A Phase IIIb, Randomized, Multicenter, Active-controlled, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every Two Months From a Bictegravir/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen in HIV-1 Infected Adults Who Are Virologically Suppressed
Phase: PHASE3
Conditions: HIV Infections
Sponsor: ViiV Healthcare

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TITLE PAGE 
Protocol Title: A Phase IIIb, Randomized, Multicenter, Active-controlled, Parallel-
group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and 
Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine 
administered every two months from a Bictegravir/emtricitabine/tenofovir alafenamide 
Single Tablet Regimen in HIV-1 Infected Adults who are Virologically Suppressed 
Protocol Number: 213500/ 03 
Compound Number 
or Name: 
GSK1265744/Cabotegravir 
Study Phase: IIIB  
Short Title: PH3b, CAB LA + RPV LA vs BIK, IM Every 2 Months, Non-inferiority, 
Efficacy and Safety Study in Participants with HIV-1 Who are Virologically Suppressed 
SOLAR (Switch Onto Long Acting Regimen) 
Sponsor Name and Legal Registered Address:  
This study is sponsored by ViiV Healthcare. GlaxoSmithKline is supporting ViiV 
Healthcare in the conduct of this study. 
Sponsor Name and Legal Registered Address (excluding US): 
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK  
US IND Sponsor Legal Registered Address: 
ViiV Healthcare Company 
Five Moore Drive 
P.O. 13398 
Research Triangle Park, NC 27709-3398, USA 
Telephone:  +1 919 438 2100 
In some countries, local law requires that the Clinical Trial sponsor is a local company 
legal entity.  In these instances, the appropriate company to be identified as Sponsor must 
be agreed with the global ViiV Healthcare clinical team and signed off by the Vice 
President, Global Research and Medical Strategy. 
Copyright 2022 ViiV Healthcare group of companies. All rights reserved. Unauthorised 
copying or use of this information is prohibited. 

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Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual  
Regulatory Agency Identifying Number(s):  
IND No. 109,678 
EudraCT No. 2020-002623-11 
Approval Date: 10-FEB-2022 
 

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

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Amendment 3 
10-FEB-2022 
Amendment 2 
8-SEP-2021 
DEU Amendment 1 
12-JAN-2021 
GBR Amendment 1 
20-NOV-2020 
FR Amendment 1 
16-NOV-2020 
Amendment 1  
30-JUN-2020  
Original Protocol 
27-MAY-2020 
 
Amendment 03: 10-FEB-2022 
This amendment is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for Amendment 03:  
The primary reason for protocol amendment 03 is to address and clarify comments raised 
during the course of the study  
Section # and Name 
Description of Change 
Brief Rationale 
Headers 
Change to protocol reference 
number 
Due to sponsor protocol writing 
procedures 
Section 1.1. Synopsis and 
Section 3 Objectives 
Removed endpoint “Change 
from Baseline in incident 
metabolic syndrome at 
Months 6 and 12 (OLI and 
BIK)/Month 5 and Month 11 
(D2I) in Metabolic Syndrome 
Objective  
 
Not required 
Section 1.1. Synopsis and 
Section 3 Objectives 
Removed reference to BIK in 
the endpoint addressing 
Preference objective 
Not required 
Section 1.3 Schedule of 
Assessments 
Removal of height, weight, 
(BMI), waist and hip 
circumference assessments 
in “BIK to Direct to Injection” 
arm at Month 14 
Assessments not required 
Section 1.3 Schedule of 
Footnote aa. Addition of text 
BIK Participant who withdraw at or 

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

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

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

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

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

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

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

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

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

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

TMF-14364917 
CONFIDENTIAL 
 
 
 
213500 
 
15 
 
1.2. 
Schema 
 
 

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

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

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

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

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

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

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

T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 3  
 
Ti m e a n d E v e nt s T a bl e f or BI K t o Or al L e a d I n –  E xt e n si o n P h a s e:  
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
M o nt h  
1 3  
1 4  
1 5  
Q 2 M After M o nt h 
1 5  
Eli gi bility V erific ati o n (I ncl usi o n/  
Excl usi o n Crit eri a)  
X d  
 
 
 
 
 
Sy m pt o m Dir ect e d P hysic al Ex a m a n d M e dic al 
Ass ess m e nt f 
X  
X  
X  
X  
X  
X  
W ei g ht, H ei g ht a n d B MI g  
 
 
 
 
X  
 
W aist Circ u mf er e nc e  
 
 
 
 
X  
 
Hi p Circ u mf ere nc e  
 
 
 
 
X  
 
Vit al Si g ns ( B P, H R, T e m p er at ur e) h  
 
 
 
 
X  
 
1 2 -l e a d E C Gi  
 
 
 
 
 
X  
 
HI V Ass oci at e d Co n diti o ns  
X  
X  
X  
X  
X  
X  
A Es, S A Es, Co nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
 
X  
X  
X  
X  
X  
Cli nic al c h e mistry a n d He mat ol o gy 
X  
X  
X  
X  
X  
X  
Pre g n a ncy T esti n g l 
S  
U  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st ora g e ( S) m  
X  
X  
X  
X  
X  
X  
C D 4 + c ell c o u nt  
 
X  
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
 
 
 
X  
 
Uri n alysis n 
 
X  
 
 
X  
 
F asti n g L a bs  
Gl uc os e, Ch ol est erol ( T ot al, H D L a n d L D L) a n d 
Tri glyc eri d es o 
 
X  
 
 
X  
 
W h ol e Bl o o d ( Vir ol o gy)  
 
 
 
 
X  
 
P B M Cs q  
 
 
 
 
X  
 
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Procedure 
Extension Phase 
Withdrawal 
Assessmentsy 
Long-Term 
Follow-up z 
Month 
13 
14 
15 
Q2M After Month 
15 
PK sampling u 
(S)=Storage only 
 
S 
S 
 
X 
S 
Oral CAB and Oral RPV Dispensation v 
X 
 
 
 
 
 
IP accountability (Pill Counts) 
X 
X 
 
 
 
 
IM treatment administration w 
 
X 
X 
X 
 
 
Reason for Switchcc,ee 
X 
 
 
 
 
 
 
 
Time and Events Table for BIK to Direct to Injection – Extension Phase: 
Procedure 
Extension Phase 
Withdrawal 
Assessmentsy 
Long-Term 
Follow-up z 
Month 
13 
14 
Q2M After Month 14 
Eligibility Verification (Inclusion/ 
Exclusion Criteria) 
Xd 
 
 
 
 
Symptom Directed Physical Exam and Medical Assessmentf 
X 
X 
X 
X 
X 
Weight, Height and BMIg 
 
 
 
X 
 
Waist Circumference 
 
 
 
X 
 
Hip Circumference 
 
 
 
X 
 
Vital Signs (BP, HR, Temperature)h 
 
 
 
X 
 

T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 5  
 
Pr o c e d ure  
Ext e n si o n P h a s e  
Wit h dra w al 
A s s e s s m e nt s y  
L o n g -T er m  
F oll o w -u p z  
M o nt h  
1 3  
1 4  
Q 2 M After M o nt h 1 4  
1 2 -l e a d E C Gi  
 
 
 
 
X  
 
HI V Ass oci at e d Co n diti o ns  
X  
X  
X  
X  
X  
A Es, S A Es, Co nc o mit a nt M e dic ati o ns  
X  
X  
X  
X  
X  
I S R Ass ess m e nt f or I M i nj ecti o n 
X  
X  
X  
X  
X  
Cli nic al c h e mistry a n d He mat ol o gy  
X  
X  
X  
X  
X  
Pre g n a ncy T esti n g l 
S  
U  
U  
S  
U  
HI V -1 R N A  a n d s a m pl e f or st ora g e ( S) m  
X  
X  
X  
X  
X  
C D 4 + c ell c o u nt  
 
X  
X  
X  
X  
C D 8 + c ell c o u nt  
 
 
 
X  
 
Uri n alysis n 
 
X  
 
X  
 
F asti n g L a bs  
Gl uc os e, Ch ol est erol ( T ot al, H D L a n d L D L) a n d Tri glyc eri d es o 
 
X  
 
X  
 
W h ol e Bl o o d ( Vir ol o gy)  
 
 
 
X  
 
P B M Cs q  
 
 
 
X  
 
P K s a m pli n g u 
( S) = St ora g e o nly 
 
S  
 
X  
S  
I P acc o u nt a bility ( Pill Co u nts) 
X  
 
 
 
 
I M tre at m e nt a d mi nistrati o n w  
X  
X  
X  
 
 
R e as o n f or S witc h cc,e e 
X  
 
 
 
 
 
S af ety F oll o w U p Visit:  C o n d uct a p pr oxi m at ely 4 w e eks aft er t h e l ast d os e of I P.  R e q uir e d o nly if t h e p artici p a nt h as o n g oi n g A Es or l a b a b n or m aliti es at t h e l ast o n -st u dy visit.  T his 
visit m ay b e c o n d uct e d by t el e p h o n e. 
N ot e: B P –  Bl o o d pr ess ur e, H R –  H e art R at e, B MI –  Bo dy M ass I n d ex, H D L –  Hi g h D e nsity Li p o pr ot ei n, L D L –  L o w D e nsity Li p o pr ot ei n, P T - P r ot hr o m bi n Ti m e, P T T - P arti al 
T hr o m b o pl asti n Ti m e, I N R - I nt er n ati o n al n or m aliz e d r ati o, P B M C –  p eri p h er al bl o o d m o n o n ucl e ar c ell, R N A –  Ri b o n ucl eic aci d, H b A 1c = Glyc at e d h e m o gl o bi n, H Bs A g = h e p atitis B 
s urf ac e a nti g e n, H C V = h e p atitis C vir us, HI V-1 = h u m a n i m m u n o d efici e ncy vir us ty p e 1.  
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a. 
Complete all Screening assessments within 35 days.  Participants may begin the Maintenance Phase as soon as all Screening assessments are complete.  Participants may be 
rescreened once and will be assigned a new participant number.  
b. 
For participants who elect to participate in the oral lead in period, oral CAB 30 mg + RPV 25 mg will be administered and the oral lead will start on Day 1.  For participants who 
choose to go directly into injections, the first loading dose will be administered on Day 1. Visits for participants on the BIK arm are expected to occur every 56 days as projected 
according to the Day 1 visit.  There is a 3 day visit window, from the projected visit date (Maintenance Phase of the study). 
c. 
For participants who elect to participate in the oral lead in period, the first loading dose will be administered and the oral lead in will end.  For participants who choose to go directly 
into injections, the second loading dose will be administered.   
d. 
Confirmation of eligibility to continue the Maintenance Phase, and eligibility to enter the Extension Phase.  
e. 
Collect full routine medical history plus (report at Baseline visit): HIV risk factors (may be collected at a later study visit), cardiovascular risk factors (assessments include smoking 
status and history, family history of cardiac events), recent [6 months] illicit drug use, intravenous drug use, gastrointestinal disease, metabolic, psychiatric, renal, bone, and 
neurologic disorders.  At Month 11 (D2I)/12 (OLI and BIK), assessments inclusive of smoking status, alcohol use and illicit drug use since the start of the study will be 
administered. 
f. 
Physical exams should be conducted as part of normal routine clinical care.  Medical assessments include any decisions the study staff must make for participants management 
and/or care of participant.   
g. 
Height collected at Baseline Day 1 only.  Recommended procedures to measure weight, waist and hip circumference can be found in Section 10.10.  Weight related 
measurements to be collected are weight, body fat %, total body water %, muscle mass, and bone mineral mass. 
h. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
i. 
A 12-lead ECG will be performed after resting in a semi-supine position for at least 5 minutes.  ECGs will be performed pre-dose. ECG pre-dose will be performed in triplicate at 
Day 1.  A 2-hour post-dose ECG will also be performed at Day 1 (D2I), Month 1 (OLI) and Month 12 (OLI)/Month 11 (D2I) for participants receiving CAB LA + RPV LA with an 
allowable window of  30 minutes.  
j. 
Only SAEs related to study participation or to a concomitantly administered ViiV/GSK product will be collected between obtaining informed consent and administration of study 
drug at Day 1. 
k. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  The eC-SSRS will be completed at the beginning of the visit following administration of other PROs required 
prior to injections.  The eC-SSRS is not required during the Withdrawal visit if withdrawal occurs during the Extension Phase. 
l. 
Women of childbearing potential only.  S=serum, U=urine.  Pregnancy events will be captured starting at Day 1 following initial exposure to study drug.  Serum pregnancy test can 
substitute for urine pregnancy test if locally required but must be appropriately timed to confirm pregnancy status prior to randomization and first IM administration.  If the urine test 
is positive, perform a serum test and do not administer injection.  The frequency of pregnancy tests should be performed according to local legal requirements. 
m. Month 12 (OLI and BIK) and Month 11 (D2I) HIV-1 RNA retest (within 4 weeks) for results > 50 c/mL will be captured as unscheduled visit.  Plasma for storage samples will be 
used for possible future analyses. 
n. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; urine phosphate; beta-2-microglobulin; and retinol binding 
protein.   
o. 
An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
p. 
Only collect if the Withdrawal visit occurs at Month 6 or Month 12 (OLI and BIK); Month 5 or Month 11 (D2I). 
q. 
Whole blood/PBMC collection samples may be used for virologic analyses.  PBMCs will be collected at baseline Day 1, Month 6, Month 12, or Withdrawal if prior to Month 12 (OLI 
and BIK). PBMCs will be collected at baseline Day 1, Month 5, Month 11, or Withdrawal if prior to Month 11 (D2I) 
r. 
Blood sample for insulin, HbA1c, and renal and bone biomarker assessments:  Renal: CystatinC; Beta-2-Microglobulin; Retinol Binding Protein (RBP); Bone: bone specific 
alkaline phosphatase, procollagen type 1-N-propeptide, type 1 collagen cross-linked C-telopeptide, osteocalcin, 25 hydroxy-Vitamin D. 

T M F -1 4 3 6 4 9 1 7  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
 
2 7  
 
s. 
 
t. 
I nf or m e d c o ns e nt f or g e n etic r es e arc h m ust b e o bt ai n e d b ef or e s a m pl e c oll ecti o n.  Sa m pl e m ay b e c oll ect e d at a ny visit aft er si g ni n g i nf or m e d c o ns e nt, b ut pr ef er a bly at t h e D ay 1 
visit. 
u.  
O n e bl o o d s a m pl e f or C A B a n d R P V e a c h t o b e c oll e ct e d at e ac h P K ti m e p oi nt .  At M o nt h 1, f or p artici p a nts w h o el ect e d t o p artici p at e i n t h e Or al L e a d i n, a n d M o nt h 1 4 f or 
p artici p a nts w h o w er e r a n d o miz e d t o BI K a n d s witc h e d t o C A B L A + R P V L A i n t h e Ext e nsi o n Ph as e a n d will p artici p at e i n t h e Or al L e a d i n, Pr e d os e P K s a m p l es ar e t o b e 
c oll ect e d: P RI O R t o t h e fi n al or al d os e of C A B + R P V.  F or pre g n a nt p arti ci p a nt s  ( o n C A B + R P V ar m): t w o bl o o d s a m pl es f or C A B a n d o n e R P V s a m pl e at e ac h P K ti m e p oi nt. 
R ef er t o S ecti o n 1 0. 6. 6. 3 . 
v. 
P artici p a nts w h o el ect e d t o p artici p at e i n t h e Or al L e a d i n b ef or e s witc hi n g t o C A B L A + R P V L A i nj ecti o ns, will t ak e fi n al d os e of or al l e a d -i n r e gi m e n i n t h e cli nic at t h e M o nt h 
1/ M o nt h 1 4 visit a n d b e gi n i nj ecti o ns.   
w.  If p ossi bl e, i nj ecti o ns s h o ul d b e s p ac e d a p pr oxi m at ely 2 c m fr o m o n e a n ot h er a n d fr o m t h e sit e of a ny pr evi o us i nj ecti o n a n d or a ny i nj ecti o n sit e r e acti o n.  Bri n g R P V L A t o 
a p pr oxi m at ely r o o m t e m p er at ur e pri or t o i nj ecti n g.  Ti m e a n d l oc ati o n of i nj ecti o n (ri g ht or l eft) as w ell as n e e dl e l e n gt h us e d will b e c oll ect e d i n t h e e C R F.  T h e first i nj ect i o n c a n 
b e p erf or m e d b ef or e c e ntr al l a b res ults b ec o m e av ail a bl e a n d s af ety p ar a m et ers ar e r evi e w e d .  
x. 
C oll ect s a m pl e f or t h es e ass e ss m e nts O N L Y if t h e Wit h dr a w al visit occ urs at M o nt hs 6 a n d 1 2 ( O LI a n d BI K); M o nt h 5 a n d 1 1 ( D 2I).  
y. 
R ef er t o S ecti o n 7. 1  of t h e pr ot oc ol f or a d diti o n al i nf or m ati o n o n p erf or mi n g wit h dr a w al ass ess m e nts  
z. 
P artici p a nts r ec eivi n g o n e or m or e i nj ecti o ns wit h C A B L A a n d/ or R P V L A will b e ass ess e d wit h cli nic visits at M o nt hs 3, 6, 9  a n d 1 2 d uri n g t h e L o n g -T er m F oll o w -U p P h as e  
a a.  BI K dis p e ns ati o n ( 1 -m o nt h s u p ply) f or p artici p a nts w h o pl a n o n e nt eri n g i nt o t h e Ext e nsi o n Ph as e.  P artici p a nts w h o d o n ot e nt er  t h e E xt e nsi o n P h as e or d o n ot wis h t o tr a nsiti o n 
t o t h e c o m m erci al s u p ply will n o t r ec eiv e 1-m o nt h s u p ply at M 1 2 . 
b b.  D at a fr o m visit will b e us e d t o d et er mi n e p artici p a nt’s eli gi bility t o e nt er t h e Ext e nsi o n Ph as e of st u dy.  If p artici p a nt el ects t o e nt er t h e Ext e nsi o n P h as e, d et er mi n e if t h e p artici p a nt 
will el ect t o st art i nj ecti o ns i m m e di at ely or st art wit h or al l e a d i n.  
cc. All P R Os ar e r ec o m m e n d e d t o b e a d mi n ist er e d b ef or e ot h er ass ess m e nts a n d i nj ecti o ns t ak e pl ac e at e ac h d esi g n at e d visit. 
d d.  O nly c oll ect e d if Wit h dr a w al visit occ urs d uri n g t h e M ai nt e n a nc e P h as e.  
e e.  Will b e a d mi nist er e d o nly t o p artici p a nts r a n d o miz e d t o BI K, s ucc essf ully c o m pl eti n g t h e M ai nt e n a nc e P h as e a n d d eci di n g t o e nt er Ext e nsi o n P h as e a n d s witc hi n g t o C A B L A + 
R P V L A.  
ff. 
W h e n ass essi n g C D C st a g e at Scr e e ni n g/ B as eli n e, c o nsi d er o nly t h e l at est av ail a bl e C D 4 T -c ell c o u nt, exc e pt w h e n t h e p artici p a nt h a d a n activ e St a g e 3 ev e nt 6 m o nt hs pri or t o 
S cr e e ni n g. 
g g.  At M o nt h 1 1 ( D 2I) / M o nt h 1 2 ( O LI or BI K) or wit h dr a w al , (d e p e n di n g w hic h is s o o n er) p artici p a nts will b e ask e d if a ny c os m etic pr oc e d ur es w er e p erf or m e d d uri n g t h e c o n d uct of 
t h e st u dy. 
 
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2. 
INTRODUCTION 
The current paradigm in the treatment of Human Immunodeficiency Virus (HIV) 
involves life-long therapy with multiple antiretrovirals.  This dependency on medical 
therapy requires additional improvements on the durability, safety and tolerability, and 
convenience of all antiretroviral classes.  Fixed-dose combinations (FDCs) have greatly 
advanced HIV treatment by allowing simplification of dosing and reducing pill burden.  
However, adherence to therapy is essential to achieve viral suppression and prevent 
emergence of resistance mutations.  Among regimens of comparable efficacy, physicians 
and HIV-1-infected patients who receive ART rate total pill burden, dosing frequency, 
and safety concerns among the greatest obstacles to achieving adherence.  Drug resistant 
virus eventually emerges in most patients who struggle with consistent adherence.  
Different HIV treatment modalities are being developed to help improve adherence and 
patient outcomes and prevent resistance and transmission of the virus.  
There is also an increasing desire to develop nucleoside reverse transcriptase inhibitor 
(NRTI)-sparing regimens for long-term treatment of HIV infection as an approach to 
avoid known NRTI-associated adverse drug reactions and long-term toxicities.  In 
addition, simplifying treatment has long been a goal to increase treatment compliance and 
improve the quality of life for patients with HIV.   
Cabotegravir (CAB) is a potent integrase inhibitor that possesses attributes that allow 
formulation and delivery as a long-acting (LA) parenteral product.  Rilpivirine (RPV) is a 
diarylpyrimidine derivative and a potent non-nucleoside reverse transcriptase inhibitor 
(NNRTI) with in vitro activity against wild type HIV-1 and select NNRTI-resistant 
mutants.  RPV is a globally marketed product available as oral 25 mg tablets [Edurant 
Product Information, 2019], and is also formulated as a LA product.  Intramuscular 
administration of a two-drug combination therapy with CAB LA plus RPV LA may offer 
a better tolerability and resistance profile, as well as improved adherence and treatment 
satisfaction in virologically suppressed patients. 
2.1. 
Study Rationale 
The overall objective of the CAB LA + RPV LA clinical development program is to 
develop a highly effective, well tolerated two drug long-acting injectable regimen which 
has the potential to offer improved treatment convenience, compliance and improved 
quality of life for individuals with HIV compared to current standard of care.  Week 160 
efficacy (GSK data from study 200056 (LATTE-2)) [GlaxoSmithKline Document 
Number 2018N380094_00, 2019] demonstrated that 90% of patients randomized to the 
CAB LA + RPV LA Q8W dosing arm and 83% of patients randomized to the Q4W 
dosing arm maintained virologic suppression (HIV-1 RNA <50 c/mL), with both 
regimens being well tolerated.  In study 207966 (ATLAS-2M), 1.7% of participants in 
the CAB + RPV Q8W group and 1.0% of participants in the CAB + RPV Q4W group 
met the primary efficacy endpoint of plasma HIV-1 RNA 50◦c/mL at Week◦48. In both 
studies, both regimens were well tolerated, and the results justify further evaluation of 
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The current study, 213500 (SOLAR – Switch Onto Long Acting Regimen) is designed 
to demonstrate the non-inferior antiviral activity of CAB LA 600 mg + RPV LA 900 mg 
administered every 2 months (Q2M) compared to Biktarvy (BIK) administered orally 
once daily for 12 months.  The study will also provide important comparative antiviral 
activity, safety, tolerability of these regimens through Month 12 of the Maintenance 
Phase of the study. Additionally, eligible participants (HIV-1 RNA <50 c/mL at Month 
12) will be given an option to continue their randomized CAB LA + RPV LA regimen 
(Q2M) or start CAB LA + RPV LA Q2M after 12 months of oral therapy in the 
Extension Phase of the study. 
2.1.1. 
Optional Oral Lead In 
Throughout the course of the clinical development program for CAB and RPV LA 
including the large P3 trials of FLAIR, ATLAS and ATLAS 2M, an oral lead-in phase of 
cabotegravir (30 mg) along with rilpivirine (25mg), administered  daily for 30 days, was 
an integral component of these trials and allowed for a safety assessment before study 
participants were allowed to advance to the LA phase of these studies. As a result, all 
study participants underwent a one-month period of oral dosing with CAB/RPV followed 
by an evaluation of safety labs, and if labs were within normal limits, participants were 
allowed to transition into LA dosing.  
An assessment of the safety data specific to four weeks of oral lead-in for participants on 
FLAIR and ATLAS (ViiV’s two registrational clinical trials) was recently undertaken 
and as a result of the accumulated safety data which has been generated, the safety of oral 
CAB and RPV during these four weeks of oral lead-in was not significantly different than 
at any other time during the FLAIR/ATLAS studies. The SOLAR study will also allow 
an optional oral lead in for participants randomized to the LA arm of SOLAR. This 
decision to dose with or without an oral-lead-in will be determined by the study 
participant following informed consent discussions with the investigator. 
2.1.2. 
Weight Gain 
Weight gain in people living with HIV is multifactorial with both traditional (diet, 
exercise, concomitant medications such as selective serotonin reuptake inhibitor and 
others) and HIV specific modifiable risks likely contributing factors. Which factor or 
factors are most significant in the pathogenesis of weight gain in HIV disease has not 
been fully elucidated. 
Whereas lipodystrophy involved accumulation of central abdominal or visceral fat, and 
loss of subcutaneous fat, weight gain in HIV-infected individuals receiving newer, more 
recently approved antiretroviral treatment consists of general fat gain – both 
subcutaneous and central fat – with an increase in waist circumference. Weight gain 
among HIV-infected individuals often occurs after the initiation of antiretroviral therapy 
with certain antiretrovirals linked more closely to weight gain than others.  Teasing out 
what is considered appropriate weight gain for individuals returning back to health versus 
what is consider more pathogenic weight gain has been challenging. Recent studies have 
demonstrated increase weight gain with integrase strand transfer inhibitor (INSTI)-based 
regimens compared to other classes of antiretroviral therapy [Bourgi, 2019; Kerchberger, 
2019; McComsey, 2019]. Moreover, additional components of the antiretroviral regimen, 

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

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either prediabetes (impaired fasting glucose) or diabetes. This new cutpoint should be applicable for identifying the 
lower boundary to define an elevated glucose as one criterion for metabolic syndrome. 
 
Additionally, non-alcoholic fatty liver disease (steatosis) is increasingly associated with 
chronic liver disease and diabetes and is an important contributor to insulin resistance and 
metabolic syndrome. Features of steatosis include hepatocellular injury, inflammation 
and fibrosis. The fibrosis-4 score (FIB-4) is a simple, non-invasive test to determine the 
degree of hepatic fibrosis. The FIB-4 score combines standard biochemical values (ALT, 
AST, platelets), and age into a simple formula that estimates the amount of scarring in the 
liver.    
Fibrosis 4 Score Formula: 
(Age x AST) / (Platelets x (√ALT)) 
In a previous study, A FIB-4 index < 1.45 had a negative predictive value of 94.7% to 
exclude severe fibrosis with a sensitivity of 74.3%. A FIB-4 index > 3.25 had a positive 
predictive value to confirm the existence of significant fibrosis (F3-4) of 82.1% with a 
specificity of 98.2% [Vallet-Pichar, 2007] 
Therefore, this study will explore whether there is a meaningful difference between these 
two regimens with respect to alterations in BP, blood glucose and cholesterol (and TG) 
levels, and whether there are changes in hip and waist circumferences in participants 
randomized to continue with Biktarvy versus those who are randomized to switch to LA 
CAB/RPV.  
2.2. 
Background 
It is estimated that 37.9 million people are currently living with HIV/Acquired 
Immunodeficiency Syndrome (AIDS) and that the worldwide epidemic continues to grow 
at a rate of 1.7 million new infections and cause 770, 000 deaths per year [UNAIDS, 
2019].  Chronic HIV infection in adults continues to be characterized by increased 
development of resistant virus, increasing transmission of resistant virus and issues 
associated with long term toxicity of ART.  The current paradigm in the treatment of HIV 
involves life-long therapy with multiple antiretrovirals.  This dependency on medical 
therapy requires a need for continuous improvement on the durability, tolerability and 
convenience of all antiretroviral classes. 
A study by the Antiretroviral Therapy Cohort Collaboration [ART-CC, 2013] found that 
of more than 21,000 patients in a European and North American cohort on their first 
combination antiretroviral therapy (cART) regimen (either PI or NNRTI-based), 51% 
modified or interrupted their first cART regimen during a median of 28 months of 
follow-up with one third of interruptions occurring within the first 6 months of starting 
therapy.  Forty percent of all treatment interruptions were due to the secondary side 
effects or toxicities of cART, 17% were due to the desire for simplification of the 
regimen and 14% were due to patient choice. These observations have led to numerous 
“switch” ART studies, designed to understand the efficacy, safety, and tolerability of 
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Previous studies have evaluated switches to ritonavir-boosted PI monotherapy in 
virologically suppressed patients [Bierman, 2009 and Arribas, 2012].  These studies 
suggest that simplifying from a three-drug dual class regimen to a single boosted protease 
inhibitor may be a safe and effective option for the majority of participants studied, who 
have effectively maintained viral suppression.  In the OLE study, virologically 
suppressed (HIV-1 RNA <50 c/mL) HIV-1 infected participants receiving a lopinavir-
ritonavir (LPV/r) + lamivudine (3TC) or emtricitabine (FTC) based NRTI regimen 
simplified to a dual regimen of LPV/r + 3TC or FTC.  In a modified Intent-to-Treat (m-
ITT) analysis, dual therapy with LPV/r + 3TC demonstrated non-inferiority efficacy and 
comparable safety to LPV/r + 2 NRTIs [Arribas, 2015]. 
CAB LA + RPV LA is indicated as a complete regimen for the treatment of human 
immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current 
antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 
50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure 
and with no known or suspected resistance to either CAB or RPV. 
Three Phase IIb studies (LAI116482 [LATTE], 200056 [LATTE-2], and 209035 
[POLAR]) have been conducted with oral CAB and/or IM CAB LA, evaluating an 
induction/maintenance simplification approach. Three Phase III studies (201584 
[FLAIR], 201585 [ATLAS], and 207966 [ATLAS-2M]) conducted with CAB LA + RPV 
LA are ongoing.  Details of these studies can be found in the CAB IB [GlaxoSmithKline 
Document Number  RPS-CLIN-004375, 2021]. 
Biktarvy (BIK) is a three-drug combination of bictegravir (BIC), a human 
immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and 
emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog 
reverse transcriptase inhibitors (NRTIs), and is indicated as a complete regimen for the 
treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to 
replace the current antiretroviral regimen in those who are virologically suppressed (HIV-
1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of 
treatment failure and no known substitutions associated with resistance to the individual 
components of BIK.  Clinical trial results of studies with BIK can be found in Biktarvy 
Prescribing Information, 2019. 
Long-acting 2-class therapy consisting of CAB LA + RPV LA as an IM regimen has the 
benefit of being a NRTI-sparing regimen for long-term treatment of HIV infection which 
will avoid known NRTI-associated adverse drug reactions and long-term toxicities. 
Additionally, a 2-drug combination therapy with CAB LA plus RPV LA  may offer a 
better tolerability and resistance profile, as well as improved adherence and treatment 
satisfaction in virologically suppressed participants improving the quality of life for 
people living with HIV. 

