.  ECG evaluations at 
other visits should be obtained after dosing, preferably 2-4 hours post dosing.
g.
A (-) urine pregnancy test is required prior to any injection and as required by medical monitor after a treatment interruption. A (+) urine test should be confirmed with a stat serum test.  If 
(+), participant will need to be WD.
h.
Plasma for storage samples are collected for possible future analyses, back-up in cases of loss/damage in transit and geno/pheno analyses for virologic failures.
i.
Fast overnight; however, a minimum of a 6 hour fast is acceptable.
j.
Take PK samples pre-dose.
k.
Q2M Injections are 1 x CAB LA 600 mg IM + 1 x RPV LA 900 mg IM.  If possible, injections should be spaced approximately 2 cm from one another and from the site of any previous 
injection and or any injection site reaction.  Bring RPV LA to approximately room temperature prior to injecting.   Time and location of injection (right or left) as well as needle length used 
will be collected in the eCRF.  IM dosing is expected to occur during the month in which the participant’s projected visit falls (as according to the Day 1 visit).  An additional (+ 
or -) 7 day window from date of projected visit is stipulated for IM dosing.  All decisions regarding dose interruption/ resumption must be discussed with the medical monitor 
in advance.
l.
Or Long-Term Follow Up
m.
Follow Up Visit - Conduct ~4 weeks after the last dose of IP if not entering Long-Term Follow Up and only if the participant has ongoing AEs or lab abnormalities at the last on-study visit.  
May be conducted by telephone.


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8.1.2.
Time and Events Table for DTG + RPV Administration
Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j
Notes
Written Informed Consent 
X
a.
The Day 1 visit will take place during Week 312 (or Week 324 in 
the event of unavoidable delays) of the LATTE study, the 
participant’s last week on study.  LATTE participants eligible for 
POLAR study dosing will take final dose of CAB 30 mg + RPV 25 
mg in the clinic.  See Section 6.2 for dosing administration.
b.
Physical exams should be conducted as part of normal routine 
clinical care but data will not be collected in the eCRF. Medical 
assessments include any decisions the study staff must make for 
participant management.
c.
Measure vital signs after about 5 minutes of rest in a semi-supine 
position.
d.
Height collected at Day 1 only.
e.
On Day 1, ECGs should be performed in triplicate at least 5 
minutes apart and following 5 minutes of rest in a semi-supine 
position within 1 hour prior to first dose.  Also on Day 1, a 2-hour 
post dose ECG will be performed for all participants.  The 2-hour 
post dose ECG on Day 1 can also be used for the LATTE Week 
312 (or Week 324, if needed) visit.  ECG evaluations at other 
visits should be obtained after dosing, preferably 2-4 hours post 
dosing.
f.
Plasma for storage samples are collected for possible future 
analyses, back-up in cases of loss/damage in transit and 
geno/pheno analyses for virologic failures.
g.
A (-) urine pregnancy test is required prior to any administration 
of drug and as required by medical monitor after a treatment 
interruption. A (+) urine test should be confirmed with a stat 
serum test.  If (+), participant will need to be WD.
h.
Fast overnight; however, a minimum of a 6 hour fast is 
acceptable.
i.
DTG 50 mg + RPV 25 mg.  Administer daily with food
j.
Follow Up Visit - Conduct ~4 weeks after the last dose of IP and 
only if the participant has ongoing AEs or lab abnormalities at the 
last on-study visit.  May be conducted by telephone.
Demography
X
Eligibility Verification
X
Physical Exam
X
Medical History
X
CDC Classification
X
RPR
X
Symptom Directed Physical Exam and 
Medical Assessment b
X
X
X
X
X
Vital Signs (BP, HR) c
X
X
X
X
X
X
Weight, Height & BMI d
X
X
X
X
X
X
HIV Associated Conditions, AE and 
SAE Assessments, Con Meds
X
X
X
X
X
X
12-Lead ECG e
X
X
X
HIV-1 RNA
X
X
X
X
X
X
CD4+
X
X
X
X
X
X


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Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j
Notes
Plasma for Storage f
X
X
X
X
X
X
PK Sample for Storage
S
Clinical Chemistry and Hematology
X
X
X
X
X
X
Pregnancy Testing g
U
U
U
U
U
U
Urinalysis
X
X
Fasting:  Glucose, Cholesterol (Total, 
HDL and LDL) and Triglycerides h
X
X
PT/PTT/INR
X
X
HIVTSQc
X
X
HIVTSQs
X
X
X
X
HIVDQoL
X
X
X
X
Participant Visit Reminder Contact
X
X
X
X
X
Participant Contact Detail Confirmation
X
X
X
X
X
Study intervention Dispensation i
X
X
X
X
X


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8.1.3.
Time and Events Table for Long Term Follow Up 
Procedures for Long-Term Follow Up
Month 1 a
Month 
3
Month 
6
Month 
9
Month 12
WD
Notes
HIV Associated Conditions, AE and SAE 
Assessments, Con Meds
X
X
X
X
X
X
Every effort should be made to enter participants into the Long-
Term Follow Up if they withdraw from or discontinue the study after 
receiving at least one dose of CAB LA and / or RPV LA.
a)
The start of the 52-week follow up period begins the day 
of the last CAB LA and/or RPV LA dose.
b)
Women of childbearing potential only.  S = Serum
c)
Fast overnight; however, a minimum of a 6 hour fast is 
acceptable.
d)
Women of childbearing potential should continue to 
receive counselling on the need to use adequate 
contraception for the entirety of the Long-Term Follow-Up 
Period. 
e)
Investigators must discuss choice of HAART 
regimen and timing of initiation with the medical 
monitor before initiating.  This regimen may be 
supplied regionally by GSK or reimbursement will be 
provided.
HIV-1 RNA
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
Plasma for Storage
X
X
X
X
X
X
PK Sample for Storage
S
S
S
S
S
S
Clinical Chemistry and Hematology
X
X
X
X
X
X
Pregnancy Testing b
S
S
S
S
S
S
Urinalysis
X
X
X
Fasting:  Glucose, Cholesterol (Total, 
HDL and LDL) and Triglycerides c
X
X
PT/PTT/INR
X
X
Contraception Counselling d
X
X
X
X
X
X
HAART Dispensation e
X
X
X
X
X
X


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8.2.
Baseline Assessments
At Day 1, any changes to the eligibility parameters must be assessed and any results 
required prior to randomization (e.g., Day 1 urine pregnancy test for women of 
childbearing potential) must be available and reviewed. The following demographic 
parameters will be captured: year of birth, sex, race and ethnicity. 
Medical/medication/family history will be assessed as related to the inclusion/exclusion 
criteria listed in Section 5. 
HIV-1 genotypic resistance testing and plasma HIV-1 RNA measurement results from 
the LATTE study must be available prior to the Baseline visit.
Baseline information to be collected at Day 1 includes general medical history and 
current medical conditions. Laboratory and health outcomes assessments will also be 
assessed.  Questionnaire/surveys are recommended to be administered at the beginning of 
the visit before any other assessments are conducted, in the order specified.  For 
participants who agree to the optional assessment, a whole blood sample for genetic 
research should be collected at Day 1 (if not already collected during participation in the 
LATTE study).
In addition to a full routine medical history at Baseline, more detailed information will be 
collected for some disease processes such as:

Cardiovascular medical history/risk factors (as detailed in the eCRF) will be 
assessed at Baseline and assessments will include height, weight, blood pressure, 
smoking status and history, pertinent medical conditions (e.g., hypertension, 
diabetes mellitus), and family history of premature cardiovascular disease.  In 
addition, medical history/risk factors for renal disease such as nephropathy, renal 
failure, and nephrolithiasis will be assessed.

history of illicit drug use [e.g., cocaine, heroin, and methamphetamine use]);

intravenous drug use history;

gastrointestinal disease (e.g., gastrointestinal [GI] bleeding, peptic ulcer disease 
[PUD], etc);

metabolic (e.g., Type I or II diabetes mellitus);

psychiatric (e.g., depression);

renal (e.g., nephrolithiasis, nephropathy, renal failure); and,

neurologic disorders
Procedures conducted as part of the participant’s routine clinical management [e.g., 
laboratory assessments] and obtained prior to signing of informed consent may be 
utilized for baseline purposes provided the procedure meets the protocol-defined criteria 


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and has been performed in the timeframe of the study.  Where possible local lab results 
should be confirmed by submission of samples to the central lab.
8.3.
Efficacy Assessments
8.3.1.
Plasma HIV-1 RNA
Plasma for quantitative HIV-1 RNA will be collected according to the Time and Events 
schedule (Section 8.1).  Methods to be used may include but are not limited to the Abbott 
RealTime HIV-1 Assay lower limit of detection (LLOD) 40 c/mL.  In some cases, (e.g., 
where the HIV-1 RNA is below the lower limit of detection for a given assay) additional 
exploratory methods will be used to further characterize HIV-1 RNA levels.
8.3.2.
Lymphocyte Subsets, CD4+ and CD8+
Lymphocyte subsets will be collected for assessment by flow cytometry (total 
lymphocyte counts, percentage and absolute CD4+ and CD8+ lymphocyte counts, ratios) 
according to Time and Events schedule (Section 8.1) and Laboratory Assessments 
(Section 8.4.2).
8.3.3.
HIV Associated Conditions
HIV-associated conditions will be recorded as per Time and Events schedule 
(Section 8.1).  HIV-associated conditions will be assessed according to the 2014 CDC 
Revised Classification System for HIV Infection (see Section 12.8).
8.4.
Safety Assessments
8.4.1.
Clinical Evaluations
The following clinical evaluations will be performed according to the Time and Events 
schedule:

Monitoring and recording of all AEs and SAEs.  Additional information on the 
Time Period and Frequency of Detecting AEs and SAEs is provided in Section 
8.5.2.

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).

Height and weight will be measured and recorded.  Height collected on the Day 1 
(Baseline) only.

Vital signs will include systolic and diastolic blood pressure and heart rate 
collected after resting for about 5 minutes.  Temperature will also be collected.

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.


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
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 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, and fasting glucose and 
lipids (parameters to be tested listed below).  

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 
Time and Events Schedule (Section 8.1).

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.  
Any appropriately qualified site personnel (e.g., Investigator, sub-Investigator, or study 
coordinator/nurse) can perform assessments.
8.4.2.
Laboratory Assessments
All protocol required laboratory assessments, as defined in the Time and Events Schedule 
(see Section 8.1), must be performed by the central laboratory.  Laboratory assessments 
must be conducted in accordance with the Central Laboratory Manual and Protocol Time 
and Events Schedule.  Laboratory requisition forms must be completed and samples must 
be clearly 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 


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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 12.3 “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 3 includes lab parameters to be assessed as per the Time and Events Schedule (see 
Section 8.1).  In addition to the protocol-specified laboratory assessments the study 
Medical Monitor, in collaboration with the site investigator, may request additional 
central laboratory assessments be performed to support safety profiling and case 
management of individual study participants.


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Table 3
Safety Laboratory Assessments
Hematology
Platelet count 
Automated WBC differential:
RBC count
Neutrophils
WBC count (absolute) 
Lymphocytes
Hemoglobin
Monocytes
Hematocrit
Eosinophils
MCV
Basophils
Clinical Chemistry
BUN
Potassium
AST 
Total bilirubina
Creatinine
Chloride
ALT 
Albumin 
Glucosec
Total CO2
Alkaline phosphatase
Creatine phosphokinase
Sodium
Lipase
Phosphate
Creatinine clearanceb
Fasting Lipid Paneld
Total cholesterol
HDL cholesterol
LDL cholesterol
Triglycerides
Other Tests
Plasma HIV-1 RNAe
CD4+ and CD8+ cell counts [CD4/CD8 ratio]f
Peripheral Blood Mononuclear Cells (PBMCs):  Day 1 and Withdrawal only
Rapid Plasma Reagin (RPR)
Prothrombin Time (PT)/International Normalized Ratio (INR)/ Partial Thromboplastin Time (PTT)
Pregnancy test for women of childbearing potentialg
Urinalysis, urine albumin/creatinine ratio, and urine protein/creatinine ratio, urine phosphate
Genetics Sample 
Follicle stimulating hormone (FSH) and estradiol (only for instances when postmenopausal status is questionable)
MCV = mean corpuscular volume, RBC = red blood cells, WBC = white blood cells, BUN = Blood urea nitrogen, 
AST=aspartate aminotransferase, ALT = alanine aminotransferase, CO2 = carbon dioxide, HDL = high density 
lipoprotein, LDL = low density lipoprotein, HBsAg= hepatitis B virus surface antigen, PT/INR = prothrombin 
time/international normalized ratio.
a)
Direct bilirubin will be reflexively performed for all total bilirubin values >1.5 × ULN.
b)
Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) [Levey, 2009].
c)
For fasting glucose assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments.
d)
For fasting lipids assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable 
for participants with afternoon appointments.
e)
For participants meeting virologic withdrawal criteria, plasma samples will be analyzed in attempt to obtain 
genotype/phenotype data.
f)
CD8+ cells will only be reported at Baseline, Day 1, Months 12 and end of the study.
g)
Urine pregnancy test/ serum pregnancy test will be performed according to the Time and Events Table (Section 
8.1).  
8.4.3.
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.  


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Height and weight will also be measured and recorded as per the Time and 
Events Table in Section 8.1 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 8.7.9 for additional information.
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
8.4.4.
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 Time and Events Table in Section 8.1.
8.4.5.
Electrocardiograms
A 12-lead ECG will be performed in a semi-supine position.  On Day 1, ECGs should be 
performed in triplicate prior to first dose.  At Day 1, a 2 hour post dose ECG will be 
performed for all participants.  ECG evaluations at other visits should be obtained after 
dosing, preferably 2-4 hours post dosing. The 2-hour post dose ECG on Day 1 can also be 
used for the LATTE Week 312 (or Week 324, if needed) visit.  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 Time and Events Table for collection timepoints (Section 
8.1).  Refer to Section 7.1.2 for [QTc] withdrawal criteria and additional [QTc] readings 
that may be necessary.
8.4.6.
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 participants being treated with INIs
including DTG.  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 


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suicidal ideation/attempts) develop, because medical intervention and discontinuation of 
the study medication may be required.
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.
8.4.7.
Pregnancy
8.4.7.1.
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 Time and Events 
Table (Section 8.1) 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.
8.4.7.2.
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.
Female participants that have received at least one dose of CAB LA or RPV LA and do 
not enter the LTFU Phase should use a highly-effective method of contraception (see the 
SPM and Appendix 5 (Section 12.5) for a listing of examples of highly-effective
hormonal contraception) until at least 52 weeks after the last dose of study drug.  If a 
participant becomes pregnant within 52 weeks of the last dose of study drug the 
participant should notify the study site.
8.4.7.3.
Action to be Taken if Pregnancy Occurs
Any individual who becomes pregnant (intrauterine) while participating in this study 
must be withdrawn from the study and must immediately discontinue study drug.  
Participants who have received at least one dose of CAB LA and/or RPV LA should 
discontinue further dosing and continue oral HAART in the LTFU Phase (see Section 
4.2.3 above), after discussion with the Medical Monitor.  
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 Section 12.5, Appendix 5.


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Participants who have received at least one IM injection of CAB LA and RPV LA and 
become pregnant during the study will have additional PK samples collections to monitor 
CAB LA and RPV LA exposure throughout the pregnancy and at the time of delivery.  
Additionally, there will be an optional umbilical cord blood collection at time of delivery 
and/or breast milk after delivery, requiring additional parental informed consent.  Cord 
blood and breast milk samples would be used to better understand the level of PK 
exposure to the neonate, if any.
The pregnancy must be followed up to determine outcome (including premature 
termination) and status of mother and child(ren).  Pregnancy complications and elective 
terminations for medical reasons must be reported as an AE or SAE.  Abnormal 
pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAE.
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 intervention, 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.
8.5.
Adverse Events and Serious Adverse Events
The investigator and their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE. 
Please refer to Appendix 10 in Section 12.10 for study management information during 
the COVID-19 pandemic.
8.5.1.
Time Period and Frequency for Collecting AE and SAE 
Information

Any SAEs assessed as related to study participation (e.g., protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK 
product will be recorded from the time a participant consents to participate in 
the study up to and including any follow-up contact. 

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being 
available.

AEs will be collected from the start of Study intervention until the final follow-
up contact, at the timepoints specified in the Time and Events Table (Section 
8.1).

Medical occurrences that begin prior to the start of study intervention but after 
obtaining informed consent may be recorded on the Medical History/Current 
Medical Conditions section of the eCRF.


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
The method of recording, evaluating and assessing causality of AEs and SAEs 
plus procedures for completing and transmitting SAE reports to GSK are 
provided in Section 12.4, Appendix 4.

Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, 
at any time after a participant has been discharged from the study, and he/she 
considers the event reasonably related to the study intervention or study 
participation, the investigator must promptly notify GSK.
8.5.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 4, 
Section 12.4
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.  Appropriate questions include:

“How are you feeling?” 

“Have you had any (other) medical problems since your last visit/contact?”

“Have you taken any new medicines, other than those provided in this study, 
since your last visit/contact?”
8.5.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  All SAEs, and non-serious AEs of special 
interest (as defined in Section 8.7) will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the participant is lost to follow-
up (as defined in Section 7). Further information on follow-up procedures is given in 
Section 12.4, Appendix 4).
8.5.4.
Prompt Reporting of Serious Adverse Events and Other Events
SAEs, pregnancies, and liver function abnormalities meeting pre-defined criteria will be 
reported promptly by the investigator to the medical monitor as described in Table 4 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 4.
Criteria for liver chemistry stopping and follow-up criteria are in Section 7.1.1.


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Table 4
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 (CV) 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 standard of care
(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” documents


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Initial Reports
Follow-up Information on a Previous 
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
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 8.5.7 and Section 8.5.8, respectively.
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.
SAE reporting to GSK via electronic data collection tool

Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool.

If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the Medical Monitor.

Site will enter the serious adverse event data into the electronic system as soon as it 
becomes available.

After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) will be taken off-line to prevent the entry of new data or changes to 
existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, the site can report this information on a paper SAE form or to the 
Medical Monitor by telephone.

Contacts for SAE receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page.

The investigator will be required to confirm review of the SAE causality by ticking 
the ‘reviewed’ box at the bottom of the eCRF page within 72 hours of submission of 
the SAE.
The method of recording, evaluating, and follow-up of AEs and SAEs plus procedures 
for completing and transmitting SAE reports to the medical monitor are provided in the 
SPM.  Procedures for post study AEs/SAEs are provided in the SPM.  Primary and 


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secondary Medical Monitor/SAE contact information is provided on the Medical 
Monitor/Sponsor Information Page of the current protocol.
8.5.5.
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs
Disease related events (DREs) or outcomes listed in the CDC Classification System for 
HIV-1 Infections (Section 12.8) can be serious/life threatening and will be recorded on 
the HIV-Associated Conditions eCRF page if they occur. However, these individual 
events or outcomes, as well as any sign, symptom, diagnosis, illness, and/or clinical 
laboratory abnormality that can be linked to any of these events or outcomes are not 
reported to GSK as AEs and SAEs even though such event or outcome may meet the 
definition of an AE or SAE. However, if either of the following conditions applies, then 
the event must be recorded and reported as an SAE (instead of a DRE):

The investigator determines that the event or outcome qualifies as an SAE 
under part ‘other situations’ of the SAE definition (see Section 12.4.2), 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.
If any of the above conditions is met then record the DRE on the SAE page rather 
than the HIV Associated Conditions eCRF page and report promptly (i.e., expedited 
reporting, see Section 8.5.4) to GSK.
8.5.6.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to GSK of SAEs related to study intervention
(even for non- interventional post-marketing studies) is essential so that legal obligations 
and ethical responsibilities towards the safety of participants and the safety of a product 
under 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 product under clinical investigation.  GSK 
will comply with country specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/ IEC and investigators.


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Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.
8.5.7.
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 medical dictionary for regulatory activities 
(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.
8.5.8.
Death Events
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.


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8.6.
Toxicity Management
Adverse events that occur during the trial should be evaluated by the Investigator and 
graded according to the Division of AIDS (DAIDS) toxicity scales (See Section 12.3. 
“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 8.5 and Section 12.4.
8.6.1.
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 6.8).  IM dosing is 
expected to occur during the month 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 stipulated for IM dosing.   Any interruption outside of this 
guidance MUST be discussed with the Medical Monitor prior to reinitiating IM IP (see 
Section 6.8.1).
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 6.7.1.1.  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 human leukocyte antigen
(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.


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8.6.2.
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
8.6.3.
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 8.7.1).  Isolated Grade 3 lipid abnormalities do not 
require withdrawal of IP.
8.6.4.
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 / 


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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 8.7.1).  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.
8.7.
Specific Toxicities/Adverse Event Management
General guidelines for the management of specific toxicities that are considered to be 
associated with treatment of HIV participants. 
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 8.5.3.
8.7.1.
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. All Phase 3 participants who meet liver stopping criteria will be 
adjudicated by the ViiV Safety and Labelling Committee (VSLC) – resulting in a case 
summary, adjudication, and management plan. The VSLC contains an external expert 
hepatologist, familiar with both DILI and cabotegravir, who will participate in this 
review. This committee meets on a 3-weekly basis, and can be convened on an ad hoc 
basis as needed.
8.7.2.
Diarrhea
Participants with Grade 1 or 2 diarrhea may continue study intervention without 
interruption.  Participants with diarrhea of any toxicity grade may be treated 
symptomatically with anti-motility agents; however, the recommended daily dose of the 
chosen anti-motility agent must not be exceeded.  If symptoms persist or get worse on the 
recommended daily dose of the chosen anti-motility agent, then the anti-motility agent 
must be discontinued and consultation made with the Medical Monitor.
For participants with Grade 3 diarrhea that is unresponsive to the recommended dose of 
the anti-motility agents and for which an alternative etiology (e.g., infectious diarrhea) is 
not established, the treatment with the anti-motility agent and IP must be interrupted until 
resolution of diarrhea to Grade 2 or Baseline, after which IP and background ART may 
be resumed after discussion and agreement with the Medical Monitor.  If Grade 3 
diarrhea recurs within 28 days upon the resumption of IP, the IP should be permanently 
discontinued and the participant withdrawn from the study.  Any participant receiving at 


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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.
If loperamide is used for treatment of diarrhea, local prescribing information should be 
followed with respect to dose and frequency of administration.  Loperamide dosing 
should not exceed local prescribing information.
8.7.3.
Hypertriglyceridemia/ Hypercholesterolemia
Samples for lipid measurements must be obtained in a fasted state according to the Time 
and Events table (Section 8.1).  Participants who experience asymptomatic triglyceride or 
cholesterol elevations may continue to receive IP.  Clinical management of participants 
with hypertriglyceridemia/hypercholesterolemia should not be based upon non-fasting 
samples (obtained in the fed state).  A confirmatory fasting triglyceride and/or cholesterol 
level should be obtained prior to the institution of medical therapy for hyperlipidemia.  
Isolated Grade 3 and Grade 4 lipid abnormalities do not require withdrawal of IP.
Please see the Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular 
Disease Focus Group [Dube, 2003] for full discussion of management of hyperlipidemia 
in the context of HIV therapy.
8.7.4.
Seizures
Four cases of seizures have occurred in the CAB program cumulatively through 04 May 
2018.  
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 central nervous system (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.


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8.7.5.
Creatine Phosphokinase (CPK) Elevation
A Grade 3 or higher elevation in CPK should result in a repeat assessment within 2-
4 weeks to ensure the result is transient or due to exercise and will not require a change in 
study intervention.  A history regarding use of drugs known to cause increase of CPK 
(such as statins) physical activity or exercise preceding the CPK evaluation should be 
obtained. 
Grade 4 elevations in CPK should have a repeat assessment after the participant has 
abstained from exercise for >24 hours.  For persistent Grade 4 CPK elevations that are 
considered possibly or probably related to the IP, IP should be discontinued and the 
participant withdrawn from the study.  Any participant receiving at least one dose of 
CAB LA and /or RPV LA who discontinue IP / Withdraw will initiate treatment with 
HAART enter the LTFU Phase for 52 weeks of follow-up.
8.7.6.
Lipase Elevations and Pancreatitis
Participants with asymptomatic Grade 1 or 2 elevations in lipase may be followed closely 
for the development of symptoms.
Participants with asymptomatic Grade ≥3 elevations in lipase that are considered possibly 
or probably related to IP should have IP interrupted until serum lipase returns to 
Grade 2.  The lipase assay should be repeated within 2 weeks of any Grade ≥3 result.  
Participants with persistence of Grade ≥3 lipase in the absence of other diagnoses or 
reoccurrence of lipase elevation (at Grade ≥2) following reintroduction of IP should 
permanently discontinue IP.
Participants with a confirmed diagnosis of clinical pancreatitis that is considered possibly 
or probably related to IP should have IP held.  After complete resolution of the episode, 
participants may be re-challenged with IP after discussion with the Medical Monitor, 
only if the Investigator has compelling evidence that the event was not caused by IP.  
Upon re-challenge, lipase determinations should be performed every 2 weeks for at least 
6 weeks after re-initiation of treatment.  With any elevation of lipase of Grade ≥2 or any 
recurrence of symptoms, the participant should discontinue IP and be withdrawn from 
study.
Any participant receiving at least one dose of CAB LA and /or RPV LA who discontinue 
IP / Withdraw will initiate treatment with HAART and enter the LTFU Phase for 
52 weeks of follow up.
Drug Restart Following Transient Resolving Liver Events Not Related to Study Drug
Approval by VSLC for drug restart can be considered where:
Liver chemistries have a clear underlying cause (e.g., biliary obstruction, hypotension, 
and liver chemistries have improved to normal or are within 1.5 × baseline and 
ALT <3 × ULN). Ethics Committee or IRB approval of drug restart must be obtained, as 
required.


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If restart of drug is approved by 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 VSLC. 
Participants approved by VSLC for restarting study drug 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.
Refer to Section 12.3, 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
Refer to Section 12.7, Appendix 7: Liver Safety – Study intervention Restart Guidelines 
for further details.
8.7.7.
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.
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.  
8.7.7.1.
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;


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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.
8.7.7.2.
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. 
8.7.8.
QTc Prolongation
Participants with an average QTc interval >550 msec from three or more tracings 
separated by at least 5 minutes should have IP discontinued.  These criteria are based on 
an average QTc value of triplicate ECGs.  If an ECG demonstrates a prolonged QT 
interval, obtain 2 more ECGs over a brief period (~5-10 minutes) and use the averaged 
QTc values of the 3 ECGs to determine whether the participant should be discontinued 
from the study.  If an alternative cause of the QT prolongation is determined (e.g., 
participant receiving drug known to cause prolonged QT or TdP), then IP may be 
restarted after consultation with, and agreement by, the Medical Monitor. 
8.7.9.
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.  


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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.
8.7.10.
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.
8.7.11.
Abacavir Hypersensitivity Reaction (ABC HSR)
*This section applies to participants who discontinue LA treatment and enter LTFU and 
are administered a regimen containing ABC.*
The most significant toxicity associated with ABC is the well-characterized drug-related 
hypersensitivity reaction (HSR).  A detailed clinical description of this reaction 
(including the type and severity of events that can occur on re-challenge or reintroduction 
following ABC interruption for non-HSR reasons) and guidance regarding its 
management are included in the Local Country Prescribing Information for 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 participants, significantly reduced 
the incidence of clinically suspected ABC HSR from 7.8% (66 of 847) to 3.4% (27 of 
803) (p<0.0001).  In clinical studies EPZ108859 (ARIES) and CNA109586 (ASSERT), 


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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.
8.7.11.1.
Essential Participant Information
With reference to Local Country Prescribing Information and the ‘Participant Information 
and Consent Form’, Investigators must ensure that participants are fully informed 
regarding the following information on the hypersensitivity reaction prior to commencing 
ABC therapy:

Participants must be made aware of the possibility of a hypersensitivity reaction 
to abacavir that may result in a life-threatening reaction or death and that the risk 
of a hypersensitivity reaction is increased in individuals who are HLA-B*5701
positive.

Participants must also be informed that HLA-B*5701 negative individuals can 
also experience abacavir hypersensitivity reaction.  Therefore, ANY participant
who develops signs or symptoms consistent with a possible hypersensitivity 
reaction to abacavir MUST CONTACT their doctor IMMEDIATELY.

Participants who are hypersensitive to abacavir should be reminded that they must 
never take any abacavir containing medicinal products (e.g., 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 
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. 
8.7.11.2.
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 12.4.2
then, in addition to reporting the case as an SAE, the ABC HSR eCRF should also be 


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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.
8.7.12.
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.
Participants who develop rash of any grade should be evaluated for the possibility of an 
ABC HSR or a serious skin reaction such as Stevens - Johnson syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) or Erythema Multiforme.  SJS, TEN, and Erythema 
Multiforme have been reported very rarely in participants taking ABC-containing 
products.  These participants generally do not have the cluster of additional symptoms 
(e.g., gastrointestinal and respiratory) that characterize the ABC HSR, but they do have 
features typical of these serious skin reactions.
If a serious skin reaction develops, ABC (and / or all other concurrent medication(s) 
suspected in the Investigators causality assessment) should be discontinued, and the 
participant should not be re-challenged with any ABC-containing medicinal product (i.e., 
ZIAGEN, TRIZIVIR, EPZICOM, or KIVEXA).
As many products, other than abacavir, also cause rash and/or serious skin reactions, all 
other medicinal products that the participant is receiving should also be reviewed and 
discontinued as appropriate.
The following guidance is provided for clinical management of participants who 
experience rash alone in the absence of accompanying diagnosis of ABC HSR, systemic 
or allergic symptoms or signs of mucosal or target lesions.
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 10 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 SJS, 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 RH2009/00003/07].
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.


