Clinical trial NCT05896761
Conditions: Human Immunodeficiency Virus Type 1 (HIV-1)
Keywords: Cabotegravir Efficacy Human immunodeficiency virus Pharmacokinetic Rilpivirine Safety Tolerability
Sponsor: ViiV Healthcare
Start date: 2021-10-28; Completion date: 2022-08-23
Enrollment: 118 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This sub-study will assess the pharmacokinetics (PK), safety, tolerability, virologic efficacy and health outcomes of CAB (GSK1265744) and RPV long acting (LA) in HIV-infected adult participants currently enrolled in the Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS2M \[A2M\]) study (NCT03299049).

Detailed description:

Arms: arm 1: Participants will receive an Intramuscular (IM) injection of CAB LA 400 mg on one lateral thigh and RPV LA 600 mg into the opposite lateral thigh on Day 1 in every 4 weeks (Q4W) for a total of 16 weeks during Thigh injection phase. Participants will then return to the clinic 4 weeks later to receive their first IM gluteal injection (at Week 16) of CAB LA 400 mg and RPV LA 600 mg during the Return to Gluteal Injection Phase. The subsequent gluteal injection will occur at Week 20. arm 2: Participants will receive an IM injection of CAB LA 600 mg on one lateral thigh and RPV LA 900 mg into the opposite lateral thigh on Day 1 in every 8 weeks (Q8W) for a total of 16 weeks during Thigh injection phase. Participants will then return to the clinic 8 weeks later receive their first IM gluteal injection (at Week 16) of CAB LA 600mg and RPV LA 900 mg during the Return to Gluteal Injection phase. The subsequent gluteal injection will occur at Week 24.
Interventions: intervention 1: Cabotegravir Injectable Suspension intervention 2: Rilpivirine Injectable Suspension
Intervention descriptions: intervention 1: CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 milligrams per milliliter (mg/mL) of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be frozen. intervention 2: RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be frozen. RPV LA should also be protected from light.

Protocol documents:
Prot_000.pdf: 
Protocol
Study ID:  207966
Official Title of Study: A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-
inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-
acting Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 
4 Weeks in HIV-1-infected Adults who are Virologically Suppressed (ATLAS-2M), 
further referred to as A2M.
NCTID: NCT03299049
Sub-study Protocol Amendment Title: Sub-sudy to the A2M study to Evaluate the 
Pharmacokinetics, Tolerability and Efficacy of Cabotegravir and Rilpivirine Long-Acting 
Injections Following Intramuscular Administration in the Vastus Lateralis Muscle (thigh) 
in HIV-infected Adult Participants who have Received at Least Three Years of Gluteal 
Injections in the A2M Study. 
NCTID: NCT05896761
Date of Document: 11 August 2021
The sub-study was added to the protocol of the main study via an amendment. Details of 
the sub-study can be found in the protocol section 11.13 Appendix 13: Vastus Lateralis 
Muscle (Thigh) PK sub-study Amendment. A separate record has been created on 
ClinicalTrials.gov for the sub-study. 


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ViiV Healthcare group of companies 
 
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TITLE PAGE 
Protocol Title: A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-inferiority, 
Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting 
Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 4 
Weeks in HIV-1-infected Adults who are Virologically Suppressed. 
Protocol Number: 207966/06 
Short Title: Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting 
Cabotegravir Plus Long-acting Rilpivirine administered every 8 weeks in Virologically 
Suppressed HIV-1-infected Adults. 
Compound Number: GSK1265744  
 
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 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. 
This study is sponsored by ViiV Healthcare. GlaxoSmithKline is supporting ViiV 
Healthcare in the conduct of this study 
Copyright 2021 ViiV Healthcare group of companies.  All rights reserved.  Unauthorized 
copying or use of this information is prohibited. 