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2.3. 
Benefit/Risk Assessment 
Summaries of findings from both clinical and non-clinical studies conducted with oral 
and CAB LA or RPV LA can be found in the Investigator’s Brochures [GlaxoSmithKline 
Document Number RPS-CLIN-004375, 2021; RPV IB, 2021]. 
The following section outlines the risk assessment and mitigation strategy for this 
protocol:   
2.3.1. 
Risk Assessment 
Oral CAB and CAB LA (GSK1265744/GSK1265744 LA) 
Since CAB exposure in humans with or without HIV infection is limited, the clinical 
safety profile in humans has yet to be fully elucidated.  The following risks have 
primarily been identified during routine preclinical testing and/or from the clinical trial 
experience to date and are considered of potential relevance to clinical usage in the 
context of this protocol.  Additional information about the clinical experience to date and 
possible risks associated with treatment using CAB can be found in the Summary of Data 
and Guidance for the Investigator section of the IB [GlaxoSmithKline Document Number  
RPS-CLIN-004375, 2021]. 

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

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and include events of pain, tenderness, erythema, 
or nodule formation of several days’ duration 
(median duration for individual events <1 week). 
ISRs may occur more than once in an individual 
participant receiving multiple injections.  
Although some Grade 3 ISRs were reported, 
overall ISRs have been well tolerated and have 
not to date been associated with an excess of 
participants withdrawing.  
 
treatment of ISRs is given in study 
documentation  
 
• Advice will be given to participants on care of 
injection site on day/days immediately post 
administration, use of analgesia, compresses 
where appropriate. 
 
• Participants will be closely monitored for ISRs 
particularly for signs of pain, tenderness, 
infections, erythema, swelling, induration, or 
nodules (granulomas or cysts) throughout the 
study.   
 
• Complications of ISRs such as infections 
(abscess, cellulitis) and collections of fluid 
requiring drainage will be monitored  
Hypersensitivity 
Reactions (HSR) 
 
Hypersensitivity reactions have been reported as 
uncommon occurrences with integrase inhibitors, 
including the closely related compound 
dolutegravir, and were characterized by rash, 
constitutional findings, and sometimes, organ 
dysfunction, including liver injury.  
While there have been no clinical cases of 
hypersensitivity to CAB to date, there is a 
theoretical risk of systemic or severe 
hypersensitivity reactions with or without hepatic 
• The potential risk of developing a 
hypersensitivity reaction post administration of 
IM CAB may be minimized by the use of a 4-
week oral lead-in of oral CAB to determine 
individual safety and tolerability prior to the 
introduction of IM CAB if the participant is 
randomized to CAB LA administration and 
chooses to participate in the oral lead in.  
 
• Clinical assessments, laboratory tests (including 

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symptoms associated with use of IM CAB.  The 
long exposures anticipated after IM CAB 
injection may complicate the management of a 
drug hypersensitivity reaction, were it to occur. 
 
liver transaminases) and vital signs will be 
performed throughout this study (refer to 
Schedule of Activities, Section 1.3). Results 
from these assessments may aid early detection 
of HSR.  
 
• Oral CAB will be withdrawn immediately for 
participants with suspected HSR during the oral 
CAB lead-in phase and they would not proceed 
to the injection phase.  Participants in the 
injection phase would not receive further 
injections.  During oral and IM CAB treatment, 
any HSR reactions that occur would be 
managed supportively. 
Effects in late stage 
pregnancy seen in non-
clinical studies 
In animal reproduction studies, CAB when 
administered to rats at >30 times the systemic 
exposure at the maximum recommended oral 
human dose (MRHD) of 30 mg during 
organogenesis through delivery, had adverse 
effects on labor and delivery that may be related 
to a delay in the onset of parturition, resulting in 
increased fetal mortality (stillbirths) and neonatal 
deaths immediately after birth. 
A delay in the onset of parturition, increased 
stillbirths and neonatal deaths were observed in a 
rat pre- and postnatal development study at 
greater than 30 times the exposure at the 
• Pregnant females are excluded from enrolment 
in this study and women of childbearing 
potential (WOCBP) are required to adopt 
highly reliable means of contraception during 
participation and throughout the long term 
follow up phase of this study following 
exposure to CAB LA. 
• WOCBP are also required to undergo regular 
pregnancy testing throughout study conduct. 
Pregnant participants who remain in the study 
do not need pregnancy testing for the duration 
of the pregnancy 

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recommended human dose (RHD). No evidence 
of adverse developmental outcomes was observed 
with oral cabotegravir in rats or rabbits (greater 
than 30 times or similar to [approximately 0.7] 
times the exposure at the RHD, respectively) 
given during organogenesis.  
The clinical significance of these findings in 
humans is unknown. 
For pregnant participants remaining in the study, 
refer to Appendix 6 for additional data regarding 
CAB and pregnancy.  
• Participants who become pregnant during the 
study may remain in the study provided all 
protocol defined pregnancy related assessments, 
procedures and documentation are completed, 
and a pregnancy specific informed consent 
form (ICF) addendum is signed by the 
participant. Details regarding management of 
pregnant participants are found in Appendix 6 
 
 
Potential effects in women 
exposed to dolutegravir 
during conception and 
early pregnancy 
A preliminary analysis of an ongoing birth 
outcome surveillance study in Botswana 
involving women exposed to dolutegravir (DTG), 
a different molecule in the same integrase class of 
medications as CAB, identified four cases (as of 
May 2018) of neural tube defects (NTDs) in 426 
infants born to mothers who were exposed to 
DTG-containing regimens from the time of 
conception. In the same study, no infant born to a 
woman who started DTG during pregnancy had a 
NTD, out of 2,824 women. A causal relationship 
of these events to the use of DTG has not been 
established. The incidence of NTDs in the 
general population ranges from 0.5-1 cases per 
1,000 live births. As NTDs occur within the first 
• Pregnant females are excluded from enrolment 
in clinical trials of CAB at this time and women 
of childbearing potential (WOCBP) are 
required to adopt highly reliable means of 
contraception during participation and 
throughout the long term follow up phase of the 
studies after exposure to CAB LA. 
• WOCBP also undergo regular pregnancy 
testing throughout study conduct. Pregnant 
participants who remain in the study do not 
need pregnancy testing for the duration of the 
pregnancy. It should be noted that CAB 
concentration could remain for prolonged 

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4 weeks of fetal development (at which time the 
neural tubes are sealed) this potential risk would 
concern women exposed to DTG at the time of 
conception and in early pregnancy. Recently 
updated data (April 2020) for this birth outcome 
study showed that among women who were on 
DTG when they became pregnant, 7/3591 NTD 
occurred (0.19%). In comparison, NTDs were 
identified in 21/19,361 (0.11%) women 
delivering on any non-DTG antiretrovirals. There 
was not a significant difference in the number of 
NTDs between births to women taking DTG and 
those taking other non-DTG antiretroviral 
treatments (0.09% difference).  
The clinical relevance of either of these findings 
in relation to CAB use is unknown.  
periods despite discontinuation of CAB LA. 
• Participants who become pregnant during the 
study may remain in the study, provided that all 
protocol defined pregnancy related assessments, 
procedures and documentation are completed 
and a pregnancy specific ICF addendum is 
signed by the participant. Details regarding 
management of pregnant participants is found 
in Appendix 6.  
 
Development of 
Resistance following 
discontinuation of CAB 
LA 
 
Residual concentrations of CAB would remain in 
the systemic circulation for prolonged periods 
(more than 1 year in some cases) in participants 
who stop CAB LA treatment, (e.g., for 
tolerability issues or treatment failure). 
Participants discontinuing CAB LA regimen may 
therefore be at risk for developing HIV-1 
resistance to CAB after discontinuing injectable 
therapy.  
• After participants stop CAB LA, Oral HAART 
regimens will be prescribed within 8 weeks 
after the last Q2M dose, and following 
consultation with the medical monitor.  This 
would be anticipated to result in continued 
suppression or rapid resuppression of HIV-1 
RNA thus minimizing the risk of emergent 
resistance 
 
• The participants in this study who discontinue 
IM CAB for any reason will be monitored for a 

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minimum of 52 weeks from the time of the last 
IM CAB injection. 
Drug-Drug Interactions 
(DDIs) 
For a complete listing of permitted and prohibited 
concurrent medications for CAB and CAB LA, 
refer to Section 6.11 
CAB and CAB LA should not be co-administered 
with the following medicinal products, as 
significant decreases in CAB plasma 
concentrations may occur (due to UGT enzyme 
induction), which may result in loss of 
therapeutic effect of CAB. 
- the anticonvulsants carbamazepine, 
oxcarbazepine, phenobarbital, phenytoin 
- the antimycobacterials rifampicin, 
rifapentine, rifabutin 
- St John’s wort (Hypericum perforatum) 
Oral CAB administration only:  Antacid products 
containing divalent cations (e.g., aluminum, 
calcium, and magnesium) must be taken at least 2 
hours before or at least 4 hours after CAB.  
Participants discontinuing a LA regimen may be 
at risk for developing DDIs many weeks after 
• All participants will be informed of prohibited 
medications throughout the study and updates 
provided as needed via the informed consent. 

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discontinuing injectable therapy.   

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Inadvertent Intravenous 
Injection (Accidental 
Maladministration) 
As with any intramuscular injection, it is possible 
that CAB LA can be inadvertently administered 
intravenously instead of intramuscularly possibly 
resulting in higher than expected concentrations 
of CAB shortly after injection and lower 
concentrations thereafter.  This could be due to 
administrator error, improper injection technique 
and / or improper needle length used based on 
body type.     
The clinical consequences of overdose with CAB 
LA are currently unknown.  HIV-1 viral 
suppression may not be effective following 
accidental maladministration. 
 
• Training will be provided to all sites on proper 
injection technique.   
 
• Should IM maladministration be suspected at 
any time (e.g. suspected under or overdose or 
inadvertent IV dosing), a post dose 
electrocardiogram (ECG), vital signs, or any 
other supportive testing may be obtained at the 
discretion of the investigator, and the medical 
monitor will be notified.   
 
• Laboratory samples for safety parameters and 
HIV-1 RNA will be closely monitored in all 
participants. Additionally, an unscheduled PK 
sample may be drawn approximately 2 hours 
post dosing for future evaluation of CAB 
concentrations. 

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ORAL RPV 
For safety and risk mitigation for oral RPV refer to the RPV local prescribing information [Edurant Product Information, 2021].   
RPV LA 
Information about the clinical experience to date and possible risks associated with treatment using RPV LA can be found in the Summary 
of Data and Guidance for the Investigator section of the IB [RPV IB, 2021].  Systemic reactions following RPV LA injections have been 
observed in clinical trials. These occur infrequently (in less than 0.5% of participants) and typically begin to resolve within minutes of the 
injection, some participants have required supportive care.  Where PK data was available, high RPV PK plasma concentrations have been 
observed which may have resulted from an accidental partial IV injection of RPV. The following risks are considered to be of specific 
clinical relevance in the context of IM use. 

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

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Eosinophilia and Systemic Symptoms (DRESS), 
with oral RPV containing regimens.  While some 
skin reactions were accompanied by constitutional 
symptoms such as fever, other skin reactions were 
associated with organ dysfunctions, including 
elevations in hepatic serum biochemistries. 
allowed to continue treatment, depending on the 
clinical judgment of the investigator. 
 
• All participants experiencing a Grade 3 or 4 rash 
should discontinue their ARV medication (study 
medication) and be withdrawn from the study. 
 
• All rash events should be assessed with special 
attention to systemic symptoms, laboratory 
abnormalities, or mucosal involvement.  Close 
clinical follow-up, including follow-up of 
laboratory abnormalities, and appropriate 
medical intervention, including referral to 
dermatologist as appropriate, should be instituted 
for these events; daily follow-up is 
recommended for 5 days from the onset of the 
event to monitor for progression of the event.  
See Section 8.3.11.9 for additional guidance on 
management of rash events. 

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Development of 
Resistance 
 
Residual concentrations of RPV LA can remain in 
the systemic circulation of participants who 
stopped treatment (e.g., for tolerability issues or 
treatment failure) for prolonged periods (months to 
more than a year, in some participants, McGowan, 
2016).   
 
Participants discontinuing a LA regimen may be at 
risk for developing resistance to RPV many weeks 
after discontinuing injectable therapy. 
• After participants stop RPV LA, Oral HAART 
regimens will be prescribed within 8 weeks after 
the last Q2M dose and following consultation 
with the medical monitor.  This would be 
anticipated to result in rapid resuppression of 
HIV-1 RNA thus minimizing the risk of 
emergent resistance 
 
• The Sponsor will continue to monitor 
participants in this study who discontinue a LA 
regimen for any reason for a minimum of 52 
weeks from the time of the last LA 
administration. 
Drug-Drug Interactions 
(DDIs) 
For a complete listing of permitted and prohibited 
concurrent medications for RPV and RPV LA, 
refer to Section 6.11 
RPV LA should not be co-administered with the 
following medicinal products, as significant 
decreases in RPV plasma concentrations may 
occur (due to CYP3A enzyme induction), which 
may result in loss of therapeutic effect of RPV LA. 
- the anticonvulsants carbamazepine, 
oxcarbazepine, phenobarbital, phenytoin 
- the antimycobacterials rifampicin, rifapentine, 
• All participants will be informed of prohibited 
medications throughout the study and updates 
provided as needed via informed consent. 

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rifabutin 
- the glucocorticoid systemic dexamethasone, 
except as a single dose treatment 
- St John’s wort (Hypericum perforatum). 
Of note, evidence to date indicates that clinically 
relevant DDIs with RPV LA and other 
antiretrovirals are unlikely to occur.  
Oral RPV administration only:   
- Antacid products containing divalent cations 
(e.g., aluminum, calcium, and magnesium) 
must be taken at least 2 hours before or at least 
4 hours after RPV. 
- H2-antagonists must be taken at least 12 hours 
before or at least 4 hours after taking RPV. 
- RPV should not be co-administered with 
proton pump inhibitors, such as esomeprazole, 
lansoprazole, omeprazole, pantoprazole, 
rabeprazole; 
Participants discontinuing a LA regimen may be at 
risk for developing DDIs many weeks after 

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discontinuing injectable therapy.   
Inadvertent 
Intravenous Injection 
(Accidental 
Maladministration) 
As with any intramuscular injection, it is possible 
that RPV LA can be inadvertently administered 
intravenously instead of intramuscularly possibly 
resulting in higher than expected concentrations of 
RPV shortly after injection and lower 
concentrations thereafter.  This could be due to 
administrator error, improper injection technique 
and / or improper needle length used based on 
body type.   
In addition, HIV-1 viral suppression may not be 
effective following accidental intravenous 
maladministration. 
• Training will be provided to all sites on proper 
injection technique.   
• Should IM maladministration be suspected at 
any time (e.g., suspected under or overdose or 
inadvertent IV dosing), post dose ECG 
monitoring and vital signs or any other 
supportive testing may be obtained at the 
discretion of the investigator, and the medical 
monitor notified 
• Laboratory samples for safety parameters and 
HIV-1 RNA will be closely monitored in all 
participants.  Additionally, an unscheduled PK 
sample may be drawn approximately 2 hours 
post dosing for future evaluation of RPV 
concentrations. 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Other Study Related Risks  
Venipuncture 
Participants will be required to have blood samples 
taken.  Risk of bruising, and rarely, infection 
• Trained personnel will perform venipuncture 
Risks of ECG pad 
removal 
Participants will be required to have ECG tracings 
recorded periodically throughout the study 
Some discomfort and rash may occur where the 
ECG pads are removed. 
• ECGs will be conducted by appropriately trained 
personnel and effort made to minimize contact 
time for application of the pads. 
Risk of Treatment 
Failure 
This study employs a novel 2 drug LA ART 
maintenance regimen for the treatment of HIV-1 
infection that remains experimental.  Both IM 
CAB and RPV have demonstrated antiviral 
activity in large clinical studies and the two-drug 
combination has demonstrated sustained antiviral 
activity in studies, LAI116482, 200056, 201584, 
201585 and 207966.    
Doses of the CAB LA and RPV LA have been 
selected to achieve exposures that are expected to 
maintain virologic efficacy on the basis of 
available data with the oral and LA formulations. 
Due to administration error, it is possible that a 
participant could receive an inadequate dose of 
CAB LA or RPV LA.  Sub-therapeutic 
concentrations of either CAB LA or RPV LA 
• Viral loads and CD4+ cell counts will be closely 
monitored throughout the study (maintenance 
and extension phases), allowing for early 
detection of failing treatment.  Where confirmed 
virological failure occurs, participants would be 
discontinued from study drugs and transferred to 
an oral HAART regimen. 
• Plasma samples will be collected and stored 
throughout the Maintenance Phase for potential 
determination of CAB and RPV concentrations 
and possible pharmacokinetic correlation with 
virologic response. 

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

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

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

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

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

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

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

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

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

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requires a new participant number.  Participants who are randomized into the trial and 
subsequently withdrawn from the study, for any reason, may not be re-screened.  
Participants may be randomized as soon as all eligibility requirements have been 
confirmed at the site. 
4.1.2. 
Maintenance Phase 
At Day 1, eligible participants will be randomized 2:1 to either the CAB LA + RPV LA 
Q2M arm or the BIK arm. For participants who are randomized to the CAB LA + RPV 
LA arm, they will be able to choose to begin oral therapy with CAB 30 mg + RPV 25 mg 
once daily to determine individual safety and tolerability, prior to administration of CAB 
LA + RPV LA or transition directly to injections: 

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Oral Lead In 
Participants will remain on oral BIK until the Day 1 visit, and until any required 
Screening visit retest results are available for review.  On Day 1, participants who choose 
to participate in the oral lead in will be administered oral CAB 30 mg + RPV 25 mg once 
daily for one month (participants will be assessed for tolerability after one month).  At 
Month 1, participants will have the assessments completed as per the SoA (Section 1.3.), 
including clinical chemistries.  The participant will take the last dose of oral CAB + RPV, 
and to receive the first CAB LA + RPV LA injections (within 2 hours of the final oral 
dose).  The first injection visit with IM CAB LA 600 mg and RPV LA 900 mg can be 
performed before central lab results are available and safety parameters are reviewed.  
The second IM injection with CAB LA 600 mg and RPV LA 900 mg will be performed 
at Month 2 with a visit window of -7 days allowed.  Receiving LA dosing up to +7 days 
is not recommended and the Medical Monitor must be contacted.  Subsequent 
injections with CAB LA 600 mg and RPV LA 900 mg will occur every 2 months 
thereafter, from the projected visit date, with a dosing window of 7 days allowed If the 
injection is expected to fall outside of the dosing window, the Medical Monitor must be 
contacted to discuss individual participant case management. 
Direct to Inject (no oral lead-in) 
Central lab results (or local lab results if a central lab is not available) and safety 
parameters from the Screening visit must be available and reviewed for participants who 
choose to transition directly to injections without an oral lead-in.  Participants with 
ongoing safety issues or laboratory abnormalities of clinical concern (e.g. Grade 3 or 
Grade 4 liver chemistry elevations) will require consultation and agreement with the 
Medical Monitor prior to proceeding directly to injections in the Maintenance Phase. If a 
clinical chemistry retest is required based on Screening visit labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following the 
Screening visit).  Participants will remain on BIK until the Day 1 injection visit, and until 
any required Screening visit retest results are available for review. 
At Day 1, eligible participants will take the last dose of BIK and receive the first 
injections of CAB LA (600 mg) + RPV LA (900 mg) as initial loading doses.  Clinical 
chemistries will also be obtained at Day 1.  The second and third injections (CAB LA 
600 mg + RPV LA 900 mg) will be administered at Month 1 and Month 3.  The second 
IM injection with CAB LA 600 mg and RPV LA 900 mg will be performed at Month 1 
with a visit window of -7-days .  For the second IM injection, a visit window for LA 
dosing from +1 to +7 days is not recommended and the Medical Monitor must be 
contacted before  the second IM injection is given. Subsequent injections (CAB LA 
600 mg + RPV LA 900 mg) will occur every 2 months thereafter, from the projected visit 
date, with a 7-day dosing window being allowed.   If the injection is expected to fall 
outside of the dosing window, the Medical Monitor must be contacted to discuss 
individual participant case management. 
Note:  Study participants with Grade 1 ALT at screening and or Day 1 must be 
discussed with the Medical Monitor prior to initiation of LA dosing; continuation in 
the study or progression onto LA dosing may require additional evaluations, including 
labs drawn after a period of oral dosing with CAB + RPV. 

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BIK 
Continue on current ART (BIK) regimen for 12 months.  Participants who successfully 
complete Month 12 (without meeting study defined withdrawal criteria and who remain 
virologically suppressed (HIV-1 RNA <50 c/mL) will be given the option to switch to the 
LA arm in the Extension Phase (with or without an OLI) or to successfully complete and 
withdraw from the study (no withdrawal visit needed). 
4.1.3. 
Extension Phase 
All eligible participants who transition into the Extension Phase will continue study 
treatment until CAB LA and RPV LA are either locally approved and commercially 
available, the participant no longer derives clinical benefit, the participant meets a 
protocol-defined reason for discontinuation or until development of either CAB LA or 
RPV LA is terminated.  Visits will continue to occur every 2 months.  
Participants not eligible to enter the Extension Phase will end their study participation.  
Sites may be reimbursed for up to a one-month supply of antiretroviral medication to 
facilitate transition to non-study ART for participants that do not qualify for the 
Extension Phase. 
NOTE: the transition plan to marketed product (either CAB+RPV LA or alternative 
HAART) should be done in consultation with the Central Study Team and the Medical 
Monitor. Participants with ongoing safety issues or laboratory abnormalities of clinical 
concern (e.g. Grade 3 or Grade 4 liver chemistry elevations) will require consultation and 
agreement with the Medical Monitor prior to proceeding to commercial supply.  
 
4.1.3.1. 
Participants Entering from the CAB LA + RPV LA Arm 
All participants who successfully complete 12 months of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to both CAB LA and RPV LA in 
the Extension Phase.  See the SoA (Section 1.3) for more information. 
4.1.3.2. 
Participants Entering from the BIK Arm 
Participants randomized to continue BIK will have the option to either continue study 
participation by switching to CAB LA + RPV LA in the Extension Phase, or to complete 
their study participation at Month 12 (no withdrawal visit needed).  The transition from 
BIK to CAB LA + RPV LA within the Extension Phase can be completed with or 
without an oral lead-in prior to commencement of injectable treatment.  The participant’s 
decision will be taken in consultation with the investigator and must be appropriately 
documented.  As participants approach the Month 13 visit, sites must ensure sufficient 
CAB and RPV supply are available to support the participant’s decision for transition to 
LA. 
Participants who choose to continue on to the Extension Phase will need to be assessed 
for eligibility to begin the CAB LA + RPV LA regimen.  Participants will continue on 
BIK while eligibility is being confirmed.  

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All participants with an undetectable HIV-1 RNA (<50 c/mL) result from the Month 12 
visit are eligible to enter the Extension Phase.  A single repeat of HIV-1 RNA for any 
participant with a HIV-1 RNA 50 c/mL and < 400 c/mL at Month 12 must be 
performed. The retest should be scheduled as soon as possible (but no later than 4 weeks 
from the Month 12 visit).  Participants with a HIV-1 RNA <50 c/mL upon retest are 
eligible to enter the Extension Phase.  Participants with HIV-1 RNA ≥400 c/mL at Month 
12 are not eligible to enter the Extension Phase, will not be allowed a repeat to determine 
eligibility, and will therefore be withdrawn from the study. 
Result of HIV-1 RNA at Month 12 
Action 
<50 c/mL 
Begin Extension Phase for participants 
randomized to BIK at Month 13  
50 c/mL but <400 c/mL 
Perform HIV-1 RNA retest as soon as possible 
(not later than 4 weeks). 
Single repeat <50 c/mL 
Begin Extension Phase for participants 
randomized to BIK at Month 13  
Single repeat 50 c/mL 
Cannot begin Extension Phase and must be 
withdrawn from study; Complete withdrawal visit 
400 c/mL 
Cannot begin Extension Phase and must be 
withdrawn from study; Complete withdrawal 
visit. 
 