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Participants with an isolated Grade 1 rash may continue study drug at the Investigator’s 
discretion.  The participant should be advised to contact the Investigator immediately if 
there is any worsening of the rash, if any systemic signs or symptoms appear, or if 
mucosal involvement develops.
Participants may continue study drug for an isolated Grade 2 rash.  However, study drug 
(and all other concurrent medication(s) suspected in the Investigators causality 
assessment) should be permanently discontinued for any Grade ≥2 rash that is associated 
with an increase in ALT.  The participant should be advised to contact the physician 
immediately if rash fails to resolve (after more than 2 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 12.3, Appendix 3).
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 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.
8.8.
Pharmacokinetics
Plasma samples for determination of CAB and RPV concentrations will be collected at 
Day 1, Month 12 and Withdrawal visits of the study. For participants receiving oral DTG 
+ RPV, plasma samples for determination of DTG and RPV concentrations will be 
collected at the Withdrawal visit of the study. Additional samples will be collected for 
storage during the LTFU Phase (blood and plasma). Samples (blood and plasma) for 
determination of RPV concentrations will be protected from light at all times, from 
sampling collection through analysis.


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8.8.1.
PK Sample Collection
Blood samples for evaluation of CAB (2 mL each), RPV (2 mL each) and DTG (2 mL 
each) plasma PK concentrations will be collected from Q2M and oral DTG + RPV study
participants as described in Table 5. 
For participants transitioning from the LATTE study and receiving the CAB LA + RPV 
LA Q2M regimen at Day 1, PK samples should be collected within the window of 20-
28 hours after the last 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 at Day 1 after the 
pre-dose PK sample.
These participants will be expected to complete a PK dosing diary card noting the date 
and time of the last three oral doses of IP prior to the scheduled clinic visits at Day 1.  
The information from the diary card and the actual date and time of the PK samples will 
be recorded in the eCRF.  Additionally, dosing information on the clinic day, including 
dosing and the actual date and time of the PK samples, must be recorded on the eCRF.  
Plasma concentrations will be summarized and used to evaluate potential exposure-
response relationships.
The timing of PK samples may be altered and/or PK samples may be obtained at 
additional time points to ensure thorough PK monitoring.  
Table 5
CAB and RPV Plasma Pharmacokinetic Sample Schedule
Participants receiving 
CAB LA + RPV LA 
Q2M injections
CAB and RPV
PK samples for storage only:
Pre-dose: Day 1, Month 12, and Withdrawal
LTFU Period (off-drug; storage sample)
Months 1, 3, 6, 9, and 12
Participants receiving 
oral DTG + RPV
once daily
DTG and RPV
PK samples for storage only:
Withdrawal
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 Day 1 (for participants transitioning from the 
LATTE study to Q2M dosing) should be collected 20 to 28 hours after the last oral dose 
of CAB and RPV was taken.
If a participant withdraws from the study a PK sample should be collected as early as 
practically possible (i.e., at withdrawal visit or on the day the withdrawal decision was 
made). 


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Additional details concerning handling of PK samples, labeling and shipping directions 
will be supplied in the central laboratory manual.
Samples for determination of RPV will be protected from light until analyzed.
8.8.2.
Rationale for PK Sampling Strategy
Blood sampling for CAB, DTG and RPV concentrations will be performed during the 
course of the study to evaluate PK in HIV infected participants.  The proposed PK visits 
and sampling scheme at each visit presented in Section 8.1 is based on consideration of 
available PK data to support interim and final PK analysis planned in this study.
8.8.3.
Sample Analysis
8.8.3.1.
CAB and DTG Sample Analysis
Plasma CAB and DTG analysis will be performed under the control of PTS-DMPK, 
GlaxoSmithKline, the details of which will be included in the SPM. Concentrations of 
CAB and DTG will be determined in plasma samples using the currently approved 
bioanalytical methodology. Raw data will be archived at the bioanalytical site (detailed 
in the SPM).
Once the plasma has been analyzed for CAB and DTG, any remaining plasma may be 
analyzed for other compound-related metabolites and the results reported under a 
separate GSK platform technology and science - drug metabolism and pharmacokinetics
(PTS-DMPK), GSK protocol.  No human deoxyribonucleic acid (DNA) analysis will be 
performed on these samples.
8.8.3.2.
RPV Sample Analysis
Plasma RPV analysis will be performed under the control of Janssen R&D. 
Concentrations of RPV will be determined in plasma samples using the currently 
approved bioanalytical methodology.  Raw data will be archived at the bioanalytical site.
Once the plasma has been analyzed for RPV any remaining plasma may be used by the 
sponsor for further exploratory work on pharmacokinetics, metabolites, plasma protein 
binding, protein analysis, and biochemistry.  No human DNA analysis will be performed 
on these samples.
8.9.
Genetics
Information regarding genetic research is included in Section 12.6, Appendix 6:  Genetic 
Research.
8.10.
Viral Genotyping and Phenotyping
Whole venous blood samples will be obtained from each participant to provide peripheral 
blood mononuclear cells (PBMCs) and plasma for storage samples according to the Time 
and Events Table (see Section 8.1) for potential viral genotypic and phenotypic analyses.


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Details concerning the handling, labelling and shipping of these samples will be supplied 
separately. Genotypic and phenotypic analyses may be carried out by Monogram 
Biosciences using, but not limited to, their Standard PhenoSense and GenoSure testing 
methods for protease (PRO), reverse transcriptase (RT), and integrase assays.
8.10.1.
HIV-1 Polymerase Viral Genotyping and Phenotyping
Participants meeting confirmed virologic failure will have plasma samples tested for 
HIV-1 PRO and RT genotype and phenotype and HIV-1 integrase genotype and 
phenotype from samples collected at the time of meeting suspected virologic failure; 
these results will be reported to the investigator as soon as available to provide guidance 
for election of an alternative regimen.
8.10.2.
HIV-1 Exploratory Analysis
Additional analyses for HIV-1 resistance may, for example, be carried out on PBMC 
samples collected at Baseline and/or on stored blood samples from other relevant time 
points.  These analyses may include but are not limited to additional viral genotyping 
and/or phenotyping, as well as other virologic evaluations such as linkage and minority 
species analyses, low level HIV-1 RNA quantitation and measurement of viral replicative 
capacity. HIV-1 PRO and RT genotype and phenotype and HIV-1 integrase genotype and 
phenotype will also be determined on the last on-treatment isolates from participants who 
have HIV-1 RNA 200 c/mL regardless of confirmatory HIV-1 RNA.
8.11.
Value Evidence and Outcomes
Health outcomes assessments will be conducted according to the Time and Events Table 
(Section 8.1).  Assessments are recommended to be administered at the beginning of the 
visit prior to collection of blood for analysis and other scheduled assessments.
The original HIVTSQ included 10 items and underwent two stages of psychometric 
validation (Woodcock, 2001; Woodcock 2006). Recently, the HIVTSQ was adapted to 
include injectable treatment for HIV following a qualitative study with HIV participants 
in five European countries. The adaptation of the HIVTSQ included two additional items 
related to the mode of administration (ie: long acting intramuscular injection). These are: 


Psychometric analyses from three datasets (one from the UK, one from the USA, and one 
from the LATTE-2 trial) reveal that the addition of the two items in the original version 
of the HIVTSQ is suitable and does not reduce the overall validity of the questionnaire.
The current study will be using the HIVTSQs (status version) and the revised HIVTSQc 
(change version) of this recently developed HIVTSQ 12-item questionnaire.  The 
HIVTSQ 12-item questionnaire retains the option of calculating the total score as if it 
only had the original 10 items (as the original 10 items are included in the HIVTSQ 12).  
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are 
protected by third party copyright laws and therefore have been excluded.


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In addition, it allows for calculation of an 11-item scale score including the 
 item (item-
).  The
 item (item-
 will be included in 
the questionnaire as a stand-alone item to evaluate potentially painful injectables.  These 
measures will assess change in treatment satisfaction over time (in the same subjects) and 
compare current satisfaction with previous treatment satisfaction, from an earlier time 
point.
The HIV Dependent Quality of Life (HIVDQoL) is an individualised, self-completion 
questionnaire, specifically designed to measure quality of life in people living with HIV. 
The HIVDQoL was based on Audit of Diabetes-Dependent Quality of Life (ADDQoL) –
a widely used questionnaire designed previously for participants with diabetes and 
linguistically validated in more than 60 languages (Bradley, 1999; Speight, 2001, 
Wee, 2006). The HIVDQoL includes two overview items, 26 condition-specific domain 
items and a free text box. The overview items ask participants to rate their generic 
‘present QoL’ (7-point Likert scale, ranging from 
 to 
) and 
HIV-specific ‘impact of HIV on QoL’ (5-point Likert scale, ranging from
to 
).
The “Preference” question will contain a single item exploring whether participants 
prefer the CAB LA + RPV LA injectable to the oral CAB + RPV regimen administered 
in LATTE. 
The “Reason for Switch” question will contain a single item exploring the reasons why 
participants are interested in switching to the CAB LA + RPV LA.
8.11.1.
Value Evidence and Outcomes Endpoints (Secondary)

Change from Baseline (Day 1) in total “treatment satisfaction” score, and 
individual item scores of the HIVTSQs at Months 6, 12 (or Withdrawal).

Change in treatment satisfaction over time (using the HIVTSQc) at Month 12 (or 
Withdrawal).

Change from Baseline (Day 1) in HIVDQoL at Months 6, and 12, (or 
Withdrawal).
8.11.2.
Value Evidence and Outcomes Endpoints (Exploratory)

The “Preference” question will be assessed in participants from LATTE, to assess 
preference for CAB LA + RPV LA Q2M to oral CAB + RPV regimen, at 
Month 12 using a single dichotomous preference question.

The “Reason for Switch” question will be administered at Day 1 (Baseline) to 
assess the reasons for willingness to switch to LA injectable ART.
8.12.
Digital Reminder
The Ensemble personalized health record tool by Epividian will be used to remind 
participants of their injection visits and administration of other medications. This would 
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be using a streamlined version of Ensemble that utilizes a combination of short message 
service (short message service [SMS] text messages) and small web pages that are loaded 
from links included in SMS messages. This product architecture of combined SMS and 
web pages allows a participant with virtually any smart phone to use the application, 
whereas a full-featured smart phone app would require support for specific operating 
systems and devices.  Use of this tool is optional, but encouraged.
9.
DATA MANAGEMENT

For this study, participant data will be entered into GSK defined eCRFs, 
transmitted electronically to GSK or designee and combined with data provided 
from other sources in a validated data system.  

Management of clinical data will be performed in accordance with applicable 
GSK standards and data cleaning procedures to ensure the integrity of the data, 
e.g., removing errors and inconsistencies in the data.

Adverse events and concomitant medications terms will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) and an internal validated 
medication dictionary, GSKDrug.  

eCRFs (including queries and audit trails) will be retained by GSK, and copies 
will be sent to the investigator to maintain as the investigator copy.  Participant
initials will not be collected or transmitted to GSK according to GSK policy.
Please refer to Appendix 10 in Section 12.10 for study management information during 
the COVID-19 pandemic.
10.
STATISTICAL CONSIDERATIONS
10.1.
Statistical Hypotheses
No statistical hypotheses of treatment comparisons will be conducted within this study.
10.2.
Sample Size Determination
Approximately 100 participants will be enrolled into this study from the LATTE study.
10.2.1.
Sample Size Sensitivity
For the primary endpoint, antiviral response which will be assessed according the 
proportion of participants who have HIV-1 RNA ≥50 c/mL at Month 12, given the 
sample size of 100 participants and if the observed rate is around 3% then the upper 
bound of the 95% CI would be 6.3% (Table 6).


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Table 6
Precision in Estimation According to Sample Size and Observed 
Proportion with HIV-1 RNA 50 c/mL
Sample Size 
Observed Proportion
HIV-1 RNA 50 c/mL
Upper limit of 95% Confidence 
Interval †
90
2%
4.9%
100
2%
4.7%
110
2%
4.6%
90
3%
6.5%
100
3%
6.3%
110
3%
6.2%
90
4%
8.0%
100
4%
7.8%
110
4%
7.7%
† Two-sided confidence Interval calculated using the normal approximation method.
10.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled
All participants who sign the informed consent form (ICF)
Safety
All participants who take at least 1 dose of study intervention. 
Participants will be analyzed according to the intervention they 
actually received.  This population will be used for all summaries 
unless otherwise specified.
10.4.
Statistical Analyses
Endpoint
Statistical Analysis Methods
Primary
Descriptive summaries of the proportion of participants with plasma HIV-1 RNA 
50 c/mL as per FDA Snapshot algorithm at Month 12.
Secondary
Descriptive summaries of the following secondary efficacy endpoints will be 
produced:
Proportion of participants with plasma HIV-1 RNA <50 c/mL (c/mL) at Month 12 
using the FDA Snapshot algorithm (Missing, Switch or Discontinuation = Failure, 
Intent-to-Treat Exposed [ITT-E] population)
Proportion of participants with protocol-defined confirmed virologic failure (CVF) 
through over time
Proportion of participants with HIV-RNA greater than or equal to 50 c/mL as per 
FDA Snapshot algorithm overtime
Absolute values and changes from Baseline in viral load and CD4+ cell counts 


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Endpoint
Statistical Analysis Methods
over time
Exploratory
Will be described in the reporting and analysis plan (RAP)
10.4.1.
Safety Analyses
All safety analyses will be performed on the Safety Population. 
Endpoint
Statistical Analysis Methods
Secondary
Descriptive summaries of the following safety endpoints will be produced:
Incidence and severity of AEs and laboratory abnormalities over time 
Proportion of participants who discontinue treatment due to AEs over time
Change from Baseline in laboratory parameters over time
Exploratory
Will be described in the reporting and analysis plan 
10.4.2.
Other Analyses
PK, viral resistance, health outcomes and digital assistance program analyses will be 
described in the reporting and analysis plan. The population PK analysis and 
pharmacodynamic analyses will be presented separately from the main clinical study 
report (CSR). 
10.5.
Interim Analyses
The Reporting and Analysis Plan will describe the planned interim analyses in greater 
detail.


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11.
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Bierman WF, van Aqtamael MA, Nijhuis M, Danner SA, Boucher CA. HIV 
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Bradley C, Todd C, Gorton T, Symonds E, Martin A, Plowright R. The development of 
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Centers for Disease Control and Prevention (CDC) Revised surveillance case definition 
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Department of Health and Human Services (DHHS). Panel on Antiretroviral Guidelines 
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Department of Health and Human Services, Food and Drug Administration FDA, Center 
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Guidelines for the evaluation and management of dyslipidemia in human 
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Ford, SL, Gould, E, Chen, S, Margolis D, Spreen W, Crauwels H et al.  Lack of 
Pharmacokinetic Interaction between Rilpivirine and Integrase Inhibitors Dolutegravir 
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Intramuscular and Subcutaneous Injections in Healthy Adult.  Effective Date:  
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Evaluating a Long-Acting Intramuscular Regimen of GSK1265744 plus TMC278 For 
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III, Randomized, Multicenter, Parallel-Group, Non-Inferiority Study Evaluating the 
Efficacy, Safety, and Tolerability of Switching to Dolutegravir plus Rilpivirine from 
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equation to estimate glomerular filtration rate.  Ann Int Med. 2009; 150: 604-12.
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injury following positive drug rechallenge.  Regul Tox Pharm. 2009;54:84-90.
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12.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
12.1.
Appendix 1:  Abbreviations and Trademarks
3TC
Lamivudine, EPIVIR
ABC
Abacavir, ZIAGEN
ABC/3TC
Abacavir/lamivudine, EPZICOM, KIVEXA
ABC/DTG/3TC
Abacavir/dolutegravir/lamivudine, TRIUMEQ
ADR
Adverse drug reaction
AE
Adverse event
AIDS
Acquired immunodeficiency syndrome
ALT
Alanine aminotransferase
Anti-HBc
Hepatitis B core Antibody
Anti-HBs
Hepatitis B surface antibody
Anti-HbsAg
Antibodies against Hepatitis B surface Antigen
APAP
N-acetyl-para-aminophenol
ARV
Antiretroviral
ART
Antiretroviral therapy
AST
Aspartate aminotransferase
AUC
Area under the curve
AUC(0-)
Area under the concentration curve from 0 hours to the time 
of next dosing
BMI
Body Mass Index
BP
Blood Pressure
BUN
Blood Urea Nitrogen
CAB
Cabotegravir
CABG
Coronary artery bypass grafting
CAB LA
Cabotegravir long-acting
c/mL
Copies/milliliter
cART
Combination antiretroviral therapy
CHORUS
Clinical Health Outcomes Reporting and Utilization Service
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
CNS
Central Nervous System
CO2
Carbon Dioxide
ConART
Concomitant Antiretroviral Therapy
COVID-19
Coronavirus Disease 2019
CPK
Serum creatine phosphokinase
CSR
Clinical Study Report
Ctrough
Trough Concentrations
CI
Confidence interval
CIOMS
Council for International Organizations of Medical Sciences


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C
Trough Concentration
CV
Cardiovascular
CVF
Confirmed Virologic Failure
DAIDS
Division of Acquired Immunodeficiency Syndrome
DDI
Drug-Drug Interaction
DILI
Drug induced liver injury
dL
Deciliter
DNA
Deoxyribonucleic acid
DRE
Disease-Related Events
DRESS
Drug Reaction with Eosinophilia and Systemic Symptoms
DTG
Dolutegravir, TIVICAY
DVT
Deep vein thrombosis
ECG
Electrocardiogram
eCRF
Electronic case report form
EFV
Efavirenz
EFV/TDF/FTC
Efavirenz/tenofovir disoproxil fumarate/emtricitabine
GFR
Glomerular filtration rate
EVG
Elvitegravir
FDA
Food and Drug Administration
FDC
Fixed-dose combination
FRP
Females Of Reproductive Potential
FSH
Follicle Stimulating Hormone
GCP
Good Clinical Practice
GCSP
Global Clinical Safety and Pharmacovigilance
GI
Gastrointestinal
GSK
GlaxoSmithKline
HAART
Highly active antiretroviral therapy
HbsAg
Hepatitis B surface Antigen
HBV
Hepatitis B virus
HCG
human chorionic gonadotrophin
HCV
Hepatitis C virus
HDL
High density lipoprotein
HDPE
High density polyethylene
HIPPA
Health Insurance Portability and Accountability Act
HIV
Human immunodeficiency virus 
HIVDQoL
HIV Dependent Quality of Life
HIV TSQ
HIV treatment satisfaction questionnaire
HIV TSQ(c)
HIV treatment satisfaction questionnaire change version 
HIV TSQ(s)
HIV treatment satisfaction questionnaire status version
HLA
Human leukocyte antigen
HR
Heart Rate
HRT
Hormone Replacement Therapy
HSR
Hypersensitivity reaction
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee


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IEC
Independent Ethics Committee
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IM
Intramuscular
INH
Isonicotinylhydrazid
INI
Integrase inhibitor
INR
International normalized ratio
IP
Investigational Product
IRB
Institutional Review Board
ITT-ME
Intent-to-Treat Maintenance Exposed
ITT-E
Intent-to-treat exposed
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
ISR
Injection Site Reaction
IV
Intravenous
Kg
Kilogram
LA
Long Acting
LATTE
Long Acting anTiretroviral Treatment Enabling Study
LATTE-2
Long Acting anTiretroviral Treatment Enabling Study - 2
LDH
Lactate Dehydrogenase
LDL 
Low density lipoprotein
LLOD
Lower Limit Of Detection
LOC
Local Operating Company
LTFU
Long-Term Follow-UP
MCV
Mean corpuscular volume
MedDRA
Medical dictionary for regulatory activities
meq
Milliequivalence
MDL
Medicines Development Leader
Mg
Milligram
Mg/dL
Milligram
mmol
Millimolar
MSDS
Material Safety Data Sheet
msec
Milliseconds
g
Microgram
ng
Nanogram
NOAEL
No-Observed-Adverse-Effect-Level
NNRTI
Non-Nucleoside reverse transcriptase inhibitor
NRTI
Nucleoside reverse transcriptase inhibitor
NVP
Nevirapine
OCT-2
Organic cation transporter
PA-IC90
Protein-Adjusted 90% Inhibitory Concentration
PBMCs
Peripheral Blood Mononuclear Cells
PDVF
Protocol-defined virologic failure
PI
Protease inhibitor
PK
Pharmacokinetic
PO
Per-oral


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PP
Per-protocol
PPL
Project Physician Leader
PPN
Pre- and Postnatal
PrEP
Pre-exposure prophylaxis
PRO
Protease
PRTD
Proximal Renal Tubule Dysfunction
PSRAE
Possible suicidality-related adverse event
PT
Prothrombin Time
PTS-DMPK
Platform Technology and Science - Drug Metabolism and 
Pharmacokinetics
PTT
Partial Thromboplastin Time
PTCA
Percutaneous transluminal coronary angioplasty
PUD
Peptic Ulcer Disease
QTc
Corrected QT interval 
Q2M
Every 2 months
Q8W
Every 8 weeks
Q4W
Every 4 weeks
RAP
Reporting and Analysis Plan
RBC
Red blood cell
RNA
Ribonucleic acid
RPR
Rapid plasma reagin
RPV
Rilpivirine, Edurant
RPV LA
Rilpivirine long-acting
RT
Reverse transcriptase
SAE
Serious adverse event
SJS
Stevens-Johnson syndrome
SMS
Short message service
SOC
Standard of Care
SPM
Study Procedures Manual
STR
Single tablet regimen
SVF
Suspected Virologic Failure
TDP
Torsade des Pointes
TEN
Toxic epidermal necrolysis
TMC278
Tibotec Medicinal Compound 278
UDP
UDP-glucuronosyltransferase
ULN
Upper limit of normal
US
United States
VSLC
ViiV Safety and Labeling Committee
WBC
White blood cell
WOCBP
Woman of Childbearing Potential


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Trademark Information
Trademarks of ViiV Healthcare
Trademarks not owned by ViiV 
Healthcare
EPZICOM/KIVEXA
Edurant
TIVICAY
Genosure
TRIUMEQ
InForm
TRIZIVIR
MedDRA
ZIAGEN
PhenoSense


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12.2.
Appendix 2: Regulatory, Ethical, and Study Oversight 
Considerations
12.2.1.
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) GCP and applicable country-specific regulatory 
requirements.
The study will be conducted in accordance with all applicable regulatory requirements, 
and with ViiV/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
12.2.2.
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. 


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Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study.
12.2.3.
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 ICF.
The ICF may contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research in accordance with SOP-GSKF-410. The 
investigator or authorized designee will explain to each participant the objectives of the 
exploratory 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 signature will be required to document a participant's agreement to allow any 
remaining specimens to be used for exploratory research. Participants who decline to 
participate will not provide this separate signature.
12.2.4.
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 also be explained to the participant. 

The participant must be informed that his/her medical records may be 
examined by Clinical Quality Assurance auditors or other authorized 


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personnel appointed by the sponsor, by appropriate IRB/IEC members, 
and by inspectors from regulatory authorities.
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.
12.2.5.
Dissemination of Clinical Study Data

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 protocol and 
results summary and for development of a manuscript for publication for 
this study will be in accordance with GSK Policy.

GSK intends to make anonymized participant-level data from this trial 
available to external researchers for scientific analyses or to conduct 
further research that can help advance medical science or improve 
participant care. This helps ensure the data provided by trial participants 
are used to maximum effect in the creation of knowledge and 
understanding

A manuscript will be progressed for publication in the scientific literature 
if the results provide important scientific or medical knowledge.
12.2.6.
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. 


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
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.

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 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. 
12.2.7.
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.
12.2.8.
Study and Site Closure
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.


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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 ViiV/GSK determines such action is needed, ViiV/GSK will discuss the reasons 
for taking such action with the investigator or the head of the medical institution 
(where applicable).  When feasible, ViiV/GSK will provide advance notification to 
the investigator or the head of the medical institution, where applicable, of the 
impending action.

Upon completion or premature discontinuation of the study, the GSK monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and ViiV/GSK Standard 
Operating Procedures.

If the study is suspended or prematurely discontinued for safety reasons, ViiV/GSK 
will promptly inform all investigators, heads of the medical institutions (where 
applicable) and/or institution(s) conducting the study. ViiV/GSK will also promptly 
inform the relevant regulatory authorities of the suspension or premature 
discontinuation of the study and the reason(s) for the action.  

If required by applicable regulations, the investigator or the head of the medical 
institution (where applicable) must inform the IRB/IEC promptly and provide the 
reason for the suspension or premature discontinuation.
12.2.9.
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.


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12.3.
Appendix 3: 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.
12.3.1.
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.


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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


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12.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
12.4.1.
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. 

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. Also, "lack of 
efficacy" or "failure of expected pharmacological action" constitutes an AE or SAE.


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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 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.
12.4.2.
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.


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Results in persistent 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 (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
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.
12.4.3.
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


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
Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularization
12.4.4.
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 (eg, 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.
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.


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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.


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12.4.5.
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 in SRM.
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 in SRM.


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12.5.
Appendix 5: Contraceptive Guidance and Collection of 
Pregnancy Information
12.5.1.
Definitions
12.5.1.1.
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.
12.5.1.1.1. 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.


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12.5.2.
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 7.
Table 7
Highly Effective Contraceptive Methods

CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:

Highly Effective Methodsb That Have Low User Dependency 

Implantable progestogen-only hormone contraception associated with inhibition of ovulationc

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)c

Bilateral tubal occlusion

Vasectomized partner
Note: Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the absence 
of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days.

Highly Effective Methodsb That Are User Dependent

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc
oral
intravaginal
transdermal
injectable

Progestogen-only hormone contraception associated with inhibition of ovulationc
oral
injectable

Sexual abstinence
Note: 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 intervention. 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
a.
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies.
b.
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those when 
used consistently and correctly.
c.
Male condoms must be used in addition to hormonal contraception If locally required, in accordance with Clinical 
Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those which inhibit 
ovulation as the primary mode of action.
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for this 
study. Male condom and female condom should not be used together (due to risk of failure with friction)


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Pregnancy Testing
o
WOCBP should only be included after a confirmed menstrual period and a 
negative highly sensitive serum pregnancy test 
o
Additional pregnancy testing should be performed as per the study Time and 
Events Table.
o
Pregnancy testing will be performed whenever a menstrual cycle is missed or 
when pregnancy is otherwise suspected 
o
Pregnancy testing will be performed and assayed in the central laboratory OR 
using the test kit provided by the central laboratory / provided by the sponsor 
/approved by the sponsor and in accordance with instructions provided in its 
package insert]  
12.5.3.
Collection of Pregnancy Information:
Female Participants who become pregnant

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 participant and neonate, 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 intervention by the investigator, will be reported to 
GSK as described in Appendix 4 (Section 12.4). 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. 
Any female participant who becomes pregnant while participating  

will discontinue study intervention or be withdrawn from the study


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12.6.
Appendix 6: Genetics Research
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 (LA and oral), DTG + RPV (oral)
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 a priori hypothesis has been 
identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.  

A 6 mL blood sample will be taken for deoxyribonucleic acid (DNA) extraction.  
A blood sample is collected at the baseline visit, after the 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.


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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 
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.


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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 
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.


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12.7.
Appendix 7: Liver Safety: Study intervention Restart or 
Rechallenge Guidelines
12.7.1.
VSLC Guidelines for Drug Restart or Rechallenge after stop for 
Liver criteria
Drug Rechallenge refers to resuming study intervention following drug induced liver 
injury (DILI). Because of the risks associated with rechallenge after DILI (see Drug 
Rechallenge Background below) this should only be considered for a participant for 
whom there is compelling evidence of benefit from a critical or life-saving medicine, 
there is no alternative approved medicine available, and a benefit:risk assessment of 
rechallenge is considered to be favorable (Table 8, Figure 4).
Drug Restart refers to resuming study intervention 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 9; Figure 5).
As this determination can be difficult, for the purpose of these guidelines, cases 
should be treated as rechallenges if there is any reasonable likelihood that the liver 
event is related to study drug. Restarts should be limited to cases in which there is 
clear evidence that the underlying cause of the liver event is not related to study 
drug.
DRUG RECHALLENGE
Background: Following drug-induced liver injury, drug rechallenge is associated with a 
13% mortality across all drugs in prospective studies [Andrade, 2009].  Clinical outcomes 
vary by drug, with nearly 50% fatality with halothane re-administered within one month 
of initial injury.  However, some drugs seldom result in recurrent liver injury or fatality.
Risk factors for a fatal drug rechallenge outcome include:

hypersensitivity [Andrade, 2009] with initial liver injury (e.g. fever, rash, 
eosinophilia)

jaundice or bilirubin >2xULN with initial liver injury (direct bilirubin >35% of 
total)

participant currently exhibits severe liver injury defined by: ALT3xULN, 
bilirubin 2xULN (direct bilirubin >35% of total), or INR1.5

prior serious adverse event or fatality has earlier been observed with drug 
rechallenge [Papay, 2009; Hunt, 2010]

evidence of drug-related nonclinical liability (e.g. reactive metabolites; 
mitochondrial impairment [Hunt, 2010])


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12.7.2.
VSLC Decision Process for Drug Rechallenge Approval or 
Disapproval

Principal Investigator (PI) requests consideration of drug rechallenge for a 
participant receiving compelling benefit from a critical or life-saving drug, who 
exhibits liver chemistry elevation meeting participant stopping criteria in relation 
to DILI, with no alternative treatment

By definition treatment naïve participants will only be considered for rechallenge 
if they were infected with a multi-resistant virus.