Please refer to Section 6.11.1 for a list of prohibited medications concurrent with either 
formulation for CAB and/or RPV. 
Participants Transitioning Direct to Injection in the Extension Phase:   
Central lab results (or local lab results if a central lab is not available) and safety 
parameters from the Month 12 visit must be available and reviewed for participants who 
choose to transition directly to injections.  Participants with ongoing safety issues or 
laboratory abnormalities of clinical concern (e.g. Grade 3 or Grade 4 liver chemistry 
elevations) will require consultation and agreement with the Medical Monitor prior to 
proceeding directly to injections in the Extension Phase. 
If a clinical chemistry retest is required based on Month 12 labs, the retest should be 
performed as soon as possible (and preferably no later than 7 days following Month 
12).  Participants will remain on oral BIK until the Month 13 injection visit, and until any 
required Month 12 retest results are available for review. 
At Month 13, eligible participants will take the last dose of BIK and receive the first 
injections of CAB LA (600 mg) + RPV LA (900 mg) as initial loading doses.  Clinical 
chemistries and safety assessments will also be obtained at Month 13.  The second 
injection (CAB LA 600 mg + RPV LA 900 mg) will be administered at Month 14, with a 
visit window of -7-days . Receiving LA dosing from +1 to +7 days is not 
recommended and the Medical Monitor must be contacted before the next injection 
is given. Subsequent injections (CAB LA 600 mg + RPV LA 900 mg) will occur every 2 
months thereafter, from the projected visit date, with a 7-day dosing window being 

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allowed. If the injection is expected to fall outside of the dosing window, the Medical 
Monitor must be contacted to discuss individual participant case management. 
Participants Receiving Optional Oral Lead-In in the Extension Phase: 
As participants approach the Month 13 visit, sites must ensure sufficient oral CAB and 
RPV are available for participants who choose to use the oral lead-in. 
At Month 13, eligible participants who after discussion with the investigator, choose to 
receive the optional oral lead-in will initiate a 4-week lead-in of oral CAB 30 mg + oral 
RPV 25 mg once daily.  It is not necessary to dose BIK on the day the participant begins 
the oral lead-in with CAB + RPV.  However, if the participant takes BIK prior to coming 
into the clinic, initiation of oral CAB and RPV should continue as planned.  Clinical 
chemistries will be assessed at Month 13.  At Month 14, following the 4-week CAB + 
RPV oral lead-in, participants will have additional safety assessments including clinical 
chemistries as per the SoA (Section 1.3).  At the Month 14 visit, participants will take the 
last dose of oral CAB + RPV and receive the first CAB LA (600 mg) + RPV LA (900 
mg) injections (within 2 hours of the final oral dose of CAB + RPV).  The first injections 
can be performed before central lab results become available and safety parameters are 
reviewed.  The second injection (CAB LA 600 mg + RPV LA 900 mg) will be 
administered at Month 15 with a - 7-day window being allowed. Receiving LA dosing 
up to +7 days is not recommended and the Medical Monitor must be contacted.  
Subsequent injections (CAB LA 600 mg + RPV LA 900 mg) will occur every 2 months 
(bi-monthly) thereafter, from the projected visit date, with a 7-day dosing window being 
allowed. If the injection is expected to fall outside of the dosing window, the Medical 
Monitor must be contacted to discuss individual participant case management. 
4.1.4. 
LTFU Phase – IM Regimen Only 
Any participant who receives at least one dose of CAB LA and/or RPV LA and 
discontinues the CAB LA + RPV LA regimen for any reason must remain on suppressive 
HAART for at least 52 weeks after the last dose of CAB LA and/or RPV LA in order to 
prevent selective pressure on HIV and the potential for selection of resistant mutants.  
Investigators must discuss the choice of the follow-up HAART regimen with the 
Medical Monitor prior to initiating the new regimen with the participant.  HAART 
therapy should be initiated within 8 weeks ( 7 days) after the last Q2M injection.  
The LTFU will begin the day of the last CAB LA and/or RPV LA dose and continue for 
52 weeks, or until the assigned CAB LA + RPV LA regimen is locally approved and 
commercially available.  These participants will complete Withdrawal assessments and 
will then enter into the LTFU as per the Time and Events Schedule.  In addition, for 
participants who withdraw during the LTFU, the final visit will be considered the study 
withdrawal visit.  
After receiving at least one dose of LA CAB and LA RPV, participants who decide to no 
longer continue with LA dosing for whatever reason must transition to the 52 week long 
term follow up (LTFU) phase of SOLAR. These participants are considered on study but 
off IP and should return for follow up visits at 3, 6, 9 and 12 months after the last LA was 
administered.Female participants of child bearing potential must continue to use adequate 

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

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20% women.  Sites are expected to take into account gender in their screening strategies 
in order to achieve women enrolment. .  
4.3. 
Scientific Rationale for Study Design 
The design of this study (2:1 randomized, open-label, active-controlled, multicenter, 
parallel group, non-inferiority study) is well established for confirming the non-
inferiority of an investigational agent compared with an active comparator and is 
generally accepted by regulatory authorities as rigorous proof of antiviral activity. The 
primary endpoint, proportion of participants defined as virologic failures by the FDA 
Snapshot algorithm is recommended in the FDA’s 2015 guidance document [CDER, 
2015] for assessing efficacy in Switch Trials.  The key secondary endpoints, proportion 
with plasma HIV-1 RNA <50 c/mL at Month 6 and Month 12, is also a well-established 
surrogate endpoint for prognosis of HIV-1 infection and disease progression. The 
Extension Phase will allow for a collection of longer-term efficacy, safety and tolerability 
data for the CAB LA + RPV LA Q2M regimen. 
Various approaches to simplify a patient's antiretroviral therapy (ART) regimen, after 
achieving viral suppression, have been studied.  Previous studies have evaluated switches 
to ritonavir-boosted PI monotherapy therapy in virologically suppressed patients 
[Bierman, 2009 and Arribas, 2012].  While the data from these studies have shown both 
long-term non-inferiority and inferiority to continual Highly Active Antiretroviral 
Therapy (HAART), they suggest that simplifying from a three-drug dual class regimen to 
a single boosted protease inhibitor may be a safe and effective option for the majority of 
participants studied who have effectively maintained viral suppression. 
The 200056 (LATTE-2) [GlaxoSmithKline Document Number 2013N168152_09, 2017] 
and the ATLAS-2M [GlaxoSmithKline Document Number 2017N326521_02, 2018] 
clinical trials evaluated a different simplification approach and served as proof of concept 
for this study.  In 200056, HIV-1 RNA suppression was induced with a three-drug 
antiretroviral regimen consisting of CAB + ABC/3TC FDC, and then participants 
switched to a two-drug two-class regimen consisting of CAB LA + RPV LA for the 
maintenance of HIV-1 RNA suppression.  Results demonstrate that through 96 weeks on 
two-drug maintenance therapy, 94% (Q8W IM arm) and 87% (Q4W IM) of participants 
maintained virologic suppression (HIV-1 RNA <50 c/mL) compared to 84% of 
participants continuing oral CAB + 2 NRTIs. CAB LA + RPV LA was well tolerated 
through Week 96 for both the Q8W and Q4W dosing regimens, as demonstrated by a low 
discontinuation rate due to AEs, including injection site reaction (ISR) related AEs in 
either dosing arm, with no significant dose-dependent trends in safety parameters.  On the 
basis of 200056 Week 48, and Week 96 data, Q4W and Q8W IM dosing are being 
progressed into Phase 3 for further clinical development, respectively.  In 207966, 1.7% 
of participants in the CAB + RPV Q8W group and 1.0% of participants in the CAB + 
RPV Q4W group met the primary efficacy endpoint of plasma HIV-1 RNA 50◦c/mL at 
Week◦48.  Based on a 4% non-inferiority margin, CAB◦+◦RPV Q8W is non-inferior to 
CAB + RPV Q4W at Week◦48 because the upper bound of the 95% CI for the adjusted 
treatment difference [0.8 (-0.6, 2.2)] is less than 4%.  

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The open-label design for 213500 (SOLAR) best suits the objectives of this study.  A 
double-blind, double-dummy design for this study would result in an increased pill 
burden in all participants, a requirement for placebo injections across the comparator 
arms, elevated risk of oral ART non-adherence in participants receiving placebo 
injections, limitations to patient reported preference data comparing injectable and oral 
ART, as well as considerable trial design complexities. A blinded design is also 
complicated by the requirement for an oral lead-in, in participants who elect to receive 
this short-term regimen at the start of study before the initiation of CAB LA + RPV LA 
injections.  Blinding the oral lead-in would require additional placebo pills for 5 weeks in 
the ART continuation arm, that otherwise would not be required.  This study utilizes a 
2:1 randomization that provides advantages with respect to costs, gathering additional 
safety information, reduces the effect of any learning curves due to injection 
administration or metabolic testing and improves recruitment. 
In addition to study design challenges, the impact of blinding carries the potential risk of 
oral regimen non-compliance, in participants on the ART continuation arm, who may 
believe that they are receiving active drug via injection (and therefore possibly increased 
risk of HIV transmission to uninfected partners).  The additional risk of inadvertent non-
adherence to oral ART outweighs any benefits that may be gained through a blinded 
design.  
Importantly, a key objective for the planned Phase 3 studies is to understand the 
acceptability and patient reported preferences to this novel injectable regimen, relative to 
daily oral standard of care (SOC) ART.  An unblinded study design supports collection of 
participant preference data in a way that would not be possible if a double-blind, double-
dummy design were implemented.  Due to the complexities, limitations and risks of 
blinding, this study is planned as an open label study. 
To maintain the integrity of the trial, data aggregated by actual treatment group will not 
be made available to members of the Study Team and will not be shared with 
Investigators until the primary analysis at Month 12.  In addition, central stratified 
randomization will be used to ensure that selection bias is avoided (see Section 6.2).  The 
stratification factors gender and BMI will be considered based on historical studies.  
Lastly, ascertainment bias affecting the primary efficacy analysis is unlikely since the 
primary endpoint is inherently objective, being primarily determined by HIV-1 RNA 
laboratory assessment. The open label design should therefore have no impact on the 
analysis of study endpoints.   

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

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

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

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

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

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An safety Follow-Up visit will be conducted approximately 4 weeks after the last dose of 
study medication for participants with ongoing AEs, and serious adverse events (SAEs) 
and also any laboratory abnormalities that are considered to be AEs or potentially 
harmful to the participant, at the last on-study visit.  Assessments at the safety Follow-up 
visit should reflect any ongoing complaints (e.g., blood draws to follow a laboratory 
abnormality).  Safety Follow-Up visits are not required for successful completion of the 
study and can be in clinic or conducted by phone. 
5. 
STUDY POPULATION 
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the investigational regimen or other study treatment 
that may impact participant eligibility is provided in the current  IBs for CAB 
[GlaxoSmithKline Document Number  RPS-CLIN-004375, 2021 and RPV IB, 2021], 
Edurant Prescribing Information, 2021 and Biktarvy prescribing information, 2019. 
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
participant safety.  Therefore, adherence to the criteria as specified in the protocol is 
essential. 
5.1. 
Inclusion Criteria 
A participant will be eligible for inclusion in this study only if all of the following criteria 
apply: 
• 
Be able to understand and comply with protocol requirements, instructions, and 
restrictions; 
• 
Understand the long-term commitment to the study and be likely to complete the 
study as planned; 
• 
Be considered appropriate candidates for participation in an investigative clinical 
trial with oral and intramuscularly injectable medications (e.g., no active 
substance use disorder, acute major organ disease, or planned long-term work 
assignments out of the country, etc.).   
The following are study specific eligibility criteria unless stated otherwise.  In addition 
to these criteria, Investigators must exercise clinical discretion regarding selection of 
appropriate study participants, taking into consideration any local treatment 
practices or guidelines and good clinical practice (GCP).  All participants must be 
considered appropriate candidates for antiretroviral therapy in accordance with 
local treatment guidelines. 
Laboratory results from the central laboratory services provided by this trial will be used 
to assess eligibility.  In exceptional circumstances only, if a repeat lab is required because 
a central lab result cannot be generated, local labs can be reviewed and approved by the 
Medical Monitor for consideration of participant eligibility.  A repeat central lab will be 
submitted concurrently or at the next planned visit. 

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Source documentation to verify entry criteria must be reviewed by the Principal 
Investigator or designee prior to randomization.  Source documents from other medical 
facilities must be located/received during the 14-day screening phase (or up to 35 days) 
and under no circumstances may the participant be randomized in the absence of source 
documentation.  
All Participants eligible for enrolment in the study must meet all of the following 
criteria: 
AGE 
1. Aged 18 years or older (or ≥19 where required by local regulatory agencies), at 
the time of signing the informed consent. 
SEX 
2. A female participant is eligible to participate if she is not pregnant (as confirmed 
by a negative serum human chorionic gonadotropin (hCG) test at screen and a 
negative urine hCG test at Randomization), not lactating, and at least one of the 
following conditions applies: 
a. Non-reproductive potential defined as: 
• Pre-menopausal females with one of the following: 
• Documented tubal ligation 
• Documented hysteroscopic tubal occlusion procedure with follow-up 
confirmation of bilateral tubal occlusion 
• Hysterectomy 
• Documented Bilateral Oophorectomy 
• Postmenopausal defined as 12 months of spontaneous amenorrhea [in 
questionable cases a blood sample with simultaneous follicle stimulating 
hormone (FSH) and estradiol levels consistent with menopause (refer to 
laboratory reference ranges for confirmatory levels)].  Females on 
hormone replacement therapy (HRT) and whose menopausal status is in 
doubt will be required to use one of the highly effective contraception 
methods if they wish to continue their HRT during the study.  Otherwise, 
they must discontinue HRT to allow confirmation of post-menopausal 
status prior to study enrolment.  
b. Reproductive potential and agrees to follow one of the options listed in the 
Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of 
Reproductive Potential (FRP) from 30 days prior to the first dose of study 
medication, throughout the study, for at least 30 days after discontinuation of all 
oral study medications, and for at least 52 weeks after discontinuation of CAB LA 
and RPV LA.  

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The investigator is responsible for ensuring that participants understand how to properly 
use these methods of contraception.   
INFORMED CONSENT 
3. Capable of giving signed informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form and in this protocol.  
Eligible participants or their legal guardians (and next of kin when locally 
required), must sign a written Informed Consent Form before any protocol-
specified assessments are conducted.  Enrolment of participants who are unable to 
provide direct informed consent is optional and will be based on local 
legal/regulatory requirements and site feasibility to conduct protocol procedures. 
OTHER 
4. Participants enrolled in France must be affiliated to, or a beneficiary of, a social 
security category.   
 
5. Must be on the uninterrupted current regimen of BIK for at least 6 months prior to 
Screening with an undetectable HIV-1 viral load for at least 6 months prior to 
Screening.  BIK must be the participant’s first or second regimen.  If BIK is the 
second regimen, the first regimen must be an INI regimen.  Any history of non-
INSTI regimens (ie. NNRTI, PI, C-C chemokine receptor type 5 [CCR5] and 
other entry inhibitors) are not permitted. Any prior change in regimen, defined as 
a change of a single drug or multiple drugs simultaneously, must have occurred 
due to tolerability/safety, access to medications, or convenience/simplification, 
and must NOT have been done for treatment failure (HIV-1 RNA ≥400 c/mL).  
 
The following are limited exceptions:  
 
• A change from TDF to TAF will not be considered a regimen change.   
 
• Historical perinatal use of an NRTI when given in addition to an ongoing 
HAART will not be considered a change in ART regimen. 
 
• The past use of ARVs in the context of PEP or PrEP while the patient was 
HIV negative will be allowed. Such cases will be evaluated on a case by 
case basis with the Medical Monitor, and may require documentation of 
HIV negative serology during time of PEP or PrEP 
 
• A change in dosing scheme of the same drug from twice daily to once 
daily will not be considered a change in ART regimen if data support 
similar exposures and efficacy. 
 
• A change in formulation from multiple class regimens to single treatment 
regimens (of the same medications) would not be considered a change in 
ART regimen. 

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6. Documented evidence of plasma HIV-1 RNA measurements <50 c/mL in the 6 
months prior to Screening . 
 
7. Plasma HIV-1 RNA <50 c/mL at Screening. 
All participants participating in the study should be counseled on safer sexual practices 
including the use and benefit/risk of effective barrier methods (e.g., male condom) and on 
the risk of HIV transmission to an uninfected partner. 
5.2. 
Exclusion Criteria 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability, or participant 
safety.  Therefore, adherence to the criteria as specified in the protocol is essential.  A 
participant will not be eligible for inclusion in this study if any of the following criteria 
apply: 
Exclusionary Criteria prior to Screening or Day 1  
 
1. Within 6 months prior to Screening, any plasma HIV-1 RNA measurement 
50 c/mL 
2. Within the 6 to 12-month window prior to Screening, documented evidence of 
any plasma HIV-1 RNA measurement >200 c/mL, or 2 or more plasma HIV-1 
RNA measurements 50 c/mL.  NOTE: This statement does not apply to study 
participants who started treatment within the 6 to 12-month window prior to 
screening. 
3. History of prior treatment failure to any DHHS recommended ART regimen. 
4. History of drug holiday >1 month for any reason prior to Screening visit, except 
where all ART was stopped due to tolerability and/or safety concerns 
5. Any change to a second line regimen, defined as change of a single drug or 
multiple drugs simultaneously, due to virologic failure to therapy (defined as a 
confirmed plasma HIV-1 RNA measurement 200 c/mL after initial suppression 
to <50 c/mL while on first line HIV therapy regimen)  
6. Participants who are currently participating in or anticipate being selected for any 
other interventional study. 
Exclusionary medical conditions- for all participants 
7. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed 
during the study 
8. Any evidence of a current Center for Disease Control and Prevention (CDC) 
Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring 

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systemic therapy, and CD4+ counts <200 cells/L are not exclusionary. 
9. Participants with moderate to severe hepatic impairment 
10. Any pre-existing physical or mental condition (including substance use disorder) 
which, in the opinion of the Investigator, may interfere with the participant’s 
ability to comply with the dosing schedule and/or protocol evaluations or which 
may compromise the safety of the participant 
11. Participants determined by the Investigator to have a high risk of seizures, 
including participants with an unstable or poorly controlled seizure disorder.  A 
participant with a prior history of seizure may be considered for enrolment if the 
Investigator believes the risk of seizure recurrence is low.  All cases of prior 
seizure history should be discussed with the Medical Monitor prior to enrolment 
12. All participants will be screened for syphilis.  
• Participants with untreated secondary (late latent) or tertiary syphilis 
infection, defined as a positive RPR and a positive treponemal test without 
clear documentation of treatment, are excluded.  
• Participants with a false positive RPR (with negative treponemal test) or 
serofast RPR result (persistence of a reactive nontreponemal syphilis test 
despite history of adequate therapy and no evidence of re-exposure) may 
enroll after consultation with the Medical Monitor. 
• Participants with primary syphilis or early latent secondary syphilis 
(acquired within the preceding year) who have a positive RPR test and 
have not been treated may be treated during the screening period and if 
completion of antibiotic treatment occurs during the screening period, may 
be allowed entry after consultation with the Medical Monitor. If antibiotic 
treatment cannot be completed before the screening window ends, 
participants may be rescreened once following completion of antibiotic 
therapy for primary or early latent secondary syphilis.  
13. Participants who, in the investigator's judgment, pose a significant suicide risk.  
Participant’s recent history of suicidal behavior and/or suicidal ideation should be 
considered when evaluating for suicide risk 
14. The participant has a tattoo, gluteal implant/enhancements or other dermatological 
condition overlying the gluteus region which may interfere with interpretation of 
injection site reactions 
15. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at 
Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody 
(anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV DNA as follows: 
a. Participants positive for HBsAg are excluded; 
b. Participants negative for anti-HBs but positive for anti-HBc (negative 
HBsAg status), whether negative or positive for HBV DNA, are excluded 
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for 
anti-HBs (past and/or current evidence) are immune to HBV and are not 
excluded. 

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16. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not 
be excluded, however Investigators must carefully assess if therapy specific for 
HCV infection is required; participants who require or qualify for immediate 
HCV treatment are excluded (see Section 5.3.1 for those co-infected participants 
who post entry into SOLAR decide treatment for HCV infection is warranted or 
desired either by the participant or by the treating physician.   
Participants with HCV co-infection will be allowed entry into this study if:  
a. Liver enzymes meet entry criteria 
b. HCV Disease has undergone appropriate work-up, and is not advanced, 
and will not require treatment prior to the Month 14 visit.  Additional 
information (where available) on participants with HCV co-infection at 
screening should include results from any liver biopsy, Fibroscan, 
ultrasound, or other fibrosis evaluation, history of cirrhosis or other 
decompensated liver disease, prior treatment, and timing/plan for HCV 
treatment. 
c. In the event that recent biopsy or imaging data is not available or 
inconclusive, the Fib-4 score will be used to verify eligibility  
i. Fib-4 score >3.25 is exclusionary  
ii. Fib-4 scores 1.45 – 3.25 requires Medical Monitor consultation 
Fibrosis 4 Score Formula:  
(Age x AST) / (Platelets x (sqr [ALT]) 
17. Unstable liver disease (as defined by any of the following:  presence of ascites, 
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, 
or persistent jaundice or cirrhosis, or decompensated cirrhosis (eg. ascites, 
encephalopathy, or variceal bleeding)), known biliary abnormalities (with the 
exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable 
chronic liver disease per investigator assessment) 
18. History of liver cirrhosis with or without hepatitis viral co-infection. 
19. Ongoing or clinically relevant pancreatitis 
20. Clinically significant cardiovascular disease, as defined by history/evidence of 
congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary 
artery bypass grafting (CABG) surgery or percutaneous transluminal coronary 
angioplasty (PTCA) or any clinically significant cardiac disease 
21. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell 
carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or 
cervical intraepithelial neoplasia; other localized malignancies require agreement 
between the investigator and the Study medical monitor for inclusion of the 
participant prior to randomization 
22. Any condition which, in the opinion of the Investigator, may interfere with the 
absorption, distribution, metabolism or excretion of the study drugs or render the 
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23. History or presence of allergy or intolerance to the study drugs or their 
components or drugs of their class.  In addition, if heparin is used during PK 
sampling, participants with a history of sensitivity to heparin or heparin-induced 
thrombocytopenia must not be enrolled 
24. Current or anticipated need for chronic anti-coagulation with the exception of the 
use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and 
platelet disorders such as haemophilia or Von Willebrand Disease. 
25. Corrected QT interval (QTc (Bazett)) >450 msec or QTc (Bazett) >480 msec for 
participants with bundle branch block. 
26. Known or suspected active COVID-19 infection OR has had contact with an 
individual with known COVID-19, within 14 days of study enrolment. 
 
Exclusionary Laboratory Values or Clinical Assessments at Screening (a single repeat to 
determine eligibility is allowed) 
27. Known or suspected presence of resistance mutations as defined by the IAS-USA 
resistance guidelines [IAS-USA, 2019] to the individual components of BIK 
(BIC, FTC, TAF), RPV, and CAB by any historical resistance test result. 
Note: Prior genotypic resistance testing (genotyping of plasma vRNA 
and/or PBMC vDNA) is not required but if available it must be provided 
to ViiV, after screening and before randomization according to guidance 
in the SPM, to provide direct evidence of no pre-existing exclusionary 
resistance mutations. You must wait for the study virologists to confirm 
the lack of exclusionary resistance mutations, which will be provided 
before the screening window closes. Details regarding baseline or prior 
resistance data must be noted in the source documentation 
28. Any verified Grade 4 laboratory abnormality. A single repeat test is allowed 
during the Screening phase to verify a result  
29. Any acute laboratory abnormality at Screening, which, in the opinion of the 
investigator, would preclude the participant’s participation in the study of an 
investigational compound 
30. Participant has estimated creatine clearance <30mL/min per 1.73m2 via Chronic 
Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method 
31. Alanine aminotransferase (ALT) 3 × ULN 

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

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

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metabolic endpoints. Cosmetic procedures involving the face and neck are out of scope as 
such procedures are unlikely to have an impact on these metabolic endpoints. 
6. 
STUDY INTERVENTION 
The term ‘study treatment’ is used throughout the protocol to describe any combination 
of products received by the participant as per the protocol design.  Study treatment is 
defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to 
the study protocol. Study treatment may therefore refer to the individual study 
treatments or the combination of those study treatments. 
In this study, investigational product (IP) refers to oral BIK single tablet regimen (or 
alternately BIK), oral CAB, and CAB LA, which will be supplied by GlaxoSmithKline 
and oral RPV and RPV LA which will be supplied by Janssen Pharmaceuticals. 
Participants entering the Long-Term Follow-Up Phase will not have their selected 
HAART provided as clinical trial material.  The selected HAART will be recorded on the 
Concomitant Antiretroviral Therapy (ConART) eCRF page. 
6.1. 
Study Intervention(s) Administered 
6.1.1. 
Formulations of CAB + RPV 
6.1.1.1. 
Cabotegravir Tablets (CAB) 
CAB is manufactured by GlaxoSmithKline and is formulated as white to almost white 
oval shaped film coated 30 mg tablets for oral administration, packaged in high density 
polyethylene (HDPE) bottles with desiccant and child-resistant closure that include an 
induction seal. CAB tablets will be packaged in bottles of 30 tablets.  Participants must 
keep all IP in its original pack container.  GSK will notify sites if and when data are 
available to support the use of pill boxes.  CAB tablets are to be stored according to the 
product labeling. 
CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline 
cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-
coating.  The white film-coating contains hypromellose, titanium dioxide and 
polyethylene glycol. 
6.1.1.2. 
Rilpivirine Tablets (RPV) 
RPV is provided by Janssen Research & Development, LLC, a division of Janssen 
Pharmaceuticals, as 25 mg tablets that are off-white, round, biconvex, film-coated and 
debossed on one side with “TMC” and the other side with “25”.  RPV is manufactured by 
Janssen-Cilag S.p.A, Latina, Italy.  RPV will be provided as a globally marketed product 
which includes approvals in the US and the European Union.  RPV will be overlabeled 
and packaged in bottles of 30 tablets.  RPV tablets should be stored according to the 
product labeling. 

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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.  CAB LA injectable suspension is to be stored 
according to the product labeling.  
CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 
3350, mannitol, and water for injection. 
6.1.1.4. 
Rilpivirine Injectable Suspension (RPV LA) 
RPV LA (also named JNJ-16150108-AAA), 300 mg/mL Extended Release Suspension 
for Injection (G001), is provided by Janssen Research & Development, LLC, a division 
of Janssen Pharmaceuticals, as a sterile white suspension containing 300 mg/mL of RPV 
as the free base. The route of administration is by intramuscular (IM) injection. RPV LA 
is packaged in a single use 4 mL glass vial with a 13 mm grey stopper and aluminum 
seal. Each vial contains a nominal fill of 2.0 mL (600 mg) or 3.0 mL (900 mg) and does 
not require dilution prior to administration. RPV LA injectable suspension is to be stored 
according to product labeling. RPV LA should also be protected from light. 
RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate 
monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water 
for injection. 
6.1.2. 
Biktarvy Tablets (BIK) 
BIK is a three-drug fixed dose combination product containing 50 mg of BIC, 200 mg of 
FTC, and 25 mg of TAF manufactured by Gilead Sciences.  The recommended dosage of 
BIK is one tablet taken orally once daily with or without food in adults and pediatric 
patients weighing at least 25 kg.  The tablets are purplish brown, capsule-shaped, film-
coated, and debossed with “GSI” on one side and “9883” on the other side.  Each bottle 
contains 30 tablets, a silica gel desiccant, polyester coil, and is closed with a child 
resistant closure.  BIK tablets are to be stored according to product labelling.  
6.1.3. 
Medical Devices 
• 
The medical devices to be used in this study are: syringe, vial adaptor and needle. 
• 
Instructions for medical device use are provided in the Study Reference Manual 
(SRM).  