Medical Monitor and Global Clinical Safety and Pharmacovigilance (GCSP) 
Physician review the participant’s rechallenge risk factors (consultation with the 
Hepatotoxicity Panel is available) and complete checklist (Table 8).

The local operating company (LOC) medical directors (ViiV and/or GSK where 
applicable) should be informed that study drug rechallenge is under consideration 
and of the final decision, whether or not to proceed.

The Medical Monitor and GCSP Physician are accountable to review and agree 
on the following prior to preparing request for rechallenge documentation for 
presentation to VSLC:
–
Compelling benefit of the investigational product (IP) for this participant and 
no alternative therapy 
o
must present source data defining the participant’s current 
resistance profile with documented evidence of extensive drug 
resistance and previous drug history 

Relative benefit-risk of drug rechallenge, with consideration of the following high 
risk factors:

Initial liver injury event included: fever, rash, eosinophilia, or bilirubin
2xULN (or direct bilirubin >35% of total, if available)

Participant currently exhibits severe liver injury defined by: ALT 
>3xULN, bilirubin >2xULN (direct bilirubin >35% of total, if available), 
or INR>1.5

SAE or fatality has earlier been observed with IP rechallenge

IP is associated with known nonclinical hepatic liability/ injury

Relevant physicians (listed below) must review and agree on action to be taken 
regarding request for drug rechallenge:  

Safety Review Team Leader, Safety Development Leader, or Senior 
Safety Physician

Medicines Development Leader (MDL) and Project Physician Leader 
(PPL) 

Request is taken to full VSLC for final decision


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Table 8
Checklist for drug rechallenge for critical medicine (Following drug-
induced liver injury, drug rechallenge is associated with 13% 
mortality across all drugs in prospective studies)
Yes
No
Compelling benefit of IP for this participant and no alternative therapy.  
Provide brief explanation:
Relative benefit-risk favorable for drug rechallenge, after considering the 
following high risk factors:
Initial liver injury event included:
fever, rash, eosinophilia, or hypersensitivity
bilirubin2xULN (direct bilirubin >35% of total)
Participant currently exhibits ALT >3xULN, bilirubin >2xULN (direct 
bilirubin >35% of total, if available), or INR>1.5
SAE or fatality has earlier been observed with IP rechallenge
If yes, please provide brief explanation:
IP associated with known nonclinical hepatic liability/ injury
Source data defining the participant’s current resistance profile
Previous drug history


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Figure 4
VSLC process for drug rechallenge approval or disapproval
Participant exhibits liver injury on drug while disease condition 
stable or improving
Medical Monitor and Safety Physician(s) to discuss benefit:risk 
and
Any fever, rash, eosinophilia, hypersensitivity with initial liver injury 
[Andrade, 2009] in this participant?
Currently ALT>3xULN and Bilirubin >2xULN or INR >1.5x in this 
participant suggesting failing liver
Any prior severe/fatal outcomes reported on drug rechallenge [Papay, 
2009; Hunt, 2010] with this drug?
Any Evidence of nonclinical hepatic liability/injury with this drug?
LOC Medical Director to be informed of rechallenge consideration and 
final decision
Relevant physicians (from Safety and Clinical functions) review and 
agree on rechallenge 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 twice weekly for 
a minimum of one month and thereafter for 
as long as clinically indicated
Safety Review Teams record rechallenge 
outcome
VSLC notified of rechallenge outcome
PI promptly informed of decision
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.


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12.7.3.
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< 5xULN. 

GSK Medical Monitor and GCSP Physician to review the participant’s diagnosis 
restart risk factors (Hepatotoxicity Panel consultation is available) and complete 
checklist (Table 9).
–
must present source data defining the participant’s current resistance 
profile with documented evidence of extensive drug resistance and previous 
drug history.

The local operating company (LOC) medical director should be informed that 
study drug restart is under consideration and of the final decision, whether or not 
to proceed.

Relevant physicians (listed below) must review and agree on action to be taken 
regarding request for drug restart:  

Safety Review Team Leader, Safety Development Leader, or Senior Safety 
Physician

MDL and PPL

Request is taken to VSLC for final decision
Table 9
Checklist for Phase IIb drug restart after well-explained liver injury 
(e.g. biliary, pancreatic, hypotensive events, congestive heart failure 
(CHF), acute viral hepatitis), and improvement of liver chemistry to 
normal or 1.5x baseline & ALT<5xULN
Yes
No
Is 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 participant’s current resistance profile
Previous drug history


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Figure 5
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 
<5xULN
Any fever, rash, eosinophilia in this participant or HLA genetic marker 
associated with liver injury [Andrade, 2009]?
Any evidence of alcoholic hepatitis or DILI in this participant?
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 rechallenge 
outcome
VSLC notified of rechallenge outcome
PI promptly informed of decision
12.7.4.
Medical monitor, GCSP Physician and PI actions for Restart or 
Rechallenge following VSLC decision
12.7.4.1.
Medical Monitor and GCSP Physician Actions

Medical Monitor must notify PI of VSLC’s rechallenge (or restart) decision and 
recommended dosing regimen in writing and Medical Monitor must record note 
in study files.

The Safety Review Team must record rechallenge (or restart) outcomes and the 
GCSP Physician must send these to the VSLC (see template below).

All severe reactions (rechallenge associated with bilirubin>2xULN or jaundice, 
or INR1.5), SAEs or fatalities which occur following a drug rechallenge (or 
restart) must be immediately reported to Line Management including, VSLC 


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Chair, VP Global Medical Strategy and EU Qualified Person for 
Pharmacovigilance. 
12.7.4.2.
PI Actions:

The PI must obtain Ethics Committee or Institutional Review Board approval of 
drug rechallenge or restart, as required. 

If VSLC approves drug rechallenge or restart, the participant must sign a new 
informed consent containing a clear description of possible benefits and risks of 
drug administration including recurrent, more severe liver injury or possible 
death.

Targeted drug rechallenge or drug restart consent form must be used.

The participant’s informed consent must be recorded in the study chart, and the 
drug administered at agreed dose, as communicated by Medical Monitor.

Liver chemistries must be followed twice weekly for ‘rechallenge’ cases and 
once weekly for ‘restart’ cases for a minimum of one month and thereafter for as 
long as clinically indicated following drug re-initiation.  If participant exhibits 
protocol-defined liver chemistry elevations, IP should be discontinued as protocol 
specified.

Medical Monitor and the Ethics Committee or Institutional Review Board must 
be informed of the participant’s outcome following drug rechallenge or restart.
Drug Rechallenge or Drug Restart Outcomes Table Template
To be completed/updated and provided to VSLC with each event recorded across 
studies and indications
Drug Rechallenge/Restart Outcomes Table – Update with each event
Protocol#
Participant#
Rechallenge or 
Restart?
Safety 
outcome*
Drug 
benefit
Rechallenge/restart safety outcomes:
0 = no liver chemistry elevation
1 = recurrent liver chemistry elevation not meeting participant stopping criteria
2 = recurrent liver chemistry elevation meeting participant stopping criteria
3 = serious adverse event
4 = fatality


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12.8.
Appendix 8: 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


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
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.


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12.9.
Appendix 9: Country-specific requirements
12.9.1.
Study Duration
In this study, the intention to provide access to CAB LA + RPV LA Q2M or DTG + RPV 
based on participants elected assignment until the regimen receives local (by country) 
Regulatory approval, and becomes commercially available. Therefore, the duration of 
the study will vary from country to country and is dependent on the recruitment time for 
the study and the time taken to achieve local approval for marketing. During this time, 
participants will be monitored at minimum every 2 months to ensure they continue to 
derive clinical benefit from CAB LA + RPV LA and DTG + RPV.


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12.10.
Appendix 10:  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. 
12.10.1.
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 


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authorised/accredited local laboratory (or other relevant clinical facility), if this 
can be done within local restrictions on physical distancing. The site should 
proactively inform the sponsor about such instances. Local laboratory results may 
be used to inform safety decisions. Results should be retained in source records.

When on-site visits are reduced, it is important that the investigator continue 
collecting relevant clinical information, including adverse events, from the 
participant through alternative means, e.g. by telephone contact.

There may be cases where the current principal investigator (PI) of a site is 
indisposed for a period and may need to delegate parts of his/her duties 
temporarily, e.g. to a sub-investigator. Any such changes should be documented 
in the site’s source records. Any permanent changes in PI should be 
communicated to the sponsor.

There may also be circumstances where immediate actions are required by the 
sponsor and/or investigator, outside of what is contemplated in the protocol, in 
order to protect a study participant from immediate hazard. Any such measures 
will be carefully documented and conducted in accordance with the National 
Competent Authority (NCA)/IRB/IEC regulations.
12.10.2.
Changes to Informed Consent
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.  
Any updated informed consent form or other subject-facing materials should be provided 
to participants by e-mail, mail or courier before re-consent is obtained. Any consent 
obtained this way should be documented in source records and confirmed by way of 
normal consent procedure at the earliest opportunity when participants attend their next 
on-site study visit.
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval.
12.10.3.
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:


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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 6.7.1.1. 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.


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Oral bridging with Standard of Care Antiretroviral Therapy (SOC ART)
For participants impacted by COVID-19, where the participant is unable to receive IM 
injections, and oral CAB + RPV is not available for use, oral bridging with any 
commercially available, guideline-recommended, SOC ART regimen is permitted. The 
start date of oral bridging should be within the dosing window for the missed IM dosing 
visit.  Please reach out to your study medical monitor for approval of SOC ART as oral 
bridging, in order to document the use of commercially available SOC ART within the 
study.
Participants who use oral SOC ART as short-term oral bridging as a result of COVID-19 
will not be considered formally withdrawn insofar as they wish to continue on the study.  
Individuals who bridge with SOC ART will be permitted to return to IM dosing, on 
study, once the COVID-19 conditions permit resumption of site activities.  
The investigator should reach out to the medical monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with SOC ART is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the medical monitor to 
continue with oral bridging therapy.  Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging.
12.10.4.
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.


2018N356280_02
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
Please refer to your CRA or local study manager for support with the DTP 
process, ensuring reference to current sponsor guidance and arrangement of a 
courier that can support shipment of IMP directly to participants.
12.10.5.
COVID-19 Experimental Agents
If any treatments for COVID-19 are planned for a study participant, please consult with 
the study medical monitor to ensure that relevant drug interactions are considered and to 
ensure that continued study participation remains appropriate.
12.10.6.
COVID-19 Specific Data Capture
12.10.6.1. Capturing COVID-19 Specific Protocol Deviations
In order to summarise the impact of COVID-19 in a systematic way and in line with 
regulatory authorities’ recommendations, any study-level impact around COVID-19 will 
be documented as a protocol deviation. This will include the permissible actions 
summarized in this Appendix, which are taken to protect patient safety, including the use 
of CAB + RPV or SOC ART as oral bridging as well as missed visits and assessments as 
a result of logistical challenges resulting from COVID-19.
Although the conduct of remote visits and the continuity of antiretroviral therapy, via oral 
bridging, are being utilized to protect patient safety, these events fall outside of the intent 
of the original protocol design, may have an impact on data interpretation, and thus will 
be characterized as protocol deviations for the purposes of data summary and analysis.
Any protocol deviations resulting from COVID-19 will be clearly identified as such 
within the protocol deviation description and summarised separately.
Please refer to your study procedure manual for specific details on capturing protocol 
deviations as a result of COVID-19.
12.10.6.2. Capturing COVID-19 Specific AEs and SAEs
It is important for the study team to describe COVID-19 related adverse events/serious 
adverse and their impact on study data and outcomes. Standardization of case definitions 
will facilitate future data analysis. 
Please use the following guidance: 
1. AEs should continue to be evaluated as to whether they meet SAE criteria as 
defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. SAEs and AEs should be submitted following usual 
study procedures and timelines. 


2018N356280_02
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2. When an in-person clinic visit is not possible, please conduct a remote telehealth 
visit to assess for, and document any AEs/SAEs.
3. Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released March 20, 2020, represents a time point for 
standardized collection. We recognize definitions are likely to continue to 
evolve. When reporting both serious and non- serious adverse events (related 
to COVID-19 infection, investigators should use the following Verbatim 
terms: 
a) Suspected COVID-19 infection; or 
b) Probable COVID-19 infection; or 
c) Confirmed COVID-19 infection 
4. Sites should contact the study Medical Monitor for questions related to definitions 
and reporting, and decisions around impact to study drug continuation. 
5. A new COVID-19 infection Case Report Form will be added to the eCRF to 
collect additional details about the reported COVID-19 AE or SAE data. It is 
important to collect the correct information from each participant reporting a 
COVID-19 AE or SAE. Therefore, please use the CRF templates to help you 
collect this information, once available.
WHO Case Definition - March 20, 2020 Version (https://www.who.int/publications-
detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov)):
Suspected case: 
A. A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or 
residence in a location reporting community transmission of COVID-19 disease 
during the 14 days prior to symptom onset; 
OR 
B. A patient with any acute respiratory illness AND in contact (see definition of 
“contact” below) with a confirmed or probable COVID-19 case (see definition of 
contact) in the last 14 days prior to symptom onset; 
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. 


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Probable case: 
A. A suspect case for whom testing for the COVID-19 virus is inconclusive 
(Inconclusive being the result of the test reported by the laboratory). 
OR 
B. A suspect case for whom testing could not be performed for any reason. 
Confirmed case: 
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms. 
Covid-19 Contact:
A contact is a person who experienced any one of the following exposures during the 2 
days before and the 14 days after the onset of symptoms of a probable or confirmed case: 
1. Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes; 
2. Direct physical contact with a probable or confirmed case; 
3. Direct care for a patient with probable or confirmed COVID-19 disease without 
using proper personal protective equipment; OR 
4. Other situations as indicated by local risk assessments. 
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken which led to 
confirmation.


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12.11.
Appendix 11: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC).
Amendment 1, 22-Jun-2018
Overall Rationale for the Amendment: This amendment was completed to clarify 
procedures, adjust exclusion criteria, add missing risk assessment language and to clean 
up minor grammatical errors.
Section # and 
Name
Description of Change
Brief Rationale
Title page
Update of abbreviated study title
Updated to match eTrack
Section 1.1 
Synopsis
Update of abbreviated study title
Updated to match title page
Section 1.3 
Schedule of 
Activities
Clarification of procedures in SoA
Updated to provide clarity, removed 
completion of ISR diaries and match Time 
and Events tables in main protocol body.
Section 2.3.1 
Risk Assessment
Addition of DTG + RPV risk 
assessment
Updated to add in most up to date safety 
and risk information
Section 5.2 
Exclusion Criteria
Removal of Exclusion Criteria #7
Participants who are diagnosed with 
syphilis can enrol in study and be treated.
Section 8.1 Time 
and Events Table
Update of procedures
Updated to provide clarity and remove 
completion of ISR diaries.
Section 8.8 
Pharmacokinetics
Addition of DTG PK storage 
sample information
Left out in error in original document
Section 11 
References
Updated DTG IB reference to 
most up to date version
Update to ensure most up to date DTG 
safety and efficacy data is utilized.
Throughout
Minor editorial and document 
formatting revisions
Minor, therefore have not been 
summarized

SAP_001.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
209035
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for A Phase IIb, Multicenter, 
Open-label, Rollover Study Evaluating the Efficacy, Safety 
and Tolerability of Long-acting Cabotegravir Plus Long-
acting Rilpivirine Administered Every Two Months in HIV-1 
infected Adults who are Virologically Suppressed and 
Participated in Study LAI116482
Compound Number
:
GSK1265744
Effective Date 
:
31-JAN-2020
Description:

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 209035.

This RAP is intended to describe the efficacy, safety and tolerability analyses 
required for the study.

This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s):
Approver
Date
Approval Method
Senior Statistician II, Quanticate
31-01-2020
Email
Copyright 2020 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD


CONFIDENTIAL
The GlaxoSmithKline group of companies
209035
2
RAP Team Approvals:
Approver
Date
Approval Method
Clinical Development Manager, ([HIV] [ViiV 
Sci Med Officer])
31-01-2020
Email
Programming Manager (HIV, Clinical 
Programming)
31-01-2020
Email
Clinical Statistics and Clinical Programming Line Approvals:
Approver
Date
Approval Method
Manager, Statistics (Infectious Diseases, Clinical 
Statistics)
31-01-2020
Email
Programming Manager (Infectious Diseases, 
Clinical Programming)
31-01-2020
Email
PPD
PPD
PPD
PPD


CONFIDENTIAL
209035
3
TABLE OF CONTENTS
PAGE
1.
INTRODUCTION......................................................................................................6
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................6
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................6
2.2.
Study Objective(s) and Endpoint(s)...............................................................6
2.3.
Study Design ................................................................................................8
2.4.
Statistical Hypotheses / Statistical Analyses .................................................9
3.
PLANNED ANALYSES ..........................................................................................10
3.1.
Interim Analyses .........................................................................................10
3.2.
Final Analyses ............................................................................................10
4.
ANALYSIS POPULATIONS ...................................................................................10
4.1.
Protocol Deviations.....................................................................................11
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................12
5.1.
Study Treatment & Sub-group Display Descriptors.....................................12
5.2.
Baseline Definitions ....................................................................................12
5.3.
Multicentre Studies .....................................................................................12
5.4.
Examination of Covariates, Other Strata and Subgroups............................12
5.4.1.
Covariates and Other Strata ........................................................12
5.4.2.
Examination of Subgroups...........................................................13
5.5.
Multiple Comparisons and Multiplicity .........................................................14
5.5.1.
Primary Comparison of Interest ...................................................14
5.6.
Other Considerations for Data Analyses and Data Handling 
Conventions................................................................................................14
6.
STUDY POPULATION ANALYSES .......................................................................15
6.1.
Overview of Planned Study Population Analyses........................................15
6.2.
Prior and Concomitant Medications ............................................................16
7.
EFFICACY ANALYSES..........................................................................................18
7.1.
Primary Efficacy Analyses ..........................................................................18
7.1.1.
Endpoint / Variables.....................................................................18
7.1.2.
Summary Measure ......................................................................18
7.1.3.
Population of Interest...................................................................18
7.1.4.
Strategy for Intercurrent (Post-treatment selection) Events..........18
7.1.5.
Statistical Analyses / Methods .....................................................18
7.2.
Secondary Efficacy Analyses......................................................................19
7.2.1.
Endpoint / Variables.....................................................................19
7.2.2.
Summary Measure ......................................................................19
7.2.3.
Population of Interest...................................................................19
7.2.4.
Strategy for Intercurrent (Post-treatment selection) Events..........19
7.2.5.
Statistical Analyses / Methods .....................................................19
7.3.
Exploratory Efficacy Analyses.....................................................................20
8.
SAFETY ANALYSES .............................................................................................21
8.1.
Adverse Events Analyses ...........................................................................21


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209035
4
8.1.1.
Injection Site Reactions ...............................................................21
8.2.
Clinical Laboratory Analyses.......................................................................21
8.3.
Adverse Events of Special Interest Analyses..............................................22
8.4.
Other Safety Analyses ................................................................................23
9.
HEALTH OUTCOMES ANALYSES........................................................................23
9.1.
Endpoint / Variables....................................................................................23
9.2.
Summary Measure .....................................................................................24
9.3.
Population of Interest..................................................................................24
9.4.
Strategy for Intercurrent (Post-treatment selection) Events.........................24
9.5.
Statistical Analyses / Methods ....................................................................24
10. VIROLOGY ............................................................................................................24
11. REFERENCES.......................................................................................................26
12. APPENDICES........................................................................................................27
12.1.
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population.....................................................................................27
12.1.1.
Exclusions from Per Protocol Population .....................................27
12.2.
Appendix 2: Schedule of Activities ..............................................................29
12.2.1.
Protocol Defined Schedule of Events for CAB LA + RPV 
LA Q2M Administration................................................................29
12.2.2.
Protocol Defined Schedule of Events for DTG + RPV 
Administration..............................................................................33
12.2.3.
Protocol Defined Schedule of Events for Long Term 
Follow Up.....................................................................................35
12.3.
Appendix 3: Assessment Windows .............................................................37
12.3.1.
Definitions of Assessment Windows for Analyses........................37
12.3.2.
Definitions of Assessment Windows for Data Other than 
Health Outcomes.........................................................................37
12.3.3.
Assessment Window for Study Conclusion..................................41
12.3.4.
Assessment Window for Health Outcome Data ...........................41
12.3.4.1.
HIVTSQs, HIVTSQc, HIVDQoL, Preference...............41
12.3.4.2.
Reasons for Switch.....................................................42
12.3.5.
Multiple assessments within an Analysis Window........................42
12.4.
Appendix 4: Study Phases and Treatment State.........................................43
12.4.1.
Study Phases ..............................................................................43
12.4.2.
Treatment State...........................................................................44
12.4.2.1.
Treatment States for AE Data.....................................45
12.5.
Appendix 5: Data Display Standards & Handling Conventions....................47
12.5.1.
Reporting Process .......................................................................47
12.5.2.
Reporting Standards....................................................................47
12.6.
Appendix 6: Derived and Transformed Data ...............................................49
12.6.1.
General........................................................................................49
12.6.2.
Study Population..........................................................................50
12.6.3.
Efficacy........................................................................................52
12.6.4.
Safety ..........................................................................................54
12.6.5.
Health Outcomes.........................................................................58
12.6.6.
Virology .......................................................................................70
12.7.
Appendix 7: Reporting Standards for Missing Data.....................................74
12.7.1.
Premature Withdrawals................................................................74


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209035
5
12.7.2.
Handling of Missing Data.............................................................74
12.7.2.1.
Handling of Missing and Partial Dates ........................75
12.8.
Appendix 8: Values of Potential Clinical Importance ...................................76
12.8.1.
Laboratory Values........................................................................76
12.8.2.
ECG.............................................................................................76
12.9.
Appendix 9: Snapshot Algorithm Details .....................................................77
12.10. Appendix 10: Identification of Adverse Events of Special Interest...............81
12.11. Appendix 11: Abbreviations & Trade Marks ..............................................111
12.11.1. Abbreviations.............................................................................111
12.11.2. Trademarks ...............................................................................112
12.12. Appendix 12: List of Data Displays............................................................113
12.12.1. Data Display Numbering............................................................113
12.12.2. Mock Example Shell Referencing ..............................................113
12.12.3. Deliverables...............................................................................113
12.12.4. Study Population Tables............................................................114
12.12.5. Efficacy Tables ..........................................................................118
12.12.6. Efficacy Figures .........................................................................120
12.12.7. Safety Tables.............................................................................121
12.12.8. Safety Figures ...........................................................................129
12.12.9. Health Outcomes Tables ...........................................................132
12.12.10.Virology Tables..........................................................................134
12.12.11.ICH Listings ...............................................................................136
12.12.12.Non-ICH Listings........................................................................139
12.13. Appendix 13: Example Mock Shells for Data Displays ..............................140


CONFIDENTIAL
209035
6
1.
INTRODUCTION
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol:
Revision Chronology:
2018N356280_00
16-MAY-2018
Original
2018N356280_01
22-JUN-2018
This amendment was completed to clarify procedures, adjust 
exclusion criteria, add missing risk assessment language and 
to clean up minor grammatical errors.
2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
The following are changes or deviations to the originally planned statistical analysis 
specified in the 209035 protocol amendment 1 [(Dated: 22/JUN/2018)]:

PK samples would not be analysed and no PK outputs would be produced. Due to the 
vast amount of PK data available from other studies examining CAB LA + RPV LA 
PK data, CPMS decided not to evaluate PK data from this study. Additionally, the 
time points of PK sample collection correspond to peak, rather than trough, 
concentrations.

Data from the digital assistance program was not collected due to cost concerns of 
using Ensemble and will not be analysed.
2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints

To demonstrate the antiviral 
activity of CAB LA + RPV LA every 
2 months in suppressed HIV-1 
infected antiretroviral therapy ART-
experienced participants

Proportion of participants with HIV-RNA 50 c/mL 
as per FDA Snapshot algorithm at Month 12
Secondary Objectives
Secondary Endpoints

To demonstrate the antiviral and 
immunologic activity of CAB LA + 
RPV LA every 2 months and oral 
DTG +RPV once daily

Proportion of participants with plasma HIV-1 RNA 
<50 c/mL (c/mL) at Month 12 using the FDA 
Snapshot algorithm 

Proportion of participants with protocol-defined 
confirmed virologic failure (CVF) over time

Proportion of participants with HIV-RNA greater than 
or equal to 50 c/mL as per FDA Snapshot algorithm 
over time

Absolute values and changes from Baseline in viral 
load and CD4+ cell counts over time 

To demonstrate the safety and 

Incidence and severity of AEs and laboratory 


CONFIDENTIAL
209035
7
Objectives
Endpoints
tolerability of CAB LA + RPV LA 
every 2 months and oral DTG + 
RPV once daily
abnormalities over time 

Proportion of participants who discontinue treatment 
due to AEs over time

Change from Baseline in laboratory parameters over 
time

To assess viral resistance in 
participants experiencing protocol-
defined confirmed virologic failure

Incidence of treatment emergent genotypic and 
phenotypic resistance to CAB, RPV, and DTG + RPV

To assess participant reported 
health-related quality of life, 
treatment satisfaction, injection 
tolerability, and treatment 
acceptance.

Change from Baseline (Day 1) in HIVDQoL at Months 
6 and 12 (or Withdrawal)

Change from baseline (Day 1) in total “treatment 
satisfaction” score, and individual item scores of the 
HIV Treatment Satisfaction Status Questionnaire 
(HIVTSQs) at Months 6 and 12 (or Withdrawal)

Change in treatment satisfaction over time using the 
HIV Treatment Satisfaction Change Questionnaire 
HIVTSQc at Month 12 (or Withdrawal).
Exploratory Objectives
Exploratory Endpoints
To assess reason for switching 
using a single question
To assess preference using a single 
question
The ‘Preference” question will be used to assess 
preference for CAB LA + RPV LA every 2 months 
compared to prior oral CAB + RPV regimen, at Month 
12 using a single dichotomous preference question.
The “Reason for Switch” question will be administered 
at Day 1 (Baseline) to assess the reasons for 
willingness to switch to LA injectable ART or to 
another oral regimen.


CONFIDENTIAL
209035
8
2.3.
Study Design
Overview of Study Design and Key Features
§ All participants in LATTE administered oral CAB 30 mg + RPV 25 mg
† Access commercially once Q8W is approved
# Access longer term via commercial route. Participants will continue to receive DTG + RPV if located in a region
where not commercially available.
Design
Features
The study is a Phase IIb, open-label, 2 arms, multicenter rollover study designed to 
assess the antiviral activity and safety of CAB LA + RPV LA administered every 2 
months in approximately 100 adult HIV-1 infected participants from the LATTE 
study.
Participants who fulfill eligibility requirements will be entered into the study to 
receive CAB LA + RPV LA Q2M or the oral DTG + RPV regimen for at least 12 
months, until commercially available.
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 will enter a 52-week LTFU 
Phase. Those participants must remain on suppressive HAART for at least 52 weeks after 
the last dose of CAB LA and/or RPV LA.
Dosing
Group 1:
First Injections (Loading Doses) – Day 1 and Month 2
Day 1:

Receive last dose of oral CAB + RPV regimen

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
Month 2:

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 2
Month 4 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


CONFIDENTIAL
209035
9
Overview of Study Design and Key Features
Group 2:
Day 1 to Month 12 (once daily FDC tablet taken with food):

Take one tablet of DTG 50 mg + RPV 25 mg once daily
See the protocol Table 2.
Time & 
Events
Refer to Appendix 2: Schedule of Activities
Treatment 
Assignment
Participants transitioning from the LATTE study on oral CAB + RPV treatment will
transition to their elected treatment regimen, either Q2M administration of CAB LA 
+ RPV LA or oral DTG + RPV single tablet regimen.
Interim 
Analysis
No Interim Analysis will be conducted.
2.4.
Statistical Hypotheses / Statistical Analyses
No statistical hypotheses of treatment comparisons will be conducted within this study.


CONFIDENTIAL
209035
10
3.
PLANNED ANALYSES
At least one analyses will be conducted to evaluate primary and secondary objectives of 
the protocol after all subjects have completed their visits at Month 12. Further data cuts 
and analyses may be conducted as necessary after Month 12 to support regulatory 
publications. The Month 12 analysis will be primary. Further analyses may be conducted 
when all subjects on CAB LA + RPV LA have completed their Month 26 visit or when 
all subjects have completed the study (final End-of-Study analysis).
3.1.
Interim Analyses
No Interim Analysis will be conducted.
3.2.
Final Analyses
The primary analysis will be conducted to evaluate the primary objective of the study at 
Month 12. These analyses will be performed after the completion of the following 
sequential steps:
1.
All participants have completed Month 12 as defined in the protocol.
2.
All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management.
A final End-of-Study analysis will be conducted when all subjects have completed the 
study as defined in the protocol. Additional analysis may be conducted when all subjects 
on CAB LA + RPV LA have completed their Month 26 visit.
4.
ANALYSIS POPULATIONS
Population
Definition / Criteria
Analyses Evaluated
All Participants 
Screened
All participants screened for inclusion in the study. 
For disposition displays, except for the listing of 
subjects who were rescreened, only the latest re-
screening data will be included. All screening data 
will be summarized or listed for other displays.