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• All device deficiencies, (including malfunction, use error and inadequate labelling) 
shall be documented, and reported by the investigator throughout the clinical 
investigation (see Section 8.3.8 and Section 10.9 and appropriately managed by the 
sponsor. 
6.2. 
Treatment Assignment 
Informed consent must be obtained prior to any study procedures, including Screening 
visit activities. Participants will be assigned to study treatment in accordance with the 
randomization schedule. The randomization schedule, including stratification, will be 
generated using the GSK validated randomization software RANDALL NG. The 
randomization schedule is comprised of a series of blocks, with 2:1 treatment allocation 
within each block, which are shared across centers via central randomization.  
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1. 
Randomization 
Given the open-label study design, central randomization was used to eliminate selection 
bias due to foreknowledge of randomized treatment.  With central randomization, 
knowledge at a site of the randomized treatment group for previous participants does not 
predict which treatment group will be assigned to the next randomized participant.  
Randomization and study treatment assignment will be facilitated by the interactive 
response technology (IRT) through the central Randomization and Medication Ordering 
System Next Generation (RAMOS NG).  
Following confirmation of fulfillment of study entry criteria, study site personnel will be 
required to register participants using RAMOS NG for assignment of a unique identifier 
(designating the participant’s randomization code and treatment sequence assignment) for 
each participant participating in the study.  On Day 1, A unique treatment number 
(randomization number) in ascending numerical order will be assigned for each 
participant participating in the study at each study site. Participants will be randomized in 
a 2:1 ratio to CAB LA + RPV LA Q2M or to continue BIK in accordance with the 
computer-generated randomization schedule.  Returned study intervention should not be 
re-dispensed to participants. 
Participants who successfully complete 12 months of treatment and have a viral load 
<50 c/ml at Month 11/12 (or upon retest 4 weeks later) will be given the opportunity to 
enter the Extension Phase in which they will continue to receive their CAB LA + RPV 
LA regimen or switch from BIK to CAB LA + RPV LA.  In addition, RAMOS NG will 
facilitate the initial supply and subsequent resupply of IP to study sites. 
6.3.2. 
Blinding 
This will be an open-label study and therefore no blinding is required.  No summaries of 
the study data according to actual randomized treatment groups will be available to 
sponsor staff prior to the planned Month 6 interim analysis. Public presentation of the 

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

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Maintenance Phase and Extension Phase (Day 1 to End of Study+) 
Q2M Arm – Optional Oral Lead In (OLI) 
Oral Lead-In   
 
• Receive last dose of BIK regimen during Day 1 visit 
• Take 1 tablet CAB 30 mg once daily. 
• Take 1 tablet RPV 25 mg once daily. 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injections (Loading Dose) – Month 1 
Month 1 
(two 3mL injections once) 
• Receive last dose of oral CAB + RPV regimen during 
Month 1 visit 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection  
Maintenance Injections – every 2 months (Q2M) following Month 1 
Month 2 to End of Study+ 
(two 3 mL injections every 2 
months) 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection 
Q2M Arm- No Oral Lead In (D2I) 
First Injections (Loading Doses) – Day 1 
Day 1  
(two 3 mL injections once) 
• Receive last dose of BIK regimen during Day 1 visit 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection 
Maintenance Injections – every 2 months (Q2M) following Month 1 
Month 1 to End of Study+ 
(two 3 mL injections every 2 
months) 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection  
Continuing BIK  
Day 1 to Month 13+ 
• Take 1 tablet BIC 50 mg/FTC 200 mg/TAF 25 mg once 
daily with or without a meal 

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(1 tablet dosed orally) 
Extension Phase (Month 13 through End of Study) 
BIK Arm (Transition to CAB LA + RPV LA) – Optional OLI 
Oral Lead-in 
Month 13 to Month 14 
(2 tablets once daily) 
• Take 1 tablet CAB 30 mg once daily. 
• Take 1 tablet RPV 25 mg once daily. 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injection (Loading Dose) – Month 14 – Optional Oral Lead-in 
Month 14 
(two 3 mL injections once) 
• Receive last dose of oral CAB + RPV during Month 14 
visit 
• Receive CAB LA 600 mg given as 1 X 3mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3mL IM injection 
Maintenance Injections – every 2 months (Q2M) following Month 14 
Month 15 to End of Study+ 
(two 3 mL injections every 2 
months) 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection 
Direct to Inject Dosing – if Not Using Oral Lead-in 
First Injection (Loading Dose) – Month 13– Optional Oral Lead-in 
Month 13 
(two 3 mL injections once) 
• Receive last dose of oral BIK during Month 13 visit 
• Receive CAB LA 600 mg given as 1 X 3mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3mL IM injection 
Maintenance Injections – every 2 months (Q2M) following Month 13 – No Oral Lead-in 
Month 14 to End of Study+ 
(two 3 mL injections every 2 
months) 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection 
+Until locally approved and commercially available, the participant no longer derives clinical benefit, the participant 
meets a protocol-defined reason for discontinuation or until development of CAB LA or RPV LA is terminated 
Participants will be given an option to continue their randomized Q2M CAB LA + RPV LA regimen, switch from BIK to 
Q2M CAB LA + RPV LA (or complete trial participation) at Month 12.  If the participant decides not to continue 
participation in the study, any arrangements for off-study ART should be made in advance of the Month 12 visit. 
NOTE: Refer to Section 6.6.1 and Section 6.6.2 for Dosing Considerations for CAB LA + RPV LA and BIK, 
respectively. 

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6.5. 
Packaging and Labelling 
The contents of the label will be in accordance with all applicable regulatory 
requirements. 
6.6. 
Preparation/Handling/Storage/Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study interventions 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study intervention 
are provided in the Study Reference Manual.  
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff.  Take adequate precautions to avoid 
direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or GSK 
study contact. 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from GSK. 
IP accountability will be evaluated using pill counts of unused IP for patients receiving 
oral treatment (oral CAB, oral RPV, BIK).  This assessment will be conducted, when the 
participant completes oral CAB and RPV lead-in treatment and BIK in the Maintenance 
Phase, or any withdrawal that occurs during an oral treatment phase. 
IP accountability for participants receiving CAB LA + RPV LA will be performed at the 
‘vial’ level (e.g., correct number of vials were used for each injection).  There may be a 
small amount of solution remaining in the vial which does not require quantification.  
Used vials may be discarded at the site once accountability is complete. 

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

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6.7. 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from 
the investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents.  The dose of study 
intervention and study participant identification will be confirmed at the time of dosing 
by a member of the study site staff other than the person administering the study 
intervention.  If oral study treatment is dosed at site, study site personnel will examine 
each participant’s mouth to ensure that the study intervention was ingested. 
When participants self-administer study intervention(s) at home, compliance with CAB, 
RPV and BIK dosed orally once daily will be assessed by counting returned 
tablets/capsules during the site visits and documented in the source documents and CRF.   
A record of the number of CAB, RPV and BIK tablets dispensed to and taken by each 
participant must be maintained and reconciled with study intervention and compliance 
records. Intervention start and stop dates, including dates for intervention delays and/or 
dose reductions will also be recorded in the CRF. 
6.8. 
Protocol Permitted Substitutions 
6.8.1. 
Oral Bridging 
In exceptional circumstances, to address pre-planned missed CAB LA + RPV LA dosing 
visits, in consultation with and approval by the medical monitor, Investigators may 
provide daily oral CAB 30 mg and RPV 25 mg as a short-term “bridging” strategy for 
participants who have begun CAB LA + RPV LA.  In certain circumstances (e.g., prior to 
steady state dosing and following a >8-week oral bridge) repeating the loading doses of 
CAB IM and RPV IM may be required.  Should a participant require “oral bridging”, 
sites must contact the study Medical Monitor for guidance with treatment and dosing 
strategies prior to a missed CAB LA + RPV LA dose.  
Please refer to Appendix 11in Section 10.11 for study management information during 
the COVID-19 pandemic. 
6.9. 
Interruption of Study Intervention and Visit/Dosing Windows 
IP may be interrupted at the discretion of the Investigator in the event of an AE, 
according to the severity of the AE. 
If one or more antiretroviral medications is held due to toxicity or adverse events, all 
antiretroviral medications must be held to reduce the risk of development of resistance 
taking into account both the length of the planned interruption and the pharmacokinetic 
half-life of each antiretroviral of the regimen, in a way to minimize the risk of 
development of resistance. 
It is important to note that keeping to the participant’s visit schedule is a very 
important component to the study.   

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Note: All decisions regarding dose interruption / resumption must be discussed with 
the medical monitor in advance. 
6.9.1. 
IM Dosing 
Participants receiving CAB LA and/or RPV LA are anticipated to be at risk for 
development of virologic resistance if ART is interrupted.  The time period during which 
participants are at risk for development of virologic resistance may be determined by the 
period between when drug levels fall below therapeutic values and when they fall below 
levels which exert selective pressure on HIV.  This time period will vary by ART agent 
and is dependent upon effective concentration, inhibitory concentration, and half-life.  
Plasma concentrations of both LA drugs may be measurable for more than one year 
following IM injections. Any interruption in IM dosing should be discussed with the 
Medical Monitor.  Investigators should ensure that the participant initiates alternative 
highly active ART to minimize the risk of developing resistance as concentrations of 
CAB and RPV decline over time. 
IM dosing is expected to occur during the week in which the participant’s projected visit 
falls (as according to the date of the first injection).  The first injections for participants 
who choose to start injections immediately will occur at Day 1.  The first injections for 
participants electing to participate in the oral lead are administered at Month 1 (can be 
performed before lab results become available), and the second injections are given at 
Month 2.   
The participant’s projected visit is determined by their first injection date and, ideally, is 
the same date for every injection. For example, if the1st dose (Month 1) is January 15th, 
then dose 2 (Month 2) will be February 15th, and dose 3 (Month 4) will be April 15th, etc. 
Since the first injection visit (Day 1 or Month 1) will determine the future injection visit 
schedule for participants, planning for the first injection visit date (within allowed visit 
windows) should take into consideration the availability of the participants to adhere to 
future visit windows (planned vacations, business trips, weekends, holidays, etc.). 
Dosing for participants randomized to CAB LA + RPV LA is as follows: 
All injections should be planned as single injections per drug. 
6.9.1.1. 
IM injections every 2 months (Oral Lead In): 
Month 1 – CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 2 - CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 4 and Q2M thereafter - CAB LA 600 mg + RPV LA 900 mg IM, every 2 months 
until Month 12, each given as 1 X 3 mL IM injection 
At Month 1, participants will return to the clinic, take the last dose of their oral (CAB 
30 mg + RPV 25 mg), and receive the first CAB LA (600 mg) + RPV LA (900 mg) 
injections (within 2 hours of the final oral dose of CAB + RPV).  The first injection visit 

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with IM CAB LA + RPV LA at Month 1 can be performed before central lab results are 
available and safety parameters are reviewed from the Month 1 visit.   
The second loading injection will be administered at Month 2 (CAB LA 600 mg + RPV 
LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring 
every 2 months thereafter.  A -7-day dosing window for the second injection is allowed.  
Receiving LA dosing from +1 to +7 days is not recommended and the Medical 
Monitor must be contacted before  the second IM injection is given.  Starting at Month 
4 and at subsequent visits, a 7 day dosing window for injections is allowed. If the 
injection is expected to fall outside of the dosing window, the Medical Monitor must be 
contacted to discuss individual participant case management.  
6.9.1.2. 
IM injections every 2 months (Q2M) (Direct to injections): 
Participants electing not to receive the oral lead in and are receiving CAB LA + RPV LA 
Q2M will initiate dosing at the Day 1 visit: 
Day 1- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Month 1 and Q2M thereafter- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 
X 3 mL IM injection 
The second injection will be administered at Month 1 (CAB LA 600 mg + RPV LA 
900 mg, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) every 2 
months thereafter.  A -7-day dosing window for the second injection is allowed.  
Receiving LA dosing from +1 to +7 days is not recommended and the Medical 
Monitor must be contacted before  the second IM injection is given.  Starting at Month 
3 (third injection) and every 2 months thereafter, a 7-day dosing window for injections 
is allowed. If the injection is expected to fall outside of the dosing window, the Medical 
Monitor must be contacted to discuss individual participant case management. 
Any request for the visit/dosing to occur outside of the allowed window must be 
discussed and agreed with the Medical Monitor prior to dosing.  In the event of a late 
dose, a revised dosing schedule for subsequent dosing may be required and will be 
communicated to the site staff at the time of approval for continued dosing.  Temporary 
switch to oral dosing of CAB and/or RPV may be an option based on individual 
participant circumstance as described in Section 6.8.1. 
See the SPM for scheduling guidance and further information and examples. 
Note: All decisions regarding dose interruption/ resumption must be discussed with 
the Medical Monitor in advance. 

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6.9.2. 
Oral Dosing 
The Month 1 Visit during the Oral Lead-in Phase for participants randomized to CAB + 
RPV but choosing to participate in the oral lead in is expected to occur 4 weeks (3 days) 
after the Day 1 visit.  Visits for participants on the BIK arm are expected to occur every 
56 days as projected according to the Day 1 visit.  There is a 3-day visit window, from 
the projected visit date (Maintenance Phase of the study). However, the number of tablets 
dispensed should be considered when scheduling the next visit. 
Any interruption in therapy (scheduling conflicts, life circumstances, etc.) during any oral 
dosing period that is greater than 7 consecutive days must be discussed with the Medical 
Monitor prior to resumption of therapy.  The Medical Monitor must be contacted upon 
site staff becoming aware of resumption in therapy, if therapy was resumed without prior 
approval. 
Visits for participants in the Long Term Follow Up are expected to occur as projected 
according to the last injection.  There is no calendar defined visit window in the Long 
Term Follow Up Phase.  In general, four LTFU visits should occur from the last date of 
LA therapy until week 52 with clinic visits at months 3, 6, 9 and 12, although the timing 
of the actual visits are flexible, but not the frequency, in LTFU. 
6.10. 
Treatment after the End of the Study 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition, whether or not ViiV/GSK is providing 
specific post-study treatment.  Participants randomized to CAB LA + RPV LA arm, who 
have successfully completed 12 months of treatment will continue to have access to both 
CAB LA and RPV LA in the Extension Phase until study treatment is either locally 
approved and commercially available, the participant no longer derives clinical benefit, 
the participant meets a protocol-defined reason for discontinuation or until development 
of either CAB LA or RPV LA is terminated.  Participants randomized to the BIK arm 
who have successfully completed 12 months of treatment will be given the option of 
continuing onto the Extension Phase to receive CAB LA + RPV LA.  If these participants 
choose not to continue, they will end participation in the study after Month 12 will be 
responsible for obtaining post-study treatment. 
6.11. 
Concomitant Therapy 
Participants should be advised to notify their investigator of any current or proposed 
concomitant medication, whether prescribed or over-the-counter, because of the potential 
drug:drug interactions between such treatments and the study drugs.  The investigator 
should evaluate any potential drug:drug interactions at every visit, including reviewing 
the most current version of the investigator brochures, the U.S and/or local prescribing 
information for RPV and BIK, especially if any new concomitant medications are 
reported by participants.  All concomitant medications, blood products, and vaccines 
taken during the study will be recorded in the eCRF.  The minimum requirement is that 
the drug name, route, and the dates of administration are to be recorded. 

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Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study (except prohibited medications described in 
Section 6.11.1).  Chemoprophylaxis for HIV-associated conditions is encouraged, if 
appropriate, at the discretion of the participant and their physician.   
Because non-HIV vaccines may cause a temporary increase in the level of plasma HIV-1 
RNA, it is highly recommended that a vaccine, if necessary, be given during or 
immediately after a scheduled visit after all laboratory tests have been drawn.  This 
approach will minimize the risk of non-specific increases in the level of plasma HIV-1 
RNA at the next scheduled assessment. 
Other IM injectables (with exceptions below) are permitted but must be administered 
away from the site of IP administration if possible (should be spaced 2 cm or more away 
from site of IP injection). 
Hepatitis C infection treatment is allowed throughout the entire study.  If HCV treatment 
occurs during the study, a DHHS approved HCV regimen should be used to limit any 
drug-drug interactions that may occur. Options for treatment of HCV should be discussed 
with the Medical Monitor prior to initiation of therapy. 
Antacid and H2 Antagonist Use: 
While both oral CAB and RPV have dosing requirements with antacid products 
containing divalent cations, only oral RPV has requirements for dosing with H2 
antagonists.  Since co-administration of oral CAB and RPV is required in this study, the 
most restrictive dosing requirements must be taken into consideration.  
CAB oral administration only:  Antacid products containing divalent cations (e.g., 
aluminium, calcium, and magnesium) must be taken at least 2 hours before or at least 4 
hours after CAB. 
Concurrent administration of multivitamins is acceptable. 
Oral RPV administration only:   
• Antacid products containing divalent cations (e.g., aluminium, calcium, and 
magnesium) must be taken at least 2 hours before or at least 4 hours after RPV. 
• H2-Receptor antagonists (e.g. cimetidine, famotidine, nizatidine, ranitidine) may 
cause significant decreases in RPV plasma concentrations.  H2-antagonists must 
be taken at least 12 hours before or at least 4 hours after taking RPV. 
• RPV should not be co-administered with proton pump inhibitors, such as 
esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole. 
Administration of clarithromycin, erythromycin and telithromycin is not recommended 
with RPV due to possible increase in plasma concentration of RPV due to CYP3A 
enzyme inhibition.  Where possible, alternatives such as azithromycin should be 
considered. 

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Drugs that cause Torsade de Pointes (TdP) should be used with caution when taking 
rilpivirine (see SPM for list of drugs associated with TdP). 
BIK:  BIK and calcium-containing supplements can be taken together, without regard to 
food. 
 
BIK should be administered at least 2 hours before iron supplements or taken together 
with food. 
 
BIK should not be taken simultaneously with supplements containing magnesium and/or 
aluminium due to the expected substantial decrease of BIC exposure. 
 
BIK should be administered at least 2 hours before, or with food 2 hours after antacids 
containing magnesium and/or aluminium.  
Metformin concentrations may be increased by BIK.  Refer to the prescribing 
information of metformin for assessing the benefit and risk of concomitant use of BIK 
and metformin.  
Clinical monitoring is recommended for participants taking methadone as methadone 
maintenance therapy may need to be adjusted in some participants. 
Approved hormonal contraception may be administered. However, the investigator 
should consult local prescribing information for guidance on the use of hormonal 
contraceptives with background ART as some antiretrovirals have clinically significant 
drug interactions with these products. 
Please refer to the local prescribing information for other drugs that should be used with 
caution, require dose adjustment, or increased clinical monitoring if taken with BIK. 
6.11.1. 
Prohibited Medications and Non-Drug Therapies 
The following concomitant medications or therapies are not permitted at any time during 
the study: 
• 
HIV immunotherapeutic vaccines are not permitted at any time during the study.  
• 
Other experimental agents, antiretroviral drugs not otherwise specified in the 
protocol, cytotoxic chemotherapy, or radiation therapy may not be administered 
(see Section 5.2).  
• 
Systemically administered immunomodulators (such as interleukin and interferon 
agents) are prohibited (a list of examples is provided in the SPM).  This includes 
topical agents with substantial systemic exposure and systemic effects.   Use of 
topical imiquimod is permitted. 
• 
Acetaminophen (paracetamol) cannot be used in participants with acute viral 
hepatitis [James, 2009]. 
• 
Chronic use of systemic (oral or parenteral) glucocorticoids must be avoided due 
to the immunosuppressive effect and potential decreases in RPV plasma 

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concentrations; however, short treatment courses with oral prednisone/ 
prednisolone/methylprednisolone (e.g. adjunctive treatment of pneumocystis 
pneumonia with 21 days of tapering prednisone) are allowed.  A single dose of 
systemic dexamethasone is permitted, but more than a single dose in a treatment 
course may cause a significant decrease in RPV plasma concentration and is 
prohibited.  Topical, inhaled or intranasal use of glucocorticoids will be allowed.   
Note: Any prohibited medications that decrease CAB or RPV concentrations should be 
discontinued for a minimum of four weeks or a minimum of three half-lives (whichever 
is longer) prior to the first dose and any other prohibited medications should be 
discontinued for a minimum of two weeks or a minimum of three half-lives (whichever is 
longer) prior to the first dose. 
For additional information on concurrent therapies and interactions suspected to be 
relevant to other antiretroviral therapy used during the study (e.g. BIK), please consult 
the current BIC Investigator brochure and local prescribing information. 
Concurrent with CAB and/or RPV 
For participants receiving either formulation of CAB and/or RPV, the following 
medications could significantly decrease the levels of CAB and/or RPV due to enzyme 
induction and therefore must not be administered concurrently:  
• Carbamazepine 
• Oxcarbazepine 
• Phenobarbital  
• Phenytoin 
• Rifabutin 
• Rifampicin / Rifampin 
• Rifapentine 
• St. John’s wort (Hypericum perforatum) 
Concurrent with RPV 
In addition, participants must discontinue the following (or change to an allowable 
alternative) while receiving treatment with RPV: 
• Oral RPV:  proton pump inhibitors, such as esomeprazole, lansoprazole, 
omeprazole, pantoprazole, rabeprazole; 
• Both Oral and RPV LA:  systemic dexamethasone (more than a single dose). 
If the participant cannot discontinue use or change to an allowable alternative while 
receiving treatment with RPV, the participant should not be randomized into the study. 

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Please refer to the current RPV Investigator brochure and local prescribing information 
for other drugs that are prohibited, should be used with caution, require dose adjustment, 
or increased clinical monitoring if taken with oral RPV. 
Concurrent with either CAB LA or RPV LA 
In addition, for participants receiving CAB LA and RPV LA, use of anticoagulation 
agents for greater than 14 days is prohibited, with the exception of the use of 
anticoagulation for DVT prophylaxis (e.g., postoperative DVT prophylaxis) or the use of 
low dose aspirin (daily doses 325mg).  Systemic anticoagulation (including prophylaxis 
doses) on the day of an IM injection should be avoided. 
Concurrent with BIK 
The following medications or their equivalents may cause decreased concentrations of 
BIC.  Therefore, the following medications must not be administered concurrently with 
BIC: 
• Carbamazepine 
• Oxcarbazepine 
• Phenobarbital 
• Phenytoin 
• Rifampicin / Rifampin 
• Rifabutin 
• Rifapentine  
• St. John’s wort (Hypericum perforatum) 
• Dofetilide is prohibited as BIC may inhibit renal tubular secretion resulting in 
increased dofetilide/pilsicainide concentrations and potential for toxicity. 
Note:  Any prohibited medication that decrease BIC concentrations should be 
discontinued for a minimum of four weeks or a minimum of three half-lives (whichever 
is longer) prior to the first dose.  Any other prohibited medication should be discontinued 
for a minimum of two weeks or a minimum of three half-lives (whichever is longer) prior 
to the first dose. 
Please refer to the current local prescribing information for other drugs that should be 
used with caution, require dose adjustment, or increased clinical monitoring if taken with 
BIK. 
6.12. 
Dose Modification 
No dose reductions, modifications, or changes in the frequency of any components of 
each regimen will be allowed during the study beyond what is allowed within the 
protocol or directly approved by the study Medical Monitor.  Protocol waivers or 

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exemptions are not allowed.  Therefore, adherence to the study design requirements is 
essential and required for study conduct. 
In exceptional circumstances, and in consultation with the Medical Monitor, Investigators 
may provide oral CAB and/or RPV as a short-term “bridging” strategy for participants 
who have begun CAB LA + RPV LA (see Section 6.8.1 for additional details).  Should a 
participant need “oral bridging”, sites must contact the Medical Monitor for guidance on 
treatment strategies prior to a missed CAB LA + RPV LA dose.  Should a participant not 
notify the site in advance, the Medical Monitor must be contacted for further treatment 
guidance. 
Please refer to Appendix 11 in Section 10.11 for study management information during 
the COVID-19 pandemic. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM), which is available on 
the online Study Web Portal.  The SPM will provide the site personnel with 
administrative and detailed technical information. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Participant Discontinuation/Withdrawal from the Study 
Participants permanently discontinuing study treatments prior to the Month 12 visit are 
considered to be withdrawn from the study treatments.  Participants who enter the 
Extension Phase but permanently discontinue participation in the Extension Phase prior 
to commercially available CAB LA + RPV LA are considered to be withdrawn from the 
study treatments but are not considered to be withdrawn from the study because they will 
enter the follow Follow-up Phase. 
A participant may withdraw consent and discontinue participation in this study at any 
time at his/her own request. The investigator may also, at his or her discretion, 
discontinue the participant from participating in this study at any time (e.g., safety, 
behavioral or administrative reasons).  Participants may have a temporary interruption to 
their study treatment for management of toxicities. If a participant withdraws from the 
study, he/she may request destruction of any samples taken, and the investigator must 
document this in the site study records. Withdrawn participants will not be replaced.   
All participants who discontinue prematurely from the study, irrespective of arm, will be 
asked for additional information to establish the reason for withdrawal. 
Participants are not obligated to state the reason for withdrawal.  However, the reasons 
for withdrawal, or failure to provide a reason, must be documented by the Investigator on 
the Completion/Withdrawal Section of the electronic case report form (eCRF). Every 
effort should be made by the Investigator to follow-up participants who withdraw from 
the study.  

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An in-clinic withdrawal visit will also be used to assess participants with ongoing AEs, 
and serious adverse events (SAEs) related & not related to study drug and also any 
laboratory abnormalities that are considered to be AEs or potentially harmful to the 
participant.  The withdrawal visit will be distinct from visits conducted during the LTFU 
Phase. 
Following completion of withdrawal assessments, all participants who received one or 
more injections of CAB LA+ RPV LA will subsequently enter the LTFU Phase initiating 
with the Month 3 LTFU visit.  

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Withdrawal decision coincides with a planned clinic visit:  
• For any participant who withdraws prematurely from the Maintenance or 
Extension Phase during a planned in-clinic study visit, withdrawal assessments 
and procedures are to be performed (according to the SoA (Section 1.3) instead of 
the assessments for the active planned visit during which the withdrawal decision 
is made.   
Withdrawal decision occurs between planned clinic visits: 
• In the event that a decision to withdraw a participant occurs between clinic visits, 
participants will be instructed to return for an unscheduled withdrawal visit 
(within 8 weeks of the last Q2M LA injection received or within 4 weeks if 
participant is randomised to BIK or during the administration of the OLI (oral 
CAB and oral RPV)  if randomized to CAB LA + RPV LA and choosing to 
perform the OLI) during which withdrawal assessments according to the SoA 
(Section 1.3) will be completed.   For participants who received one or more 
injections of CAB LA+ RPV LA withdrawal assessments must occur prior to 
initiation of the next ART regimen.  
If withdrawal coincides with the active planned Month 13 visit, HIV-1 RNA will only be 
assessed if the last HIV-RNA measurement from Month 12 was 50 copies per mL (i.e. 
retest for viral load blip). This will ensure that only the Month 12 viral load assessment or 
required retest will be counted towards the primary and secondary efficacy endpoint 
windows.  
The in-clinic visit will be recorded as an unscheduled withdrawal visit with the following 
exception. A withdrawal visit and assessments coinciding with the planned Month 13 
visit will be recorded as the Month 13 visit such that the participant can be considered a 
completer, consistent with the definition of study completer in Section 4.5. 
Participants may be prematurely discontinued from the study treatment for any of 
the following reasons: 
• Adverse event / Serious adverse event 
• Protocol deviation 
• Intolerability of injections 
• Participant lost to follow-up 
• Participant or Investigator non-compliance; 
• Termination of the study by the Sponsor 
• At the request of the participant, Investigator, GSK or ViiV Healthcare; 
• The participant requires concurrent prohibited medications during the course of 
the study. The participant may remain in the study if in the opinion of the 
Investigator and the medical monitor; such medication will not interfere with the 
conduct or interpretation of the study or compromise the safety of the participant. 

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Participants must be discontinued from study treatment for any of the following 
reasons: 
• 
Participants who are not eligible to continue into the Maintenance Phase. 
• 
Participants who are not eligible, or do not wish to continue on to the Extension 
Phase. 
• 
Virologic withdrawal criteria as specified in Section 7.1.6 are met; 
• 
Participant requires substitution of ART;  
• 
Participant requires substitution or dose reduction of CAB LA or RPV LA (oral 
bridging supply and potential for a second loading dose may be permissible 
following discussion with the Medical Monitor). 
• 
Liver toxicity where stopping criteria are met and no compelling alternate cause 
is identified (see Section 7.1.2); 
• 
Renal toxicity is met and no compelling alternate cause is identified; 
• 
QT interval (QTc) interval >550 msec from three or more tracings separated by 
at least 5 minutes and considered causally related to IP.   
• 
Grade 4 clinical AE considered causally related to study drug;  
• 
Participant has a Grade 3 or higher rash or Grade 2 rash with evidence of 
systemic involvement and no compelling alternative cause is identified 
• 
Pregnancy (intrauterine), regardless of termination status of pregnancy (for 
participants on BIK only)Participant withdrew consent 
Efficacy data for participants withdrawing from the study will be considered evaluable up 
to the point at which they are withdrawn using the same criteria for evaluability as for 
participants who complete the study. 
Safety data for all participants who receive any amount of study drug, including 
participants who withdraw from the study, will be included in evaluations of safety. 
All data from the Withdrawal visit will be recorded, as they comprise an essential 
evaluation that should be done prior to discharging any participant from the study. 
The following actions must be taken in relation to a participant who fails to attend the 
clinic for a required study visit: 
a. 
The site must attempt to contact the participant and re-schedule the missed visit 
as soon as possible.  
b. The site must counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study.  
c. 
In cases where the participant is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the participant (where 
possible, 3 telephone calls and if necessary, a certified letter to the participant’s 

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

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

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7.1.2.1. 
Liver Chemistry Stopping Criteria, Participant Management and Follow-
Up 
Participants who develop ALT ≥5xULN must be followed weekly until resolution or 
stabilization (ALT <5xULN on 2 consecutive evaluations). 
When any of the liver chemistry stopping criteria is met, do the following: 
• Immediately hold IP.  If on LA therapy, do not administer another injection until 
approval is received from the ViiV Safety and Labelling Committee. 
• Report the event to the Medical Monitor within 24 hours of learning its 
occurrence. 
• Complete the liver event eCRF and SAE eCRF, where applicable. 
• Complete the liver imaging and/or liver biopsy eCRFs if these tests are 
performed. 
• Perform liver event follow up assessments (described below), and monitor the 
participant until liver chemistries resolve, stabilize, or return to Baseline values as 
described below. 
• Make every reasonable attempt to have participants return to clinic within 24 
hours for repeat liver chemistries, liver event follow-up assessments (see below), 
and close monitoring. 
• A specialist or hepatology consultation is recommended. 
• Monitor participants twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilize or return to within Baseline values. 
Make every attempt to carry out the liver event follow-up assessments described below: 
• Viral hepatitis serology including: 
o Hepatitis A immunoglobulin M (IgM) antibody; 
o Hepatitis B surface antigen (HBsAg) and Hepatitis B Core Antibody 
(IgM); 
o Hepatitis C RNA; 
o Hepatitis E IgM antibody; 
o Cytomegalovirus IgM antibody; 
o Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); 
• Syphilis screening; 
• Drugs of abuse screen including alcohol; 
• Serum acetaminophen test (N-acetyl-para-aminophenol [APAP] adduct test).  The 
site must contact GSK when this test is required.  Please refer to the central 
laboratory manual. 