Study Population
All Participants 
Enrolled
All participants transitioning from the LATTE study 
and signed the informed consent form (ICF).

Study Population
Safety Population
All participants who receive at least one dose of IP 
on or after Day 1 visit.  
Participants will be assessed according to actual 
treatment received.

Safety 
Intent-to-Treat 
Exposed 
Population (ITT-
E)
All participants who receive at least one dose of IP 
during on or after Day 1 visit.
Participants will be analyzed according to the 
selected treatment regardless of what treatment was 
actually received. This population will be used for all 
summaries unless otherwise specified.

Study Population

Efficacy


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209035
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Population
Definition / Criteria
Analyses Evaluated
Per-Protocol 
Exposed (PP-E)
All participants in the ITT-E Population who comply 
with the protocol except for major protocol violators.  
Protocol deviations that would exclude subjects from 
the PP-E population are defined in Section 4.1
(Protocol Deviations) and Appendix 1 (Protocol 
Deviation Management and Definition for Per-
Protocol Population).

PP
Confirmed 
Virologic Failure 
(CVF)
All participants in the ITT-E population who met 
Confirmed Virologic Failure (CVF) criteria.

Virology

Efficacy
Long-tem Follow-
up
All subjects receiving at least one dose of CAB LA 
and/or RPV LA who have discontinued the CAB LA + 
RPV LA regimen and have at least one Long-term 
Follow-up phase clinic visit (i.e. have at least one 
long-term follow-up visit shown in the study 
database, LTFU month 1, LTFU month 3, etc).

Safety 
Refer to Appendix 12: 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.
o Data will be reviewed prior to freezing the database to ensure all important 
deviations and deviations which may lead to exclusion from the analysis are 
captured and categorised on the protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of protocol 
deviations.
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF.


CONFIDENTIAL
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5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA
HANDLING CONVENTIONS
5.1.
Study Treatment & Sub-group Display Descriptors
Treatment Group Descriptions
RandAll NG
Data Displays for Reporting 
Code
Description
Description
Order in TLF 
A
CAB LA (600 mg) + RPV LA (900 
mg) Q2M
Q2M
1
B
Oral DTG (50mg) + RPV (25mg)
daily
DTG + RPV 
2
5.2.
Baseline Definitions
Baseline information to be collected at Day 1 includes general medical history and
current medical conditions. Laboratory and health outcomes assessments will also be
assessed. Questionnaire/surveys are recommended to be administered at the beginning of 
the visit before any other assessments are conducted, in the order specified. For 
participants who agree to the optional assessment, a whole blood sample for genetic 
research should be collected at Day 1 (if not already collected during participation in the
LATTE study). 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 visits. If time is not collected, Day 1 assessments are assumed to be 
taken prior to first dose and used as baseline. See the protocol Section 8.2 for more 
details.
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing.
5.3.
Multicentre Studies
Data will be summarized for all centres combined. The primary efficacy endpoint will be 
summarized by Country. Countries will be combined if the number of participants 
enrolled is low.
5.4.
Examination of Covariates, Other Strata and Subgroups
5.4.1.
Covariates and Other Strata
The list of covariates may be used in descriptive summaries. Additional covariates of 
clinical interest may also be considered.
Category
Details
Strata
None
Covariates
See details in Section 5.4.2


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5.4.2.
Examination of Subgroups
The following is a list of subgroups that may be used in descriptive summaries. 
Additional subgroups of clinical interest may also be considered.

If the percentage of subjects is small within a particular subgroup, then the subgroup 
categories may be combined.

Additional covariates of clinical interest may also be considered.
Category
Covariates and / or Subgroups
Demographic and Baseline 
Characteristic Subgroups 

Age (years):
o
<35, 35 - <50,≥50
o
≤18, 19 - 64, ≥65 (FDAAA requirement)
o
18 - 64, 65 - 84, ≥85 (EMA requirement)

Race:
o
White, Non-White
o
Black/African American, Non-Black/African American

Sex at birth:
o
Female
o
Male

Country:
o
Canada
o
United States

Derived Baseline Centers for Disease Control and Prevention 
(CDC) category:
o
Stage I
o
Stage II
o
Stage III

Baseline BMI (kg/m2)
o
<30
o
≥30
Additional subgroup for 
common drug-related study 
drug injection site reaction 
(ISR) with maximum toxicity 
grade
For each preferred term of the common drug-related study drug 
ISR with maximum toxicity grade (pain, induration, nodules and 
any other study drug ISR with ≥5% subjects in either treatment 
arm) during the maintenance phase:

Needle Length for Last CAB Injection prior to and 
including the onset date of the earliest corresponding 
drug-related CAB ISR with maximum toxicity grade 
during the maintenance phase: ≤1.5, >1.5 to <2, ≥2 
inches

Needle Length for Last RPV Injection prior to and 
including the onset date of the earliest corresponding 
drug-related RPV ISR with maximum toxicity grade 
during the maintenance phase: ≤1.5, >1.5 to <2, ≥2 
inches
Note: If there is no ISR of interest reported during maintenance 


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Category
Covariates and / or Subgroups
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
5.5.1.
Primary Comparison of Interest
No formal statistical analysis will be performed for this study.  The primary endpoint will 
be summarized based on the ITT-E population.  
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
12.3
Appendix 3: Assessment Windows
12.4
Appendix 4: Study Phases and Treatment Emergent Adverse Events
12.5
Appendix 5: Data Display Standards & Handling Conventions
12.6
Appendix 6: Derived and Transformed Data
12.7
Appendix 7: Reporting Standards for Missing Data
12.8
Appendix 8: Values of Potential Clinical Importance
12.9
Appendix 9: Snapshot Algorithm Details
12.10
Appendix 10: Identification of Adverse Events of Special Interest


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6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Study Population Analyses
The study population will be based on the Intent-to-Treat Exposed population, unless 
otherwise specified.
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and exposure and treatment compliance will be based on GSK Core Data Standards.  
Table 1 provides an overview of the planned study population analyses, with details of
the planned displays presented in Appendix 12: List of Data Displays.
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
Y
Reasons for Screening Failures [3]
Y
Y
Rescreened Subjects [3]  
Y
Age Ranges
Y
Subject Disposition
Y[4][5]
Reasons for Withdrawal by Visit
Y[4][5]
Y
IP Discontinuation
Y
Y
Important Protocol Deviations
Y
Y
Deviations leading to exclusion from PP
Y
Y
Inclusion and Exclusion Criteria Deviations
Y
Y 
Demography and Baseline
Demographics Characteristics 
Y
Y
Race & Racial Combinations [6]
Y
Y
Hepatitis Status
Y
CDC Classification of HIV infection (2014) 
Y
Distribution of CD4+ Cell Counts at Baseline
Y
HIV-1 Risk Factors
Y


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Display Type
Data Displays Generated
Table
Listing
Medical Conditions, Concomitant Medications & Antiretroviral Therapy
Medical Conditions (Current/Past) [7]
Y
Medical Conditions: Sub-conditions (Current/Past) [7,8]
Y 
Concomitant Medications (non-ART)
Y[9]
Concomitant Antiretroviral Medications During Maintenance 
Phase
Y
ART Medications Received During LTFU Phase
Y
Lipid Modifying Agents (Baseline and During Maintenance 
Phase)
Y
Substance use
Y
Medical History of Seizure
Y
Other 
Extent of Exposure to IP[10]
Y
Adherence to Injection Dosing Schedule for CAB/RPV[10]
Y
NOTES :

T = Tables, L = Listings, Y = Display Generated,
1.
All Participants Enrolled population
2.
Listing of planned and actual treatment.
3.
All Participants Screened population.
4.
Subjects 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 will be performed for each study phase separately, as well as for overall 
study conclusion.
6.
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.
7.
Medical conditions will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).
8.
Sub conditions are Cardiovascular, Gastrointestinal, Metabolism and Nutrition, Psychiatric, Renal and 
Urinary, Nervous System Conditions and Hepatobiliary
9.
Summarised by Ingredient ATC Level 1, Ingredient combinations and Combination term ATC Level 1 
(EG Includes single-ingredient medications with multi-ingredient medications labeled according to the 
sum of their ingredients, e.g., “TYLENOL Cold and Flu” would appear as “CHLORPHENAMINE 
MALEATE + DEXTROMETHORPHAN HYDROBROMIDE + PARACETAMOL +  
PSEUDOEPHEDRINE HYDROCHLORIDE” under the ATC headings for “Nervous System” and 
“Respiratory System” (the combination’s ATC classifications).)
10. Safety Population
6.2.
Prior and Concomitant Medications
Non-ART and/or ART Medications will be classified by categories shown in Table 2. 
The same medication may be classified by more than one category. For example, if the 
Non-ART medication was started prior to the Maintenance treatment start date and was 
stopped at Month 6 while subject was still receiving study treatment, this medication 
would be considered both ‘prior’ and ‘concomitant during maintenance’.


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Table 2
Derived Data for Non-ART Medications/ART Medications
Definition
Prior
ART Medication Taken ≤ Maintenance Treatment Start Date
Non-ART Medication Taken < Maintenance Treatment Start Date
Concomitant during 
Maintenance
Maintenance Treatment Start Date ≤ Non-ART Medication Taken < LTFU 
ART Start Date
Maintenance Treatment Start Date < ART Medication Taken < LTFU ART 
Start Date
Received during 
Long-term Follow-up
For subjects Who received at least one CAB and/or RPV injection and 
have started LTFU ART:
Non-ART/ART Medication Taken ≥ LTFU ART Start Date
NOTES:

Please refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and partial dates
for medications. Use the rules in this table if medication date is completely missing.

If subjects have missing LFTU ART start date, only the lower bound will be considered in the derivation.


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7.
EFFICACY ANALYSES
7.1.
Primary Efficacy Analyses
No formal statistical analysis will be performed for the primary endpoint of the study.
7.1.1.
Endpoint / Variables
Proportion of participants with plasma HIV-1 RNA ≥50 copies/mL as per Food and 
Drug Administration (FDA) Snapshot algorithm at Month 12.
7.1.2.
Summary Measure
Number of subjects and percentage of participants with HIV-1 RNA 50 c/mL at Month 
12 (defined by the US FDA snapshot algorithm) will be provided by treatment group.
7.1.3.
Population of Interest 
The primary efficacy results will be based on the Intent-To-Treat Exposed population, 
unless otherwise specified.
7.1.4.
Strategy for Intercurrent (Post-treatment selection) Events
As defined by the Snapshot algorithm, HIV-1 RNA ≥50 c/mL is determined by the last 
available HIV-1 RNA measurement while the participant is on treatment within the 
analysis visit window of interest.
Participants without on-treatment HIV-1 RNA data for the visit of interest and who 
discontinue treatment for reasons not related to adverse event while having HIV-1 RNA 
≥50 c/mL at time of discontinuation or who change study treatment not permitted per 
protocol before the analysis window are classified as having HIV-1 RNA ≥50 c/mL.
Full details of the snapshot algorithm are defined in Appendix 9: Snapshot Algorithm 
Details.
7.1.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: 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.


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7.2.
Secondary Efficacy Analyses
7.2.1.
Endpoint / Variables
The secondary efficacy endpoints for the study are listed below:

Proportion of participants with plasma HIV-1 RNA <50 c/mL (c/mL) at Month 12 
using the FDA Snapshot algorithm 

Proportion of participants with protocol-defined confirmed virologic failure 
(CVF) over time

Proportion of participants with HIV-1 RNA ≥50 c/mL as per FDA Snapshot 
algorithm over time

Absolute values and changes from Baseline in viral load and cluster of 
differentiation 4 (CD4+) cell counts over time
7.2.2.
Summary Measure
Number of subjects and percentage of participants with HIV-1 RNA < 50 c/mL at Month 
12 (defined by the US FDA snapshot algorithm) will be presented by treatment group.
Number of subjects and percentage of participants with protocol-defined confirmed 
virologic failure (CVF) will be presented by treatment group and by visit.
Number of subjects and percentage of participants with HIV-1 RNA ≥50 c/mL (defined 
by the US FDA snapshot algorithm) will be presented by treatment group and by visit.
Descriptive statistics of the absolute values and changes from Baseline in viral load and 
cluster of differentiation 4 (CD4+) cell counts will be presented by treatment group and 
by visit.
7.2.3.
Population of Interest
The secondary efficacy analyses will be based on the Intent-to-Treat Exposed population, 
unless otherwise specified.
7.2.4.
Strategy for Intercurrent (Post-treatment selection) Events
As defined by the snapshot algorithm, participants with last available HIV-1 RNA 
measurement < 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.
Participants without on-treatment HIV-1 RNA data for the visit of interest and who 
discontinue treatment for reasons not related to adverse event while having HIV-1 RNA 
≥ 50 c/mL at time of discontinuation or who change study treatment not permitted per 
protocol before the analysis window are classified as having HIV-1 RNA ≥ 50 c/mL.
7.2.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles.


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Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed.
7.3.
Exploratory Efficacy Analyses
Table 3 provides an overview of the planned exploratory efficacy analyses. Details of the 
planned displays are provided in Appendix 12: List of Data Displays and will be based on 
GSK data standards and statistical principles. The exploratory efficacy analyses will be 
based on the Intent-to-Treat Exposed population, unless otherwise specified.
Table 3
Overview of Exploratory Efficacy Analyses  
Endpoints
Absolute
Change from Baseline
Summary
Individual
Summary
Individual
T
F
F
L
T
F
F
L
Plasma HIV-1 RNA over time
By visit
Y[1]
Y[2]
Y[3]
Y[1]
Y[3]
Target Detected vs 
Target Not Detected by 
visit [4]
Y
Y[5]
Confirmed Virologic Failure (CVF)
CVF overall
Y
Plasma HIV-1 RNA at 
time of suspected and 
confirmed virologic failure
Y
CD4+ cell counts over time
Observed[6]
Y
Y
HIV-1 conditions and disease progression
HIV Conditions 
including/excluding 
Recurrences as recorded 
in eCRF
Y
Y
HIV Disease 
Progressions[7]
Y
NOTES:

T = Table, F = Figure, L = Listing, Y = Yes display generated.

Summary = Represents TF related to any summaries (i.e. descriptive statistics) of data.

Individual = Represents FL related to any displays of individual participant’s data.
1.
Using log10 transformed values.
2.
Individual plasma HIV-1 RNA only for participants who are in the category of ‘viral load ≥50 c/mL’ at Month 12 per 
Snapshot algorithm or who are CVF participants. The figures will display all HIV-1 RNA values collected.
3.
For CVF participant and, participants with viral load ≥ 50 c/mL during the Maintenance Phase.
4.
See Section 12.6.3 for definition of “Target Detected” and “Target Not Detected”, and for the specification of 
corresponding summary table.
5.
Target Detected” and “Target Not Detected” are included in the listing for plasma HIV-1 RNA by visit.
6.
Using available data without imputation for missing values.
7.
See Section 12.6.3 for HIV disease progressions.


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8.
SAFETY ANALYSES
The safety analyses will be based on the Safety population, unless otherwise specified.
8.1.
Adverse Events Analyses
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs)
and other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 12: List of Data Displays.
8.1.1.
Injection Site Reactions
For the summary of Injection Site Reaction Adverse Events by Visit and Maximum 
Severity (Overall and by Common ISRs): ISRs will be assigned based on onset date to 
the most recent planned IM injection visit prior or equal to the AE onset date. 
Maximum grade at each visit will be derived as the maximum grade among ISRs 
assigned to the particular visit, with consideration for whether the summary applies to a 
particular preferred term (vs. across preferred terms), or drug-related associated to CAB 
and/or RPV, or stratification by needle length (refer to Section 5.4.2).
Drug-related ISRs (based on investigator discretion) will be attributed to the causal agent 
(CAB vs. RPV) when this can be determined specifically based the side of injection 
administration and the side of the reported ISR (as collected in the eCRF). If we are 
unable to determine the causal agent in those cases where both drugs are given on one 
side and the ISR is reported non-specifically, then the attribution to a specific causal 
agent will remain unknown.
Common study drug ISR adverse events 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 CAB LA + RPV LA arm, coming 
from study drug injections. 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 (≤1.5, >1.5 to <2, ≥2 inches) when this can be 
determined specifically based on the side of injection administration and the side of the 
reported ISR (as collected in the eCRF). If we are unable to determine the needle length 
in those events where both drugs are given on one side and their needle lengths are 
different, then the attribution to a needle length will remain unknown.
8.2.
Clinical Laboratory Analyses
Laboratory evaluations including the analyses of chemistry laboratory tests, hematology 
laboratory tests, urinalysis, and liver function tests will be based on GSK Core Data 
Standards. The details of the planned displays are in Appendix 12: List of Data Displays.


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8.3.
Adverse Events of Special Interest Analyses
Adverse events of special interest (AESI) are determined for CAB and/or RPV based on 
pre-clinical and clinical experience, along with information for the Integrase Inhibitor 
class of HIV medications and RPV safety profile. Table 4 shows the currently identified 
AESI, drug(s) of Interest and the reasons for inclusion. Changes to the MedDRA 
dictionary may occur between the start of the study and the time of reporting, and/or 
emerging data from on-going studies may highlight additional adverse events of special 
interest, therefore the list of AESIs may change at the time of reporting. 
A summary by system organ class and preferred term will be provided for each of AESI. 
For Depression, anxiety and suicidal ideation/behaviour AESI, a summary by system 
organ class, maximum DAIDS toxicity grade and prior history will be provided. The 
details of the planned grouping and planned displays are provided in Section 12.10 and 
Appendix 12: List of Data Displays.
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
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


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Adverse Events of Special Interest
Drug(s) of Interest
Reason for Inclusion
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
More prevalent in HIV 
population
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 8.1.1.
8.4.
Other Safety Analyses
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. The details of the 
planned displays are presented in Appendix 12: List of Data Displays.
ECG values of potential clinical importance are defined as a QTc of > 500 msec or 
increase from baseline in QTc ≥ 60 msec.
9.
HEALTH OUTCOMES ANALYSES
9.1.
Endpoint / Variables

Change from Baseline (Day 1) in HIVDQoL at Months 6 and 12 (or Withdrawal)

Change from baseline (Day 1) in total “treatment satisfaction” score, and 
individual item scores of the HIV Treatment Satisfaction Status Questionnaire 
(HIVTSQs) at Months 6 and 12 (or Withdrawal)


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
Change in treatment satisfaction over time using the HIV Treatment Satisfaction
Change Questionnaire HIVTSQc at Month 12 (or Withdrawal).

Preference between injections of LA HIV treatment and daily oral HIV treatment 
at Month 12. This is an exploratory endpoint.

Reasons for switching to injectable HIV treatment at Baseline (Day 1). This is an 
exploratory endpoint.
9.2.
Summary Measure
Summary statistics of the above endpoints will be presented by treatment group.
9.3.
Population of Interest 
The health outcomes outputs will be based on the Intent-to-Treat Exposed population, 
unless otherwise specified.
9.4.
Strategy for Intercurrent (Post-treatment selection) Events
No imputations would be performed for any missing data.
9.5.
Statistical Analyses / Methods
Details of the planned displays are provided in Appendix 12: List of Data Displays and
will be based on GSK Data Standards and statistical principles.
Unless otherwise specified, endpoints / variables defined in Section 9.1 will be
summarised using descriptive statistics, graphically presented (where appropriate) and
listed.
10.
VIROLOGY
The virology analyses will mainly use genotype and phenotype data based on plasma
sample for CVF population, unless otherwise specified. Additional analyses for HIV-1
resistance may be carried out on peripheral blood mononuclear (PBMC) samples
collected at Day 1 or Withdrawal.
If pre-treatment genotypic/phenotypic results are available from both the central
laboratory and Monogram Biosciences, then Baseline genotype/phenotype will be
determined based only upon the data provided by Monogram assays.  
Table 5
Overview of Planned Virology Analyses
Endpoints
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


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Endpoints
Absolute
Summary
Individual
T
F
F
L
Fold Change to CAB and RPV
Y
Y[4]
IN, PR/RT Replication Capacity
Y
Other
Viral load, Genotypic and Phenotypic data for 
Participants with genotype and/or phenotype data 
for CVF participants
Y[4]
Net Assessment
Y
NOTES:

T = Table, F = Figure, L = Listing, Y = Yes display generated.

Summary = Represents TF related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual participant observed raw data.
1.
For the CVF as indicated by two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 
c/mL, the first visit of these two consecutive visits is defined as ‘the suspected visit’, and the 2nd one is the 
confirmed visit. Sample used for resistance testing is taken at the suspected visit, and only tested once a 
participant confirms virological failure at a subsequent visit. If the test fails with the sample at the suspected visit, 
we will just report it as ‘no data’. The sample from the confirmed visit may be used for exploratory analyses.
2.
No. and percentage of participants with IN resistance mutations or major mutations in the classes of NNRTI, 
NRTI, PI, respectively, as defined in Section 12.6.6.
3.
Separate outputs by phenotypic susceptibility and by number of drugs to which participants are phenotypic 
resistant or partial sensitive or sensitive.
4.
Fold change to CAB and RPV will be included in the listing for viral load, genotypic and phenotypic data for 
participants with genotype and/or phenotype data for CVF and non-CVF participants.


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11.
REFERENCES

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.

HIVDQoL user guidelines, Health Psychology Research Unit, Royal Holloway, 
University of London, 2018

HIVTSQ user guidelines, Health Psychology Research Unit, Royal Holloway, 
University of London, 2016

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.

Wee HL, Tan CE, Goh SY, Li SC.  Usefulness of the Audit of Diabetes-Dependent 
Quality-of-Life (ADDQoL) questionnaire in participants with diabetes in a multi-
ethnic Asian country. Pharmacoeconomics. 2006;24(7):673-82.

Wensing AM et al. 2019 Update of the Drug Resistance Mutations in HIV-1 Volume 
27 Issue 3 July/August 2019


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12.
APPENDICES
12.1.
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population
12.1.1.
Exclusions from Per Protocol Population
Important protocol deviations leading to exclusion from the Per Protocol population are 
those deviations which may
i.
directly impact the efficacy endpoint of HIV-1 RNA; or
ii.
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), will lead to exclusion of a subject 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 subject meeting any of the following criteria will be excluded from the Per Protocol 
population based on case-by-case clinical determination:
Number
Exclusion Description
01
Participant deviates from any inclusion or exclusion criteria that may significantly 
affect exposure, response to therapy or participant safety or that are fundamentally 
inconsistent with the intended study population, as recorded in the Protocol 
Deviation form in the eCRF based on study team review (where indicated in the 
PDMP as case-by-case determination).
02
Participant has maintenance phase non-compliance (including IM dosing errors) 
with investigational product up to an analysis timepoint of interest, meeting one of 
the following conditions:
1.
Month 12 analysis only:

Q2M arm: two or more injection intervals affected by over dosage 
deviations (e.g. extra injection or excessive volume administered, length 
of time between injections less than 7 weeks, excluding split doses).
2.
≥10% of total time on-treatment with under dosing deviations. The percentage 
of total time on-treatment with under dosing deviations will be calculated by (the 
total number of non-compliant dosing days / the total number of intended 
exposure days) * 100%.
Number of Intended Exposure Days = Date of Last Viral Load – Start Date of 
Study Treatment + 1,
where the last viral load refers to the last on-treatment viral load up to Study 
Day 360 for Q2M arm and study day of last nominal Month 12 visit for DTG + 
RPV arm during maintenance phase for Month 12 analysis.


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Number
Exclusion Description
The 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 (summing across all instances):

Q2M arm: 
o
Length of time (in days) until next injection from date of dosage 
deviation (e.g. 2 mL administered instead of 3 mL).
o
Length of time (in days) in excess beyond 67 days between 
injections.
o
Length of time (in days) in excess beyond 67 days from last 
injection until start of oral bridging post Month 4.
o
Interrupted days in 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.

DTG + RPV arm: Durations of interruptions for reasons other than 
treatment-related adverse events or laboratory abnormalities (based on 
Exposure eCRF forms).
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).
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).


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12.2.
Appendix 2: Schedule of Activities
12.2.1.
Protocol Defined Schedule of Events for CAB LA + RPV LA Q2M Administration
Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Written Informed Consent 
X
Demography
X
Eligibility Verification
X
Physical Exam
X
Medical History
X
Center for Disease Control 
and Prevention (CDC) 
Classification
X
Rapid Plasma Reagin (RPR)
X
Symptom Directed Physical 
Exam, injection site reaction 
(ISR) and Medical 
Assessment c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs
(blood pressure [BP], heart 
rate [HR]) d
X
X
X
X
X
X
X
X
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Weight, Height & body mass 
index (BMI)e
X
X
X
X
X
X
X
X
X
HIV Associated Conditions, 
AE and serious adverse 
event (SAE) Assessments, 
Con Meds
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-Lead electrocardiogram 
(ECG) f
X
X
X
Clinical Chemistry and 
Hematology
X
X
X
X
X
X
X
X
X
Pregnancy Testing 
(U)rine or (S)erum g
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
HIV-1 RNA and sample for 
storage h
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
X
X
X
Urinalysis
X
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Fasting Glucose, 
Cholesterol (Total, high 
density lipoprotein [HDL] 
and low density lipoprotein
[LDL]) and Triglycerides i
X
X
X
X
Prothrombin time (PT)/
partial thromboplastin time
(PTT)/international 
normalized ratio (INR)
X
X
PK Diary 
(D)ispensation and (R)eview
R
PK Sample 
(S)torage j
S
S
S
LA Study Intervention 
Administration k
X 
X 
X
X
X
X
X
X
X
X
X
X
X
X
HIVTSQc
X
X
HIVTSQs
X
X
X
X
HIVDQoL
X
X
X
X
Preference
X
Reason for Switch
X


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Procedures Q2M 
Day 1 a
Month
WD l, m
2 o
4
6
8
10
12
14
16
18
20b
22b
24
26
Participant Visit Reminder 
Contact
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Participant Contact Detail 
Confirmation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
See footnote “b” for continuation of visit schedule after Month 26.  Continue until either locally approved and commercially available, the participant no longer derives clinical benefit or meets a 
protocol-defined reason for discontinuation or until development is terminated.
a.
The Day 1 visit will take place during Week 312 (or Week 324 in the event of unavoidable delays) of the LATTE study, the participant’s last week on study.  LATTE participants eligible for 
POLAR study dosing will take final dose of CAB 30 mg + RPV 25 mg in the clinic within 2 hours of the Q2M IM regimen.  For IM dosing administration loading doses are required. (Day 
1=1st loading dose; Month 2=2nd loading dose)
b.
Continue this pattern for visits for the remainder of the study.  For example, Month 28 will be conducted just like Month 20, Month 30 will be conducted just like Month 22 and so on.
c.
Physical exams should be conducted as part of normal routine clinical care but data will not be collected in the electronic case report form (eCRF). Medical assessments include any 
decisions the study staff must make for participant management.
d.
Measure vital signs after about 5 minutes of rest in a semi-supine position.
e.
Height collected at Day 1 only.
f.
On Day 1, ECGs should be performed in triplicate at least 5 minutes apart and following 5 minutes of rest in a semi-supine position within 1 hour prior to first dose.  Also on Day 1, a 2-hour 
post dose ECG will be performed for all participants.  The 2-hour post dose ECG on Day 1 can also be used for the LATTE Week 312 (or Week 324, if needed) visit.  ECG evaluations at 
other visits should be obtained after dosing, preferably 2-4 hours post dosing.
g.
A (-) urine pregnancy test is required prior to any injection and as required by medical monitor after a treatment interruption. A (+) urine test should be confirmed with a stat serum test.  If 
(+), participant will need to be withdrawn.
h.
Plasma for storage samples are collected for possible future analyses, back-up in cases of loss/damage in transit and geno/pheno analyses for virologic failures.
i.
Fast overnight; however, a minimum of a 6 hour fast is acceptable.
j.
Take PK samples pre-dose.
k.
Q2M Injections are 1 x CAB LA 600 mg IM + 1 x RPV LA 900 mg IM.  If possible, injections should be spaced approximately 2 cm from one another and from the site of any previous 
injection and or any injection site reaction.  Bring RPV LA to approximately room temperature prior to injecting.   Time and location of injection (right or left) as well as needle length used 
will be collected in the eCRF.  IM dosing is expected to occur during the month in which the participant’s projected visit falls (as according to the Day 1 visit).  An additional (+ 
or -) 7day window from date of projected visit is stipulated for IM dosing.  All decisions regarding dose interruption/ resumption must be discussed with the medical monitor in 
advance.


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l.
Or Long-Term Follow Up
m.
Follow Up Visit - Conduct ~4 weeks after the last dose of investigational product (IP) if not entering Long-Term Follow Up and only if the participant has ongoing AEs or lab abnormalities at 
the last on-study visit.  May be conducted by telephone.
12.2.2.
Protocol Defined Schedule of Events for DTG + RPV Administration
Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j 
Notes
Written Informed Consent 
X
a.
The Day 1 visit will take place during Week 312 (or Week 324 in 
the event of unavoidable delays) of the LATTE study, the 
participant’s last week on study.  LATTE participants eligible for 
POLAR study dosing will take final dose of CAB 30 mg + RPV 25 
mg in the clinic.  See Section 6.2 of the protocol for dosing 
administration.
b.
Physical exams should be conducted as part of normal routine 
clinical care but data will not be collected in the eCRF. Medical 
assessments include any decisions the study staff must make for 
participant management.
c.
Measure vital signs after about 5 minutes of rest in a semi-supine 
position.
d.
Height collected at Day 1 only.
e.
On Day 1, ECGs should be performed in triplicate at least 5 
minutes apart and following 5 minutes of rest in a semi-supine 
position within 1 hour prior to first dose.  Also on Day 1, a 2-hour 
post dose ECG will be performed for all participants.  The 2-hour 
post dose ECG on Day 1 can also be used for the LATTE Week 
312 (or Week 324, if needed) visit.  ECG evaluations at other 
visits should be obtained after dosing, preferably 2-4 hours post 
dosing.
f.
Plasma for storage samples are collected for possible future 
analyses, back-up in cases of loss/damage in transit and 
geno/pheno analyses for virologic failures.
g.
A (-) urine pregnancy test is required prior to any administration 
of drug and as required by medical monitor after a treatment 
interruption. A (+) urine test should be confirmed with a stat 
Demography
X
Eligibility Verification
X
Physical Exam
X
Medical History
X
CDC Classification
X
RPR
X
Symptom Directed Physical Exam and 
Medical Assessment b
X
X
X
X
X
Vital Signs(BP, HR) c
X
X
X
X
X
X
Weight, Height & BMI d
X
X
X
X
X
X
HIV Associated Conditions, AE and 
SAE Assessments, Con Meds
X
X
X
X
X
X


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Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j 
Notes
12-Lead ECG e
X
X
X
serum test.  If (+), participant will need to be WD.
h.
Fast overnight; however, a minimum of a 6 hour fast is 
acceptable.
i.
DTG 50 mg + RPV 25 mg.  Administer daily with food
j.
Follow Up Visit - Conduct ~4 weeks after the last dose of IP and 
only if the participant has ongoing AEs or lab abnormalities at the 
last on-study visit.  May be conducted by telephone.
HIV-1 RNA
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
Plasma for Storage f
X
X
X
X
X
X
PK Sample for Storage
S
Clinical Chemistry and Hematology
X
X
X
X
X
X
Pregnancy Testing g
U
U
U
U
U
U
Urinalysis
X
X
Fasting:  Glucose, Cholesterol (Total, 
HDL and LDL) and Triglycerides h
X
X
PT/PTT/INR
X
X
HIVTSQc
X
X
HIVTSQs
X
X
X
X
HIVDQoL
X
X
X
X
Participant Visit Reminder Contact
X
X
X
X
X
Participant Contact Detail Confirmation
X
X
X
X
X


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Procedures for DTG+RPV
Day 1 a
Month 3
Month 6
Month 9
Month 12
WD j 
Notes
Study Treatment Dispensation i
X
X
X
X
X
12.2.3.
Protocol Defined Schedule of Events for Long Term Follow Up
Procedures for Long-Term Follow Up
Month 1 a
Month 
3
Month 
6
Month 
9
Month 12
WD
Notes
HIV Associated Conditions, AE and SAE 
Assessments, Con Meds
X
X
X
X
X
X
Every effort should be made to enter participants into the Long-
Term Follow Up if they withdraw from or discontinue the study after 
receiving at least one dose of CAB LA and / or RPV LA.
a.
The start of the 52-week follow up period begins the day of the 
last CAB LA and/or RPV LA dose.
b.
Women of childbearing potential only.  S = Serum
c.
Fast overnight; however, a minimum of a 6 hour fast is 
acceptable.
d.
Women of childbearing potential should continue to receive 
counselling on the need to use adequate contraception for the 
entirety of the Long-Term Follow-Up Period. 
e.
Investigators must discuss choice of HAART regimen and 
timing of initiation with the medical monitor before initiating.  
This regimen may be supplied regionally by GlaxoSmithKline 
(GSK) or reimbursement will be provided.
HIV-1 RNA
X
X
X
X
X
X
CD4+
X
X
X
X
X
X
Plasma for Storage
X
X
X
X
X
X
PK Sample for Storage
S
S
S
S
S
S
Clinical Chemistry and Hematology
X
X
X
X
X
X
Pregnancy Testing b
S
S
S
S
S
S
Urinalysis
X
X
X
Fasting:  Glucose, Cholesterol (Total, 
HDL and LDL) and Triglycerides c
X
X
PT/PTT/INR
X
X


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Procedures for Long-Term Follow Up
Month 1 a
Month 
3
Month 
6
Month 
9
Month 12
WD
Notes
Contraception Counselling d
X
X
X
X
X
X
HAART Dispensation e
X
X
X
X
X
X


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12.3.
Appendix 3: Assessment Windows
12.3.1.
Definitions of Assessment Windows for Analyses
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. In general, the 
nominal target study day for Month m is ((m-1)*30)+1 for Q2M and (m*30)+1 for DTG
+ RPV.  
For parameters which are not scheduled to be assessed at particular visits, the all-
inclusive assessment windows will still be used; however, data summaries will only 
report scheduled visits. Assessments at unscheduled visits will be included for ‘any time 
On-treatment’ time points and in data listings, as well any algorithms that make use of 
additional data (e.g., Snapshot).
Prior to visit slotting, assessments are first assigned to a study phase (maintenance, and
Long Term Follow Up) based on the Tables in Section 12.4.1 and treatment state based 
on Section 12.4.2.
Maintenance phase assessments other than health outcomes are assigned based on 
Maintenance Phase Study Day, as shown in Table 6, Table 7, Table 8 and Table 9. The 
analysis visits from Month 2 to Month 12 and so on should be only applied to the 
assessments that are already assigned to Maintenance phase (on-treatment).
Long-term Follow-up phase assessments are assigned based on the LTFU study day as 
shown in Table 10. The analysis visits in LTFU should be only applied to the assessments 
that are already assigned to LTFU phase regardless of treatment state. See Section 12.6.1
for derivation of Maintenance and LTFU Study Day.
12.3.2.
Definitions of Assessment Windows for Data Other than Health 
Outcomes 
Table 6
Assessment Windows for Screening and Maintenance Phase Data
for CAB LA + RPV LA arm
All Parameters 
(except for 
where noted)
Target Study 
Day
Analysis Window
Analysis 
Timepoint
1
Baseline information to be 
collected at nominal visit Day 1 
which is the last available 
recorded value up to and including 
the Maintenance treatment start 
Baseline


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All Parameters 
(except for 
where noted)
Target Study 
Day
Analysis Window
Analysis 
Timepoint
date, excluding 2-hour post-dose 
ECG taken on the Maintenance 
treatment start date
1
Date of first maintenance dose of 
IP+
Day 1
31
2 Study Day 60
Month 2*
91
61 Study Day 120
Month 4
151
121 Study Day 180
Month 6
211
181 Study Day 240
Month 8
271
241 Study Day 300
Month 10
331
301 Study Day 360
Month 12
391
361 Study Day 420
Month 14
451
421 Study Day 480
Month 16
511
481 Study Day 540
Month 18
571
541 Study Day 600
Month 20
631
601 Study Day 660
Month 22
691
661 Study Day 720
Month 24
751
721 Study Day 780
Month 26
((m-1)*30)+1
(((m-1)*30)-29) ≤ Study Day ≤ 
(((m-1)*30)+30)
Month m, m=28, 
30,…
If a participant permanently discontinued study treatment:
Date > max (Date of Last Oral 
Dose of CAB+RPV + 1, Date of
Last Injection + 67 )
Follow-up#
NOTES:
+ Only non-baseline records from the mentioned assessment window will be assigned to Day 1. 
* The second loading injections will be administered 1 month (Month 2 visit, start of the second month of the study) 
after initial loading dose (CAB LA 600 mg + RPV LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 
900 mg) occurring every 2 months thereafter.
# Follow-up will be derived only for participants who permanently discontinued study treatment.
Table 7
Assessment Windows for Screening and Maintenance Phase Data
for DTG + RPV arm
All Parameters 
(except for 
where noted)
Target Study 
Day
Analysis Window
Analysis 
Timepoint
1
Baseline information to be 
collected at nominal visit Day 1 
which is the last available 
recorded value upto and including 
the Maintenance treatment start 
date, excluding 2-hour post-dose 
Baseline


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All Parameters 
(except for 
where noted)
Target Study 
Day
Analysis Window
Analysis 
Timepoint
ECG taken on the Maintenance 
treatment start date 
1
Date of first maintenance dose of 
IP+
Day 1 
91
2 Study Day 135
Month 3
181
136 Study Day 225
Month 6 
271
226 Study Day 315
Month 9 
361
316 Study Day (Study Day of 
Nominal Month 12 visit)
Month 12 
If a participant permanently discontinued study treatment:
Date > Date of Last Oral Dose of 
DTG + 1
Follow-up#
NOTES:
+ Only non-baseline records from the mentioned assessment window will be assigned to Day 1. 
# Follow-up will be derived only for participants who permanently discontinued study treatment.
Table 8
Assessment Windows for Summary of Snapshot Data for CAB LA + 
RPV LA arm— Data assigned to Maintenance Phase Only 
Snapshot Analysis Windows
(If no on-treatment viral load data in default window, use expanded 
window)
Analysis Timepoint
Default
Expanded +45 Day Upper 
Windowa
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
Baseline
2 Study Day 60
2 Study Day 75
Month 2
61 Study Day 120
61 Study Day 135
Month 4
121 Study Day 180
121 Study Day 195
Month 6
181 Study Day 240
181 Study Day 255
Month 8
241 Study Day 300
241 Study Day 315
Month 10
285 Study Day 375
285 Study Day 375
Month 12
361 Study Day 420
301 Study Day 435
Month 14
421 Study Day 480
421 Study Day 495
Month 16
421 Study Day 540
421 Study Day 555
Month 18
541 Study Day 600
421 Study Day 615
Month 20
601 Study Day 660
601 Study Day 675
Month 22
661 Study Day 720
601 Study Day 735
Month 24
721 Study Day 780
601 Study Day 795
Month 26
(((m-1)*30)-29) ≤ Study Day ≤ 
(((m-1)*30)+30)
(((m-1)*30)-29) ≤ Study Day ≤ 
(((m-1)*30)+45)
Month m, m=28, 30,…
NOTES:


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
For post-baseline visits (i.e. Month 2 and afterwards), apply Snapshot analysis windows only to viral load data that 
is on-treatment (per Table 15) within the Maintenance Phase (per Table 13).

An on-treatment viral load assessment may be assigned to more than one snapshot analysis window, e.g. on-
treatment assessment taken on Study Day 300 will be in both Month 10 and Month 12.
a.± 45 Day window is always used at key analysis timepoint of Month 12.
Table 9
Assessment Windows for Summary of Snapshot Data for DTG + RPV 
arm— Data assigned to Maintenance Phase Only 
Snapshot Analysis Windows
(If no on-treatment viral load data in default window, use expanded 
window)
Analysis Timepoint
Default
Expanded +67 Day Upper 
Windowa
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
Baseline
2 Study Day 135
2 Study Day 157
Month 3
136 Study Day 225
136 Study Day 247
Month 6
226 Study Day 315
226 Study Day 337
Month 9
293 Study Day (Study Day of 
Nominal Month 12 Visit)
293 Study Day (Study Day of 
Nominal Month 12 Visit)
Month 12
NOTES:

For post-baseline visits (i.e. Month 3 and afterwards), apply Snapshot analysis windows only to viral load data that 
is on-treatment (per Table 15) within the Maintenance Phase (per Table 13).

An on-treatment viral load assessment may be assigned to more than one snapshot analysis window, e.g. on-
treatment assessment taken on Study Day 300 will be in both Month 9 and Month 12.
a.- 67 Day window is always used at key analysis timepoint of Month 12.
Table 10
Assessment Windows for Summaries of Long-Term Follow Up 
Phase Data for Subjects Who Received At least One Injection of 
CAB+RPV and Permanently Discontinued from Study Treatment
Analysis Window
Analysis 
Timepoint
Target Study 
Day of Window
1 LTFU Study Day 67
LTFU Month 1
30
68 LTFU Study Day 135
LTFU Month 3
90
136 LTFU Study Day 225
LTFU Month 6
180
226 LTFU Study Day 315
LTFU Month 9
270
316 LTFU Study Day 405
LTFU Month 12
360
(30*m - 44) LTFU Study Day(30*m + 45)
LTFU Month m,
m = 15, 18,,
7*m
NOTES:
An assessment may be slotted to both LTFU and Maintenance Phase


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12.3.3.
Assessment Window for Study Conclusion
The study conclusion and phase conclusion records in disposition data will be slotted 
based on Table 6 and Table 7 However, if the discontinuation date is post-treatment
(based on Table 15), the record will be slotted to the last on-treatment visit within the 
same phase rather than follow up.
12.3.4.
Assessment Window for Health Outcome Data 
12.3.4.1.
HIVTSQs, HIVTSQc, HIVDQoL, Preference
HIVTSQs, HIVTSQc, HIVDQoL, and Preference questionnaire assessments will be 
assigned to analysis visits as follows:
1. Baseline: Like other data, Baseline will be defined as last available recorded value up 
to and including the date of first Maintenance phase dose of study treatment. Baseline 
is not applicable for HIVTSQc and Preference assessments
2. Post-Baseline: 
a.
if the nominal visit identifier as captured in the source dataset corresponds to a 
scheduled collection per the Time and Events Schedule (see Section 12.2 and 
Table 11 ) and the assessment is collected in the Maintenance Phase (per
Table 13), then the nominal visit identifier will be kept as the analysis visit.
b. if the nominal visit identifier is unscheduled or withdrawal, then the following 
procedure will be used:
i. Assign the assessment to a study phase according to Table 13. Proceed 
to step ii if the assessment is assigned to the Maintenance Phase.
ii. Identify the ‘last nominal visit’ with the HO assessment performed 
prior to the unscheduled/withdrawal visit to be slotted.
iii. The unscheduled/withdrawal visit will be slotted to the planned 
nominal visit subsequent to the ‘last nominal visit’. If the ‘last nominal 
visits’ does not exist (e.g. no records originate from a planned nominal 
visit), then the unscheduled/withdrawal visit will be slot to the first 
planned nominal visit after Day 1.
Example 1, for HIVDQoL, the planned nominal visits are Day 1, Month 6 and Month 12. 
If a participant has the ‘last nominal visit’ (with HIVDQoL assessment) at Month 6 prior 
to withdrawal at Month 8, the withdrawal assessment will be slotted to the subsequent 
planned nominal visit of Month 12.
Example 2, for HIVDQoL, if there is unscheduled visit between Month 6 and Month 12. 
This unscheduled visit will be slotted to Month 12 per the rule. In this case, there are two 
assessments with analysis visit equal to Month 12 (i.e. the slotted value and the value at 
original nominal Month 12 visit). The original nominal value will be selected for 
summary per the rule below for multiple records—see Section 12.3.5.


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Table 11
Planned Nominal Visit of Health Outcome Data
Endpoints
Day 1
Month 6
Month 12
HIVTSQc
X
HIVTSQs
X
X
X
HIVDQoL
X
X
X
Preference *
X
NOTE: 
* not collected for DTG+RPV.
12.3.4.2.
Reasons for Switch
Reasons for Switch assessments are planned to be taken at nominal Day 1 visit only. The 
assessments taken within ± 2 weeks window from Maintenance phase treatment start date will be 
regarded as evaluable. The assessments taken outside this window will be excluded from the 
summary.
12.3.5.
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 
1.
The assessment closest to the window target Study Day;
2.
If there are multiple assessments equidistant from the target Study Day, then the mean of 
these values will be used. For HIV-1 RNA, the geometric mean of the number of copies will 
be used as opposed to the arithmetic mean.
For Health outcome data, 
1.
If there are multiple on-treatment assessments assigned to the same analysis visit, the 
assessment from the planned nominal visit will be used for summary statistics.
2.
If there are multiple on-treatment assessments assigned to the same analysis visit and none 
originates 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 appear in the 
associated listings. Also, all applicable valid assessments, irrespective of proximity to 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).


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12.4.
Appendix 4: Study Phases and Treatment State
12.4.1.
Study Phases
Assessments and events will be classified according to the time of occurrence relative to the 
Treatment Start Date defined in Section 12.6.1.
AEs will be assigned to study phases as defined in Table 12. For example, adverse events on/after 
start of Maintenance phase IP and prior to start of LTFU ART will be assigned to the Maintenance 
Phase.
Laboratory data (efficacy, safety and virology), HIV associated Conditions, health outcomes 
assessments, vital signs, and ECGs will be assigned to study phases as defined as in Table 13. 
For example, assessments/events occurring after start of Maintenance Phase IP and up to and 
including start of LTFU ART will be assigned to the Maintenance Phase.
Assessments/events are assigned to study phases sequentially, starting from the top of each table.
No study phases will be assigned to medications.
Table 12
Assignment of Study Phases for AEs
Study Phase
Date range
Screening
Date < Maintenance Treatment Start Date
Maintenance
CAB LA + RPV LA:Maintenance Treatment Start Date ≤ Date < LTFU ART 
Start Date 
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.
DTG + RPV:
Maintenance Treatment Start Date ≤ Date < Date of nominal Month 12 visit
NOTES:

Date = AE Start date

If participants have the missing LTFU ART start date, only the lower bound will be considered.

Maintenance Treatment Start Date: refer to Treatment Start Date in Section 12.6.1


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Table 13
Assignment of Study Phases for Lab Assessments (including 
Virology), ECG, Vital Sign, Health Outcomes, and HIV associated 
conditions 
Study Phase
Date range
Screening
Date ≤ Maintenance Treatment Start Date
Note: 2-hour post-dose ECG taken on the Maintenance Treatment Start Date 
will be excluded.
Maintenance
CAB LA + RPV LA:
Maintenance Treatment Start Date < Date ≤ LTFU ART Start Date
DTG + RPV:
Maintenance Treatment Start Date < Date ≤Date of nominal Month 12 visit
Note: 2-hour post-dose ECG taken on the Maintenance Treatment Start Date 
will be included.
NOTES:

Date = start or assessment date

If participants have the missing LTFU ART start date, only the lower bound will be considered.

Maintenance Treatment Start Date: refer to Treatment Start Date in Section 12.6.1
Table 14
Assignment to Long-Term Follow-Up Phase 
Study Phase
Date range
Long-Term 
Follow-Up
Date > max(Last IM Injection Date, Last Oral Dose End Date)
NOTES:

Date = start or assessment date

For AEs leading to withdrawal and started on the same date as LTFU HAART Start Date, maintenance 
phase instead of long-term follow-up phase, will be assigned. Refer to Table 12 for details.
Only participants who received at least one CAB and/or RPV injection will enter the 
long-term follow-up.
Note that the long-term follow-up phase and maintenance phase are not necessarily 
mutually exclusive and are to be defined with separate phase variables in the datasets.  
For example, CAB LA + RPV LA subject who has Month 10 injection and withdrawal at 
Month 12 without receiving Month 12 injection, the “Month 12 withdrawal visit” belongs 
to both the maintenance phase and long-term follow-up phase.  
12.4.2.
Treatment State
Within each treatment study phase (i.e. Maintenance and LTFU—based on assignment of 
study phase described in Section 12.4.1), only those assessments which occur within the 
ranges shown in Table 15 will be considered ‘on-treatment’ for the given phase. No 
treatment states will be assigned to medications.


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Table 15
Treatment State within Study Phases
Study Phasea
Treatment State
Date Range
Screening
Pre-treatment
All assessments/events within the phase
Maintenance
On-treatment
CAB LA + RPV LA:
Date max (Date of Last Oral Dose of 
CAB+RPV + 1, Date of Last Injection + 67)
DTG + RPV: 
Date Last Oral Dose Date + 1
Post-treatment
CAB LA + RPV LA:
Date > max (Date of Last Oral Dose of 
CAB+RPV + 1, Date of Last Injection + 67)
DTG + RPV: 
Date > Last Oral Dose Date + 1
Long-Term 
Follow-up
On-treatment
Date min(LTFU ART start date, max(Last 
Injection Date + 67, Last Oral dose Date + 1))
Post-treatment
Date > min(LTFU ART start date, max(Last  
Injection Date + 67, Last Oral dose Date + 1))
NOTES:
a.
Treatment State is determined after data has been assigned to the study phases as defined in 
Section 12.4.1
b.
Last injection and/or last oral dose of CAB+RPV are only applied to subjects who permanently 
discontinue from study treatment. The assessments for participants who did not permanently 
discontinue the study treatment will be considered ‘On-treatment’
c.
Date = Assessment/Start Date.
12.4.2.1.
Treatment States for AE Data
For adverse events, partial AE start date will use imputation as described in Section 
12.7.2.1. In the case of a completely missing start date, the event will be considered to 
have started On-treatment at Maintenance phase unless an end date for the AE is 
provided which is before start of study treatment at Maintenance phase; in such a case the 
AE is assigned as Pre-treatment. 
Within each treatment study phase, only those AE with onset date within the ranges 
shown in Table 15 will be considered ‘on-treatment’ for the given phase. The onset date 
will be derived based on Table 16. 


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Table 16
Days since First Dose of Each Study Phase, Days since Phase Start, 
AE Duration and Relation to Study Treatment
Definition
Days since
First Dose
(Days)a
AE Start Date – Maintenance Treatment Start Date + 1
Days since
Last Dose 
(Days)a
AE Start Date – Date of Last Dose of Study Treatment prior to/on 
the Start Date of AE + 1
Days since 
Phase Start
For AEs in Maintenance Phase:
AE Start Date - Maintenance Treatment Start Date + 1
For AEs in Long-term Follow-up Phase:
AE Start Date – Date of Last Dose of Study Treatmentb
Duration 
(Days) 
AE Resolution Date – AE Start Date + 1
Drug-related
If relationship is marked ‘YES’ on Inform/CRF OR value is 
missing.
NOTES:
a.
Days since First/Last Dose will only be derived for AEs assigned to maintenance phase and 
long-term follow-up phase.
b.
Date of Last Dose of Study Treatment = max (Last IM Injection Date, Last Oral Bridging End 
Date), only applicable to participants who permanently discontinued study treatment.


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12.5.
Appendix 5: Data Display Standards & Handling 
Conventions
12.5.1.
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
: us1salx00259
HARP Compound
: \ARPROD\GSK1265744\mid209035
Analysis Datasets 

Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & 
ADaM IG Version 1.1).

For creation of ADaM datasets (ADCM/ADAE), the same version of dictionary datasets will 
be implemented for conversion from SI to SDTM.
Generation of RTF Files

RTF files will be generated for every reporting effort described in the RAP.
12.5.2.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx):

4.03 to 4.23: General Principles

5.01 to 5.08: Principles Related to Data Listings

6.01 to 6.11: Principles Related to Summary Tables

7.01 to 7.13: Principles Related to Graphics
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated.

Numeric data will be reported at the precision collected on the eCRF.

The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as appropriate.

Reporting for Data Listings: 

Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the subject’s listings.


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Unscheduled Visits
Unscheduled visits will be assigned to a study visit using the all-inclusive windows defined in 
Section 12.3.
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’ planned 
assessment time points and in data listings, as well any algorithms that make use of additional data 
(e.g., Snapshot).
Descriptive Summary Statistics
Continuous Data
Refer to IDSL Statistical Principle 6.06.1
Categorical Data
N, n, frequency, %
Graphical Displays

Refer to IDSL Statistical Principals 7.01 to 7.13.


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12.6.
Appendix 6: Derived and Transformed Data
12.6.1.
General
Multiple Measurements at One Time Point

If after window assignment there are multiple valid assessments of a parameter within the 
same window, refer to Section 12.3.5 for determination of the value to be used for summary 
statistics of observed values. Assessments not chosen for use in summary statistics will still 
appear in the associated listings. Also, all applicable valid 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).
Treatment Start Date
Treatment start date is defined for the Maintenance Phase as follows:

For subjects who were on CAB LA + RPV LA, this is the date of the first injection dose 
entered onto the IP exposure eCRF form.

For subjects who were on oral DTG + RPV, this is the date of the first oral dose entered 
onto the IP exposure eCRF form.
For the long-term follow-up phase (only for CAB LA + RPV LA arm):

If a participant is still on study treatment, or permanently discontinued the study 
treatment and did not have any previous injections, treatment start date is missing.

If a participant permanently discontinued the study treatment and had at least one 
injection, treatment start date is the date of first HAART treatment after the last dose of 
study treatment (oral or injection).
Study Day
The Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of AE or HIV 
associated condition) will be derived as the number of days between the date of the event and 
the start date of study treatment on Maintenance phase as follows:
if date of event start date of study treatment, then

Study Day = Date of Event – Start Date of Maintenance Phase IP + 1
if date of event < start date of study treatment, then

Study Day = Date of Event – Start Date of Maintenance Phase IP 
Note that the start date of study treatment on Maintenance phase is considered to be on Study 
Day 1 and the day before this is Study Day -1; i.e., there is no Study Day 0.


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Long-Term Follow Up Study Day
The Long-Term Follow Up (LTFU) Study Day of an event (e.g., lab assessment, start date of AE 
or HIV associated 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
Change from Baseline
Post-Dose Visit Value – Baseline

Unless otherwise specified, the baseline definitions specified in Section 5.2 will be used 
for derivations for endpoints / parameters.
12.6.2.
Study Population
Demographics and Baseline Characteristics
Age

Age, in whole years, will be calculated with respect to the subject’s Baseline visit.  

GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed 
as follows:
o
Any subject 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 subject will not be calculated and will remain missing.
Body Mass Index (BMI)

Calculated as Weight (kg) / Height (m)2
Hepatitis Status

Hepatitis C status will be determined using antibody 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.

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.

Hepatitis status at entry will be based on the assessments prior to/on the start of the study 
treatment.


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Demographics and Baseline Characteristics
Lipid-modifying Agents

The following ATC codes correspond to lipid-modifying agents:

ATC Level 2: C10

ATC Level 3: C10A, C10B (if Level 2 is not available)

ATC Level 4: C10AA, C10AB, C10AC, C10AD, C10AX, C10BA, C10BX (if level 2, 3 are not 
available)

Participants are considered to have used a lipid-modifying agent at baseline if they are taking 
the medication at the time of their baseline 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.
Extent of Exposure
Exposure to CAB LA +RPV LA injection and to DTG + RPV oral will be calculated from the IP eCRF 
pages.  
CAB LA + RPV LA:

Exposure = Number of IP injections received during Maintenance Phase.

Overall exposure to IP = min(Date of Latest Maintenance Phase visit, max(Date of Last 
Injection + 67, Date of Last Dose of Oral CAB+RPV)) – Date of First Study Injection + 1
Note: Last Injection and/or Last Dose of Oral CAB+RPV are only applicable to those who 
permanently discontinued study treatment.
DTG + RPV:

Exposure = IP Stop Date – IP Start Date + 1

Overall exposure to IP = min(Date of Latest Maintenance Phase visit, Date of Last Dose of 
DTG + RPV) – Date of First Dose + 1

There will be no adjustments to the exposure duration for any missed doses.
Duration of dosing in subject years will be calculated as the sum of subject duration of dosing in 
days (across all subjects)/365.25.
Subjects who were enrolled but did not report an IP start date will be categorised as having zero 
days of exposure. 
For DTG + RPV arm, missing IP discontinuation date will be imputed, for purposes of calculating 
exposure, as the date of last visit or the recorded date of withdrawal/completion, whichever is 
earlier.
Adherence to CAB LA + RPV LA Injection Schedule
Timeliness of Injections relative to Date of Projected Dosing Visits is 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. Each injection visit is counted only once. Individual CAB and 
RPV injections administered at the same visit are not counted twice. "Extra" unscheduled injections 
are excluded from all derivations. For example, if during a scheduled visit a participant receives 1 ml 


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of injection instead of 3 ml due to a dosing error, but this participant returns one week later for the 
remaining 2 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 planned interval is 60 days for the CAB LA + RPV LA arm. Relative days between two planned 
consecutive visits for injections relative to the planned interval will be calculated as below:
                      Relative Days=Actual number of days between adjacent injections – 60. 
For example, if the time interval between two scheduled consecutive visits for injections is 55 days 
then relative days = 55 – 60 = -5; if the interval is 60 days then relative days = 65 – 60 = 5
The relative days will be grouped as below:
< -14 days
-14 to   - 8 days
-7   to   - 4 days 
-3   to    -2 days
-1 day 
0 days 
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
In the case that a scheduled injection visit is missed, the time interval between the preceding and 
the subsequent scheduled injection will be calculated. For example, if Month 8 injection is missed, 
then the number of days between the actual Month 6 and Month 10 injections will be calculated. 
To calculate the proportion of injection intervals for each of the above category of relative days, the 
denominator is the total count of time intervals between adjacent injection visits for CAB LA + RPV 
LA arm.
12.6.3.
Efficacy
Snapshot

The Snapshot algorithm is intended to be primarily a virologic assessment of the endpoint, and 
as such follows a “virology first” hierarchy.