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• Blood sample for pharmacokinetic (PK) analysis, obtained during follow up 
assessments.  Record the date/time of the PK blood sample draw and the date/time 
of the last dose of investigational product prior to blood sample draw on the 
eCRF.  If the date or time of the last dose is unclear, provide the participant’s best 
approximation.  If the date/time of the last dose cannot be approximated OR a PK 
sample cannot be collected in the time period indicated above, do not obtain a PK 
sample.  Instructions for sample handling and shipping are in the SPM. 
• Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH); 
• Fractionated bilirubin, if total bilirubin is greater than 1.5xULN; 
• Obtain complete blood count with differential to assess eosinophilia; 
• Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver kidney 
microsomal antibodies, and quantitative total immunoglobulin G (IgG or gamma 
globulins); 
• Liver imaging (ultrasound, magnetic resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver disease; complete Liver Imaging and/or Liver 
Biopsy CRF forms. 
• Record the appearance or worsening of clinical symptoms of hepatitis, or 
hypersensitivity, fatigue, decreased appetite, nausea, vomiting, abdominal pain, 
jaundice, fever, or rash as relevant on the AE report form; 
• Record use of concomitant medications, acetaminophen, herbal remedies, other 
over the counter medications, or putative hepatotoxins, on the concomitant 
medications report form.  Record alcohol use on the liver event alcohol intake 
case report form. 
7.1.3. 
General Guidance on Restart 
• The definition of restart is not always clear cut in medical practice. Restarts 
should be limited to cases in which there is clear evidence that the underlying 
cause of the liver event is not related to study drug.  
• For long acting agents, a restart may actually be continuation of therapy rather 
than a true re-start due to the timeframe between dose administration relative to 
decision making on allowing a restart. 
• If protocol defined stopping criteria for liver chemistry elevations are met 
(Section 7.1.2), study drug must be stopped. Participants who meet liver 
chemistry stopping criteria should not be retreated with investigational product 
unless an exemption has been approved by the VSLC.  The guideline for Restart 
approved by the VSLC, which is maintained as a separate document must be 
followed. 
• If the restart is approved by the VSLC in writing, the participant must be provided 
with a clear description of the possible benefits and risks of drug administration, 
including the possibility of recurrent, more severe liver injury or death.  

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• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• The participant must also provide signed informed consent specifically for the IP 
restart. Documentation of informed consent must be recorded in the study chart. 
• Study drug must be administered at the dose specified by the VSLC. 
• Participants approved by the VSLC for restart of IP must return to the clinic once 
a week for liver chemistry tests for a minimum of one month and thereafter for as 
long as clinically indicated and then laboratory monitoring may resume as per 
protocol. Longer durations of close monitoring may be required for long acting 
IP. 
7.1.3.1. 
Drug Restart 
“Drug restart” can be approved by the VSLC for defined non-drug-induced liver injury 
if no evidence of: 
• 
immunoallergic injury /HLA association with injury 
• 
alcoholic hepatitis 
Study drug must be held while labs and evaluation are completed to assess diagnosis. 
7.1.3.1.1. Drug Restart Following Transient Resolving Liver Events Not Related 
to IP 
Approval by the VSLC for drug restart or additional IM administration can be considered 
where: 
• Abnormalities in liver chemistries have a clear underlying cause (e.g., biliary 
obstruction, hypotension, acute viral hepatitis, and liver chemistries have 
significantly improved. 
• If definitive non-study drug related diagnosis, restart will be considered once ALT 
< 3x ULN (for participants with baseline ALT < 1.5x ULN) or < 3x baseline ALT 
value (for participants with baseline ALT > 1.5x ULN).    
• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• If restart / redosing of drug is approved by the VSLC in writing, the participant 
must be provided with a clear description of the possible benefits and risks of 
drug administration, including the possibility of recurrent, more severe liver 
injury or death. 
• The participant must also provide signed informed consent specifically for the 
restart.  Documentation of informed consent must be recorded in the study chart. 
• Study drug must be administered at the dose specified by the VSLC. 

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Participants approved by the VSLC for restarting or re-dosing IP must return to the clinic 
once a week for liver chemistry tests for a minimum of one month and thereafter for as 
long as clinically indicated and then laboratory monitoring may resume as per protocol.  
If protocol defined stopping criteria for liver chemistry elevations are met, study drug 
must be stopped. 
7.1.4. 
QTc Stopping Criteria 
A participant who has a QTc interval >550 msec considered causally related to IP will be 
withdrawn from the study.  The QTc should be based on averaged QTc values of 
triplicate electrocardiograms obtained over a brief (e.g., 5 to 10 minute) recording 
period.   
If an alternative cause of the QT prolongation is determined (e.g., participant receiving 
drug known to cause prolonged QT or TdP), the IP may be restarted (or continued) after 
consultation and agreement with the Medical Monitor. RPV and RPV LA should not be 
administered to patients who are receiving a drug known to be associated with TdP. 
When performing ECGs, the same QT correction formula must be used for each 
individual participant to determine eligibility for, and discontinuation from, the 
study.  This formula may not be changed or substituted once the participant has been 
enrolled. 
For example, if a participant is eligible for the protocol based on QTcB, then QTcB must 
be used for discontinuation of this individual participant as well. 
Once the QT correction formula has been chosen for a participant’s eligibility, the same 
formula must continue to be used for that participant for all QTc data being collected for 
data analysis.  Safety ECGs and other non-protocol specified ECGs are an exception.   
7.1.5. 
Virologic Failure 
Only plasma HIV-1 RNA values determined by the central laboratory will be used to 
assess virologic failure. 
7.1.6. 
Definition of Protocol-Defined Confirmed Virologic Failure 
For the purposes of clinical management in this study, CVF is defined as:  
Rebound as indicated by two consecutive plasma HIV-1 RNA levels 200 c/mL (Day 1 
values are not applicable) after prior suppression to <200 c/mL.  
7.1.7. 
Managing Virologic Failure 
Following study entry, no changes, or intensification of ART will be permitted prior to 
protocol-defined virologic failure, outside of the planned protocol regimens.  Only 
plasma HIV-1 RNA values determined by the central laboratory will be used to assess 
virologic failure.  Baseline plasma HIV-1 RNA is the assessment completed on study 
Day 1.  The definition of confirmed virologic failure does not apply to participants in the 
LTFU Phase.  These participants will be followed for the emergence of viral resistance.  

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Inadequate adherence is a common cause for virologic failure and should be explored as a 
first step in the management of study participants (e.g., at the first indication of 
inadequate virologic response or rebound). Upon notification that a participant’s HIV-1 
RNA plasma level qualifies him/her as a suspected virologic failure, the Investigator 
should query the participant regarding intercurrent illness, recent immunization, or 
interruption of oral therapy. 
7.1.7.1. 
HIV-1 RNA Blips 
HIV-1 RNA “blips” are not usually associated with subsequent virologic failure [DHHS, 
2019].  Although the implications of persistent HIV-1 RNA levels between the lower 
level of detection and <200 c/mL are unclear, the risk of emerging resistance is believed 
to be relatively low.   
Participants with transient increases in HIV-1 RNA (‘blips’ HIV-1 RNA <200 c/mL) are 
not considered suspected virologic failures and do not require a change in therapy.   
Participants who have a HIV-1 RNA ≥50 c/mL and <200 c/mL at the key analysis 
timepoints (Month 6 and 12 [OLI and BIK] and Months 5 and 11 [D2]) must return to the 
clinic as soon as possible (but no later than 4 weeks after the date of the Months 6 or 12 
[OLI and BIK] and Months 5 or 11 [D2I] visits, respectively) for a repeat HIV-1 RNA 
test such that the result falls within the same analysis window. 
In order to better characterize HIV-1 RNA ‘blips,’ if there is a known reason / 
explanation for the blip (e.g., immunization, allergies, etc.), the study team should be 
notified of the reason and case context. 
If the Investigator has concerns regarding persistent low-level viremia (HIV-1 RNA 
≥50 c/mL and <200 c/mL), the Medical Monitor should be contacted to discuss 
participant management.  Following discussion with the Medical Monitor, additional 
viral load testing may be performed between visits to determine the appropriate 
participant disposition for the next scheduled visit. 
7.1.7.2. 
Suspected Virologic Failure 
Upon notification that a participant’s HIV-1 RNA plasma level meets the definition of 
virologic failure, the Investigator should confirm the definition is met by initiating a 
repeat of the HIV-1 RNA assessment. 
The following guidelines should be followed for scheduling confirmatory HIV-1 RNA 
testing in an effort to avoid false-positive results: 
• Confirmatory testing should be scheduled within 2 to 4 weeks following 
resolution of any intercurrent illness, during which time the participant should 
receive full dose of all IP. 
• Confirmatory testing should be scheduled at least 4 weeks following any 
immunization, during which time the participant should receive full dose of all IP. 

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• If therapy is interrupted* due to toxicity management, non-compliance, or other 
reasons, confirmatory testing should be scheduled 2 to 4 weeks following 
resumption of full dose of all IP. 
• The participant should have received full dose of IP for at least 2 weeks at the 
time confirmatory plasma HIV-1 RNA testing is done. 
*Note:  treatment interruption guidelines above may not apply for participants on CAB 
LA + RPV LA treatment.  The study team should be contacted to discuss any treatment 
interruptions for participants meeting the definition of virologic failure. 
In addition, the Investigator should query the participant regarding intercurrent illness, 
recent immunization, or interruption of therapy. 
Sites should contact the Medical Monitor to discuss individual participants, 
whenever necessary. 
7.1.7.3. 
Confirmed Virologic Failure 
Participants with confirmed virologic failure (CVF) must be discontinued from study 
treatment.  However, participants who have received at least one dose of CAB LA or 
RPV LA prior to confirming virologic failure will remain in the study on oral HAART in 
the LTFU Phase. 
A plasma sample from the suspected virologic failure visit as well as Day 1 (if baseline 
HIV-1 RNA level 200 c/mL) will be sent for genotypic and phenotypic resistance 
testing and the result made known to the Investigator when available.  A plasma sample 
from the confirmation visit will be obtained for storage.  This sample may be used for 
possible future analyses, e.g., for genotypic and phenotypic analyses of participants who 
experience virologic failure. 
For all participants who meet CVF, baseline and suspected virologic failure plasma 
samples with HIV-1 RNA level 200 c/mL will be analyzed in an attempt to obtain 
genotype/phenotype data on as many samples as possible.  Plasma samples for storage 
will also be obtained at unscheduled visits including confirmation of CVF.  Participants 
may continue to receive study drug at the discretion of the investigator until results of 
resistance testing are available at which time the participant must be discontinued from 
the study. Even if genotype/phenotype data cannot be generated, participant must also be 
discontinued from the study treatment. 
If a participant is prematurely discontinued from the study treatment, the investigator 
must make every effort to perform the Withdrawal Visit evaluations outlined in the Time 
and Events These data will be recorded as they comprise essential evaluations needed to 
be done before discharging any participant from the study. 
7.2. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  

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The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns.  Therefore, adherence to the study design requirements, including those 
specified in the SoA, are essential and required for study conduct. 
This Section lists the procedures and parameters of each planned study assessment.  The 
exact timing of each assessment is listed in the SoA, Section 1.3 
The following points must be noted:  
• If assessments are scheduled for the same nominal time, THEN the assessments 
should occur in the following order: 
1. 12-lead ECG 
2. vital signs 
3. blood draws 
Note: The timing of the assessments should allow the blood draw to occur at the exact 
nominal time. 
• The timing and number of planned study assessments may be altered during the 
course of the study based on newly available data to ensure appropriate 
monitoring. 
• The change in timing or addition of time points for any planned study assessments 
must be documented in a Note to File which is approved by the relevant study 
team member and then archived in the study sponsor and site study files, but this 
will not constitute a protocol amendment.  
• The IRB/IEC will be informed of any safety issues that require alteration of the 
safety monitoring scheme or amendment of the Informed Consent Form. 

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

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• Vital signs will include systolic and diastolic blood pressure and heart rate 
collected after resting for about 5 minutes.  Temperature will also be collected. 
• Past medical history, family history, social history, medication history.  Targeted 
history on cardiovascular risk (smoking history, family and personal history). 
• HIV-associated conditions will be recorded. 
• Electrocardiogram:  A 12-lead ECG will be performed in a semi-supine position 
after 5 minutes of rest.  On Day 1 (Baseline) of the Maintenance Phase, ECGs 
should be performed in triplicate prior to first dose.  An ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals is preferred (and RR if calculated manually), and these calculated 
numbers can be used for reporting purposes.  Otherwise, an appropriately 
qualified ECG reader must interpret the results.  The same interpreter should 
assess all ECGs for each participant for the site.  Regardless, each ECG should be 
reviewed by a qualified ECG reader.  The qualified ECG reader will make the 
non-calculated ECG interpretations.  The same QT correction formula must be 
used for each individual participant to determine eligibility for and 
discontinuation from the study.  This formula may not be changed or substituted 
once the participant has been enrolled. 
• Regular monitoring of hematology, blood chemistry, urinalysis and fasting 
glucose and lipids (parameters to be tested listed below).   
• Periodic assessment of glucose, insulin, and bone, cardiovascular, and renal 
markers; 
• Pregnancy testing.  A negative urine pregnancy test is required prior to initiation 
of IP, any dose of CAB LA or RPV LA or as required by the Medical Monitor 
following a treatment interruption(s).  If serum testing is required locally, the 
results should be available prior to the visit where urine testing is indicated per the 
SoA (Section 1.3). 
• Evaluation and documentation of all concomitant medications and blood products.  
• Injection Site Reactions (ISRs) will be assessed clinically during the Maintenance 
and Extension Phases for the following: 
Pain, tenderness, pruritis, warmth, bruising, discoloration, infections, rash, 
erythema, swelling, induration, and nodules (granulomas or cysts).   
• A clinical assessment (using Division of Acquired Immunodeficiency Syndrome 
[DAIDS] grading scale) should be performed both before and after an injection to 
identify resolving and new ISRs.  All injection site reactions are considered 
adverse events.  The clinical assessment and interpretation of any ISR, will be 
documented in the ISR AE eCRF.   
• Columbia Suicide Severity Rating Scale (eC-SSRS) will be assessed as per the 
SoA (see Section 1.3 and Suicidal Risk Monitoring Section 8.2.6). 
Any appropriately qualified site personnel (e.g., Investigator, sub-Investigator, or study 
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8.2.2. 
Laboratory Assessments 
All protocol required laboratory assessments, as defined in the SoA (see Section 1.3), 
must be performed by the central laboratory.  Laboratory assessments must be conducted 
in accordance with the Central Laboratory Manual and Protocol SoA.  Laboratory 
requisition forms must be completed, and samples must be clearly labeled with the 
participant number, protocol number, site/center number, and visit date.  Details for the 
preparation and shipment of samples will be provided by the central laboratory.  
Reference ranges for all safety parameters will be provided to the site by the central 
laboratory. 
• The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
Section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
• All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or medical monitor.  
• If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
• All protocol-required laboratory assessments must be conducted in accordance 
with the laboratory manual and the protocol Time and Events table.  
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification) the results must be recorded in the eCRF.  Local laboratory services may 
be used to verify pending laboratory parameters only after consultation and agreement 
with the study team. 
Refer to the lab manual for appropriate processing and handling of samples to avoid 
duplicate and/or additional blood draws. 
Labs will be automatically graded by the central lab according to the DAIDS toxicity 
scales (See Section 10.4 “Division of AIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events”). 
For fasting laboratory assessments, an overnight fast is preferred; however, a minimum of 
a 6 hour fast is acceptable. 
Table 4 includes lab parameters to be assessed as per the SoA (see Section 1.3).  In 
addition to the protocol-specified laboratory assessments the study Medical Monitor, in 

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

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g) HBV DNA will only be performed for participants with a positive anti-HBc and negative HBsAg and negative anti-
HBs (past and/or current evidence). 
h) Urine pregnancy test/ serum pregnancy test will be performed according to the SoA (Section 1.3).   
i) 
The intention is to utilize these biomarker data for research purposes; the sponsor will not be reporting real-time 
results of these assessments to the investigator, except for Cystatin C (Day 1 only) and 25 hydroxy-Vitamin D. 
 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.3. 
Physical Examinations 
Physical exams should be conducted as part of normal routine clinical care.  
Abnormalities noted during any exam must be recorded in the eCRF (e.g., in the current 
medical conditions or AE logs). 
• A complete physical examination will include, at a minimum, assessment of 
the Cardiovascular, Respiratory, Gastrointestinal, and Neurological systems.  
Height and weight will also be measured and recorded as per the SoA in 
Section 1.3 above.  
• A brief physical examination will include, at a minimum, assessments of the 
skin, lungs, cardiovascular system, and abdomen (liver and spleen). 
• The site of IM injection administration should be assessed at every visit for 
signs of any possible reaction.  See Section 8.3.11.6 for additional information. 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
8.2.4. 
Vital Signs 
Vital signs will be measured in semi-supine position after 5 minutes rest and will include 
temperature, systolic and diastolic blood pressure and pulse rate.  These will be recorded 
as per the SoA, in Section 1.3. 
8.2.5. 
Electrocardiograms 
A 12-lead ECG will be performed in a semi-supine position.  On Day 1, (Baseline), 
ECGs should be performed in triplicate prior to first dose.  At Day 1, Month 1 (OLI) and 
Month 12 (OLI)/Month 11 (D2I) of the Maintenance Phase, a 2-hour post dose ECG will 
be performed for participants receiving CAB LA + RPV LA with an allowable window 
of  30 minutes.  An ECG machine that automatically calculates the heart rate and 
measures PR, QRS, QT, and QTc intervals is preferred, and these calculated numbers can 
be used for reporting purposes.  Otherwise, an appropriately qualified ECG reader must 
interpret the results.  The same interpreter should assess all ECGs for each participant.  
Regardless, each ECG should be reviewed by a qualified ECG reader.  The qualified 
ECG reader will make the non-calculated ECG interpretations.  Refer to the SoA for 
collection timepoints (Section 1.3).  Refer to Section 7.1.4  for [QTc] withdrawal criteria 
and additional [QTc] readings that may be necessary. 

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8.2.6. 
Suicidal Ideation and Behaviour Risk Monitoring 
Participants with HIV infection may occasionally present with symptoms of depression 
and/or suicidal ideation or behavior.  In addition, there have been some reports of 
depression, suicidal ideation and behavior (particularly in participants with a pre-existing 
history of depression or psychiatric illness) in some patients being treated with INIs.  
Additionally, depression and anxiety has been reported in some participants being treated 
with RPV.  Therefore, it is appropriate to monitor and closely observe participants 
prospectively before and during treatment for suicidal ideation and/or behavior, or any 
other unusual changes in behavior.  It is recommended that the Investigator consider 
mental health consultation or referral for participants who experience signs of suicidal 
ideation or behavior. 
Participants presenting with new onset/treatment emergent depression should be advised 
to contact the investigator immediately if symptoms of severe acute depression (including 
suicidal ideation/attempts) develop, because medical intervention and discontinuation of 
the study medication may be required. 
Assessment of treatment-emergent suicidality will be monitored during this study using 
the electronic version of the Columbia Suicide-Severity Rating Scale (eC-SSRS).  The 
definitions of behavioural suicidal events used in this scale are based on those used in the 
Columbia Suicide History Form [Posner, 2007].  Questions are asked on suicidal 
behavior, suicidal ideation, and intensity of ideation.  Screening visit questions will be in 
relation to lifetime experiences and current experiences (within the past 2 months) and all 
subsequent questioning in relation to the last assessment.  The eC-SSRS is to be 
administered as a patient completed questionnaire specified in the SoA (Section 1.3).  
The eC-SSRS will be conducted electronically by telephone or by computer/tablet 
connected to the internet. 
Additionally, the investigator will collect information using the Possible Suicidality-
Related AE (PSRAE) eCRF form in addition to the Adverse Event (non-serious or 
Serious Adverse Events) eCRF form on any participant that experiences a possible 
suicidality-related adverse event while participating in this study.  This may include, but 
is not limited to, an event that involves suicidal ideation, a preparatory act toward 
imminent suicidal behavior, a suicide attempt, or a completed suicide.  The investigator 
will exercise his or her medical and scientific judgment in deciding whether an event is 
possibly suicide related.  PSRAE forms should be completed and reported to ViiV/GSK 
within one week of the investigator diagnosing a possible suicidality-related adverse 
event.  All sites should have a plan in place for managing possible risks for suicide 
related events. 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Section 10.2. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative). 

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

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8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special 
interest will be followed until the event is resolved, stabilized, otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.2). Further information on follow-
up procedures is given in Section 10.2. 
8.3.4. 
Prompt Reporting of Serious Adverse Events and Other Events 
SAEs, pregnancies, and liver function abnormalities meeting pre-defined criteria will be 
reported promptly by the investigator to the medical monitor once the investigator 
determines that the event meets the protocol definition for that event.  Any seizure or 
suspected seizure should be reported in an expedited manner, as noted in Table 5. 
Criteria for liver chemistry stopping and follow-up criteria are in Section 7.1.1. 

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Table 5 
Reporting of Serious Adverse Events and Other Events 
 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
All SAEs 
24 hours 
“SAE” data 
collection tool 
24 hours 
Updated “SAE” data 
collection tool 
 
Cardiovascular or 
death event 
Initial and 
follow-up 
reports to be 
completed when 
the 
cardiovascular 
event or death 
is reporteda  
“CV events” and/or 
“death” data 
collection tool(s) if 
applicable 
 
Initial and follow-up 
reports to be 
completed when 
the cardiovascular 
event or death is 
reporteda 
Updated “CV events” 
and/or “death” data 
collection tool(s) if 
applicable 
 
Pregnancy 
24 hours 
“Pregnancy 
Notification Form” 
Within 24 hours of 
investigator 
awareness of 
pregnancy outcome 
“Pregnancy Follow-
up Form” and SAE if 
required 
Seizure or suspected 
seizure 
24 hours 
eCRF 
24 hours 
eCRF 
Suspected ABC HSR in 
participants receiving 
Oral SOC during the 
Long-Term Follow-Up 
Phaseb 
1 week 
ABC HSR eCRF 
1 week 
Updated ABC HSR 
eCRF 
ALT3×ULN and 
bilirubin2×ULN (>35% 
direct) (or ALT3×ULN) 
24 hoursc 
“SAE” data 
collection tool. 
“Liver Event eCRF” 
and “Liver Imaging” 
and/or “Liver 
Biopsy” eCRFs, if 
applicabled 
24 hours 
Updated “SAE” data 
collection tool/“Liver 
Event” documentsd 
ALT≥5×ULN that 
persists ≥2 weeks  
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
ALT ≥8×ULN  
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
ALT ≥3×ULN (if 
baseline ALT is <ULN) 
or ALT ≥3 fold increase 
from baseline value 
with appearance or 
worsening of symptoms 
of hepatitis or 
hypersensitivity 
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
a. 
Additional details and time frames for reporting supplementary information for cardiovascular and death events 
are provided in Section 8.3.9. 
b. 
ABC HSR eCRF only required if event meets one of the ICH E2A definitions of seriousness. 
c. 
GSK must be contacted at onset of liver chemistry elevations to discuss participant safety. 
d. 
Liver event documents (i.e., “Liver Event eCRF” and updates, “Liver Imaging eCRF” and/or “Liver Biopsy eCRF”, 
as applicable) should be completed as soon as possible. 

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8.3.5. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met.  
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, 
if appropriate according to local requirements. 
8.3.6. 
Pregnancy 
8.3.6.1. 
Pregnancy testing 
Women of childbearing potential must have a negative pregnancy test at Screening, and 
at Baseline (Day 1).  Pregnancy testing will also be conducted as per the SoA (Section 
1.3) and at any time during the trial when pregnancy is suspected. 
Additionally, the Medical Monitor may request that a urine pregnancy test be performed 
in the event of a treatment interruption greater than 7 days. 
If pregnancy is confirmed, a discussion with the pregnant study participant assessing the 
benefit/risk assessment of continuing in the study will be undertaken. If, after this 
discussion, the participant would like to continue in the study, this will be allowed, 
provided the pregnant participant signs the pregnancy specific ICF addendum. See 
Appendix 6 for details. The above is applicable to participants randomised to CAB+RPV 
and not to participants on BIK. 
Pregnant participants who remain in the study do not need pregnancy testing during the 
study, for the duration of their pregnancy. 
8.3.6.2. 
Rationale for Continued Use in Pregnancy 
Additional data regarding the use of CAB + RPV LA during pregnancy and management 
of pregnant participants remaining in the study are found in Appendix 6. 
The use of CAB + RPV LA during pregnancy may offer unique benefits. It is well 
documented that treatment adherence challenges to oral therapy exists both in the peri-
partum and post-partum periods with LA dosing offering a unique opportunity to 
overcome such adherence challenges. LA therapy may also help with nausea (50% mild 

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to moderate) or hyperemesis (2%) that is frequently see, especially during the first 
trimester of gestation.  
Participants on LA dosing who become pregnant will have exposures throughout 
pregnancy due to the long half-life and PK tail of CAB/RPV. Prior to this protocol 
amendment, pregnant participants would have been withdrawn from the study, and 
initiated on an alternative oral ART regimen. Alternative regimens consist of either 2 or 3 
antiretrovirals to protect the life of the mother and for the prevention of MTCT. This 
regimen, combined with the long half-life and PK tail of CAB/RPV would potentially 
expose the fetus to additional ARVs during gestation (in some cases upwards of 5 
antiretrovirals). 
Given the risk/benefit ratio for CAB + RPV LA dosing in WOCBP coupled with 
concerns of increasing fetal exposure to several additional antiretrovirals upon participant 
withdrawal, this amendment to the protocol will allow pregnant participants to remain in 
the study after a pregnancy specific ICF addendum is signed by the participant 
8.3.6.3. 
Time Period for Collecting Pregnancy Information 
Pregnancy information will be collected from Day 1 until the last follow-up assessment.  
This includes the entirety of the LTFU Phase. 
Pregnant study participants who consent to remain in the study during pregnant will 
continue to have all clinical assessments (with the exception of pregnancy tests) 
performed as per the Schedule of Activities  (Section 1.3), including the collection of 
additional PK samples for CAB and RPV. See Appendix 6 for details. 
 
Pregnant participants who have received at least one dose of CAB LA or RPV LA and do 
not continue in the study during pregnancy will enter the Long-Term Follow-Up Phase of 
the study and will be monitored for 52 weeks after the last dose of CAB + RPV LA. 
Moreover, an alternative oral HAART will be initiated, at the discretion of the PI and in 
discussion with the Medical Monitor.   If a participant becomes pregnant within 52 weeks 
of the last dose of study drug, the participant should notify the study site. 
8.3.6.4. 
Action to be Taken if Pregnancy Occurs 
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form.  The investigator should inform GSK within 24 hours of learning of 
the pregnancy and should follow the procedures outlined in Appendix 6. 
Pregnant participants who elect to continue in the study and receive CAB + RPV LA 
must sign a pregnant specific ICF addendum. Cabotegravir and rilpivirine are detected in 
systemic circulation for up to 12 months or longer after discontinuing injections of CAB 
+ RPV LA; therefore, consideration should be given to the potential for fetal exposure 
during pregnancy and should be discussed between the study participant and the study PI.  