‘HIV-1 RNA <50 c/mL’ or ‘HIV-1 RNA ≥50 c/mL’ within an analysis window (see Table 8 and 
Table 9) is typically determined by the last available HIV-1 RNA measurement in that window 
while the subject is On-treatment in the Maintenance Phase (as assigned based on Section 
12.4.1).
When no HIV-1 RNA data is available within a window, a subject cannot be assigned to the 


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category of ‘HIV-1 RNA < 50 c/mL’.  Depending on the reason for lack of data, the subject will 
be classified as a ‘HIV-1 RNA≥50’ or reported as ‘No Virologic Data at Month X’; in the latter 
case, the algorithm further classifies the nature of the missing data. Typically, a subject 
withdrawn (i) due to AE or, (ii) for another reason yet was suppressed at the time, will be 
counted as ‘No Virologic Data at Month X’.  Should a subject withdraw for reasons other than AE 
and was not suppressed at the time, they will be categorized as ‘HIV-1 RNA≥50’.
Full details of the algorithm, including the handling of special cases, are included in Section 12.9

For each scheduled assessment time, the Snapshot response rate for a given threshold (e.g., 
<50 c/mL) is defined as:
population
  
analysis
 the
in
  
subjects
of
Number 
 window
analysis
 that 
in
  
responders
of
Number 
  Rate
esponse
Snapshot R

For each scheduled assessment time, the Snapshot ‘HIV-1 RNA≥50’rate for a given threshold 
(e.g., ≥50 c/mL) is defined as:
population
  
analysis
 the
in
  
subjects
of
Number 
  window
analysis
 that 
in
  
VFs
of
Number 
 Rate
VF
Snapshot  

Plasma HIV-1 RNA

For summaries and analyses which use HIV-1 RNA level as a continuous measure, the 
logarithm to base 10 of the value will be used.

HIV-1 RNA results may be provided as censored values, such as <40 or >9,999,999 c/mL. For 
the purposes of summary statistics, such values will be replaced by the next value beyond the 
limit of detection, e.g., 39 or 10,000,000 c/mL, respectively, for the given examples. Data 
listings will show the censored values as provided.
Target Detected / Target Non Detected/Super low viral load testing

When a measurement of plasma HIV-1 RNA is below the limit of quantification (i.e. 40 c/mL) 
and is qualitatively observable that will be denoted as a “Target Detected” measure, while HIV-1 
RNA below the limit of quantification that is not qualitatively observable that will be denoted as 
“Target Not Detected”. Any measurements <40 c/mL characterised as “Target Non Detected” or 
“Target Detected” will be captured in the database.

Super low viral load will also be tested by BioMNTR lab for Viral loads below the limit of 
quantification at some visits (e.g. Month 12)
Confirmed Virologic Failure (CVF)

The definition of CVF is provided in the Protocol, Section 7.1.4 – Definition of Protocol-Defined 
Confirmed Virologic Failure

In case there are multiple plasma HIV-1 RNA results on the same day, the worst result (i.e. the 
largest value) will be used in determination of CVF.
Summary for Participants per Viral Load Category by Visit
Summary will be based on observed available data, with no imputation for missing values. The 
proportion of participants in each viral load category will be calculated using the denominator 
and numerator specified below:
o
Denominator: Number of participants with on-treatment viral load within the 
snapshot visit window.
o
Numerator: Number of participants with plasma HIV-1 RNA in the specified 
category based on the last on-treatment viral load assessment collected within the 
snapshot visit window.


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HIV-1 Disease progression Stage

Categories:
o
CDC Stage I at Maintenance Baseline to CDC Stage III; 
o
CDC Stage II at Maintenance Baseline to CDC Stage III; 
o
CDC Stage III at Maintenance Baseline to new CDC Stage III event and 
o
CDC Stage I, II, III at Maintenance Baseline to death. 
Please refer to Protocol (Appendix 8:  CDC Classification for HIV-1 Infection (2014)) for defining 
Stage.

For the purpose of analysis, the CDC at Baseline and at post-baseline during Maintenance 
phase will be derived as below:
o
At Baseline, the ‘Baseline CDC stage’ for each subject was assessed by the 
investigator and recorded in the eCRF. However, for the analysis, Maintenance 
Baseline CDC stage will be re-derived based on Maintenance Baseline CD4+ 
values as well as whether any HIV-associated conditions present at Baseline per 
the Criteria’s thresholds (Appendix 8 in Protocol). 
o
To analyse disease progression, the most advanced post-baseline CDC stage 
within the period of interest (e.g. Maintenance Phase) will be derived based on the 
occurrences of new AIDS-defining conditions (please refer to Appendix 8 in 
Protocol for the list of AIDs-defining Conditions) as well as the nadir value of 
Maintenance CD4+. For example,

If a subject with CDC ‘Stage I’ at Maintenance Baseline had the lowest 
Maintenance Phase CD4+ =120 cell/mm3 without new AIDs-defining 
conditions, then HIV disease progression for this subject during the 
Maintenance phase would be considered as ‘CDC stage I at Baseline 
to CDC stage III’.

If a subject with CDC ‘Stage II’ at Baseline had the lowest 
Maintenance Phase CD4+ =220 cell/mm3 AND had at least one new 
AIDs-defining condition, then HIV disease progression for this subject 
during the Maintenance Phase would be considered as ‘CDC stage II 
at Baseline to CDC stage III’.
12.6.4.
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 2. 
Potential QTc Interval Prolonging Events of Interest
Potential QTc Interval Prolonging Events of Interest cases 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


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Adverse Events
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 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].will be 
used by the central laboratory to provide an estimate of GFR, in mL/min per 1.73 m2, as follows:


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Laboratory Parameters
where age (in years) is at time of assessment, κ = 0.7 if female or 0.9 if male, α = -0.329 if female 
and -0.411 if male, min() indicates the minimum of CRT/κ or 1, max() indicates the maximum of 
CRT/κ or 1, and CRTmg/dL is serum creatinine concentration in mg/dL. The serum creatinine 
concentration in mg/dL is obtained from GSK standard units of mol/L as CRTmg/dL =0.0113x 
CRTmol/L. 

The CKD-EPI GFR will also be calculated using Cystatin C, as follows
133 X min(Scys/0.8, 1) -0.499 X max (Scys/0.8, 1)-1.328 X 0.996 Age X[0.932 if female]
Where Scys is serum cystatin C mg/Liter, min indicates the minimum of Scr/0.8 or 1, and max 
indicates the maximum of Scys/0.8 or 1
Lab Toxicities – DAIDS Grading based on Version 2.1, March 2017, as specified in the 
protocol of Appendix 2

Toxicities will be based on the Division of AIDS (DAIDS) grading system, Version 2.1, March 
2017, as specified in the protocol of Appendix 2. 

Toxicity grades provided by the central laboratory do not distinguish between abnormally high 
or low criteria, when both are relevant for a particular parameter.

When summarising toxicity grades for such parameters, they will be categorised as to whether 
they are above or below the midpoint of normal range.
Parameter
Below Midpoint for 
those ≥Grade 1
Above Midpoint for 
those ≥Grade 1 
Fasted glucose
Hypoglycemia
Hyperglycemia
Sodium
Hyponatremia
Hypernatremia
Potassium
Hypokalemia
Hyperkalemia
National Cholesterol Education Program (NCEP) Lipid Categories

In addition to DAIDS toxicity grades (see protocol), lipid values will be categorized according to 
the 2001 NCEP Adult Lipid Guidelines [Grundy, 2001]
Parameter
Value Range (mmol/L)
Value Range (mg/dL)
Category
Triglycerides
<1.70
<150
Normal
1.70 to <2.26
150 to <200
Borderline High
2.26 to <5.65
200 to <500
High
5.65
500
Very High
Total Cholesterol
<5.18
<200
Desirable
5.18 to <6.21
200 to <240
Borderline High
6.21
240
High
HDL Cholesterol
<1.04
<40
Low


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Laboratory Parameters
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
Other Safety Endpoints
Corrected QTC
When not entered directly in the eCRF, corrected QT intervals by Bazett’s (QTcB) and Fridericia’s 
(QTcF) formulas will be calculated, in msec, depending on the availability of other measurements.
If RR interval (in msec) is provided then missing QTcB and/or QTcF will be derived as
1000
RR
QT
QTcB 
3
1000
RR
QT
QTcF 
where uncorrected QT interval is also measured in msec.
If RR interval is not provided directly and one of QTcB or QTcF has been entered, then RR interval 
can be obtained from the above formulas and used to calculate the other correction method value; 
i.e.,
QT
QTcF
QTcB
3

3
2
QTcB
QT
QTcF




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12.6.5.
Health Outcomes
HIVTSQs
Questionnaire (Questions 1-12 are scored 0-6)
Treatment Satisfaction Score

Total Treatment Satisfaction Score is computed with items 
 
. 

Item 12 will not be included in Total Treatment Satisfaction Score. Instead, it will be treated as a 
stand-alone item only.

Higher scores represent greater treatment satisfaction as compared to the past few weeks.

A maximum of 5 items can be missing, which can be imputed to reflect the mean of the 
completed item scores. If 6 or more items are missing, then the treatment satisfaction scale 
score should not be computed and would remain missing. 
Individual Item Scores

Items are rated as
(
, etc.) to
(
 
, etc.). 

Higher scores represent greater satisfaction with each aspect of treatment

For individual item scores outputs, missing scores will not be computed (according to Page 7 of 
the [HIVDQoL User Guidelines, 2018]) and would remain missing.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are 
protected by third party copyright laws and therefore have been excluded.
CCI
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CCI CCI
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HIVTSQc
Questionnaire (Questions 1-12 are scored -3 to 3)
Treatment Satisfaction Score (change)

Total Treatment Satisfaction Score is computed with items 
 

Item 12 will be computed as an individual item only.

The higher the score, the greater the improvement in satisfaction with treatment; the lower the 
score, the greater the deterioration in satisfaction with treatment.  A score of 0 represents no 
change. 

A maximum of 5 items can be missing, the missing scores will be imputed with the mean of the 
completed item scores. If 6 or more items are missing, then the overall treatment satisfaction 
scale score should not be computed and will remain missing.
Individual Treatment Change Item Scores

Items are rated as 
, 
etc.) to 
, etc.). 

The higher the score, the greater the improvement in satisfaction with each aspect of treatment 
and the lower the score, the greater the deterioration in satisfaction with each aspect of 
treatment.
HIVDQoL
Questionnaire (Questions I and II are overview items and 1-26 are domain-specific items)
This questionnaire has been provided in three different languages: English (US and Canadian), 
French (Canadian), Spanish (US). Below is an example of the questionnaire.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are 
protected by third party copyright laws and therefore have been excluded.
CCI
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.
CCI
CCI
CCI


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third 
party copyright laws and therefore have been excluded.


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.


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Individual Domain Items [HIVDQoL User Guidelines, 2018]

There are two overview items which are rated as:
o
I:
o
II: 

 

The 26 domain-specific items include two rating scales, one measuring impact, part a, and the 
other measuring the importance of the domain for QoL, part b.

The impact scores are rated as 
 to 
 and the importance scores are rated as 
 to 
 
Weighted Impact Scores [HIVDQoL User Guidelines, 2018]

The impact ratings are multiplied by the corresponding importance rating to provide a 
weighted-impact score for each applicable domain from 
 to
CCI
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CCI
CCI
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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which 
are protected by third party copyright laws and therefore have been excluded.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
third party copyright laws and therefore have been excluded.
CCI
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.

If one part of a domain response (i.e. either part a or part b) is missing, a weighted impact 
score cannot be imputed for that question.

If more than one option has been selected for a question, then if the options are consecutive 
(e.g. 2 and 3), then take the mid-point (i.e. 2.5) to be the final score for that question. However, 
if the two answers are not immediately next to each other (e.g., 0 and 3), treat the score as 
missing.
Average Weighted Impact (AWI) Score [HIVDQoL User Guidelines, 2018]

Weighted impact scores are summed and divided by the number of applicable domains 
(excluding domains with missing data), to give an overall AWI score. The non-applicable
domains are hence ignored.

If there are more than three items with missing scores out of the 14 core domain-specific items 
which do not have the N/A option, then the AWI score will not be computed.

Item 23 and item 25 are not included when calculating AWI scores along with the two overview 
items I and II.
Reason for Switch
Questionnaire 
You have chosen to continue participating in a clinical study where your daily oral HIV medication 
will be switched to a Long-Acting injectable HIV medication.
 
 [select all that apply]:
Data handling

If the questionnaire is taken beyond ± 2 weeks window from maintenance phase treatment 
start date (i.e. Study Day < -14 or Study Day > 14) it will be considered not evaluable and will 
not be included in the summary.

Any missing values will remain missing (i.e. no imputation).
Preference question
Questionnaire 
CCI
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questionnaires or indices, which are protected by third party copyright laws and 
therefore have been excluded.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which 
are protected by third party copyright laws and therefore have been excluded.
CCI
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Data handling

Any missing values will remain missing (i.e. no imputation)
12.6.6.
Virology
Genotype 
Amino Acid Changes

A mutation is considered present whenever the encoded amino acid residue differs from the 
amino acid that would have been encoded by the wild-type (e.g., HXB2, NL43) comparator 
gene; e.g., Q148K. 

If the encoded amino acid is seen as a mixture of wild-type and mutant amino acid, e.g., 
Q148Q/K, the mutated amino acid is considered present at the codon of interest. 

If the encoded amino acid is seen as a mixture of two or more amino acids, which may or may 
not include wild type, e.g., Q184K/H or Q184K/H/Q, etc., for the purposes of calculating the 
number of mutated amino acids, only one mutation is considered to be present at the codon of 
interest.
Representation of Amino Acid Changes
Mutations
Amino acid change
T69S
Single mutation from amino acid 'T' (vendor reference) to 'S' (sample) at codon '69' 
Q148H/K/R
Mixture of amino acid mutations ‘H’, ‘K’ and ‘R’ (sample) from amino acid ‘Q’ 
(vendor reference) at codon ‘148’
_69_1T
First insertion of amino acid 'T' (sample) at codon '69'
_69_2S
Second insertion of amino acid 'S' (sample) at codon '69'
_69_3S/A
Third insertion of a mixture of amino acids 'S' and 'A' (sample) at codon '69'
L74L/-
Mixture of amino acid 'L' (sample) and a deletion at codon '74'
V75-
Single deletion of amino acid (sample) at codon '75'
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.


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Resistance Associated Mutations

Known INI mutations associated with the development of resistance to BIC, RAL, EVG or DTG:
Amino Acids in 
HIV Integrase for 
Analysis
H51Y, T66A/I/K, E92Q/V/G, Q95K, T97A, G118R, F121Y, E138A/K/T, 
G140A/C/R/S**, Y143C/H/R/K/S/G/A, P145S, Q146P, S147G, 
Q148H/K/R/N, V151A/I/L, S153F/Y, N155H/S/T, E157Q, G163R/K, 
S230R, D232N, R263K, L68V/I*, L74I/M*, E138D*, V151I*, G193E*
NOTES:
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 25Oct2019) and accessed on 28Jan2020.
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).
**G140R is potentially associated with CAB based on in-stream data monitoring of CVF participants

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]
Phenotype
Phenotypic Susceptibility 
Phenotypic susceptibility to all licensed antiretroviral drugs and CAB will be determined using 
PhenoSense HIV assays from Monogram Inc. and will be reported as fold change (FC) in IC50 
relative to wild-type control virus NL4-3, i.e., FC of sample virus = IC50 of sample virus/IC50 of 
control virus.  
Phenotypic susceptibilities will be categorised according to FC as shown in the tables 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. 
Replication capacity is generated as part of standard phenotypic assays


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PhenoSense Algorithm
Drug
Abbreviation
Class
PhenoSense cutoff
Abacavir
ABC
NRTI
(4.5 – 6.5)a
Lamivudine
3TC
NRTI
3.5 a
Didanosine
ddI
NRTI
(1.3 – 2.2) a
Stavudine
d4T
NRTI
1.7 a
Zidovudine
AZT (ZDV)
NRTI
1.9
Emtricitabine
FTC
NRTI
3.5
Tenofovir
TDF (TAF)
NRTI
(1.4 – 4) a
Delavirdine
DLV
NNRTI
6.2
Efavirenz
EFV
NNRTI
3
Nevirapine
NVP
NNRTI
4.5
Etravirine
ETR
NNRTI
(2.9-10) a
Rilpivirine
RPV
NNRTI
2.0
Fosamprenavir/r
FPV/r
PI
(4-11) a
Atazanavir
ATV
PI
2.2a
Atazanavir/r
ATV/r
PI
5.2 a
Indinavir/r
IDV/r
PI
10 a
Lopinavir/r
LPV/r
PI
(9 – 55) a
Nelfinavir
NFV
PI
3.6
Saquinavir/r
SQV/r
PI
(2.3 – 12) a
Tipranavir/r
TPV/r
PI
(2 – 8) a
Darunavir/r
DRV/r
PI
(10 – 90) a
Ritonavir
RTV
PI
2.5
Enfuvirtide
T20
FI
6.48
Cabotegravir
CAB
INI
2.5
Raltegravir
RAL
INI
1.5
Elvitegravir
EVG
INI
2.5
Dolutegravir
DTG
INI
(4-13) a
Bictegravir
BIC
INI
(2.5 - 10)
clinical cutoff (lower cutoff – higher cutoff). 
Phenotypic susceptibility to each drug in a subject’s background regimen is determined by 
applying drug-associated cutoffs as defined by the PhenoSense algorithm to the phenotypic fold 
resistance as below: 
Full Sensitivity 
Fold Change
Interpretation
> clinical lower cutoff or biologic cutoff
resistance
clinical lower cutoff or biologic cutoff
sensitive
Partial Sensitivity 
Fold Change
Interpretation
> clinical higher cutoff
resistance
clinical higher cutoff and > clinical lower cutoff
partially sensitive
clinical lower cutoff
sensitive
PHENOTYP dataset from Monogram contains the phenotypic susceptibility for each drug derived 
from the cutoff listed above. Thus, phenotypic susceptibility (i.e. full sensitivity and partial 
sensitivity) will not be re-derived for our analysis.


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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 ‘resistance’, ‘partially sensitive’, and ‘sensitive’ as what will be performed for phenotypic 
susceptibility. Genotypic and Net assessment susceptibility will be assessed at time of CVF using 
plasma sample, Genotypic susceptibility may be assessed at baseline using PBMC.


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12.7.
Appendix 7: Reporting Standards for Missing Data
12.7.1.
Premature Withdrawals
Element
Reporting Detail
General
Subject study completion (i.e. as specified in the protocol) was defined as:
Participants are considered to have completed the study if they remain on therapy 
(i.e., have not permanently discontinued study intervention) and satisfy one of the 
following:

Assigned to either treatment group, completed the Maintenance Phase 
(Month 12 for DTG +RPV participants only), remaining on study until 
commercial supplies of CAB LA + RPV LA Q2M or DTG + RPV regimens 
become locally available or development of CAB LA + RPV LA is terminated;
Additionally, participants will continue this study until: 

the participant no longer derives clinical benefit, 

the participant meets a protocol-defined reason for discontinuation  
Participants who withdraw from CAB LA + RPV LA and go into the LTFU Phase will 
be considered to have prematurely withdrawn from the study intervention.

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 from the DTG + RPV regimen 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 Follow-up visit should 
reflect any ongoing complaints (e.g., blood draws to follow a laboratory 
abnormality). Follow-Up visits are not required for successful completion of the 
study.

Withdrawn participants will not be replaced

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.
12.7.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument:
o
These data will be indicated by the use of a “blank” in subject listing 
displays. Unless all data for a specific visit are missing in which case the 
data is excluded from the table. 


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Element
Reporting Detail
o
Answers such as “Not applicable” and “Not evaluable” are not considered to 
be missing data and should be displayed as such.
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.
12.7.2.1.
Handling of Missing and Partial Dates
Element
Reporting Detail
General

Partial dates will be displayed as captured in subject listing displays.
Adverse 
Events

The eCRF allows for the possibility of partial dates (i.e., only month and year) to 
be recorded for AE start and end dates; that is, the day of the month may be 
missing. In such a case, the following conventions will be applied for calculating 
the time to onset and the duration of the event:
o
Missing Start Day: First of the month will be used unless this is before the 
start date of study treatment; in this case the study treatment start date will 
be used and hence the event is considered On-treatment as per Appendix 
4: Study Phases and Treatment Emergent Adverse Events.
o
Missing Stop Day: Last day of the month will be used, unless this is after the 
stop date of study treatment; in this case the study treatment stop 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.
ART/Non-
ART 
Medications
/Medical 
History

Partial dates 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. If 
medications recorded in the eCRF as prior (e.g. recorded in prior ART or 
prior ATLAS ART forms, taken prior to study), the earlier date of the imputed 
and the day prior to the maintenance phase treatment start date will be 
used, i.e. min (imputed stop date, maintenance phase treatment start date -
1).

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 (e.g. recorded in prior ART form, 
taken prior to study).

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 date will be displayed in listings.
Health
outcomes

For the summary of individual item scores outputs, missing scores will not be 
computed.


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12.8.
Appendix 8: Values of Potential Clinical Importance
12.8.1.
Laboratory Values
Element
Reporting Detail
Laboratory 
Values and 
Adverse 
Events

The central laboratory will flag lab parameter toxicities directly in the 
provided datasets based on Division of AIDS Table for Grading the 
Severity of Adult and Paediatric Adverse Events Version 2.1, March 2017
12.8.2.
ECG
ECG values of potential clinical importance are defined as QTc > 500 msec or increase
from baseline in QTc ≥ 60 msec.


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12.9.
Appendix 9: Snapshot Algorithm Details
Detailed Algorithm Steps

Consider an analysis visit window for Month X as defined in Table 8 and Table 9.

The HIV1-RNA threshold of 50, copies/mL will be analysed, in this study 

The analysis window ‘Month 12’ and HIV1-RNA threshold of ’50 copies/mL’ are used for 
the purpose of illustration. A subject’s Snapshot response and reason at Month 12 are 
categorized as below.
o
HIV1-RNA < 50 copies/mL 
o
HIV1-RNA ≥ 50 copies/mL 
Data in window not below 50
Discontinued for lack of efficacy
Discontinued for other reason while not below 50
Change in background therapy*
o
No Virologic Data at Month 12 Window
Discontinued study due to AE or death
Discontinued study for other reasons
On study but missing data in window
* Note: since changes in ART are not permitted in this protocol, all such subjects who change 
ART during the maintenance phase and prior to an analysis timepoint will be considered ‘HIV1-
RNA ≥ 50 copies/mL’. Participants with protocol permitted oral bridging 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.
Detailed steps
Please note that the following scenarios will NOT be penalized Per Snapshot algorithm (i.e. 
please exclude these scenarios from Condition 1-4).

Dose reduction, dropping a component, or change in formulation (e.g. ‘Tivicay + Kivexa’ 
to ‘Triumeq’ with the identical ingredients) 
Condition (‘Month 12’ indicates Month 12 window)
Response 
Reasons
1. If non-permitted change in background therapy prior 
to Month 12
HIV1-RNA ≥ 
50 
Change in 
background 
therapy
2.  If permitted change[a] in background therapy prior to
Month 12 AND the latest on-treatment VL prior to/on the 
date of change is ≥ 50 c/m (NA to this study)
HIV1-RNA ≥ 
50 
Change in 
background 
therapy
3:  If non-permitted change in background therapy 


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during Month 12   
Last on-treatment VL during Month 12 prior to/on 
the date of change ≥ 50 c/mL
HIV1-RNA ≥ 
50 
Data in window 
not below 50
Last on-treatment VL during Month 12 prior to/on 
the date of change <50 c/mL
HIV1-RNA < 
50 
No VL during Month 12 prior to/on the date of 
change    
HIV1-RNA ≥ 
50 
Change in 
background 
therapy
4: If permitted change[a] in background therapy during
Month 12 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 Month 12
HIV1-RNA ≥ 
50 
Change in 
background 
therapy 
4. 2   this last on-treatment VL occurs during Month 12
but prior to/on the date of change
HIV1-RNA ≥ 
50 
Data in window 
not below 50
5: If none of the above conditions met
5.1 VL available during Month 12

Last on-treatment VL during Month 12  ≥ 50 
c/mL
HIV1-RNA ≥ 
50 
Data in window 
not below 50

Last on-treatment VL during Month 12 <50 
c/mL
HIV1-RNA < 
50 
5.2 No VL during Month 12   
5.2. 1 if subjects still on study i.e. a participant has not 
permanently discontinued the study treatment yet, or if a 
participant permanently discontinued the study treatment 
and the upper bound of analysis snapshot window is prior 
to the following date:  
CAB LA + RPV LA arm: 
Min (max(Date of last CAB LA + RPV LA injection + 67, 
Date of last Dose of Oral CAB + RPV + 1), withdrawal date)
DTG + RPV arm:
Min (Date of Last oral dose of DTG + RPV + 1, withdrawal 
date)
where ‘Withdrawal Date’ refers to the date the participant
No virologic 
data at Month 
12 Window 
On study but 
missing data in 
window


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failed to complete per corresponding conclusion form.
5.2.2 If subjects withdraw before/during Month 12 due to
5.2.2.1
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 Month 
12 Window
Disc due to 
AE/death
5.2.2.2
Non-safety related reasons (e.g. Lack of 
efficacy, protocol deviation, withdrew consent, 
loss to follow-up, study closed/terminated, 
investigator discretion et al, as recorded in 
eCRF Conclusion Form)
Last on-treatment VL <50 c/mL OR no on-
treatment VL available during study  
No virologic 
Data at Month 
12 Window
Disc for other 
reasons
Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to Lack of efficacy
HIV1-RNA ≥ 
50 
Disc. for lack of 
efficacy
Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to all other non-safety related 
reasons
HIV1-RNA ≥ 
50 
Disc. for other 
reason while 
not below 50
a: Excluding permitted change in background therapy where change or decision to change is made prior to/on the 
first on-treatment viral result
Examples from FDA guidance
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:
a.
HIV-RNA below 50 copies/mL at Day 336 and discontinues because of AE or 
even dies on Day 360 — this person is categorized as having HIV-RNA below 
50 copies/mL. 
b.
HIV-RNA is 552 copies/mL on Day 336 and the patient discontinues on Day 
360, the patient is categorized as having HIV-RNA greater than or equal to 50 


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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 
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.

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.


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12.10.
Appendix 10: Identification of Adverse Events of Special 
Interest
The adverse events of special interest are identified based on MedDRA coded values 
and/or AE data available in the study database. The system organ classes (SOCs), 
preferred terms (PTs) or codes, Standardised MedDRA Queries (SMQs), High Level 
Group Terms (HLGTs), and High Level Terms (HLTs) below are from MedDRA 22.0. 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. The additional 
events may also be added based on the blinded review of AE data collected on study prior 
to the database freeze.
1. Hepatic Safety Profile
Medical concept of hepatic failure and hepatitis. Sub- SMQs (1) 'Hepatic failure, fibrosis 
and cirrhosis and other liver damage-related conditions' and (2) 'Hepatitis, non-
infectious', both of parent SMQ 'Hepatic Disorders'; only narrow terms selected from 
sub-SMQs. Some preferred terms e.g. PT 'hepatitis fulminant' are duplicated.
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005
Sub-SMQ: 'Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions'
Category: A
Scope: Narrow
Preferred Term
PT Code
Acquired hepatocerebral degeneration
10080860
Acute hepatic failure
10000804
Acute on chronic liver failure
10077305
Acute yellow liver atrophy
10070815
Ascites
10003445
Asterixis
10003547
Bacterascites
10068547
Biliary cirrhosis
10004659
Biliary fibrosis
10004664
Cardiohepatic syndrome
10082480
Cholestatic liver injury
10067969
Chronic hepatic failure
10057573
Coma hepatic
10010075
Cryptogenic cirrhosis
10063075


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Diabetic hepatopathy
10071265
Drug-induced liver injury
10072268
Duodenal varices
10051010
Gallbladder varices
10072319
Gastric variceal injection
10076237
Gastric variceal ligation
10076238
Gastric varices
10051012
Gastric varices haemorrhage
10057572
Hepatectomy
10061997
Hepatic atrophy
10019637
Hepatic calcification
10065274
Hepatic cirrhosis
10019641
Hepatic encephalopathy
10019660
Hepatic encephalopathy prophylaxis
10066599
Hepatic failure
10019663
Hepatic fibrosis
10019668
Hepatic hydrothorax
10067365
Hepatic infiltration eosinophilic
10064668
Hepatic lesion
10061998
Hepatic necrosis
10019692
Hepatic steato-fibrosis
10077215
Hepatic steatosis
10019708
Hepatitis fulminant
10019772
Hepatobiliary disease
10062000
Hepatocellular foamy cell syndrome
10053244
Hepatocellular injury
10019837
Hepatopulmonary syndrome
10052274
Hepatorenal failure
10019845
Hepatorenal syndrome
10019846


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Hepatotoxicity
10019851
Intestinal varices
10071502
Intestinal varices haemorrhage
10078058
Liver dialysis
10076640
Liver disorder
10024670
Liver injury
10067125
Liver operation
10062040
Liver transplant
10024714
Lupoid hepatic cirrhosis
10025129
Minimal hepatic encephalopathy
10076204
Mixed liver injury
10066758
Nodular regenerative hyperplasia
10051081
Nonalcoholic fatty liver disease
10082249
Non-alcoholic steatohepatitis
10053219
Non-cirrhotic portal hypertension
10077259
Oedema due to hepatic disease
10049631
Oesophageal varices haemorrhage
10030210
Peripancreatic varices
10073215
Portal fibrosis
10074726
Portal hypertension
10036200
Portal hypertensive colopathy
10079446
Portal hypertensive enteropathy
10068923
Portal hypertensive gastropathy
10050897
Portal vein cavernous transformation
10073979
Portal vein dilatation
10073209
Portopulmonary hypertension
10067281
Primary biliary cholangitis
10080429
Regenerative siderotic hepatic nodule
10080679
Renal and liver transplant
10052279


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Retrograde portal vein flow
10067338
Reye’s syndrome
10039012
Reynold’s syndrome
10070953
Splenic varices
10067823
Splenic varices haemorrhage
10068662
Steatohepatitis
10076331
Subacute hepatic failure
10056956
Varices oesophageal
10056091
Varicose veins of abdominal wall
10072284
White nipple sign
10078438
SMQ: 'Hepatic Disorders'; SMQ Code: 20000005
Sub-SMQ: 'Hepatitis, non-infectious’
Category: A
Scope: Narrow
Preferred Term
PT Code
Acute graft versus host disease in liver
10066263
Allergic hepatitis
10071198
Alloimmune hepatitis
10080576
Autoimmune hepatitis
10003827
Chronic graft versus host disease in liver
10072160
Chronic hepatitis
10008909
Graft versus host disease in liver
10064676
Hepatitis
10019717
Hepatitis acute
10019727
Hepatitis cholestatic
10019754
Hepatitis chronic active
10019755
Hepatitis chronic persistent
10019759
Hepatitis fulminant
10019772
Hepatitis toxic
10019795
Immune-mediated hepatitis
10078962


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Ischaemic hepatitis
10023025
Lupus hepatitis
10067737
Non-alcoholic steatohepatitis
10053219
Radiation hepatitis
10051015
Steatohepatitis
10076331
2.
Hypersensitivity Reactions (HSR)
Medical concept of hypersensitivity reactions/DRESS. Only narrow terms selected from 
Category A of SMQ 'Drug reaction with eosinophilia and systemic symptoms syndrome'. 
Algorithmic approach for this SMQ not used due to complexity in applying and poor 
specificity of remaining categories. Category A selected as PTs because more specific for 
concept (only narrow terms) and a pre-requisite for any combination in algorithmic 
search. Overlap of some preferred terms with SMQ 'Severe Cutaneous Adverse 
Reactions'. Plus, additional preferred terms selected from HGLT 'Allergic conditions' 
under SOC 'Immune system disorders.
SMQ: Drug reaction with eosinophilia and systemic symptoms syndrome 
SMQ Code: 20000225
Category: A
Scope: Narrow
Preferred Term
PT Code
Drug reaction with eosinophilia and systemic symptoms
10073508
Pseudolymphoma
10037127
Additional preferred terms selected from HLGT 'Allergic conditions' under 
SOC 'Immune system disorders'
Preferred Term
PT Code
Drug hypersensitivity
10013700
Hypersensitivity
10020751
Type IV Hypersensitivity reaction
10053613
Eosinophillia
10014950
Eye swelling
10015967
Eyelid oedema
10015993
Lip swelling
10024570
Angioedema
10002424


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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
3.
Rash including severe cutaneous adverse reactions
Medical concept of rash including severe cutaneous adverse reactions. Only narrow terms 
from SMQ 'Severe cutaneous adverse reactions' selected. Plus several additional 
preferred terms selected from HLTs 'Rashes, eruptions and exanthems NEC', 'Pruritus 
NEC', 'Pustular conditions', 'Dermatitis ascribed to specific agent' all under SOC 'Skin 
and subcutaneous tissue disorders'.
SMQ: Severe Cutaneous Adverse Reactions
SMQ Code: 20000020
Category: A
Scope: Narrow
SMQ
PT Code
Acute generalised exanthematous pustulosis
10048799
Cutaneous vasculitis
10011686
Dermatitis bullous
10012441
Dermatitis exfoliative
10012455
Dermatitis exfoliative generalised
10012456
Drug reaction with eosinophilia and systemic symptoms
10073508
Epidermal necrosis
10059284
Erythema multiforme
10015218
Exfoliative rash
10064579


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Oculomucocutaneous syndrome
10030081
Skin necrosis
10040893
Stevens-Johnson syndrome
10042033
Target skin lesion
10081998
Toxic epidermal necrolysis
10044223
Toxic skin eruption
10057970
Additional preferred terms selected from HLTs 'Rashes, eruptions and 
exanthems NEC', 'Pruritus NEC', 'Pustular conditions', 'Dermatitis ascribed 
to specific agent' all under SOC 'Skin and subcutaneous tissue disorders'.
Preferred Term
PT Code
Eyelid rash
10074620
Genital rash
10018175
Mucocutaneous rash
10056671
Nodular rash
10075807
Perineal rash
10075364
Rash
10037844
Rash erythematous
10037855
Rash generalised
10037858
Rash macular
10037867
Rash maculo-papular
10037868
Rash maculovesicular
10050004
Rash morbilliform
10037870
Rash papular
10037876
Rash rubelliform
10057984
Rash scarlatiniform
10037890
Rash vesicular
10037898
Rash pruritic
10037884
Rash follicular
10037857
Rash pustular
10037888


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Drug eruption
10013687
4.
Prolongation of the Corrected QT Interval of the ECG in Supratherapeutic Doses
Notes: Medical concept of QT prolongation and complications. Only narrow terms from 
SMQ 'Torsade de pointes/QT prolongation' selected plus one additional PT under HLT 
‘ECG investigations'.
SMQ: Torsade de pointes/QT prolongation
SMQ Code: 20000001
Category: A
Scope: Narrow
Preferred Term
PT Code
Electrocardiogram QT interval abnormal
10063748
Electrocardiogram QT prolonged
10014387
Long QT syndrome
10024803
Long QT syndrome congenital
10057926
Torsade de pointes
10044066
Ventricular tachycardia
10047302
Additional preferred terms selected from HGLT ' ECG investigations' under 
SOC ‘Investigations’.
Preferred Term
PT Code
Electrocardiogram repolarisation abnormality
10052464
5.
Suicidal Ideation/Behaviour
Medical concept of suicidal ideation and behaviour. Sub-SMQ 'Suicide/self-injury' 
(SMQ) from parent SMQ of 'Depression and Suicide/Self Injury'. Only narrow terms 
from the sub-SMQ selected.
SMQ: 'Depression and Suicide/Self Injury'
SMQ Code: 20000035
Sub-SMQ: 'Suicide/self-injury'
Category: A
Scope: Narrow
Preferred Term
PT Code
Assisted suicide
10079105
Columbia suicide severity rating scale abnormal
10075616


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Completed suicide
10010144
Depression suicidal
10012397
Intentional overdose
10022523
Intentional self-injury
10022524
Poisoning deliberate
10036000
Self-injurious ideation
10051154
Suicidal behaviour
10065604
Suicidal ideation
10042458
Suicide attempt
10042464
Suicide threat
10077417
Suspected suicide
10082458
Suspected suicide attempt
10081704
6.
Depression
Medical concept of Depression. Sub-SMQ 'Depression (excl suicide and self injury)' 
(SMQ) from parent SMQ of 'Depression and Suicide/Self Injury'. Only narrow terms 
from the sub-SMQ selected.
SMQ: ‘'Depression and Suicide/Self Injury'
SMQ Code: 20000035
Sub-SMQ: 'Depression (excl suicide and self injury)' 
Category: A
Scope: Narrow
Preferred Term
PT Code
Activation syndrome
10066817
Adjustment disorder with depressed mood
10001297
Adjustment disorder with mixed anxiety and depressed mood
10001299
Agitated depression
10001496
Anhedonia
10002511
Antidepressant therapy
10054976
Childhood depression
10068631
Decreased interest
10011971


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Depressed mood
10012374
Depression
10012378
Depression postoperative
10012390
Depressive symptom
10054089
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
7.
Bipolar Disorder
Medical concept of bipolar disorder. All preferred terms from HLGT ‘Manic and Bipolar 
mood disorders and disturbances’ under SOC ‘Psychiatric disorders’.
Preferred Term
PT Code
Bipolar I disorder
10004939
Bipolar II disorder
10004940
Bipolar disorder
10057667
Cyclothymic disorder
10011724
Hypomania
10021030
Mania
10026749


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8.
Psychosis
Medical concept of psychosis. Only narrow terms from SMQ 'Psychosis and psychotic 
disorders' selected.
SMQ: 'Psychosis and psychotic disorders'
SMQ Code: 20000117
Category: A
Scope: Narrow
Preferred Term
PT Code
Acute psychosis
10001022
Alcoholic psychosis
10001632
Alice in wonderland syndrome
10001666
Brief psychotic disorder with marked stressors
10048549
Brief psychotic disorder without marked stressors
10056395
Brief psychotic disorder, with postpartum onset
10006362
Charles Bonnet syndrome
10063354
Childhood psychosis
10061040
Clang associations
10009232
Cotard’s syndrome
10059591
Delusion
10012239
Delusion of grandeur
10012241
Delusion of reference
10012244
Delusion of replacement
10012245
Delusional disorder, erotomanic type
10012249
Delusional disorder, grandiose type
10012250
Delusional disorder, jealous type
10012251
Delusional disorder, mixed type
10012252
Delusional disorder, persecutory type
10053195
Delusional disorder, somatic type
10012254
Delusional disorder, unspecified type
10012255
Delusional perception
10012258


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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


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Postictal psychosis
10070669
Post-injection delirium sedation syndrome
10072851
Posturing
10036437
Psychosis postoperative
10065617
Psychotic behaviour
10037249
Psychotic disorder
10061920
Psychotic disorder due to a general medical condition
10061921
Reactive psychosis
10053632
Rebound psychosis
10074833
Schizoaffective disorder
10039621
Schizoaffective disorder bipolar type
10068889
Schizoaffective disorder depressive type
10068890
Schizophrenia
10039626
Schizophreniform disorder
10039647
Schizotypal personality disorder
10039651
Senile psychosis
10039987
Shared psychotic disorder
10040535
Somatic delusion
10041317
Somatic hallucination
10062684
Substance-induced psychotic disorder
10072388
Tangentiality
10043114
Thought blocking
10043495
Thought broadcasting
10052214
Thought insertion
10043496
Thought withdrawal
10043497
Transient psychosis
10056326
Waxy flexibility
10047853


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9.
Mood Disorders
Medical concept of mood disorders. All preferred terms from HLGT 'Mood disorders and 
disturbances NEC', under SOC 'Psychiatric disorders'.
Preferred Term
PT Code
Affect lability
10054196
Affective ambivalence
10077173
Affective disorder
10001443
Alexithymia
10077719
Anger
10002368
Apathy
10002942
Blunted affect
10005885
Boredom
10048909
Constricted affect
10010778
Crying
10011469
Diencephalic syndrome of infancy
10012774
Dysphoria
10013954
Emotional disorder
10014551
Emotional distress
10049119
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


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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
10. Anxiety
Notes: Medical concept of anxiety disorders. All preferred terms from HLGT “Anxiety 
disorders and symptoms”, under SOC “Psychiatric disorders”.
Preferred Terms
PT Code
Acrophobia
10000605
Activation syndrome
10066817
Acute stress disorder
10001084
Aerophobia
10080300
Agitation
10001497
Agitation postoperative
10049989
Agoraphobia
10001502
Akathisia
10001540
Algophobia
10078056
Animal phobia
10002518
Anniversary reaction
10074066
Anticipatory anxiety
10002758
Anxiety
10002855
Anxiety disorder
10057666


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Anxiety disorder due to a general medical condition
10002859
Arachnophobia
10051408
Astraphobia
10078372
Autophobia
10071070
Body dysmorphic disorder
10052793
Burnout syndrome
10065369
Catastrophic reaction
10082329
Cibophobia
10082413
Claustrophobia
10009244
Compulsions
10010219
Compulsive cheek biting
10076510
Compulsive handwashing
10071263
Compulsive hoarding
10068007
Compulsive lip biting
10066241
Compulsive shopping
10067948
Dermatillomania
10065701
Dysmorphophobia
10049096
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


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Fear of weight gain
10016280
Fear-related avoidance of activities
10080136
Generalised anxiety disorder
10018075
Glossophobia
10080077
Haemophobia
10073458
Haphephobia
10067580
Herpetophobia
10081809
Hydrophobia
10053317
Hyperarousal
10080831
Immunisation anxiety related reaction
10075205
Kinesiophobia
10078430
Limited symptom panic attack
10024511
Mysophobia
10078769
Nail picking
10066779
Nervousness
10029216
Neurosis
10029333
Noctiphobia
10057946
Nocturnal fear
10057948
Nosophobia
10063546
Obsessive need for symmetry
10077179
Obsessive rumination
10056264
Obsessive thoughts
10029897
Obsessive-compulsive disorder
10029898
Obsessive-compulsive symptom
10077894
Ochlophobia
10050095
Osmophobia
10060765
Paediatric autoimmune neuropsychiatric disorders associated with streptococcal 
infection
10072147
Panic attack
10033664


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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
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


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Trichotillomania
10044629
11. Sleep Disorders
Medical concept of sleep disorders. All preferred terms from (1) HLGT 'Sleep Disorders 
and Disturbances', 'Psychiatric disorders' SOC plus (2) HLGT 'Sleep disturbances 
(including subtypes)', 'Nervous system' SOC. Numerous duplicated preferred terms e.g. 
middle insomnia.
HLGT Sleep Disorders and Disturbances, HLGT Code 10040991
Preferred Term
PT Code
Abnormal dreams
10000125
Abnormal sleep-related event
10061613
Advanced sleep phase
10001423
Behavioural induced insufficient sleep syndrome
10081938
Behavioural insomnia of childhood
10072072
Breathing-related sleep disorder
10006344
Cataplexy
10007737
Circadian rhythm sleep disorder
10009191
Confusional arousal
10067494
Delayed sleep phase
10012209
Dyssomnia
10061827
Exploding head syndrome
10080684
Hypersomnia
10020765
Hypersomnia related to another mental condition
10020767
Hypersomnia-bulimia syndrome
10053712
Hypnagogic hallucination
10020927
Hypnopompic hallucination
10020928
Hyposomnia
10067530
Initial insomnia
10022035
Insomnia
10022437
Insomnia related to another mental condition
10022443


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Irregular sleep phase
10022995
Irregular sleep wake rhythm disorder
10080301
Loss of dreaming
10065085
Middle insomnia
10027590
Narcolepsy
10028713
Nightmare
10029412
Non-24-hour sleep-wake disorder
10078086
Parasomnia
10061910
Periodic limb movement disorder
10064600
Pickwickian syndrome
10035004
Poor quality sleep
10062519
Rapid eye movement sleep behaviour disorder
10077299
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


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Somnolence
10041349
Somnolence neonatal
10041350
Sopor
10058709
Stupor
10042264
Terminal insomnia
10068932
Upper airway resistance syndrome
10063968
HLGT Sleep disturbances (incl subtypes), HLGT code 10040998
Abnormal dreams
10000125
Abnormal sleep-related event
10061613
Advanced sleep phase
10001423
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


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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
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
12. Injection Site Reactions (ISR) from Study Drug Injections
Study drug 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.
13. Seizures
Medical concept of seizures. Only narrow terms from SMQ 'Convulsions' selected plus 
selected PTs of possible seizure events from HLT 'Disturbances in consciousness NEC' 
under SOC 'Nervous systems disorders' and HLT 'Confusion and disorientation' under 
SOC 'Psychiatric disorders'.


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SMQ: ‘Convulsions’ 
SMQ Code: 20000079
Category: A
Scope: Narrow
Preferred Term
PT Code
1p36 deletion syndrome
10082398
2-Hydroxyglutaric aciduria
10078971
Acquired epileptic aphasia
10052075
Acute encephalitis with refractory, repetitive partial seizures
10076948
Alcoholic seizure
10056347
Aspartate-glutamate-transporter deficiency
10079140
Atonic seizures
10003628
Atypical benign partial epilepsy
10056699
Automatism epileptic
10003831
Autonomic seizure
10049612
Baltic myoclonic epilepsy
10054895
Benign familial neonatal convulsions
10067866
Benign rolandic epilepsy
10070530
Biotinidase deficiency
10071434
Change in seizure presentation
10075606
Clonic convulsion
10053398
Convulsion in childhood
10052391
Convulsions local
10010920
Convulsive threshold lowered
10010927
CSWS syndrome
10078827
Deja vu
10012177
Double cortex syndrome
10073490
Dreamy state
10013634
Drug withdrawal convulsions
10013752
Early infantile epileptic encephalopathy with burst-suppression
10071545


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Eclampsia
10014129
Epilepsy
10015037
Epilepsy surgery
10079824
Epilepsy with myoclonic-atonic seizures
10081179
Epileptic aura
10015049
Epileptic psychosis
10059232
Febrile convulsion
10016284
Febrile infection-related epilepsy syndrome
10079438
Focal dyscognitive seizures
10079424
Frontal lobe epilepsy
10049424
Generalised non-convulsive epilepsy
10018090
Generalised tonic-clonic seizure
10018100
Glucose transporter type 1 deficiency syndrome
10078727
Grey matter heterotopia
10082084
Hemimegalencephaly
10078100
Hyperglycaemic seizure
10071394
Hypocalcaemic seizure
10072456
Hypoglycaemic seizure
10048803
Hyponatraemic seizure
10073183
Idiopathic generalised epilepsy
10071081
Infantile spasms
10021750
Juvenile myoclonic epilepsy
10071082
Lafora’s myoclonic epilepsy
10054030
Lennox-Gastaut syndrome
10048816
Migraine-triggered seizure
10076676
Molybdenum cofactor deficiency
10069687
Multiple subpial transection
10079825
Myoclonic epilepsy
10054859
Myoclonic epilepsy and ragged-red fibres
10069825


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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


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Uncinate fits
10045476
Additional selected preferred terms from HLT 'Disturbances in 
consciousness NEC' under SOC 'Nervous systems disorders' and HLT 
'Confusion and disorientation' under SOC 'Psychiatric disorders'.
Preferred Term
PT Code
Confusional state
10010305
Loss of consciousness
10024855
Syncope
10042772
Sopor
10058709
Stupor
10042264
Altered state of consciousness
10001854
Depressed level of consciousness
10012373
Consciousness fluctuating
10050093
14. Weight Gain
Medical concept of weight gain. Selected PTs from HLT 'General nutritional disorders 
NEC', under SOC 'Metabolism and nutrition disorders', and HLT 'Physical examination 
procedures and organ system status', under SOC 'Investigations' and HLT 'General signs 
and symptoms NEC', under SOC 'General disorders and administration site conditions'.
Preferred Term
PT Code
Abdominal fat apron
10077983
Overweight
10033307
Abnormal weight gain
10000188
Central obesity
10065941
Obesity
10029883
Weight abnormal
10056814
Weight increased
10047899
Waist circumference increased
10064863
Body mass index abnormal
10074506
Body mass index increased
10005897
Fat tissue increased
10016251


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15. Rhabdomyolysis
Medical concept of rhabdomyolysis. Only narrow terms only for SMQ 
'Rhabdomyolysis/myopathy' plus 2 additional preferred terms selected from HGLT 
'muscle disorders' under SOC 'Musculoskeletal and connective tissue disorders'.
SMQ: 'Rhabdomyolysis/myopathy'
SMQ Code: 20000002
Category: A
Scope: Narrow
Preferred Term
PT Code
Muscle necrosis
10028320
Myoglobin blood increased
10028625
Myoglobin blood present
10059888
Myoglobin urine present
10028631
Myoglobinaemia
10058735
Myoglobinuria
10028629
Myopathy
10028641
Myopathy toxic
10028648
Necrotising myositis
10074769
Rhabdomyolysis
10039020
Thyrotoxic myopathy
10081524
Additional selected preferred terms from HLGT 'muscle disorders' under 
SOC 'Musculoskeletal and connective tissue disorders'
Preferred Term
PT Code
Myalgia
10028411
Myositis
10028653
16. Pancreatitis
Medical concept of acute pancreatitis. Only narrow terms of SMQ 'Acute pancreatitis' 
selected. Algorithmic approach for this SMQ not used due to complexity in applying and 
poor specificity of remaining categories. Category A selected as PTs because more 
specific for concept (only narrow terms).


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SMQ: 'Acute pancreatitis' 
SMQ Code: 20000022 
Category: A
Scope: Narrow
Preferred Term
PT Code
Cullen’s sign
10059029
Grey Turner’s sign
10075426
Haemorrhagic necrotic pancreatitis
10076058
Hereditary pancreatitis
10056976
Ischaemic pancreatitis
10066127
Oedematous pancreatitis
10052400
Pancreatic abscess
10048984
Pancreatic cyst drainage
10082531
Pancreatic haemorrhage
10033625
Pancreatic necrosis
10058096
Pancreatic phlegmon
10056975
Pancreatic pseudoaneurysm
10081762
Pancreatic pseudocyst
10033635
Pancreatic pseudocyst drainage
10033636
Pancreatitis
10033645
Pancreatitis acute
10033647
Pancreatitis haemorrhagic
10033650
Pancreatitis necrotising
10033654
Pancreatitis relapsing
10033657
Pancreatorenal syndrome
10056277
17. Impact on Creatinine
Medical concept of worsening renal function/renal failure in the context of impact on 
creatinine. Only narrow terms from SMQ 'Acute renal failure' plus all PTs from HLT 
'Renal failure and impairment', under SOC 'Renal and urinary disorders'. Numerous 
duplicated preferred terms e.g. renal failure.


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SMQ: ‘Acute renal failure’
SMQ Code: 20000003
Category: A
Scope: Narrow
Preferred Term
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
Haemofiltration
10053090
Neonatal anuria
10049778
Nephropathy toxic
10029155
Oliguria
10030302
Peritoneal dialysis
10034660
Prerenal failure
10072370
Renal failure
10038435
Renal failure neonatal
10038447
Renal impairment
10062237
Renal impairment neonatal
10049776
Subactute kidney injury 
10081980
Plus, all PTs from HLT 'Renal failure and impairment' under SOC 
'Renal and urinary disorders'
Preferred Term
PT Code
Acute Kidney injury
10069339
Anuria
10002847
Atypical haemolytic uraemic syndrome
10079840


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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
Scleroderma renal crisis
10062553
Traumatic anuria
10044501
18. Safety in Pregnancy
Use AE terms co-reported in pregnancy exposures to CAB and/or RPV.


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12.11.
Appendix 11: Abbreviations & Trade Marks
12.11.1.
Abbreviations
Abbreviation
Description
ADaM
Analysis Data Model
AE
Adverse Event
AESI
Adverse Events of Special Interest
ART
Antiretroviral Therapy
A&R
Analysis and Reporting 
BMI
Body Mass index
CAB
Cabotegravir
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval
CPMS
Clinical Pharmacology Modelling & Simulation
CS
Clinical Statistics
CSR
Clinical Study Report
CTR
Clinical Trial Register
DBF
Database Freeze
DBR
Database Release
DOB
Date of Birth
DP
Decimal Places
DTG
Dolutegravir
eCRF
Electronic Case Record Form
EMA
European Medicines Agency
FDA
Food and Drug Administration
FDAAA
Food and Drug Administration Clinical Results Disclosure Requirements
GSK
GlaxoSmithKline
HIVDQoL
HIV Dependent Quality of Life
HIV
Human Immunodeficiency Virus
HIVTSQc
Change Version of HIV Treatment Satisfaction Questionnaire
HIVTSQs
Status Version of HIV Treatment Satisfaction Questionnaire
HLGT
High Level Group Term
HLT
High Level Term
HSR
Hypersensitivity Reaction
IA
Interim Analysis
ICH
International Conference on Harmonization
IDSL
Integrated Data Standards Library
INI
Integrase Inhibitors
IP
Investigational Product
ITT
Intent-To-Treat
ITT-E
Intent-To-Treat Exposed
NA
Not Applicable
NCEP
National Cholesterol Education Program
NNRTI
Non-Nucleoside Reverse Transcriptase Inhibitors
NRTI
Nucleoside Reverse Transcriptase Inhibitors
PCI
Potential Clinical Importance 
PDMP
Protocol Deviation Management Plan
PI
Protease Inhibitors
PK
Pharmacokinetic


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Abbreviation
Description
PP
Per Protocol
PT
Preferred Term
QC
Quality Control
QTcF
Frederica’s QT Interval Corrected for Heart Rate
QTcB
Bazett’s QT Interval Corrected for Heart Rate
RAP
Reporting & Analysis Plan
RPV
Rilpivirine
SAE
Serious Adverse Event
SAC
Statistical Analysis Complete
SD
Standard Deviation
SDTM
Study Data Tabulation Model
SMQ
Standardised MedDRA Query
SOC
System Organ Class
SOP
Standard Operation Procedure
TA
Therapeutic Area
TFL
Tables, Figures & Listings 
12.11.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
Dolutegravir 
Rilpivirine
Triumeq
SAS


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12.12.
Appendix 12: List of Data Displays
12.12.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.01 to 1.n
1.01 to 1.n
Efficacy
2.01 to 2.n
2.01 to 2.n
Safety
3.01 to 3.n
3.01 to 3.n
Health Outcomes
6.01 to 6.n
6.01 to 6.n
Virology
7.01 to 7.n
7.01 to 7.n
Section
Listings
ICH Listings
1 to x
Other Listings
y to z
12.12.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 13: Example Mock Shells for Data Displays.
The example mock-up displays from other reporting efforts will be named in the format:
Study Number/HARP Reporting Effort/Output Type (T/ F/L)/Display Number, where T
stands for Table, F stands for Figure and L stands for Listing. For example, the Table 1.1
from primary_02 reporting effort for Study 201585 will be named by
201585/primary_02/T1.1.
Other example mock-up displays will be named using the following format.
Section
Figure
Table
Listing
Study Population
POP_Fn
POP_Tn
POP_Ln
Efficacy
EFF_Fn
EFF_Tn
EFF_Ln
Safety
SAFE_Fn
SAFE_Tn
SAFE_Ln
Health Outcomes
HO_Fn
HO_Tn
HO_Ln
Virology
VIR_Fn
VIR_Tn
VIR_Ln
NOTES: 
Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column.’
12.12.3.
Deliverables
Delivery [1]
Description
HL
Headline
M12
All participants complete Month 12
M26
All participants on CAB LA + RPV LA complete Month 26 *
EOS
End of Study
NOTES: 
*M26 and EOS analyses might not be produced
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort


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12.12.4.
Study Population Tables
Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Subject Disposition
1.01.
ITT-E
ES5
Summary of Reasons for Withdrawal at Each Study Phase
Replace ‘Epoch’ with ‘Phase’ in 
column header. Screening 
Phase will not be included. Add a 
footnote “Note: Entry into Long-
Term Follow-up is based on 
presence of a long-term follow-
up visit in the eCRF (i.e. LTFU 
Month 1, LTFU Month 3, etc.)”
M12, M26, 
EOS
1.02.
ITT-E
ES4
Summary of Subject Disposition at Each Study Phase
M12, M26, 
EOS
1.03.
Screened
ES6
Summary of Screening Status and Reasons for Screening 
Failures
M12, M26, 
EOS
1.04.
Enrolled
NS1
Summary of Number of Subjects Enrolled by Country and Site 
ID
M12, M26, 
EOS
1.05.
ITT-E
DV1
Summary of Important Protocol Deviations
M12, M26, 
EOS
1.06.
Screened
207966/pri
mary_02/T
1.12
Summary of Study Populations
M12, M26, 
EOS


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
1.07.
ITT-E
207966/pri
mary_02/T
1.13
Summary of Protocol Deviations Leading to Exclusion from 
the Per-Protocol Population
M12, M26, 
EOS
1.08.
ITT-E
ES1
Summary of Subject Accountability: Study Conclusion Record
HL, M12, M26, 
EOS
1.09.
ITT-E
207966/pri
mary_02/T
1.8
Summary of Subject Accountability: Withdrawals by Visit 
M12, M26, 
EOS
1.10.
ITT-E
207966/pri
mary_02/T
1.9
Summary of Study Drug Discontinuation
M12, M26, 
EOS
1.11.
ITT-E
207966/pri
mary_02/T
1.11
Summary of Inclusion/Exclusion Criteria Deviations
M12, M26, 
EOS
Demographic and Baseline Characteristics
1.12.
ITT-E
207966/pri
mary_02/T
1.14
Summary of Demographic Characteristics
HL, M12, M26, 
EOS
1.13.
Enrolled
207966/pri
mary_02/T
1.15
Summary of Age Ranges
M12, M26, 
EOS
1.14.
ITT-E
DM5
Summary of Race and Racial Combinations
M12, M26, 
EOS


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
1.15.
ITT-E
DM6
Summary of Race and Racial Combinations Details
M12, M26, 
EOS
1.16.
ITT-E
207966/pri
mary_02/T
1.18
Summary of Hepatitis Status at Entry
M12, M26, 
EOS
1.17.
ITT-E
207966/pri
mary_02/T
1.19
Summary of Derived Baseline CDC Stages of HIV Infection
M12, M26, 
EOS
1.18.
ITT-E
207966/pri
mary_02/T
1.21
Distribution of CD4+ Cell Count Results at Baseline
Do not include ‘Screening’
M12, M26, 
EOS
1.19.
ITT-E
207966/pri
mary_02/T
1.23
Summary of HIV Risk Factors
M12, M26, 
EOS
Medical Conditions and Medications
1.20.
ITT-E
MH1
Summary of Current Medical Conditions
M12, M26, 
EOS
1.21.
ITT-E
MH1
Summary of Past Medical Conditions
M12, M26, 
EOS
1.22.
ITT-E
MH4
Summary of Current Cardiac, Gastrointestinal, Metabolism 
and Nutrition, Psychiatric, Renal and Urinary, Nervous System 
Conditions, and Hepatobiliary Disorders
M12, M26, 
EOS