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Participants who  become pregnant during the study and elect to continue in the study and 
receive CAB + RPV LA will have additional PK samples collected to monitor CAB LA 
and RPV LA exposure throughout the pregnancy (see Appendix 6) and at the time of 
delivery.    
 
Any SAE occurring in association with a pregnancy brought to the investigator’s 
attention after the participant has completed the study and considered by the investigator 
as possibly related to the study treatment, must be promptly reported to ViiV/GSK. 
GSK’s central safety department will also forward this information to the Antiretroviral 
Pregnancy Registry.  The international registry is jointly sponsored by manufacturers or 
licensees of ARV products.  Additional information and a list of participating 
manufacturers/licensees are available from http://apregistry.com/index.htm. 
8.3.7. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
Disease related events (DREs) or outcomes listed in the CDC Classification System for 
HIV-1 Infections (Section 10.3) can be serious/life threatening and will be recorded on 
the HIV-Associated Conditions eCRF page if they occur. These individual events or 
outcomes, as well as any sign, symptom, diagnosis, illness, and/or clinical laboratory 
abnormality that can be linked to any of these events or outcomes are not reported to 
GSK as AEs and SAEs even though such event or outcome may meet the definition of an 
AE or SAE. If any of the conditions below is met, then record the event on either the AE 
or SAE page (according to severity) in addition to the HIV Associated Conditions eCRF 
page.  If it is categorized as an SAE, report promptly (i.e., expedited reporting), see 
Section 8.3.4, to GSK   
• The investigator determines that the event or outcome qualifies as an SAE under 
part ‘other situations’ of the SAE definition (see Section 10.2.2), or 
• The event is, in the investigator’s opinion, of greater intensity, frequency, or 
duration than expected for the individual participant, or 
• The investigator considers that there is a reasonable possibility that the event was 
related to treatment with the investigational product, or 
• Death occurring for any reason during a study, including death due to a disease-
related event, will always be reported promptly. 
• Lymphomas and invasive cervical carcinomas are excluded from this exemption; 
they must be reported as SAEs even if they are considered to be HIV-related. 
. 

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8.3.8. 
Medical Device Deficiencies  
The vial adaptor, syringe, and needles used in the study are classed as medical devices by 
the FDA. To fulfil regulatory reporting obligations worldwide, the investigator is 
responsible for the detecting and documentation of events meeting the definitions of 
device deficiency that occur during the study with such devices.  
The definition of a medical device deficiency can be found in Section 10.9.  
Instructions for medical device use are provided in the Study Reference Manual. 
All device deficiencies, (including malfunction, use error and inadequate labelling) shall 
be documented, and reported by the investigator to the manufacturer of the device (if 
known) 
NOTE: The medical devices supplied for the trial will not be supplied or manufactured 
by GSK/ViiV, reports of medical device deficiencies should be reported to the device 
manufacturer (if known) through the manufacturers’ complaints process.  
8.3.8.1. 
Time Period for Detecting Medical Device Deficiencies 
• Medical device deficiencies that result in an incident will be detected, 
documented, and reported during all periods of the study in which the medical 
device is used.  
• If the investigator learns of any device deficiency at any time after a participant 
has been discharged from the study, and such device deficiency is considered 
reasonably related to a medical device provided for the study, the investigator will 
notify the manufacturer of the device (if known) within 24 hours. 
 
8.3.8.2. 
Follow-up of Medical Device Deficiencies 
• Follow-up applies to all participants including those participants who discontinue 
study intervention or the study and associated persons. 
• The investigator is responsible for ensuring that follow-up includes any 
supplemental investigations as indicated to elucidate the nature and/or causality of 
the deficiency. 
8.3.8.3. 
Prompt Reporting of Medical Device Deficiencies to Manufacturer 
• Device deficiencies will be reported to the manufacturer of the device (if known) 
within 24 hours after the investigator determines that the event meets the protocol 
definition of a device deficiency. 
8.3.8.4. 
Regulatory Reporting Requirements for Medical Device Deficiencies 
The investigator will promptly report all deficiencies occurring with any medical device 
used for CAB+RPV in the study, to the manufacturer of the device (if known). In order 
for the manufacturer to fulfil the legal responsibility to notify appropriate regulatory 

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authorities and other entities about certain safety information relating to medical devices 
being used in clinical studies. 
8.3.9. 
Cardiovascular and Death Events 
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs:   
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularisation 
This information should be recorded in the specific cardiovascular eCRF within one week 
of when the AE/SAE(s) are first reported.  The CV CRFs are presented as queries in 
response to reporting of certain CV MedDRA terms. 
For any cardiovascular events detailed above, whether or not they are considered SAEs, 
and all deaths, specific Cardiovascular (CV) and Death Sections of the eCRF will be 
required to be completed.  These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death.  
The CV CRFs are presented as queries in response to reporting of certain CV MedDRA 
terms.  The CV information should be recorded in the specific cardiovascular section of 
the eCRF within one week of receipt of a CV Event data query prompting its completion. 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
In addition, all deaths will require a specific death data collection tool to be completed.  
The death data collection tool includes questions regarding cardiovascular (including 
sudden cardiac death) and noncardiovascular death. 
8.3.10. 
Toxicity Management 
Adverse events that occur during the trial should be evaluated by the Investigator and 
graded according to the Division of AIDS (DAIDS) toxicity scales (See Section 10.4. 
“Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events”).  Additional information regarding detecting, documenting and reporting AEs 
and SAEs are available in Section 8.3 and Section 10.2. 

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8.3.10.1. 
Treatment Interruption Due to an Adverse Event 
IP may be interrupted at the discretion of the investigator and according to the severity of 
the AE. If one or more ART medication is held due to toxicity or AEs, all ART 
medications should be held to reduce the risk of development of resistance taking into 
account the length of the planned interruptions and the PK half-life of each ART of the 
regimen, in order to minimize the risk of development of resistance. 
No toxicity-related dose reductions of IP will be allowed.  IP should be restarted as soon 
as medically appropriate; in general, for oral dosing, this should be no longer than 14 
days after discontinuation (unless Grade 3 or 4 toxicities persist).  Any interruption in 
therapy during the Maintenance Phase, oral dosing, of greater than 7 consecutive days 
must be discussed with and agreed by the Medical Monitor prior to resumption of 
therapy.  The Medical Monitor must be contacted upon becoming aware of resumption in 
therapy, if therapy was resumed without prior approval (Section 6.9).  IM dosing is 
expected to occur during the week in which the participant’s projected visit falls (as 
according to the first injection visit).  An additional (+ or -) 7-day window, from the 
projected visit date, is allowable for IM dosing but not preferred.  Any interruption 
outside of this guidance MUST be discussed with the Medical Monitor prior to 
reinitiating IM IP (see Section 6.9.1). 
Guidance is provided below on general participant management and IP interruptions 
based on the severity of the AE.  Information regarding permitted substitutions \ is 
provided in Section 6.8.  All changes in the IP regimen must be accurately recorded in the 
participant’s eCRF. 
Note: For participants receiving an ABC-containing product as part of the background 
regimen during the Long-Term Follow-Up (LTFU) Phase, in the event of a 
discontinuation of ABC for any reason, re-initiation of this drug should be undertaken 
with caution. The investigator should obtain a complete history of the events surrounding 
the discontinuation of the ABC-containing product, evaluate for the possibility of a 
clinically suspected HSR, and initiate participant management as outlined in the Local 
Country Prescribing Information, regardless of a participant’s HLA-B*5701 status. 
Screening for the presence of HLA-B*5701 is recommended prior to reinitiating 
treatment with ABC-containing products in participants of unknown HLA-B*5701 status 
who have previously tolerated ABC but is not required to confirm study eligibility. 
8.3.10.2. 
Grade 1 or Grade 2 Toxicity/Adverse Event 
Participants who develop a Grade 1 or Grade 2 AE or toxicity may continue study drug at 
the discretion of the investigator.  Participants who choose to withdraw from the study 
due to a Grade 1 or 2 AE should have study withdrawal and follow-up evaluations 
completed. 
Participants who develop ALT ≥3 times ULN while on study must consult with 
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8.3.10.3. 
Grade 3 Toxicity/Adverse Event 
Participants who develop a Grade 3 AE or toxicity should be managed as follows: 
• If the Investigator has compelling evidence that the Grade 3 AE or toxicity has 
not been caused by IP, dosing may continue after discussion with the Medical 
Monitor. 
• Participants who develop a Grade 3 AE or toxicity, which the Investigator 
considers related or possibly related to the IP, should have the IP withheld and be 
rechecked each week until the AE returns to Grade 2.  Once the AE is Grade 2, 
IP may be re-started.  
• Should the same Grade 3 AE recur within 28 days in the same participant, the IP 
should be permanently discontinued and the participant withdrawn from study.  
• Participants experiencing Grade 3 AEs requiring permanent discontinuation of IP 
should be followed weekly until resolution of the AE and to have withdrawal 
study evaluations completed.  A follow-up visit should be performed 4 weeks 
after the last dose of IP.  Any participant receiving at least one dose of CAB LA 
and /or RPV LA who discontinue IP / Withdraw will initiate treatment with 
HAART and enter the LTFU Phase for 52 weeks of follow up.  
• Participants with Grade 3 asymptomatic laboratory abnormalities should be 
investigated for all potential non-drug related causes, and, following discussion 
with the Medical Monitor, may continue IP if the Investigator has compelling 
evidence that the toxicity is not related to IP, with the exception of liver chemistry 
stopping criteria (See Section 8.3.11.1).  Isolated Grade 3 lipid abnormalities do 
not require withdrawal of IP. 
8.3.10.4. 
Grade 4 Toxicity/Adverse Event 
• Participants who develop a Grade 4 AE or toxicity must have IP permanently 
discontinued.  However, if the Investigator has compelling evidence that the AE is 
not causally related to the IP, dosing may continue after discussion with, and 
assent from, the Medical Monitor.  Participants should be rechecked each week 
until the AE returns to Grade 2. 
• Participants experiencing Grade 4 AEs requiring permanent discontinuation of IP 
should be followed weekly until resolution of the AE and encouraged to complete 
the withdrawal and follow-up study evaluations as noted above.  Any participant 
receiving at least one dose of CAB LA and /or RPV LA who discontinue IP / 
Withdraw will initiate treatment with HAART and enter the LTFU Phase for 52 
weeks of follow up.  
• Participants with Grade 4 asymptomatic laboratory abnormalities should be 
investigated for all potential non-drug related causes, and, following discussion 
with the Medical Monitor, may continue therapy if the Investigator has 
compelling evidence that the toxicity is not related to IP, with the exception of 
liver chemistry stopping criteria (See Section 8.3.11.1).  An in-clinic follow-up 
visit will be performed approximately 4 weeks after the last dose of study 
medication if AEs, SAEs, or laboratory abnormalities considered potentially 
harmful to the participant are ongoing at the last on-study visit.  Isolated Grade 4 
lipid abnormalities do not require withdrawal of IP. 

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8.3.11. 
Specific Toxicities/Adverse Event Management 
General guidelines for the management of specific toxicities that are considered to be 
associated with treatment of HIV patients.  
Participants who permanently discontinue study drug for reasons of toxicity should be 
followed weekly until resolution of the AE and encouraged to complete the withdrawal 
and Follow-up study evaluations as noted in Section 8.3.3. 
8.3.11.1. 
Liver Chemistry Stopping and Follow-up Criteria 
Liver chemistry threshold stopping criteria have been designed to assure participant 
safety and to evaluate liver event etiology during administration of study drug and the 
follow-up phase.  
8.3.11.2. 
Seizures 
A small number of seizure cases have been reported following CAB administration (less 
than 1% of all those receiving CAB in clinical studies).   
ViiV Healthcare has reviewed these cases in detail and does not believe they constitute a 
reasonable likelihood of causation associated with CAB.  This assessment is supported by 
the lack of preclinical signal, class effect or known CNS mechanism, the relatively low 
frequency of seizures relative to expected rates in both healthy and HIV positive 
participants and clinical confounders in each case.  The Sponsor considers the risk of 
developing seizures on the study as being no higher than that of the rest of the HIV-1 
infected population.   
Seizures that occur on study should be managed according to the local guidelines on 
emergency seizure management which may include treatment with benzodiazepines, 
general supportive treatment, exclusion of metabolic and toxicological abnormalities 
using laboratory tests, septic workup and excluding underlying structural abnormalities 
with neuroimaging. 
Where seizures occur, the Sponsor would like to better characterize these occurrences to 
enable systematic analyses. 
Investigators are requested to document and report seizure or possible seizure events 
promptly (within 24 hours of learning of the event) to the Sponsor for evaluation and 
onward reporting.  Data should be documented on the appropriate eCRF seizure page. 
8.3.11.3. 
Decline in Renal Function 
Participants who experience an increase in serum creatinine from Baseline of 
45 micromoles/liter (Mol/L) (or 0.5 milligrams/deciliter [mg/dL]) should return for a 
confirmatory assessment within 2 to 4 weeks.  A urinalysis and urine albumin/creatinine 
and urine total protein/albumin ratios should also be done at this confirmatory visit.  If 
the creatinine increase is confirmed, the investigator should contact the study medical 
monitor to discuss additional follow-up and medical management. 

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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.   

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8.3.11.3.1. Proximal Renal Tubule Dysfunctions (PRTD) 
PRTD is defined as: 
• Confirmed rise in serum creatinine of ≥0.5 mg/dL from Baseline AND serum 
phosphate <2.0 mg/dL; 
Either of the above accompanied by any two of the following: 
• Glycosuria (≥250 mg/dL) in a non-diabetic; 
• Low serum potassium (<3 mEq/L); 
• Low serum bicarbonate (<19 mEq/L). 
Participants meeting criteria for PRTD must return for a confirmatory assessment within 
2 weeks of diagnosis. A urinalysis should also be performed at the time of the 
confirmatory assessment.  If PRTD is confirmed participants should have study drug 
withheld and the investigator should contact the Study medical monitor to discuss the 
rationale for restarting study drugs (if appropriate). Consideration for confounding factors 
(e.g., NRTI backbone, other medications, dehydration, concurrent conditions) should be 
taken into account, and a nephrology consult may be obtained.  If study drug is 
reinitiated, it should have been withheld for no more than 4 weeks. 
8.3.11.4. 
Proteinuria 
Participants with an abnormal urine microalbumin/creatinine ratio (>0.3 mg/mg, 
>300 mg/g, or >34 mg/mmol) that represents a change from Baseline and no associated 
increase in creatinine, should have a repeat spot urine microalbumin/creatinine ratio 
performed within 2-4 weeks. If confirmed, then consideration should be given to 
additional evaluation after consultation with the study medical monitor. Additional 
evaluation may include a 24-hour urine protein and creatinine measurement and 
nephrology referral. 
Participants with an abnormal urine albumin/creatinine ratio (>0.3 mg/mg, 300 mg/g, or 
>34 mg/mmol and representing a change from Baseline) and a serum creatinine increase 
>45 μmol/L (or 0.5 mg/dL) should have confirmation of both results within 2 weeks. If 
confirmed, the study medical monitor should be contacted immediately. Agreement on 
further management should be agreed between the investigator and medical monitor. 
8.3.11.5. 
QTc Prolongation 
Participants with an average QTc interval >550 msec from three or more tracings 
separated by at least 5 minutes should have IP discontinued.  These criteria are based on 
an average QTc value of triplicate ECGs.  If an ECG demonstrates a prolonged QT 
interval, obtain 2 more ECGs over a brief period (~5-10 minutes) and use the averaged 
QTc values of the 3 ECGs to determine whether the participant should be discontinued 
from the study.  If an alternative cause of the QT prolongation is determined (e.g., 

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participant receiving drug known to cause prolonged QT or TdP), then IP may be 
restarted after consultation with, and agreement by, the Medical Monitor. 
8.3.11.6. 
Injection Site Reactions (ISRs) 
Injection site reactions will be managed through investigator assessment throughout the 
study.  All ISRs that are either serious, Grade 3 or higher, or persisting beyond 2 weeks 
must be discussed with the Medical Monitor to determine etiology and assess appropriate 
continued study participation.   
Digital photographs may be documented where possible on all participants who have an 
injection site reaction, with observable findings, that is either serious or Grade 3 or 
higher, or that persists beyond 2 weeks.  Dermatology will be consulted on all 
participants who have an injection site reaction considered serious, Grade 3 or above, or 
if clinically significant and persistent beyond 30 days and others if the Investigator or 
Medical Monitor feels it is medically necessary. 
Details regarding photo collection and any other follow up will be given by the Medical 
Monitor at the time of assessment. 
ISR discomfort can be managed symptomatically (e.g., cold/warm compress, 
acetaminophen, ibuprofen) if the reaction is interfering with the participant’s ability to 
perform activities of daily living.  The required intervention should be documented on the 
appropriate eCRF page. 
8.3.11.7. 
Allergic Reaction 
Participants may continue study drug for Grade 1 or 2 allergic reactions at the discretion 
of the Investigator.  The participant should be advised to contact the Investigator 
immediately if there is any worsening of symptoms or if further systemic signs or 
symptoms develop. Antihistamines, topical corticosteroids, or antipruritic agents may be 
prescribed.  
Participants with Grade ≥3 allergic reactions that are considered to be possibly or 
probably related to the study drug should permanently discontinue the CAB LA + RPV 
LA regimen and the participant should be withdrawn from the study.  Participants should 
be treated as clinically appropriate and followed until resolution of the AE. 
8.3.11.8. 
Abacavir Hypersensitivity Reaction (ABC HSR) 
If a study participant discontinues study IP, enters into the LTFU period and are 
administered an ABC-containing product, please follow the information contained within 
this section.   
Background  
The most significant toxicity associated with ABC is the well-characterized drug-related 
hypersensitivity reaction (HSR).  A detailed clinical description of this reaction 
(including the type and severity of events that can occur on re-challenge or reintroduction 
following ABC interruption for non-HSR reasons) and guidance regarding its 

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management are included in the Local Country Prescribing Information for EPZICOM.  
Investigators must familiarize themselves with this information on ABC HSR in the 
Local Country Prescribing Information for each of these products prior to initiating 
participants on ABC therapy. 
Studies have shown that carriage of the HLA-B*5701 allele is associated with a 
significantly increased risk of a HSR to ABC.  In the prospective study CNA106030 
(PREDICT-1), the use of pre-therapy screening for the presence of HLA-B*5701 and 
subsequently avoiding ABC in HLA-B*5701 positive patients, significantly reduced the 
incidence of clinically suspected ABC HSR from 7.8% (66 of 847) to 3.4% (27 of 803) 
(p<0.0001).  In clinical studies EPZ108859 (ARIES) and CNA109586 (ASSERT), 0.8% 
(4/515) and 3.1% (6/192) of participants who were HLA-B*5701 negative and who 
received ABC developed a clinically suspected ABC HSR, respectively. 
In any participant treated with ABC, the clinical diagnosis of suspected HSR (as detailed 
in the Local Country Prescribing Information) must remain the basis of clinical decision 
making.  Regardless of HLA-B*5701 status, it is important to permanently discontinue 
ABC and not re-challenge with ABC (i.e., ZIAGEN, EPZICOM/KIVEXA, TRIZIVIR, or 
TRIUMEQ) if a HSR cannot be ruled out on clinical grounds, due to the potential for a 
severe or even fatal reaction. 
8.3.11.8.1. Essential Patient Information 
With reference to Local Country Prescribing Information and the ‘Participant Information 
and Consent Form’, Investigators must ensure that participants are fully informed 
regarding the following information on the hypersensitivity reaction prior to commencing 
ABC therapy: 
• Participants must be made aware of the possibility of a hypersensitivity reaction 
to abacavir that may result in a life-threatening reaction or death and that the risk 
of a hypersensitivity reaction is increased in individuals who are HLA-B*5701 
positive. 
• Participants must also be informed that HLA-B*5701 negative individuals can 
also experience abacavir hypersensitivity reaction.  Therefore, ANY participant 
who develops signs or symptoms consistent with a possible hypersensitivity 
reaction to abacavir MUST CONTACT their doctor IMMEDIATELY. 
• Participants who are hypersensitive to abacavir should be reminded that they must 
never take any abacavir containing medicinal products (e.g., ZIAGEN, 
EPZICOM, KIVEXA, TRIZIVIR, or TRIUMEQ) again, regardless of their HLA-
B*5701 status. 
• In order to avoid restarting abacavir, participants who have experienced a 
hypersensitivity reaction should be asked to return any remaining EPZICOM / 
KIVEXA tablets to the Investigator or site staff. 
• Participants, who have stopped abacavir for any reason, and particularly due to 
possible adverse reactions or illness, must be advised to contact their doctor 

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before restarting EPZICOM / KIVEXA as more severe symptoms may recur 
within hours and may include life-threatening hypotension and death. 
• Each participant should be reminded to read the Package Leaflet included in the 
EPZICOM / KIVEXA pack.  They should be reminded of the importance of 
removing the Alert Card included in the pack and keeping it with them at all 
times.  
8.3.11.8.2. Reporting of Hypersensitivity Reactions 
If a clinically suspected case of HSR to ABC meets one of the International Conference 
on Harmonization (ICH E2A), 1994 definitions of seriousness listed in Section 10.2.2 
then, in addition to reporting the case as an SAE, the ABC HSR eCRF should also be 
completed within one week of the onset of the hypersensitivity reaction.  Clinically 
suspected cases of HSR to ABC that do not meet criteria as an SAE can be recorded as an 
AE. 
8.3.11.9. 
Rash Without ABC HSR Symptoms 
Including serious skin reactions such as Stevens-Johnson Syndrome, Toxic 
Epidermal Necrolysis, Erythema Multiforme or rash with significant liver 
dysfunction.  
Participants should be instructed to contact the Investigator as soon as possible if they 
develop a rash on study. 
CAB is an analogue of DTG and mild to moderate rash is an expected adverse reaction 
for DTG-containing ART.  Episodes generally occur within the first ten weeks of 
treatment, rarely require interruptions or discontinuations of therapy and tend to resolve 
within two to three weeks.  No instances of serious skin reaction, including 
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and erythema 
multiforme, have been reported for DTG in clinical trials.  For further characterization of 
HSR and rash observed with DTG-containing ART, please see the current version of the 
IB [GlaxoSmithKline Document Number  RPS-CLIN-004375, 2021]. 
Rash is an adverse drug reaction (ADR) for RPV.  In clinical trials, most rashes emerged 
during the first 4 weeks of treatment, were transient, and usually mild (Grade 1) to 
moderate (Grade 2).  There were no Grade 4 rashes, and none were serious.  Treatment-
related Grade 3 rash was reported in 0.1% of participants in the RPV group.  Treatment-
related rash led to permanent discontinuation in 0.1% of participants in the RPV group.  
No cases of erythema multiforme, SJS or TEN have been reported during clinical 
development of RPV. 
Participants with an isolated Grade 1 rash may continue study drug at the Investigator’s 
discretion.  The participant should be advised to contact the Investigator immediately if 
there is any worsening of the rash, if any systemic signs or symptoms appear, or if 
mucosal involvement develops. 

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Participants may continue study drug for an isolated Grade 2 rash.  However, study drug 
(and all other concurrent medication(s) suspected in the Investigators causality 
assessment) should be permanently discontinued for any Grade ≥2 rash that is associated 
with an increase in ALT.  The participant should be advised to contact the physician 
immediately if rash fails to resolve (after more than two weeks), if there is any worsening 
of the rash, if any systemic signs or allergic symptoms develop, or if mucosal 
involvement develops. 
Participants should permanently discontinue study drug [and all other concurrent 
medication(s) suspected in the Investigators causality assessment] for an isolated Grade 3 
or 4 rash, except where the etiology of the rash has been definitively diagnosed as NOT 
attributable to study drug (see below), and the participant should be withdrawn from the 
study.  Participants should be treated as clinically appropriate and followed until 
resolution of the AE.  Every effort should be made to collect as much information as 
possible about the evolution of the event and any relationship with potentially related 
medical events (e.g., viral infection) or start of concomitant medication. 
The rash and any associated symptoms should be reported as adverse events and 
appropriate toxicity ratings should be used to grade the events (based on DAIDS toxicity 
gradings – see Section 10.4). 
However, if the etiology of the rash has been definitively diagnosed as being unrelated to 
study drug and due to a specific medical event or a concomitant infection or a 
concomitant non-study medication, routine management should be performed, and 
documentation of the diagnosis provided.  In this situation, the study drug should be 
continued.  
Participants in the Follow-Up Phase who are receiving ABC as part of their regimen 
should be evaluated for the possibility of a clinically suspected ABC HSR and managed 
appropriately as outlined in the local prescribing information for ABC. 
Any rash that is possibly related to study drug, and is present between Day 1 and 
The Month 1b visit for participants in the Oral Lead-in Phase, must be discussed 
with the Medical Monitor prior to initiation of CAB LA or RPV LA. 
Any participant receiving at least one dose of CAB LA and /or RPV LA who discontinue 
IP / Withdraw will initiate treatment with HAART and enter the LTFU Phase for 52 
weeks of follow-up. 
8.4. 
Treatment of Overdose 
For participants receiving oral study intervention, any tablet intake exceeding the total 
daily dose will be considered an overdose.   
For CAB LA and RPV LA, any single dose in excess of the studied doses will be 
considered an overdose. 
Should IM maladministration, specifically overdose or inadvertent IV dosing, be 
suspected at any time, the participant will stay onsite for approximately 2-3 hours post 

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dose for safety monitoring and an ECG will be performed at 2 hours post dose.  The 
Medical Monitor will be notified in the event of a suspected maladministration.  
In the event of suspected maladministration, additional PK samples will be drawn at 
2 hours post dosing for evaluation of CAB and RPV concentrations. 
For participants randomized to BIK, in the case of an overdose, the participant should go 
to the nearest hospital emergency room immediately. 
For the purposes of this study, an overdose is not an AE (refer to Section 10.2.1) unless it 
is accompanied by a clinical manifestation associated with the overdose.  If the clinical 
manifestation presents with serious criteria, the event is a SAE (see Section 10.2.2). 
If an overdose occurs and is associated with an adverse event requiring action, all study 
medications must be temporarily discontinued until the adverse event resolves.  
The Investigator should use clinical judgement in treating overdose, as ViiV Healthcare 
is unable to recommend specific treatment. 
In the event of an overdose the investigator or treating physician should: 
1. Contact the Medical Monitor immediately 
2. Closely monitor the participant for adverse events (AEs)/serious adverse events 
(SAEs) and laboratory abnormalities until the IP can no longer be detected 
systemically (at least 5 days for oral CAB, oral RPV and BIK, and 52 weeks for 
CAB LA and RPV LA 
3. Obtain a plasma sample for pharmacokinetic (PK) analysis if possible, within 2 
days from the date of the last dose of study treatment if requested by the Medical 
Monitor (determined on a case-by-case basis). 
4. Document the quantity of the excess dose as well as the duration of the 
overdosing in the CRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
8.5. 
Pharmacokinetics 
Plasma samples will be collected throughout the Maintenance, Extension and LTFU 
Phases of the study and stored for potential determination of CAB and RPV 
concentrations. Samples (blood and plasma) for potential determination of RPV 
concentrations will be protected from light at all times, from sampling collection through 
analysis. 
8.5.1. 
Rationale of PK Sampling Strategy 
Blood sampling for CAB and RPV concentrations will be performed during the 
Maintenance Phase of the study for potential evaluation of PK in HIV infected 

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

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

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

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

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

T M F -1 4 3 6 4 9 1 7   
C O N FI D E N TI A L  
 
 
 
2 1 3 5 0 0  
1 3 8  
 
B o ne  bi o mar kers : 
•  B o ne -s p ecific al kali ne p h os p hatase 
•  Pr oc olla ge n t y p e 1 N -pr o pe pti de  
•  T y pe 1 c olla ge n cr oss -li n ke d C-tel o pe pti de 
•  Oste ocalci n  
•  2 5 h y dr o x y -Vita mi n D  
I ns uli n, H b A 1 c, a n d H O M A-I R 
Si nce t he i nte nti o n is t o utilize t hese bi o mar kers f or researc h p ur p oses a n d t he cli nical 
si g nifica n ce of t h ese res ults is u ncertai n, t he S p o ns or will n ot be re p orti n g real ti me 
res ults of t hese ass ess me nts t o t he i n vesti gat or e x ce pt f or Cystati n C a n d 2 5 h y dr o x y -
vita mi n D , I ns uli n, H b A 1c a n d H O M A-I R as per Ta ble 4 . 
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
St ati sti c al H y p ot h e s e s  
T he st u d y is t o de m o nstr ate t he n o n -i nf eri or a nti viral acti vit y of C A B L A + R P V L A 
e ver y 2  m o nt hs  c o m pare d t o a BI K si n gle ta bl et r e gi me n a d mi nistere d o nce dail y o v er 1 2  
m o nt h s i n s u p presse d HI V-1 i nfect e d a ntiretr o viral t hera p y ( A R T) -e x perie n ce d 
partici pa nts.  
N o n -i nferi orit y ca n be c o ncl u de d if t he u p per li mit of a t w o-si de d 9 5 % c o nfi de nce 
i nter val f or t he differe nce i n pr o p orti o n of partici pa nts wit h HI V-1 R N A ≥ 5 0 c/ m L at 
M o nt h 1 2  bet wee n t he t w o treat me nt ar ms ( C A B L A + R P V L A –  BI K) is l ess t ha n 4 %.   
Let p c, pb be t he pr o p orti o n of partici pa nts wit h HI V -1 R N A  ≥ 5 0 c/ m L i n t he C A B 
L A + R P V L A a n d BI K ar ms res pecti vel y, t he n t he pri mar y statistical h y p ot h esis ca n be 
writte n as f oll o ws:  
H 0:  pc - p b ≥ 4 % vs. H 1: pc - p b < 4 %  
C CI
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9.2. 
Sample Size Considerations 
9.2.1. 
Sample Size Determination 
Sample size was determined based on desired study power. A total of 654 enrolled 
participants will be randomized in a 2:1 ratio to receive either CAB LA + RPV LA or 
BIK treatment. Assuming the true proportion of participants with HIV-RNA ≥ 50 c/mL is 
2% for CAB LA+RPV LA injectable regimen and 1% for the BIK arm, a non-inferiority 
margin of 4% and a 2.5% one-sided significance level, the study will provide 
approximately 85% power to demonstrate non-inferiority of CAB LA+RPV LA to BIK 
in term of proportions participants with HIV-1 RNA ≥ 50 c/mL at Month 12 (per FDA’s 
snapshot algorithm for assessing HIV-1 RNA ≥ 50 c/mL).  Details of this calculation 
along with a couple of another sample size scenarios were provided in Table 7. 
Note: "Enrolled" means a participant's, or their legally acceptable representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process. Potential participants who are screened for the purpose of determining eligibility 
for the study, but do not participate in the study, are not considered enrolled, unless 
otherwise specified by the protocol. 
Assuming a possible 15% of screen failure, a total of ~770 would need to be recruited to 
achieve ~654 participants to be enrolled and randomized. 
Table 7 
Sample Size and Power Scenarios 
Assumptions 
Sample Size 
Power* to reject H0 at α=2.5% 
pc 
pb 
NI Margin 
CAB LA+RPV LA 
BIK 
2% 
1% 
4% 
390 
195 
80% 
2% 
1% 
4% 
436 
218 
85% 
2% 
1% 
4% 
509 
255 
90% 
* Power was calculated using PASS 2019 Non-inferiority Tests for the Difference Between Two Proportions with 
Miettinen & Nurminen Likelihood Score Test Statistics. 
 
9.2.2. 
Sample Size Assumptions 
9.2.2.1. 
Rational for non-inferiority margin 
According to the FDA’s 2015 guidance document (Human Immunodeficiency Virus-1 
Infection: Development of ART Drugs for Treatment, November 2015), the margin for 
switch trials is driven by the largest clinically tolerable virologic failure rate. Per the FDA 
document, typical rates of virologic failure seen in switch studies range from 1% to 3% 
and a margin of 4% for virologic failure rate is considered tolerable [CDER, 2015].   
9.2.2.2. 
Proportion of participants with HIV-1 RNA ≥ 50 c/mL assumptions 
It was assumed 1% and 2% for the proportion of participants with HIV-1 RNA ≥ 50 c/mL 
in BIK and CAB LA + RPV LA respectively. These assumptions were based on the 
following historical data. 

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

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treatment, regardless of the treatment they receive. Unless stated otherwise, the ITT-E 
Population will be used for efficacy analyses. 
9.3.2. 
Per-Protocol Population (PP) 
The Per-Protocol (PP) Population will consist of all participants in the ITT-E Population 
with the exception of major protocol violators. The PP will be used for sensitivity 
analysis of the primary endpoint. 
9.3.3. 
Safety Population 
The Safety Population will consist of all randomly assigned participants who receive at 
least one dose of study drug. Participants will be assessed according to actual treatment 
received. Unless otherwise stated, the Safety Population will be used for safety analyses. 
9.3.4. 
PK Population 
The PK Population will include all participants who receive CAB and or RPV and 
undergo PK sampling during the study and provide evaluable CAB and/or RPV plasma 
concentration data. Participants in this population will be included in the PK analysis. 
9.4. 
Statistical Analyses 
The statistical analysis plan will be finalized prior to database freeze and it will include a 
more technical and detailed description of the statistical analyses described in this 
section. This section is a summary of the planned statistical analyses of the most 
important endpoints including primary and key secondary endpoints. 
The study design is open label.  However, the central ViiV/GSK team responsible for the 
conduct and analysis of the study will not review any summaries of data grouped by 
treatment prior to database freeze for the Month 6 interim analysis. 
9.4.1. 
Primary Analyses 
For the primary efficacy analysis, the difference between the two randomized arms for 
the proportion of participants with HIV-1 RNA ≥50 c/mL at Month 12 (OLI and 
BIK)/Month 11 (D2I) (according to FDA snapshot algorithm) and its confidence interval 
will be calculated and be adjusted to the study stratifications using Cochran-Mantel 
Haenszel (CMH) weights. All CIs will be two-sided. For this analysis, four strata will be 
formed according to the combinations of levels of the study stratification factors: 
- 
Gender at birth: female 
- 
Gender at birth: male 
- 
BMI: <30 kg/m2 
- 
BMI: 30 kg/m2 
 
The CMH estimate of the common difference in rates across strata will be calculated as 
the weighted average of the strata-specific estimates of the difference in response rates 
between the two arms as follows: 

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If nk is the number of CAB LA + RPV LA treated participants, mk is the number of BIK 
treated participants, and Nk = nk + mk is the total number of participants in the kth 
stratum, then the CMH estimate is given by 
 


=
k
k
k
cmh
W
d
W
d
ˆ
ˆ
 
where 
 
k
k
k
k
N
m
n
W
=
 
are CMH weights and 
 k
dˆ
 are estimates of the differences in response rates between the 
two treatment arms, pc-pb, for the kth stratum. The corresponding two-sided 95% CI will 
be calculated as: 
 
using the variance estimator 
 
)
ˆ
r(
aˆ
v
cmh
d
, given by [Sato, 1989], which is consistent in both 
sparse data and large strata.  The full equation for this variance estimate will be provided 
in the statistical analysis plan. 
Female participants randomized to CAB + RPV LA who become pregnant while in the 
study are allowed to continue. Female participants randomized to BIK will not be 
allowed to continue. For the FDA snapshot algorithm-related efficacy analysis at key 
time points (Month 5/6 and Month 11/12), viral load data after confirmed pregnancy may 
be “censored”, to minimize bias between the treatment and the comparator arm. Further 
sensitivity analysis may be performed as necessary. Data handling details will be 
provided in the Reporting Analysis Plan. 
9.4.2. 
Safety and Secondary Analyses 
The proportion of participants with plasma HIV-1 RNA <50 c/mL using the Snapshot 
algorithm is a key outcome at Months 6 and 12 (OLI and BIK)/Months 5 and 11 (D2I) 
and will be judged against a pre-specified non-inferiority margin of -12%. 
Changes from baseline in CD4+ lymphocyte count and in CD4+/CD8+ lymphocyte 
counts ratio and resistance data will be summarized. The incidence of HIV-1 disease 
progression (AIDS and death) will be presented. 
The proportion of participants with plasma HIV-1 RNA <50 c/mL using the Snapshot 
algorithm and changes from baseline in CD4+ lymphocyte count will be summarized by 
subgroups (e.g., age, gender and race) 

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

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

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

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

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also be explained to the participant who will be required to give consent for their data to 
be used as described in the informed consent.  
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities 
10.1.5. 
Quality Control (Study Monitoring) 
• In accordance with applicable regulations including GCP, and GSK 
procedures, GSK monitors will contact the site prior to the start of the study to 
review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK requirements. 
• When reviewing data collection procedures, the discussion will also include 
identification, agreement and documentation of data items for which the eCRF 
will serve as the source document. 
GSK will monitor the study and site activity to verify that the: 
• Data are authentic, accurate, and complete. 
• Safety and rights of participants are being protected. 
• Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents. 
10.1.6. 
Dissemination of Clinical Study Data 
• Study information from this protocol will be posted on publicly available clinical 
trial registers before enrolment of participants begins. 
• 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report.  The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location. 
• 
GSK will also provide the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study participants, as appropriate. 
• 
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK 
Policy. 
• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
Publication Policy 

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

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

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by the applicable regulatory requirements. The Investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up 
10.1.10. 
Records Retention 
• Following closure of the study, the investigator or the head of the medical 
institution (where applicable) must maintain all site study records (except for 
those required by local regulations to be maintained elsewhere), in a safe and 
secure location.   
• The records must be maintained to allow easy and timely retrieval, when 
needed (e.g., for a GSK audit or regulatory inspection) and must be available 
for review in conjunction with assessment of the facility, supporting systems, 
and relevant site staff.   
• Where permitted by local laws/regulations or institutional policy, some or all 
of these records can be maintained in a format other than hard copy (e.g., 
microfiche, scanned, electronic); however, caution needs to be exercised before 
such action is taken.   
• The investigator must ensure that all reproductions are legible and are a true 
and accurate copy of the original and meet accessibility and retrieval standards, 
including re-generating a hard copy, if required.  Furthermore, the investigator 
must ensure there is an acceptable back-up of these reproductions and that an 
acceptable quality control process exists for making these reproductions. 
• GSK will inform the investigator of the time period for retaining these records 
to comply with all applicable regulatory requirements.  The minimum retention 
time will meet the strictest standard applicable to that site for the study, as 
dictated by any institutional requirements or local laws or regulations, GSK 
standards/procedures, and/or institutional requirements.   
• The investigator must notify GSK of any changes in the archival arrangements, 
including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated 
with the site. 
10.1.11. 
Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials Registers and 
Publication 
• Study information from this protocol will be posted on publicly available 
clinical trial registers before enrolment of participants begins. 
• Where required by applicable regulatory requirements, an investigator 
signatory will be identified for the approval of the clinical study report.  The 
investigator will be provided reasonable access to statistical tables, figures, 
and relevant reports and will have the opportunity to review the complete 
study results at a GSK site or other mutually-agreeable location. 
• GSK will also provide the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study participants, as appropriate. 

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

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10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.2.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either 
an increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study intervention administration 
even though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfill the definition 
of an AE or SAE.  
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms 

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of the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
10.2.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
o Results in death 
o Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
Results in persistent or significant disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g. sprained ankle) which may interfere with 
or prevent everyday life functions but do not constitute a substantial disruption. 

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Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
• 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
Is associated with liver injury and impaired liver function defined as: 
• ALT  3xULN and total bilirubin*  2xULN (>35% direct), or 
• ALT  3xULN and INR** > 1.5. 
* Serum bilirubin fractionation should be performed if testing is available; if unavailable, 
measure urinary bilirubin via dipstick.  If fractionation is unavailable and ALT  3xULN 
and total bilirubin  2xULN, then the event is still to be reported as an SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants.  If INR measurement is obtained, the value is to be 
recorded on the SAE form. 
 
10.2.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 

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10.2.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records 
before submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
• 
Participant-completed Value Evidence and Outcomes questionnaires and the 
collection of AE data are independent components of the study. 
• 
Responses to each question in the Value Evidence and Outcomes questionnaire 
will be treated in accordance with standard scoring and statistical procedures 
detailed by the scale’s developer. 
• 
The use of a single question from a multidimensional health survey to designate a 
cause-effect relationship to an AE is inappropriate. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is 
assessed as severe should not be confused with an SAE. Severe is a category 
utilized for rating the intensity of an event; and both AE and SAE can be 
assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe. 

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

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10.3. 
Appendix 3:  CDC Classification for HIV-1 Infection (2014) 
Note that the CD4+ T-lymphocyte count takes precedence over the CD4+ T-lymphocyte 
percentage in HIV infection stages 1, 2, and 3.  The CD4+ T-lymphocyte should only be 
considered if the count is missing. 
HIV infection, stage 0 
Indicates early HIV infection, inferred from a negative or indeterminate HIV test result 
within 180 days of a positive result.  The criteria for stage 0 supersede and are 
independent of criteria used for other stages. 
HIV infection, stage 1 
• Laboratory confirmation of HIV infection with no AIDS-defining condition, and 
o CD4+ T-lymphocyte count of ≥500 cells/L, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of ≥26%. 
HIV infection, stage 2 
• Laboratory confirmation of HIV infection with no AIDS-defining condition, and 
o CD4+ T-lymphocyte count of 200 to 499 cells/L, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of 14% to 25%. 
HIV infection, stage 3 (AIDS) 
• Laboratory confirmation of HIV infection, and 
o CD4+ T-lymphocyte count of <200 cells/L, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of <14%, or 
o Documentation of an AIDS-defining condition (see below). 
Documentation of an AIDS-defining condition supersedes a CD4+ T-lymphocyte count 
of >200 cells/L and a CD4+ T-lymphocyte percentage of total lymphocytes of >14%.  
HIV infection, stage unknown 
• Laboratory confirmation of HIV infection, and 
o No information on CD4+ T-lymphocyte count or percentage, and 
o No information on presence of AIDS-defining conditions. 
Stage-3-defining opportunistic illnesses in HIV infection 
• Candidiasis of bronchi, trachea, or lungs  
• Candidiasis of oesophagus  
• Cervical cancer, invasive 

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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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10.4. 
Appendix 4: Division of AIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events Version 2.1, March 
2017 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (“DAIDS AE Grading Table”) is a descriptive terminology which can be utilised 
for Adverse Event (AE) reporting.  A grading (severity) scale is provided for each AE 
term. 
10.4.1. 
Estimating Severity Grade for Parameters Not Identified in the 
Grading Table  
The functional table below should be used to grade the severity of an AE that is not 
specifically identified in the grading table. In addition, all deaths related to an AE are to 
be classified as grade 5. 
 
 

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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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10.5. 
Appendix 5: Contraceptive Guidance 
10.5.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the 
participant’s medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  
• 
A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). 
However, in the absence of 12 months of amenorrhea, confirmation with 
more than one FSH measurement is required.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before 
study enrollment. 
 

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10.5.2. 
Contraception Guidance 
Female participants of childbearing potential are eligible to participate if they agree to 
use a highly effective method of contraception consistently and correctly as described in 
Table 9 
Table 9 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• oral 
• intravaginal  
• transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• injectable  
Highly Effective Methods That Are User Independent  
• Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulationb 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.)  
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and 
the preferred and usual lifestyle of the participant.)  
NOTES:  
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants in clinical 
studies.  
 

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10.6. 
Appendix 6:  Information and Guidance for Managing 
Pregnant Participants 
10.6.1. 
Collection of Pregnancy Information: 
The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study.  
• 
Information will be recorded on the appropriate form and submitted to GSK 
within 24 hours of learning of a participant's pregnancy. 
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on mother and infant, which will 
be forwarded to GSK.  Generally, follow-up will not be required for longer than 
6 to 8 weeks beyond the estimated delivery date. 
• 
Any termination of pregnancy will be reported, regardless of fetal status 
(presence or absence of anomalies) or indication for procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
• 
A spontaneous abortion is always considered to be an SAE and will be reported 
as such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to 
GSK as described in the protocol in Section 8.3.4.  While the investigator is not 
obligated to actively seek this information in former study participants, he or she 
may learn of an SAE through spontaneous reporting. 
• 
Females who become pregnant while in the study may remain in study, and 
continue scheduled dosing with CAB + RPV LA, once a pregnancy ICF 
addendum is signed by the participant. 
• 
WOCBP should only be included after a confirmed menstrual period and a 
negative highly sensitive serum pregnancy test  
• 
Additional pregnancy testing should be performed as per the study Time and 
Events Table. Pregnant participants who remain in the study do not need 
pregnancy testing during the study, for the duration of their pregnancy. 
• 
Pregnancy testing will be performed whenever a menstrual cycle is missed or 
when pregnancy is otherwise suspected  
• 
Pregnancy testing will be performed and assayed in the central laboratory OR 
using the test kit provided by the central laboratory / provided by the sponsor 
/approved by the sponsor and in accordance with instructions provided.  
10.6.2. 
Introduction 
Pregnancy increases the risk of HIV progression, while HIV increases the risk for 
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to the unborn fetus.  Mother to child transmission (MTCT) of HIV can occur during 
pregnancy, labor, delivery or postpartum through breastfeeding.  In the absence of any 
interventions, vertical HIV transmission rates approximate 35%, but fall below 5% with 
effective interventions [WHO, 2010].  In the United States and other developed countries, 
the risk of perinatal infection has decreased from 25% without intervention to less than 
2% with intervention [WHO, 2012].  The HIV-infected mother who breastfeeds her 
infant while taking ARVs herself or giving ARVs to her infant reduces the risk of 
transmission to about 2% after 6 months of breastfeeding, or 4% over 12 months 
[UNAIDS, 2011]. 
The 2013 WHO Guidelines thus recommend (strong recommendation, moderate-quality 
evidence) all pregnant and breastfeeding women with HIV should initiate triple ARVs 
(ART), which should be maintained at least for the duration of mother-to-child 
transmission risk. Women meeting treatment eligibility criteria should continue lifelong 
ART [WHO, 2013]. The global benefits anticipated from ART in pregnant women who 
are eligible for treatment include treatment of the mother’s underlying HIV disease, 
eliminating pediatric transmission/infection and reducing sexual transmission of HIV 
Recent recommendation updates to treatment guidelines have included objectives to 
increase HIV screening of patients, including pregnant women (noting the importance of 
adopting HIV screening to be a part of prenatal care). 
The ART recommendation for pregnant females prioritizes the health of women over 
potential risks and increased cost.  For females who are on ARV therapy at the time that 
they become pregnant, the WHO recommends that they continue such therapy if they are 
responding to the ARV. 
In line with this recommendation, this study will allow those females participating in 
213500 who are receiving CAB + RPV LA but become pregnant on study, to continue in 
the study in order to maintain their effective regimen with minimal disruption.  The PK of 
CAB + RPV LA, characterization of the safety of CAB + RPV LA administered during 
pregnancy, and characterization of maternal, birth and infant outcomes following 
treatment with CAB + RPV LA will be examined.  
10.6.3. 
Background 
At the time of finalizing this protocol, there have been 25 pregnancies reported during the 
CAB/RPV LA P3 development program (including 6 during PK tail and 5 during OLI) 
with 8 pregnancies leading to live births (including 3 pregnancies exposed during the PK 
tail of treatment and 1 pregnancy exposure occurring during CAB oral lead-in) and 5 on-
going pregnancies. 
• 
A total of 12 pregnancy losses (11 of these occurring during the first trimester) 
• 
Missed abortions: 2 (one of these was a twin anembryonic pregnancy) 
• 
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• 
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• 
Spontaneous abortions: 4 (1 late spontaneous abortion at 23/40; severe 
Intrauterine growth restriction [IUGR], placental insufficiency; presence of risk 
factors) 
No reported congenital anomalies 
10.6.4. 
Benefit/Risk Assessment 
Discuss with the pregnant participant the benefit-risk of continuing in the study and 
continuing to receive CAB + RPV LA injections, or being withdrawn from study, as a 
result of her pregnancy. All participants who chose to stay in the study during pregnancy, 
and who choose to continue to receive CAB + RPV LA injections will need to sign a 
pregnancy specific ICF addendum. 
There is a pregnancy exposure registry that monitors pregnancy outcomes in women 
exposed to CAB + RPV LA (CABENUVA) during pregnancy. Healthcare providers are 
encouraged to register all pregnant study participants, whether or not they choose to 
remain in the study, by calling the Antiretroviral Pregnancy Registry] at 1-800-258-4263. 
10.6.4.1. 
Cabotegravir 
Cabotegravir use in pregnant females has not been evaluated and there are insufficient 
human data on the use of during pregnancy to adequately assess a drug-associated risk of 
birth defects and miscarriage.  
The rate of miscarriage is not reported in the APR. The background risk for major birth 
defects and miscarriage for the indicated population is unknown. The background rate for 
major birth defects in a U.S. reference population of the Metropolitan Atlanta Congenital 
Defects Program (MACDP) is 2.7%. The estimated background rate of miscarriage in 
clinically recognized pregnancies in the U.S. general population is 15% to 20%. The APR 
uses the MACDP as the U.S. reference population for birth defects in the general 
population. The MACDP evaluates women and infants from a limited geographic area 
and does not include outcomes for births that occurred at less than 20 weeks’ gestation. 
Animal Data (pre-clinical)  
Cabotegravir was administered orally to pregnant rats at 0, 0.5, 5, or 1000 mg/kg/day 
from 15 days before cohabitation, during cohabitation, and from Gestation Days 0 to 17. 
There were no effects on fetal viability when fetuses were delivered by caesarean 
although a minor decrease in fetal body weight was observed at 1000 mg/kg/day (greater 
than 30 times the exposure in humans at the RHD). No drug-related fetal toxicities were 
observed at 5 mg/kg/day (approximately 13 times the exposure in humans at the RHD) 
and no drug-related fetal malformations were observed at any dose. 
Cabotegravir was administered orally to pregnant rabbits at 0, 30, 500, or 
2000 mg/kg/day from Gestation Days 7 to 19. No drug-related fetal toxicities were 
observed at 2000 mg/kg/day (approximately 0.7 times the exposure in humans at the 
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In a rat pre- and postnatal development study, cabotegravir was administered orally to 
pregnant rats at 0, 0.5, 5, or 1000 mg/kg/day from Gestation Day 6 to Lactation Day 21. 
A delay in the onset of parturition and increases in the number of stillbirths and neonatal 
deaths by Lactation Day 4 were observed at 1000 mg/kg/day (greater than 30 times the 
exposure in humans at the RHD); there were no alterations to growth and development of 
surviving offspring. In a cross-fostering study, similar incidences of stillbirths and early 
postnatal deaths were observed when rat pups born to cabotegravir-treated mothers were 
nursed from birth by control mothers. There was no effect on neonatal survival of control 
pups nursed from birth by cabotegravir-treated mothers. A lower dose of 5 mg/kg/day 
(13 times the exposure at the RHD) was not associated with delayed parturition or 
neonatal mortality in rats. Studies in pregnant rats showed that cabotegravir crosses the 
placenta and can be detected in fetal tissue. 
During the pre-clinical development of CAB, there were no positive genotox findings. 
Embryo-fetal studies also showed no adverse findings including neural tube defects.  In a 
pre and postnatal study, there were some test article-related decreases in F1 pup survival 
(87.4% vs 98.9% in control) in the highest dose (1000 mg/kg/day) during postnatal days 
1-4.  No findings in the 0, 0.5 and 5 mg/kg/day doses).  
The clinical significance of these finding in humans is unknown. 
Human Data  
Cabotegravir use in pregnant females has not been evaluated and there are insufficient 
human data on the use of CAB + RPV LA during pregnancy to adequately assess a drug-
associated risk of birth defects and miscarriage.  
While there are insufficient human data to assess the risk of NTDs with exposure to CAB 
+ RPV LA during pregnancy, NTDs were associated with dolutegravir, another integrase 
inhibitor. A preliminary analysis of an ongoing birth outcome surveillance study in 
Botswana involving women exposed to DTG, a different molecule in the same integrase 
class of medications as CAB, identified 4 cases (as of May 2018) of neural tube defects 
in 426 infants born to mothers who were exposed to DTG-containing regimens from the 
time of conception. In the same study, no infant born to a woman who started DTG 
during pregnancy had a neural tube defect, out of 2824 women.  More recently, data from 
the Tsepamo study was updated.  In April 2020, the Tsepamo study team provided 
interim data from the study, which included available data through to 29 February 2020. 
Subsequently, the study team presented an updated analysis, including data through to 30 
April 2020, at the 23rd International AIDS Society (IAS) Meeting [Zash, 2020].  
The latest data from the Tsepamo study included additional data accrued between 
1 April 2019 (the cut-off for the last formal analysis) and 30 April 2020. Over this 
13-month period, 39,200 additional births were recorded, including 1908 additional 
exposures to DTG at conception. Two additional NTDs were detected in 1908 (0.10%) 
deliveries to mothers taking DTG at conception, compared with 6 NTDs in 4569 (0.13%) 
deliveries in mothers taking non-DTG regimens at conception, of which 5 NTDs in 2999 
(0.17%) deliveries were to mothers taking efavirenz at conception. The incidence in HIV 
negative mothers over the 13-month period was 17/30,258 (0.06%).  