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Study Population Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
1.23.
ITT-E
MH4
Summary of Past Cardiac, Gastrointestinal, Metabolism and 
Nutrition, Psychiatric, Renal and Urinary, Nervous System 
Conditions, and Hepatobiliary Disorders
M12, M26, 
EOS
1.24.
ITT_E
CM8
Summary of Concomitant Non-ART Medication Ingredient 
Combinations 
M12, M26, 
EOS
1.25.
ITT-E
207966/pri
mary_02/T
1.30
Summary of Lipid Modifying Agent Use at Baseline
M12, M26, 
EOS
1.26.
ITT-E
207966/pri
mary_02/T
1.31
Summary of Lipid Modifying Agent Use Started during the 
Maintenance Phase
M12, M26, 
EOS
1.27.
ITT-E
207966/pri
mary_02/T
1.32
Summary of Substance Use at Entry
M12, M26, 
EOS
Exposure and Treatment Compliance
1.28.
Safety
207966/pri
mary_02/T
3.1
Summary of Extent of Exposure to Investigational Product 
M12, M26, 
EOS
1.29.
Safety
207966/pri
mary_02/T
3.4
Summary of Adherence to CAB/RPV Injection Dosing 
Schedule 
Only display for Q2M
M12, M26, 
EOS


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12.12.5.
Efficacy Tables
Efficacy: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
Primary Efficacy Analyses
2.01.
ITT-E
207966/primar
y_02/T2.3
Summary of Study Outcomes (50 c/mL Threshold) at 
Month 12 – Snapshot Analysis – ITT-E
For M26, replace the ‘Month 12’ 
in the title with ‘Month 26’
HL, M12, M26, 
EOS
2.02.
PP
207966/primar
y_02/T2.3
Summary of Study Outcomes (50 c/mL Threshold) at 
Month 12  – Snapshot Analysis – Per-Protocol
For M26, replace the ‘Month 12’ 
in the title with ‘Month 26’
M12, M26, 
EOS
Secondary and Exploratory Efficacy Analyses
2.03.
ITT-E
207966/primar
y_02/T2.13
Proportion of Subjects with Plasma HIV-1 RNA >=50 c/mL 
by Visit – Snapshot Analysis
M12, M26, 
EOS
2.04.
ITT-E
207966/primar
y_02/T2.14
Proportion of Subjects with Plasma HIV-1 RNA >=50 c/mL 
by Subgroup and Visit – Snapshot Analysis
M12, M26, 
EOS
2.05.
ITT-E
207966/primar
y_02/T2.15
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL 
by Visit – Snapshot Analysis
M12, M26, 
EOS
2.06.
ITT-E
207966/primar
y_02/T2.16
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL 
by Subgroup and Visit – Snapshot Analysis
M12, M26, 
EOS
2.07.
ITT-E
207966/primar
y_02/T2.22
Summary of Plasma HIV-1 RNA (log10 c/mL) by Visit
M12, M26, 
EOS
2.08.
ITT-E
207966/primar
y_02/T2.23
Cumulative Proportion of Subjects Meeting Confirmed 
Virologic Failure Criteria by Visit during the Maintenance 
Phase (Up to Month 12)
For M26, replace the ‘Month 12’ 
in the title with ‘Month 26’
M12, M26, 
EOS
2.09.
ITT-E
207966/primar
y_02/T2.24
Cumulative Proportion of Subjects Meeting Confirmed 
Virologic Failure Criteria 
M12, M26, 
EOS


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Efficacy: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
2.10.
CVF
207966/primar
y_02/T2.25
Distribution of Quantitative Plasma HIV-1 RNA Results at 
Suspected and Confirmation of Confirmed Virologic Failure 
M12, M26, 
EOS
2.11.
ITT-E
207966/primar
y_02/T2.28
Summary of Subjects per Viral Load Category by Visit 
M12, M26, 
EOS
2.12.
ITT-E
207966/primar
y_02/T2.29
Summary of Change from Baseline in CD4+ Cell Count 
(cells/mm^3) by Visit 
M12, M26, 
EOS
2.13.
ITT-E
207966/primar
y_02/T2.31
Summary of CD4+ Cell Count (cells/mm^3) by Visit 
M12, M26, 
EOS
2.14.
ITT-E
207966/primar
y_02/T2.35
Summary of HIV-1 Associated Conditions Including 
Recurrences 
M12, M26, 
EOS
2.15.
ITT-E
207966/primar
y_02/T2.36
Summary of HIV-1 Associated Conditions Excluding 
Recurrences 
M12, M26, 
EOS
2.16.
ITT-E
207966/primar
y_02/T2.37
Summary of HIV-1 Disease Progression and/or Deaths 
M12, M26, 
EOS
2.17.
ITT-E
207966/primar
y_02/T2.22
Summary of Change from Baseline in Plasma HIV-1 RNA 
(log10 c/mL) by Visit 
Add footnote: “Note: Baseline 
values are actual plasma HIV-1 
RNA (log10 c/mL) values.’
Display actual values at Baseline 
and change from baseline for 
post-baseline visits 
M12, M26,
EOS


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12.12.6.
Efficacy Figures
Efficacy: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Primary Efficacy Analyses
2.01.
ITT-E
207966/primar
y_02/F2.1
Proportion (95% CI) of Subjects with HIV-1 RNA >=50 
c/mL by Visit - Snapshot Analysis
M12, M26, 
EOS
Secondary and Exploratory Efficacy Analyses
2.02.
ITT-E
207966/primar
y_02/F2.3
Proportion (95% CI) of Subjects with HIV-1 RNA <50 c/mL 
by Visit - Snapshot Analysis
M12, M26, 
EOS
2.03.
ITT-E
207966/primar
y_02/F2.7
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by Visit
– for CVF Subjects
M12, M26, 
EOS
2.04.
ITT-E
207966/primar
y_02/F2.8
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by Visit 
for Subjects Who are in the Category of 'HIV-1 RNA >=50 
c/mL' at Month 12 per Snapshot Algorithm
For M26, replace the ‘Month 12’ 
in the title with ‘Month 26’
M12, M26, 
EOS


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12.12.7.
Safety Tables
Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Adverse Events (AEs)
3.01.
Safety
AE1          Summary of All Adverse Events by System Organ Class 
and Preferred Term 
M12, M26, 
EOS
3.02.
Safety
AE3
Summary of Common (>=5%) Adverse Events by Overall 
Frequency 
M12, M26, 
EOS
3.03.
Safety
AE3
Summary of Common (>=1%) Grade 2-4 Adverse Events 
by Overall Frequency 
M12, M26, 
EOS
3.04.
Safety
AE1 
Summary All Drug-Related Adverse Events by System 
Organ Class
M12, M26, 
EOS
3.05.
Safety
207966/primar
y_02/T3.25
Summary of Subjects and Number of Occurrences of 
Common (>=5%) Non-Serious Adverse Events by System 
Organ Class 
Add footnote: ‘Note: Common 
adverse events are those with 
>=5% incidence in either 
treatment group.
M12, M26, 
EOS
3.06.
Safety
AE3
Summary of Common (>=1%) Drug-Related Grade 2-4 
Adverse Events by Overall Frequency
Add footnote: ‘Note: Common 
adverse events are those with 
>=1% incidence in either 
treatment group.
M12, M26, 
EOS
3.07.
Safety
207966/prima
yr_02/T3.26
Summary of Subjects and Number of Occurrences of 
SAEs, Fatal SAEs, and Drug-related SAEs 
HL, M12, M26, 
EOS


CONFIDENTIAL
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Other Significant Adverse Events
3.08.
Safety
AE1
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product by System Organ Class 
HL, M12, M26, 
EOS
Laboratory: Chemistry and Hematology
3.09.
Safety
207966/primar
y_02/T3.39
Summary of Chemistry Changes from Baseline by Visit 
M12, M26, 
EOS
3.10.
Safety
207966/primar
y_02/T3.41
Summary of Hematology Changes from Baseline by Visit 
M12, M26, 
EOS
Laboratory: Urinalysis
3.11.
Safety
207966/primar
y_02/T3.48
Summary of Urine Concentration Changes from Baseline 
by Visit 
M12, M26, 
EOS
Laboratory: Hepatobiliary (Liver)
3.12.
Safety
LIVER1
Summary of Liver Monitoring/Stopping Event Reporting
M12, M26, 
EOS
3.13.
Safety
207966/primar
y_02/T3.57
Summary of Subjects Meeting Hepatobiliary
Abnormality Criteria 
M12, M26, 
EOS


CONFIDENTIAL
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
ECG
3.14.
Safety
EG1
Summary of ECG Findings 
M12, M26, 
EOS
3.15.
Safety
207966/primar
y_02/T3.61
Summary of QTc Values by Category 
M12, M26, 
EOS
3.16.
Safety
207966/primar
y_02/T3.62
Summary of Change from Baseline QTc Values by 
Category 
M12, M26, 
EOS
Vital Signs
3.17.
Safety
VS1
Summary of Change from Baseline in Vital Signs by Visit 
M12, M26, 
EOS
Study Drug Injection Site Reaction Adverse Events (display for Q2M arm only)
3.18.
Safety
207966/primar
y_02/T3.28
Summary of Study Drug Injection Site Reaction Adverse 
Events (Event-level Summary) 
HL, M12, M26, 
EOS
3.19.
Safety
207966/primar
y_02/T3.29
Summary of Subject-level Characteristics of Study Drug 
Injection Site Reaction Adverse Events – Overall and 
Common 
M12, M26, 
EOS
3.20.
Safety
207966/primar
y_02/T3.30
Summary of Study Drug Injection Site Reaction Adverse 
Events by Visit and Maximum Severity – Overall and 
Common 
Replace definition of common in 
the footnote with ‘Note: Common 
ISR includes pain, induration, 
nodules and any other ISR with 
>=5% subjects in Q2M treatment 
arm’
M12, M26, 
EOS


CONFIDENTIAL
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
3.21.
Safety
207966/primar
y_02/T3.31
Summary of Drug-related Study Drug Injection Site 
Reaction Adverse Events (Event-level Summary) – CAB 
M12, M26, 
EOS
3.22.
Safety
207966/primar
y_02/T3.32
Summary of Drug-related Subject-level Characteristics of 
Study Drug Injection Site Reaction Adverse Events –
Overall and Common (CAB)
M12, M26, 
EOS
3.23.
Safety
207966/primar
y_02/T3.33
Summary of Overall and Common Drug-related Study Drug 
Injection Site Reaction Adverse Events by Visit and 
Maximum Severity – CAB
M12, M26, 
EOS
3.24.
Safety
207966/primar
y_02/T3.34
Summary of Maximum Drug-related Study Drug Injection 
Site Reaction Adverse Event Grade by Needle Length –
Common (CAB)
Replace definition of common in 
the footnote with ‘Note: Common 
ISR includes pain, induration, 
nodules and any other ISR with 
>=5% subjects in Q2M treatment 
arm’
M12, M26, 
EOS
3.25.
Safety
207966/primar
y_02/T3.35
Summary of Drug-related Study Drug Injection Site 
Reaction Adverse Events (Event-level Summary) – RPV 
M12, M26, 
EOS
3.26.
Safety
207966/primar
y_02/T3.36
Summary of Drug-related Subject-level Characteristics of 
Study Drug Injection Site Reaction Adverse Events –
Overall and Common (RPV)
M12, M26, 
EOS
3.27.
Safety
207966/primar
y_02/T3.37
Summary of Overall and Common Drug-related Study Drug 
Injection Site Reaction Adverse Events by Visit and 
Maximum Severity – RPV
M12, M26, 
EOS


CONFIDENTIAL
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
3.28.
Safety
207966/primar
y_02/T3.38
Summary of Maximum Drug-related Study Drug Injection 
Site Reaction Adverse Event Grade by Needle Length –
Common (RPV)
Replace definition of common in 
the footnote with ‘Note: Common 
ISR includes pain, induration, 
nodules and any other ISR with 
>=5% subjects in Q2M treatment 
arm’
M12, M26, 
EOS
Adverse Events of Special Interest
3.29.
Safety
207966/primar
y_02/T3.72
Summary of Depression Adverse Events of Special 
Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences)
M12, M26, 
EOS
3.30.
Safety
207966/primar
y_02/T3.76
Summary of Anxiety Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of 
Subjects and Occurrences)
M12, M26, 
EOS
3.31.
Safety
207966/primar
y_02/T3.71
Summary of Suicidal Ideation/Behaviour Adverse Events of 
Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences)
M12, M26, 
EOS
3.32.
Safety
207966/primar
y_02/T3.66
Summary of Depression, Anxiety and Suicidal 
Ideation/Behaviour Adverse Events by System Organ 
Class, Maximum DAIDS Toxicity Grade, and History of 
Depression, Anxiety and Suicidal Ideation/Behaviour at
Baseline
For M26 and EOS, include 
additional stratification by ‘any 
history’ vs. ‘no history’
M12, M26, 
EOS
3.33.
Safety
207966/primar
y_02/T3.78
Summary of Seizure Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of 
Subjects and Occurrences)
M12, M26, 
EOS


CONFIDENTIAL
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
3.34.
Safety
207966/primar
y_02/T3.67
Summary of Hepatic Safety Profile: Assessment of Risk of 
Hepatoxicity Adverse Events of Special Interest by System 
Organ Class and Preferred Term (Number of Subjects and 
Occurrences)
M12, M26, 
EOS
3.35.
Safety
207966/primar
y_02/T3.68
Summary of Hypersensitivity Reaction (HSR) Adverse 
Events of Special Interest by System Organ Class and 
Preferred Term (Number of Subjects and Occurrences)
M12, M26, 
EOS
3.36.
Safety
207966/primar
y_02/T3.69
Summary of Rash Adverse Events of Special Interest by 
System Organ Class and Preferred Term (Number of 
Subjects and Occurrences)
M12, M26, 
EOS
3.37.
Safety
207966/primar
y_02/T3.70
Summary of Prolongation of the Corrected QT Interval of 
the ECG in Supra Therapeutic Doses Adverse Events of 
Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences)
M12, M26, 
EOS
3.38.
Safety
207966/primar
y_02/T3.73
Summary of Bipolar Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences)
M12, M26, 
EOS
3.39.
Safety
207966/primar
y_02/T3.74
Summary of Psychosis Adverse Events of Special Interest 
by System Organ Class and Preferred Term (Number of 
Subjects and Occurrences)
M12, M26, 
EOS
3.40.
Safety
207966/primar
y_02/T3.75
Summary of Mood Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences)
M12, M26, 
EOS


CONFIDENTIAL
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
3.41.
Safety
207966/primar
y_02/T3.77
Summary of Sleep Disorder Adverse Events of Special 
Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences)
M12, M26, 
EOS
3.42.
Safety
207966/primar
y_02/T3.79
Summary of Weight Gain Adverse Events of Special 
Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences)
M12, M26, 
EOS
3.43.
Safety
207966/primar
y_02/T3.80
Summary of Rhabdomyolysis Adverse Events of Special 
Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences)
M12, M26, 
EOS
3.44.
Safety
207966/primar
y_02/T3.81
Summary of Pancreatitis Adverse Events of Special 
Interest by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences)
M12, M26, 
EOS
3.45.
Safety
207966/primar
y_02/T3.82
Summary of Impact on Creatinine Adverse Events of 
Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences)
M12, M26, 
EOS
3.46.
Safety
207966/primar
y_02/T3.83
Summary of Safety in Pregnancy Adverse Events of 
Special Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrences)
M12, M26, 
EOS
3.47.
Safety
207966/primar
y_02/T3.6
Summary of All Adverse Events by System Organ Class 
and Maximum Toxicity
HL, M12, M26, 
EOS
3.48.
Safety
207966/primar
y_02/T3.13
Summary of All Drug-related Adverse Events by System 
Organ Class and Maximum Toxicity
HL, M12, M26, 
EOS


CONFIDENTIAL
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Safety: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
3.49.
Safety
207966/primar
y_02/T3.43
Summary of Maximum Post-Baseline Emergent Chemistry 
Toxicities
M12, M26, 
EOS
3.50.
Safety
207966/primar
y_02/T3.45
Summary of Maximum Post-Baseline Emergent 
Hematology Toxicities
M12, M26, 
EOS


CONFIDENTIAL
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12.12.8.
Safety Figures
Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Adverse Events
3.01.
Safety
207966/primar
y_02/F3.1
Plot of Common Adverse Events and Relative Risk – Q2M 
vs. DTG + RPV - Excluding Study Drug ISRs  
M12, M26, 
EOS
Study Drug Injection Site Reaction Adverse Events (display for Q2M arm only)
3.02.
Safety
207966/primar
y_02/F3.2
Plot of Common Study Drug Injection Site Reaction 
Adverse Events 
Only display first panel
M12, M26, 
EOS
3.03.
Safety
207966/primar
y_02/F3.3
Plot of Onset, Duration, and Severity of Overall and 
Common Study Drug Injection Site Reaction AEs by 
Maximum Grade - CAB and/or RPV 
M12, M26, 
EOS
3.04.
Safety
207966/primar
y_02/F3.4
Plot of Onset, Duration, and Severity of Overall and 
Common Drug-related Study Drug Injection Site Reaction 
AEs by Maximum Grade - CAB 
M12, M26, 
EOS
3.05.
Safety
207966/primar
y_02/F3.5
Plot of Onset, Duration, and Severity of Overall and 
Common Drug-related Study Drug Injection Site Reaction 
AEs by Maximum Grade - RPV 
M12, M26, 
EOS
3.06.
Safety
207966/primar
y_02/F3.6
Plot of Incidence of Maintenance Phase Study Drug 
Injection Site Reaction Adverse Events by Visit (Overall 
and Common) - CAB and/or RPV
M12, M26, 
EOS
3.07.
Safety
207966/primar
y_02/F3.7
Plot of Incidence of Maintenance Phase Drug-Related 
Study Drug Injection Site Reaction Adverse Events by Visit 
(Overall and Common) - CAB  
M12, M26, 
EOS


CONFIDENTIAL
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Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
3.08.
Safety
207966/primar
y_02/F3.8
Plot of Incidence of Maintenance Phase Drug-Related 
Study Drug Injection Site Reaction Adverse Events by Visit 
(Overall and Common) - RPV
M12, M26, 
EOS
3.09.
Safety
207966/primar
y_02/F3.9
Plot of Incidence of Grade 3-5 Maintenance Phase Study 
Drug Injection Site Reaction Adverse Events by Visit 
(Overall and Common) - CAB and/or RPV
M12, M26, 
EOS
3.10.
Safety
207966/primar
y_02/F3.10
Plot of Incidence of Grade 3-5 Maintenance Phase Drug-
related Study Drug Injection Site Reaction Adverse Events 
by Visit (Overall and Common) - CAB
M12, M26, 
EOS
3.11.
Safety
207966/primar
y_02/F3.11
Plot of Incidence of Grade 3-5 Maintenance Phase Drug-
related Study Drug Injection Site Reaction Adverse Events 
by Visit (Overall and Common) - RPV  
M12, M26, 
EOS
Laboratory
3.12.
Safety
207966/primar
y_02/F3.12
Scatter Plot of Maximum vs. Baseline for ALT 
.
M12, M26, 
EOS
3.13.
Safety
207966/primar
y_02/F3.13
Scatter Plot of Maximum Total Bilirubin vs. Maximum ALT 
M12, M26, 
EOS
3.14.
Safety
207966/primar
y_02/F3.14
Matrix Plot of Maximum Liver Chemistries 
M12, M26, 
EOS
3.15.
Safety
207966/primar
y_02/F3.15
Bar Chart of Lipid NCEP Categories at Month 12 vs. 
Baseline - Triglycerides, Total Cholesterol, LDL Cholesterol
For M26, replace the ‘Month 12’ 
in the title with ‘Month 26’
M12, M26, 
EOS
3.16.
Safety
207966/primar
y_02/F3.16
Bar Chart of Lipid NCEP Categories at Month 12 vs. 
Baseline - HDL Cholesterol
For M26, replace the ‘Month 12’ 
in the title with ‘Month 26’
M12, M26, 
EOS


CONFIDENTIAL
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Safety: Figures
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Exposure (display for Q2M arm only)
3.17.
Safety
207966/primar
y_02/F3.17
Histogram of Timeliness of Injections 
M12, M26, 
EOS


CONFIDENTIAL
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12.12.9.
Health Outcomes Tables
Health Outcomes: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
HIV Dependent Quality of Life (HIVDQoL)
6.01.
ITT-E
HO_T1
Proportion of Subjects with Each Individual Questionnaire 
Item Score in HIVDQoL by Visit 
M12
6.02.
ITT-E
HO_T2
Summary of HIVDQoL in Overview Items, Domain 
Weighted Impact Scores and Average Weighted Impact 
Score by Visit 
M12
6.03.
ITT-E
HO_T3
Summary of HIVDQoL Change from Baseline in Overview 
Items, Domain Weighted Impact Scores and Average 
Weighted Impact Score by Visit 
M12
HIV Treatment Satisfaction Questionnaire Status Version (HIVTSQs)
6.04.
ITT-E
207966/primar
y_02/T6.14
Proportion of Subjects with HIVTSQs - Individual Item 
Scores by Visit 
Note: no LOCF 
M12
6.05.
ITT-E
207966/primar
y_02/T6.16
Summary of HIVTSQs - Total Treatment Satisfaction Score 
by Visit 
M12
6.06.
ITT-E
207966/primar
y_02/T6.18
Summary of HIVTSQs - Change from Baseline in Total 
Treatment Satisfaction Score by Visit 
Note: Do not include column for 
prior exposure
M12
6.07.
ITT-E
207966/primar
y_02/T6.20
Summary of HIVTSQs - Change from Baseline in Individual 
Item Score by Visit 
Note: no LOCF; do not include 
column for prior exposure
M12


CONFIDENTIAL
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Health Outcomes: Tables
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
HIV Treatment Satisfaction Questionnaire Change Version (HIVTSQc)
6.08.
ITT-E
207966/primar
y_02/T6.23
Proportion of Subjects with HIVTSQc - Individual Item 
Change Score at Month 12 
M12
6.09.
ITT-E
207966/primar
y_02/T6.25
Summary of HIVTSQc - Total Treatment Satisfaction 
Change Score at Month 12 
M12
6.10.
ITT-E
207966/primar
y_02/T6.27
Summary of HIVTSQc - Individual Item Change Score at 
Month 12 
M12
Preference (display for Q2M arm only)
6.11.
ITT-E
207966/primar
y_02/T6.38
Proportion of Subjects with Response to Each Individual 
Question in Preference Questionnaire at Month 12 for 
Subjects in Q2M
Display questions and responses 
per the data. Do not include 
footnotes [1] and [2]
M12
Reasons for Switch (display for Q2M arm only)
6.12.
ITT-E
207966/primar
y_02/T6.41
Reasons for Switch at Baseline for Subjects from Oral CAB 
+ RPV to Q2M
Display responses per the data. 
M12


CONFIDENTIAL
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12.12.10. Virology Tables
Virology: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
Genotype
7.01.
CVF
207966/primar
y_02/T7.1
Summary of the Prevalence of Known INI Resistance 
Mutations at Time of CVF - Plasma Sample
M12, M26, 
EOS
7.02.
CVF
207966/primar
y_02/T7.2
Summary of the Prevalence of Major Resistance Mutations 
of NRTI, NNRTI and PI Class at Time of CVF - Plasma 
Sample
M12, M26, 
EOS
7.03.
CVF
207966/primar
y_02/T7.3
Summary of Genotypic Susceptibility at Time of CVF -
Plasma Sample
M12, M26, 
EOS
Phenotype
7.04.
CVF
207966/primar
y_02/T7.4
Summary of Phenotype Susceptibility at Time of CVF -
Plasma Sample
M12, M26, 
EOS
7.05.
CVF
207966/primar
y_02/T7.5
Summary of Phenotype: Number of Drugs to Which 
Subject is Phenotypic Resistant or Partial Sensitive or 
Sensitive at Time of CVF - Plasma Sample
M12, M26, 
EOS
7.06.
CVF
207966/primar
y_02/T7.6
Summary of Fold Change to CAB and RPV at Time of CVF 
- Plasma Sample
Display for Q2M arm only
M12, M26, 
EOS
7.07.
CVF
207966/primar
y_02/T7.7
Summary of Net Assessment at Time of CVF - Plasma 
Sample
M12, M26, 
EOS


CONFIDENTIAL
209035
135
Virology: Tables
No.
Population
IDSL /  
Example 
Shell
Title
Programming Notes
Deliverable 
Miscellaneous
7.08.
CVF
207966/primar
y_02/T7.8
Summary of Viral load, Genotypic and Phenotypic data for 
Subjects Who Met Confirmed Virologic Failure Criteria 
during the Maintenance Phase
M12, M26, 
EOS


CONFIDENTIAL
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12.12.11. ICH Listings
Strata and Latest Subject Id will not be included in any listings taken from 207966/primary_02.
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Study Population
1.
Screened
207966/primar
y_02/L3
Listing of Reasons for Screen Failure
M12, M26, 
EOS
2.
ITT-E
207966/primar
y_03/L4
Listing of Reasons for Study Withdrawal
M12, M26, 
EOS
3.
Enrolled
207966/primar
y_02/L2
Listing of Treatment Assignment
Do not include footnotes and 
columns for randomization 
number, randomization and 
actual strata and deviation. Do 
not display randomized 
treatment
M12, M26, 
EOS
4.
ITT-E
207966/primar
y_02/L6
Listing of Important Protocol Deviations 
M12, M26, 
EOS
5.
ITT-E
207966/primar
y_02/L8
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations
M12, M26, 
EOS
6.
ITT-E
207966/primar
y_02/L7
Listing of Protocol Deviations Leading to Exclusion from 
the Per-Protocol Population
M12, M26, 
EOS
7.
ITT-E
207966/primar
y_02/L9
Listing of Demographic Characteristics
M12, M26, 
EOS


CONFIDENTIAL
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ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
8.
ITT-E
207966/primar
y_02/L10
Listing of Race
M12, M26, 
EOS
9.
ITT-E
207966/primar
y_02/L36
Listing of Concomitant ART Medications Received
Do not include final column for 
phase during which concomitant
M12, M26, 
EOS
10.
ITT-E
207966/primar
y_02/L5
Listing of Reasons for Study Drug Discontinuation
M12, M26, 
EOS
Efficacy
11.
ITT-E
207966/primar
y_02/L11
Listing of Study Outcome (50 c/mL Threshold) at Month 12 
- Snapshot Analysis
For M26, replace the ‘Month 12’ 
in the title with ‘Month 26’
M12, M26, 
EOS
Safety: Exposure 
12.
Safety
207966/primar
y_02/L12
Listing of Investigational Product Exposure Data
M12, M26, 
EOS
Adverse Events
13.
Safety
207966/primar
y_02/L19
Listing of All Adverse Events 
M12, M26, 
EOS
14.
Safety
207966/primar
y_02/L13
Listing of Subject Numbers for Individual Adverse Events 
M12, M26, 
EOS
15.
Safety
207966/primar
y_02/L15
Listing of Fatal Adverse Events 
M12, M26, 
EOS
16.
Safety
207966/primar
y_02/L16
Listing of Non-Fatal Serious Adverse Events
M12, M26, 
EOS


CONFIDENTIAL
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138
ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
17.
Safety
207966/primar
y_02/L14
Listing of Reasons for Considering as a Serious Adverse 
Event 
M12, M26, 
EOS
18.
Safety
207966/primar
y_02/L17
Listing of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of Investigational 
Product 
M12, M26, 
EOS
Safety: Hepatobiliary (Liver)
19.
Safety
207966/primar
y_02/L21
Listing of Medical Conditions for Subjects with Liver 
Stopping Events
M12, M26, 
EOS
20.
Safety
207966/primar
y_02/L22
Listing of Substance Use for Subjects with Liver Stopping 
Events
M12, M26, 
EOS
Safety: ECG
21.
Safety
207966/primar
y_02/L23
Listing of ECG Values for Subjects with a Value of 
Potential Clinical Importance
M12, M26, 
EOS
22.
Safety
207966/primar
y_02/L24
Listing of ECG Findings 
M12, M26, 
EOS


CONFIDENTIAL
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139
12.12.12. Non-ICH Listings
Strata and Latest Subject Id will not be included in any listings taken from 207966/primary_02.
Non-ICH: Listings
No.
Population
IDSL / 
Example 
Shell
Title
Programming Notes
Deliverable 
Study Population
23.
ITT-E
207966/primar
y_02/L34
Listing of Subjects Who were Rescreened
Do not include annotation [1]
M12, M26, 
EOS
24.
ITT-E
207966/primar
y_02/L37
Listing of ART Medications Received during Long-term 
Follow-up Phase
M12, M26, 
EOS
25.
ITT-E
207966/primar
y_02/L39
Listing of Medical History of Seizure
M12, M26, 
EOS
Adverse Events
26.
LTFU
207966/primar
y_02/L19
Listing of All Adverse Events (Long-term Follow-up Phase)
M12, M26, 
EOS
Efficacy
27.
CVF
207966/primar
y_02/L40
Listing of All Plasma HIV-1 RNA Data for Subjects with 
Confirmed Virologic Failure
M12, M26, 
EOS
28.
ITT-E
207966/primar
y_02/L41
Listing of All Plasma HIV-1 RNA Data for Subjects with 
Viral Load >=50 c/mL during the Maintenance Phase
M12, M26, 
EOS
29.
ITT-E
207966/primar
y_02/L43
Listing of HIV-1 Associated Conditions 
M12, M26, 
EOS
30.
CVF
207966/primar
y_02/L62
Listing of Replication Capacity in IN and PR/RT Region  
M12, M26, 
EOS


CONFIDENTIAL
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140
12.13.
Appendix 13: Example Mock Shells for Data Displays
Available upon request.