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A causal relationship of these events to the use of DTG has not been established.  
The incidence of NTDs in the general population ranges from 0.5-1 case per 1000 live 
births. There are insufficient human data on the use of CAB + RPV LA during pregnancy 
to adequately assess a drug-associated risk of miscarriage or birth defects, including 
NTDs. 
10.6.4.2. 
Rilpivirine 
Animal Data  
Rilpivirine was administered orally to pregnant rats (40, 120, or 400 mg/kg/day) and 
rabbits (5, 10, or 20 mg/kg/day) through organogenesis (on Gestation Days 6 through 17, 
and 6 through 19, respectively). No significant toxicological effects were observed in 
embryo-fetal toxicity studies performed with rilpivirine in rats and rabbits at exposures 
15 (rats) and 70 (rabbits) times the exposure in humans at the RHD. In a pre- and 
postnatal development study, rilpivirine was administered orally up to 400 mg/kg/day 
through lactation. No adverse effects were noted in the offspring at maternal exposures 
up to 63 times the exposure in humans at the RHD 
Human Data  
Based on prospective reports to the APR of over 390 exposures to oral rilpivirine-
containing regimens during the first trimester of pregnancy and over 170 during 
second/third trimester of pregnancy, the prevalence of birth defects in live births was 
1.3% (95% CI: 0.4% to 3.0%) and 1.1% (95% CI: 0.1% to 4.0%) following first and 
second/third trimester exposures. 
Available data from the APR show no difference in the overall risk of birth defects for 
rilpivirine compared with the background rate for major birth defects of 2.7% in a U.S. 
reference population of the MACDP 
In a clinical trial, total oral rilpivirine exposures were generally lower during pregnancy 
compared with the postpartum period. Refer to Edurant Prescribing Information for 
additional information on rilpivirine. 
10.6.5. 
Clinical Considerations 
10.6.5.1. 
Exposure 
Lower exposures with oral rilpivirine were observed during pregnancy. Cabotegravir and 
rilpivirine are detected in systemic circulation for up to 12 months or longer after 
discontinuing injections of CAB + RPV LA; therefore, consideration should be given to 
the potential for fetal exposure during pregnancy. 
With the change in volume of distribution associated with pregnancy, drug concentrations 
of CAB and RPV during pregnancy will be assessed in pregnant participants who 
contiune to receive LA therapy while on study. For these participants, plasma PK 
samples of CAB and RPV will be obtained at every study visit for Q8W and Q4W during 
the pregnancy. Additionally, all other scheduled assessments, including viral load 

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2 1 3 5 0 0  
1 9 1  
 
m o nit ori n g, will c o nti n ue as reflecte d i n as d escri b e d i n t he pr ot oc ol i n t he S O A  (see 
Secti o n 1. 3 ) 
Fi g ur e 6  
L T F U P K i n F e m al e a n d Pr e g n a nt P arti ci p a nt s  
( L A T T E-2, A T L A S ) 
W e e k s P o st Fi n al I nj e cti o n
0
1 2
2 4
3 6
4 8
6 0
Pl a s m a C A B (
g/ m L)
0. 0 1
0. 1
1
1 0
L 2 
A 
L 2 
A  
 ( + H C G)
A  
 (- H C G)
A  
 (- H C G)
A  
 (- H C G)
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D

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10.6.5.2. 
 Use of Supplements with CAB + RPV LA 
During pregnancy, additional supplements including vitamins, minerals and other 
mediations including over the counter (OTC) medications may be prescribed to the 
pregnant woman. It is important for all female participants who remain in the study to be 
aware of any potential drug drug interactions (DDIs) that may occur with study 
medications and other agents used during pregnancy. 
10.6.5.2.1. Oral Cabotegravir Only 
Antacid products containing divalent cations (e.g., aluminium, calcium and 
magnesium) must be taken at least 2 hours before or at least 4 hours after CAB. 
Concurrent administration of multivitamins is acceptable. 
10.6.5.3. 
Overall Benefit: Risk Conclusion  
All medications have AE profiles that must be assessed prior to use, allowing for an 
appropriate risk/benefit assessment.  Additional considerations when using CAB + RPV 
LA can be found in the protocol in Section 2.3.3 
There is limited data regarding the use of CAB + RPV LA in pregnant females. Based on 
animal data, the use of CAB + RPV LA is not anticipated to increase the risk of adverse 
developmental or reproductive outcomes in humans.  Available data from the APR show 
no difference in the overall risk of birth defects for rilpivirine compared with the 
background rate for major birth defects of 2.7% in a U.S. reference population of the 
MACDP. 
Refer to Section 10.6.4.1 and Section 10.6.4.2 for additional data. 
The use of CAB + RPV LA during pregnancy may offer unique benefits. It is well 
documented that treatment adherence challenges to oral therapy exists both in the 
peri-partum and post-partum periods with LA dosing offering an opportunity to 
overcome such adherence challenges. LA therapy may also help with nausea (50 % mild 
to moderate) or hyperemesis (2%). Female participants on LA dosing who become 
pregnant will have exposures throughout pregnancy due to the long half-life and PK tail 
of CAB/RPV. Pregnant participants who are withdrawn from study and are initiated on 
an alternative oral ART regimen consisting of either 2 or 3 antiretrovirals to protect the 
life of the mother and for the prevention of MTCT, potentially expose the fetus to 
additional ARVs during gestation (in some cases upwards of 5 antiretrovirals). 
In summary, taking into account the measures taken to minimize risk to participants 
participating in this study, the potential risks identified in association with CAB + RPV 
LA are justified by the anticipated benefits that may be afforded to pregnant participants 
with HIV infection. 
Given the risk/benefit ratio for CAB + RPV LA dosing in WOCBP, coupled with 
concerns of increasing fetal exposure to several additional antiretrovirals upon participant 
withdrawal, pregnant participants will be allowed to remain in the study and continue to 

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receive CAB + RPV LA injections, once the new pregnancy ICF addendum is signed by 
the participant.  
10.6.6. 
Study Assessments and Procedures: specific assessments for 
pregnant participants 
Participants who become pregnant while in the study, and who sign the informed consent 
pregnancy addendum may remain in the study and continue to receive CAB + RPV LA.  
Please note: The HIV care provider is responsible for HIV care and will collaborate and 
share information with the participant’s obstetric care provider, discuss the participant’s 
participation in this study, the necessary procedures at delivery, to share HIV 
information, and to collect birth and infant outcomes from the participant’s obstetric care 
provider and/or the pediatric health provider for the infant. 
Because obstetric and/or pediatric care will not be specifically provided via this study, the 
participant must also establish appropriate obstetric and pediatric care (including prenatal 
care) per local standard of care (SOC) in parallel.  It will be necessary for the participant 
to provide a release of medical information to facilitate collection of pregnancy and 
pregnancy outcomes by the investigator 
All assessments will be conducted in accordance with the protocol, as described in the 
protocol in the SoA (see Section 1.3) 
10.6.6.1. 
Plasma HIV-1 RNA 
Women who become pregnant while on study and consent to stay on study will have viral 
load (VL) testing obtained at every study visit during pregnancy and at the first post-
partum visit. 
10.6.6.2. 
Safety Assessments 
Pregnancy related complications and diagnoses, and outcomes will be captured as AEs 
and SAEs as outlined in the protocol in Section 8.3.2. 
Pregnancy complications (e.g., preeclampsia or eclampsia, prolonged hospitalization after 
delivery, for wound infections etc, seizures) and elective terminations for medical reasons 
must be reported as an AE or SAE.  Spontaneous abortions must be reported as an SAE. 
In the event of a pregnancy loss, after the loss is confirmed the participant may continue 
to receive CAB + RPV LA unless they meet the criteria for confirmed virologic 
withdrawal.  They may continue to CAB + RPV LA until study medications are locally 
approved and commercially available or until they no longer receive benefit.  In this case 
the participant must agree to use contraception to avoid a ‘new’ pregnancy (See 
Appendix 6). 
Any SAE occurring in association with the pregnancy brought to the investigator’s 
attention after the participant has completed the study and considered by the investigator 
as possibly related to the study treatment, must be promptly reported to GSK 

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

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10.7. 
Appendix 7: Genetics 
Genetic Research Objectives and Analyses 
The objectives of the genetic research are to investigate a relationship between genetic 
variants and:  
• Response to medicine, including CAB + RPV or any concomitant medicines;  
• HIV-1 susceptibility, severity and progression and related conditions.  
Genetic data may be generated while the study is underway or following completion of 
the study.  Genetic evaluations may include focused candidate gene approaches and/or 
examination of a large number of genetic variants throughout the genome (whole genome 
analyses). Genetic analyses will utilize data collected in the study and will be limited to 
understanding the objectives highlighted above.  Analyses may be performed using data 
from multiple clinical studies to investigate these research objectives. 
Appropriate descriptive and/or statistical analysis methods will be used. A detailed 
description of any planned analyses will be documented in a RAP prior to initiation of the 
analysis. Planned analyses and results of genetic investigations will be reported either as 
part of the clinical RAP and study report, or in a separate genetics RAP and report, as 
appropriate. 
Study Population 
Any participant who is enrolled in the clinical study can participate in genetic research. 
Any participant who has received an allogeneic bone marrow transplant must be excluded 
from genetic research. 
Study Assessments and Procedures 
A key component of successful genetic research is the collection of samples during 
clinical studies. Collection of samples, even when no  prior hypothesis has been 
identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.   
• A 6 mL blood sample will be taken for deoxyribonucleic acid (DNA) extraction.  
A blood sample is collected at the baseline visit, after the participant has been 
randomized and provided informed consent for genetic research. Instructions for 
collection and shipping of the genetic sample are described in the laboratory 
manual. The DNA from the blood sample may undergo quality control analyses to 
confirm the integrity of the sample.  If there are concerns regarding the quality of 
the sample, then the sample may be destroyed.  The blood sample is taken on a 
single occasion unless a duplicate sample is required due to an inability to utilize 
the original sample.  
The genetic sample is labelled (or “coded”) with the same study specific number used to 
label other samples and data in the study.   This number can be traced or linked back to 

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

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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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10.8. 
Appendix 8: Liver Safety: Required Actions, Follow-up 
Assessments and Study Intervention Guidelines 
10.8.1. 
VSLC Guidelines for Drug Restart after stop for Liver criteria 
 
Drug Restart refers to resuming study treatment following liver events meeting stopping 
criteria in which there is a clear underlying cause (other than DILI) of the liver event 
(e.g., biliary obstruction, pancreatic events, hypotension, acute viral hepatitis). 
Furthermore, there should be no evidence of alcoholic hepatitis or hypersensitivity, and 
the drug should not be associated with HLA markers of liver injury. (Table 10; Figure 7). 
  
DRUG RESTART 
“Drug restart” can be approved by the VSLC for transient, defined non-drug-induced 
liver injury if no evidence of: 
• 
 immunoallergic injury /HLA association with injury 
• 
alcoholic hepatitis 
Study drug must be held while labs and evaluation are completed to assess diagnosis. 
10.8.2. 
VSLC Decision Process for Drug Restart Approval or Disapproval 
• Principal Investigator (PI) requests consideration of drug re-initiation for a 
participant stable or improving on IP, who exhibits liver chemistry elevation 
meeting participant stopping criteria, which is transient, non-drug-related, and 
liver chemistries have improved to normal or are within 1.5x Baseline and ALT< 
3xULN depending on baseline ALT as per Section 7.1.3.1.1.  
• GSK Medical Monitor and GCSP Physician to review the participant’s diagnosis 
restart risk factors (Hepatotoxicity Panel consultation is available) and complete 
checklist (Table 10). 
– must present source data defining the patient’s current resistance profile 
with documented evidence of extensive drug resistance and previous drug 
history. 
• The local operating company (LOC) medical director should be informed that 
study drug restart is under consideration and of the final decision, whether or not 
to proceed. 
• Relevant physicians (listed below) must review and agree on action to be taken 
regarding request for drug restart:   
• Safety ReviewTeam Leader, Safety Development Leader, or Senior Safety 
Physician 
• MDL and PPL 

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• Request is taken to VSLC for final decision 
 
Table 10 
Checklist for Phase III drug restart after well-explained liver injury 
(e.g. biliary, pancreatic, hypotensive events, congestive heart failure 
(CHF), acute viral hepatitis), and improvement of liver chemistry to 
normal or 1.5x baseline & ALT<3xULN 
 
Yes 
No 
Is participant stable or improving on IP? 
 
 
Do not restart if the following risk factors at initial liver injury: 
 
 
fever, rash, eosinophilia, or hypersensitivity  
 
 
drug-induced liver injury  
 
 
alcoholic hepatitis (AST>ALT, typically <10xULN) 
 
 
IP has an HLA genetic marker associated with liver injury (e.g. lapatinib, 
abacavir, amoxicillin/clavulanate) 
 
 
Source data defining the patient’s current resistance profile 
 
 
Previous drug history 
 
 
 

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Figure 7 
VSLC process for drug restart approval or disapproval 
 
Participant exhibits transient, non-drug related liver injury 
while disease condition stable or improving 
 
 
 
 
 
 
 
 
Medical Monitor and Safety Physician(s) to discuss etiology of 
liver injury and 
Have liver injuries decreased to normal or to <1.5x Baseline and 
ALT <3xULN (depending on Baseline ALT) 
Any fever, rash, eosinophilia in this patient or HLA genetic marker 
associated with liver injury [Andrade, 2009]? 
Any evidence of alcoholic hepatitis or DILI in this patient? 
Any prior sever/fatal outcomes reported on drug restart [Papay, 
2009; Hunt, 2010] with this drug? 
Any Evidence of nonclinical hepatic liability/injury with this drug? 
LOC Medical Director to be informed of restart consideration and 
final decision 
 
 
 
 
 
 
 
 
Relevant physicians (from Safety and Clinical functions) review and 
agree on restart request 
 
 
 
 
 
 
 
 
Request is 
submitted to VSLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VSLC Approves Re-initiation of IP 
 
 
 
VSLC Does NOT Approve Re-
initiation of IP 
 
 
 
 
 
 
 
 
 
 
 
PI promptly informed of decision and 
dosing regimen 
Ethics Committee or IRB review, if 
needed 
Benefits/Risks discussed with participant 
and consent recorded in chart  
Liver chemistries obtained once weekly 
for a minimum of one month and 
thereafter for as long as clinically 
indicated 
Safety Review Teams record restart 
outcome 
VSLC notified of restart outcome 
 
 
 
PI promptly informed of decision 
 
10.8.3. 
Medical monitor, GCSP Physician and PI actions for Restart 
following VSLC decision 
10.8.3.1. 
Medical Monitor and GCSP Physician Actions 
• 
Medical Monitor must notify PI of VSLC’s  restart decision and recommended 
dosing regimen in writing and Medical Monitor must record note in study files. 
• 
The Safety Review Team must record  restart outcomes and the GCSP Physician 
must send these to the VSLC (see template below). 
• 
All severe reactions (associated with bilirubin>2xULN or jaundice, or INR1.5), 
SAEs or fatalities which occur following a drug or restart. must be immediately 

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

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10.9. 
Appendix 9: AEs, ADEs, SAEs, SADEs, USADEs and Device 
Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting in Medical Device 
Studies 
• The definitions and procedures detailed in this appendix are in accordance with 
ISO 14155 and the European Medical Device Regulation (MDR) 2017/745 for 
clinical device research (if applicable).  
• Both the investigator and the sponsor will comply with all local medical device 
reporting requirements for medical devices. 
• The detection and documentation procedures described in this protocol apply to 
all GSK medical devices provided for use in the study (see Section 6.1.3 for the 
list of GSK medical devices). 

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10.9.1. 
Definition of Medical Device AE and ADE 
Medical Device AE and ADE Definition  
• 
A medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether or not considered related to the investigational medical device. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated 
with the use of an investigational medical device. This definition includes events 
related to the investigational medical device or comparator and events related to the 
procedures involved except for events in users or other persons, which only include 
events related to investigational devices. 
• 
An adverse device effect (ADE) is defined as an AE related to the use of an 
investigational medical device. This definition includes any AE resulting from 
insufficient or inadequate instructions for use, deployment, implantation, installation, 
or operation, or any malfunction of the investigational medical device as well as any 
event resulting from use error or from intentional misuse of the investigational 
medical device. 
 
10.9.2. 
Definition of Medical Device SAE, SADE and USADE 
A Medical Device SAE is any serious adverse event that: 
a. 
Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
o A life-threatening illness or injury. The term ‘life-threatening' in the definition of 
‘serious' refers to an event in which the participant was at risk of death at the 
time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
o A permanent impairment of a body structure or a body function. 
o Inpatient or prolonged hospitalization. Planned hospitalization for a pre-existing 
condition, or a procedure required by the protocol, without serious deterioration 
in health, is not considered an SAE. 
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
o Chronic disease (MDR 2017/745). 
c. 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of any infectious agent via a medicinal product 

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

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

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minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE/SAE/device deficiency 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE/SAE/device deficiency as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK with a copy of any post-mortem findings 
including histopathology. 
• 
New or updated information will be recorded in the originally completed form. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 
10.9.5. 
Reporting of SADEs 
SADE Reporting to GSK  
• 
NOTE: There are additional reporting obligations for medical device 
deficiencies that are potentially related to SAEs that must fulfil the legal 
responsibility to notify appropriate regulatory authorities and other entities about 
certain safety information relating to medical devices being used in clinical studies.  
• 
Any device deficiency that is associated with an SAE must be reported to the 
manufacturer of the device (if known) within 24 hours after the investigator 
determines that the event meets the definition of a device deficiency. 
 
 

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

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

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

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

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

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10.11. 
Appendix 11:  COVID-19 Pandemic and Clinical Trial 
Continuity  
Background 
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participants ability to attend clinic visits.  In some places, medical 
visits are occurring, and in others, research clinics are operating with only emergency 
staff. 
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in HIV-1 
treatment for participants enrolled in this clinical study, through continuous access to 
antiretroviral therapy. 
In order to maintain the scientific integrity of the study, and adhere to updated guidance 
from regulators, procedures have also been put into place to ensure that the actions taken 
to mitigate against any impact of COVID-19 are well documented in the trial database. 
A “Memo to Investigators” was issued on March 18th, 2020 and served as a record of 
approved emergency actions being taken within this clinical trial to manage issues related 
to COVID-19.  That memo continues to serve as record of approved actions which can be 
fully implemented by Investigators, in advance of this protocol guidance.  This appendix 
will remain consistent with the guidance provided within the “Memo to Investigators” 
and will also serve to provide additional protocol documentation requirements and 
procedures. 
This appendix outlines the measures which are approved for implementation within this 
clinical trial, to protect patient safety and to ensure the integrity of the clinical trial, as a 
result of COVID-19 only. These measures may be implemented in accordance with any 
requirements and expectations set out by local Independent Review Boards/Independent 
Ethics Committees and National Competent Authorities, as necessary. 
This appendix does not apply to participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19.  
10.11.1. 
Changes to Study Visits and Study Procedures 
• Where site staff resource is constrained due to COVID-19, IM dosing visits may 
proceed with limited or no other protocol-defined assessments (e.g. lab tests, 
questionnaires, etc.). If lab tests will be missed for more than one consecutive 
visit, the medical monitor must be contacted, to provide guidance for safety 
monitoring.  
• For WOCBP, point of care pregnancy testing should be performed, prior to IM 
dosing. 
• If central laboratory testing cannot be performed at a particular visit, and 
monitoring for safety is required, tests may be performed at an appropriately 

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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. 
 
10.11.2. 
Changes to Informed Consent 
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   
Any updated informed consent form or other participant-facing materials should be 
provided to participants by e-mail, mail or courier before re-consent is obtained. Any 
consent obtained this way should be documented in source records and confirmed by way 
of normal consent procedure at the earliest opportunity when participants attend their 
next on-site study visit. 
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval. 
 
10.11.3. 
Permissible Use of Antiretroviral Therapy 
In order to minimize the risk of gaps in HIV-1 antiretroviral therapy (ART) for 
participants impacted by COVID-19 in the clinical trial, the following options can be 
considered with regards to ART dosing, in order of preference: 

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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 6.8.1. The process and 
required information for requesting oral bridging can be found in your Study 
Reference/Procedure Manual.  Please continue to reach out to your study medical 
monitor for approval of oral bridging, in order to document use and to ensure expeditious 
shipment of oral CAB + RPV to your site.  
Participants who use oral CAB + RPV as short-term oral bridging are permitted to return 
to IM dosing, on protocol, once the COVID-19 conditions permit resumption of site 
activities.  
The investigator should reach out to the medical monitor to confirm IM restart 
instructions, and to ensure the participant remains appropriate for resumption of IM 
dosing. If oral bridging with CAB/RPV is anticipated to continue for > 2 months, 
additional approval and guidance should be obtained from the medical monitor to 
continue with oral bridging therapy. Loading/Re-initiation doses of CAB + RPV IM may 
be required, depending on the length of oral bridging. 

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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. 
10.11.4. 
Direct-To-Patient (DTP) Shipment of Oral Study IP  
If a participant is unable to travel to the clinic, either to receive IM injections or to be 
dispensed oral bridging, sites are encouraged to consider DTP shipments of drug, from 
the site, to the participant, to ensure access to medicines.  
• If the study site is considering DTP shipment of oral CAB + RPV investigational 
product (IP), the site must first verify if DTP IP dispensing by 
investigators/hospital pharmacies is locally permitted and whether it requires 
regulatory and/or local ethics pre-approval, or post-hoc notification. 
• The study participant should express his/her agreement for DTP shipment and the 
sharing of their personal information with any third-party couriers (as applicable), 
in accordance with local requirements.  This agreement should be documented in 
source records. 
• Oral CAB + RPV IP can be shipped at ambient temperatures via ground transport 
without a temperature monitoring device, with low risk of temperature excursions. 
Sites are encouraged to use discretion in determining the need for in-transit 
temperature monitoring based on the labelled storage requirements and the 
planned mode of transport and apply this as appropriate.  Shipment of oral CAB + 
RPV via air courier continues to require appropriate temperature monitoring.  For 
shipment conditions of oral medications other than oral CAB + RPV, please 
consult the product labelling. 
• In all cases IP accountability must be maintained, and all DTP dispensing 
documentation should be reflected in source records and dispensing logs per GCP. 

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

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

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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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10.12. 
Appendix 12: Country-specific requirements 
10.12.1. 
United Kingdom (UK) 
This requirement has been included based on requests from the Medicines and Healthcare 
products Regulatory Agency (MHRA) to include information on the specific duration of 
the Extension or Continuation Phase/Study Treatment for similar Phase 3 trials.  
Study Duration:  In this study, the Extension Phase is intended to provide access to 
CAB LA + RPV LA until CAB LA + RPV LA receives local (by country) regulatory 
approval and becomes commercially available. Therefore, the duration of the Extension 
Phase may vary from country to country and is dependent on the recruitment time for the 
study and the time taken to achieve local approval for marketing. For participants in the 
UK, estimating a 4- month recruitment period, and with treatment anticipated to be 
commercially available by approximately 4Q 2021, the Extension Phase is anticipated to 
conclude around the same time. During this time, participants will be monitored on Q2M 
to ensure they continue to derive clinical benefit from CAB LA + RPV LA. 
Based on the request from Medicines and Healthcare Products Regulatory Agency 
(MHRA) in United Kingdom, to adjust the Exclusion Criteria Number 11 regarding the 
participants with a risk of seizures excluded or not in this study and the responsibility of 
the Investigator making the decision. 
Exclusion Criteria # 11: 
11.   
Participants determined by the Investigator to have a high risk of seizures, 
including participants who had a seizure within the last year without a 
clear aetiology, or had seizures within the last 12 months while receiving 
anti-seizure medications will be excluded.  Participants with a distant 
history of seizure without recent seizure activities, or any participant with 
a history of a controlled seizure disorder while on treatment who has been 
seizure free and off the anti-seizure medications for >12 months may be 
enrolled if the Investigator believes the risk of seizure recurrence is low.  
Other participants with a prior seizure history may be discussed with the 
Medical Monitor prior to participant’s enrolment 
10.12.2. 
Ireland  
This requirement has been included as a recommendation by the Health Product 
Regulatory Authority (HPRA) in Ireland.  
Section 10.11.1 (Changes to Study Visits and Study Procedures) states the following: 
“There may also be circumstances where immediate actions are required by the sponsor 
and/or investigator, outside of what is contemplated in the protocol, in order to protect a 
study participant from immediate hazard. Any such measures will be carefully 
documented and conducted in accordance with the National Competent Authority 
(NCA)/IRB/IEC regulations”.  

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In Ireland this can be submitted as an urgent safety measure or amendment as appropriate 
as described at the following link: http://www.hpra.ie/homepage/medicines/regulatory-
information/clinical-trials/covid-19-(coronavirus)-and-cts/guidance-on-the-management-of-
clinical-trials-during-covid-19/. 
10.12.3. 
France (FRA) 
This requirement has been included based on requests from the Agence nationale de 
sécurité du médicament et des produits de santé (ANSM) to adjust the Inclusion and 
Exclusion criteria regarding the INI and NNRTI resistance mutations excluded in this 
study in accordance to the EU review process of the Marketing Authorisation 
Application.  
Exclusion Criteria #27 
27. Known or suspected presence of any major INI or NNRTI resistance mutations, 
except for K103N as defined by the IAS-USA resistance guidelines [IAS-USA, 
2019] by any historical resistance test result. 
Note: Prior genotypic resistance testing (genotyping of plasma vRNA and/or 
PBMC vDNA) is not required but if available it must be provided to ViiV, 
after screening and before randomization according to guidance in the SPM, 
to provide direct evidence of no pre-existing exclusionary resistance 
mutations. You must wait for the study virologists to confirm the lack of 
exclusionary resistance mutations, which will be provided before the 
screening window closes. Details regarding baseline or prior resistance data 
must be noted in the source documentation 
10.12.4. 
Germany (DEU) 
Based on the request from the German Lead Ethics Committee: to remove study 
intervention rechallenge. 
Based on the request from the German Competent Authority, the Federal Institute for 
Drugs and Medical Devices (BfArM): to amend Exclusion Criteria 31 
Exclusion Criteria 31: 
31.  Alanine aminotransferase (ALT) ≥ 5x the upper limit of normal (ULN) or 
ALT ≥3x ULN and bilirubin ≥1.5 x ULN (with > 35% direct bilirubin) 

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

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

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

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

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

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

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

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Amendment 01 / France 01, 16-NOV-2020 
Overall Rationale for Country-Specific Amendment:  
Based on requests from the:  
• Agence nationale de sécurité du médicament et des produits de santé (ANSM) in 
France, to adjust the Exclusion criteria number 27 regarding the major INI and 
NNRTI resistance mutations excluded in this study.  
• French Ethics committee, to adjust the introduction as few biotherapies are 
proposed to simplify patients treatment.   
Section # 
and Name 
Description of Change 
Brief Rationale 
Section 2 
Introduction  
Removal of while the phrase  “there 
are no currently approved two-drug 
regimens to maintain suppression, 
simplifying treatment has long been 
a goal to increase treatment 
compliance and improve the quality 
of life for patients with HIV” from 
the second paragraph 
This request was required for France  
Section 5.2 
Exclusion 
Criteria 
Adjustments to include major INI 
and NNRTI resistance mutations 
This amendment was required for France  
 
 
 
 
Amendment 1/GBR-1: 20-NOV-2020 
Overall Rationale for Country-Specific Amendment:  
Based on the request from Medicines and Healthcare Products Regulatory Agency 
(MHRA) in United Kingdom, to adjust the Exclusion Criteria Number 11 regarding the 
participants with a risk of seizures excluded or not in this study and the responsibility of 
the Investigator making the decision. 
  
Section # 
and Name 
Description of Change 
Brief Rationale 
Section 5.2 
Exclusion 
Adjustments to clearly define the 
exclusion criteria and clarify the 
responsibility of the Investigator to 
This amendment was required for United 
Kingdom  

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

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10.14. 
Appendix 14: Abbreviations and Trademarks 
3TC 
Lamivudine, EPIVIR 
ABC 
Abacavir, ZIAGEN 
ABC/3TC 
Abacavir/lamivudine, EPZICOM, KIVEXA 
ADE 
Adverse device effect 
ADL 
Activities of Daily Living 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AIDS 
Acquired immunodeficiency syndrome 
ALT 
Alanine aminotransferase 
Anti-HBc 
Hepatitis B core Antibody 
Anti-HbsAg 
Antibodies against Hepatitis B surface Antigen 
APAP 
N-acetyl-para-aminophenol 
APR 
Antiretroviral Pregnancy Registry 
ARV 
Antiretroviral 
ART 
Antiretroviral therapy 
ATLAS 2M 
Antiretroviral Therapy as Long Acting Suppression every 2 
Months 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AUC(0-) 
Area under the concentration curve from 0 hours to the time 
of next dosing 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CAB 
Cabotegravir 
CAB LA 
Cabotegravir long-acting 
c/mL 
Copies/milliliter 
cART 
Combination antiretroviral therapy 
CCR5 
C-C chemokine receptor type 5 
CD4 
Cluster of Differentiation 4 
CD8 
Cluster of Differentiation 8 
CDC 
Centers for Disease Control and Prevention 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
Cmax 
Maximum concentration 
CMH 
Cochran-Mantel Haenszel 
ConART 
Concomitant Antiretroviral Therapy 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicidality Severity Rating Scale 
CI 
Confidence interval 
CONSORT 
Consolidated Standards of Reporting Trials 
CPK 
Creatine phosphokinase 
CPMS 
Clinical Pharmacology Modelling and Simulation 
CSR 
Clinical Study Report 
CV 
Cardiovascular 
CVF 
Confirmed Virologic Failure 

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COVID-19 
Coronavirus Disease 2019 
DDI 
Drug Drug Interaction 
DAIDS 
DILI 
Division of Acquired Immunodeficiency Syndrome 
Drug induced liver injury 
DNA 
Deoxyribonucleic acid 
DRE 
Disease-Related Events 
DRV 
Darunavir 
DTG 
Dolutegravir, TIVICAY 
DVT 
Deep vein thrombosis 
ECG 
Electrocardiogram 
eC-SSRS 
Columbia Suicide Severity Rating Scale 
eCRF 
Electronic case report form 
EFV 
Efavirenz 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
ETR 
Etravirine 
EU 
European Union 
EVG 
Elvitegravir 
FDA 
Food and Drug Administration 
FDC 
Fixed-dose combination 
FTC 
Emtricitabine 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 
HAART 
Highly active antiretroviral therapy 
HbsAg 
Hepatitis B surface Antigen 
HAT-QoL 
HIV/AIDS-targeted quality of life 
HBV 
Hepatitis B virus 
HCG 
human chorionic gonadotrophin 
HCV 
Hepatitis C virus 
HDL 
High density lipoprotein 
HDPE 
High density polyethylene 
HIV 
Human immunodeficiency virus  
HIV TSQ 
HIV treatment satisfaction questionnaire 
HLA 
Human leukocyte antigen 
HSR 
Hypersensitivity reaction 
IAS 
International AIDS Society 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IDMC 
Independent data monitoring committee 
IEC 
Independent Ethics Committee 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
INI 
Integrase inhibitor 
INR 
International normalized ratio 
INSTI 
Integrase strand transfer inhibitor 

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

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

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11. 
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