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Regulatory Agency Identifying Number(s):  
IND No. 109,678;  
EudraCT No. 2017-002946-62 
Approval Date:  11-Aug-2021 
 


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SPONSOR SIGNATORY: 
Protocol Title: A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-inferiority, 
Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting 
Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 4 
Weeks in HIV-1-infected Adults who are Virologically Suppressed. 
Protocol Number: 207966/06 
Compound Number: GSK1265744  
 
 
 
 
 
Scott McCallister,  
Head Physician, Clinical Development 
ViiV Healthcare 
 
The signed page is a separate document. 
 
 
Date 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
 
Document 
Date 
DNG Number 
Amendment 6 
11-Aug-2021 
TMF-13901227 
Amendment 5 
16-Apr-2021 
TMF-11797977 
Amendment 4 
05-Aug-2020 
2017N326521_04 
Amendment 3 
21-May-2020 
2017N326521_03 
Amendment 2 
03-Jul-2018 
2017N326521_02 
Amendment 1 
14-Sep-2017 
2017N326521_01 
Original Protocol 
17-Jul-2017 
2017N326521_00 
 
Amendment 6 11-AUG-2021 
Overall rationale for Amendment 6 
The primary purposes of this amendment are: 
• Included Thigh Injection Sub-study appendix 
• Added safety and PK laboratory assessments during pregnancy for subjects who 
become pregnant during the study and decide to continue receiving IM treatment 
in the study. 
• Medical device deficiencies reporting requirements updated to be aligned  with 
GSK reporting processes. 
• Updated safety information 
• Other minor clarifications added 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 2.3.1 Risk 
assessment  
• 
Updated animal reproduction data changed in 
line with CAB IB, to ensure the most up to date 
data is used 
• 
Information regarding systemic reactions 
following RPV LA injection updated 
• 
Removal of ‘’CAB is in clinical development’’ 
• 
Changed text from ‘’ a small proportion of’’ to 
‘’less than 1%’’ of participants have developed 
transaminitis 
• 
Removal of text regarding participants with 
suspected DILI only receiving oral cabotegravir 
 
• 
Clarification requested by 
Korean Reg Agency to 
align with IB exposure 
range 
• 
Safety information update 
CAB is now marketed in 
some countries  
• 
More accurate data using 
‘’less than 1%’’ 
• 
Some DILI were identified 
in participants taking prep 
(LA CAB)  
4.2.4 LTFU Phase  
• 
Additional clarification provided on participants 
who transition to commercial product and do 
not enter the LTFU phase that the transition 
plan to marketed product should be done in 
consultation with the Central Study Team and  
study Medical Monitor 
• 
As more countries begin to 
transition their participants 
onto commercial CAB + 
RPV LA this additional 
information provides more 
guidance for investigators  
5.3 Additional 
eligibility criteria 
• 
Additional clarification regarding participants in 
CAB studies being unable to participate in other 
clinical studies  
• 
Study teams were seeing 
a rise in requests for 
participants being involved 
in other interventional 
studies, the additional text 
clarifies that this is not 
permitted in CAB protocols  
7.1.1 and 7.2.2 
Time and Events 
table 
• 
Added Device Deficiencies reporting 
assessment 
• 
In line with Medical Device 
Reporting requirement. 
7.4.3.1. Time 
period and 
Frequency for 
collecting AE and 
SAE information 
• 
Updated medical device text to now use the 
term ‘’associated person’’ and ‘’authorization 
letter’’ 
• 
In line with GSK reporting 
processes 
7.4.3.4 Prompt 
Reporting of SAEs 
and Other Events 
• 
Added footer reference to Appendix 12 for 
Medical Device deficiencies reporting 
requirements  
• 
In line with GSK reporting 
processes 
7.4.3.5 Disease 
related events and / 
or Disease Related 
Outcomes not 
Qualifying as SAEs  
• 
Updated text in this section to ensure the 
reporting process is in line with the study 
reporting process and data management 
• 
Removed ‘’instead of a DRE’’ 
• 
Removes confusion and is 
in line with ATLAS2M 
reporting 
7.4.3.9 Medical 
device deficiencies 
  
• 
Updated medical device text to now use the 
term ‘’associated person’’ and ‘’authorization 
letter’’  
• 
Included examples of who an ‘’associated 
person’’ is  
• 
Updated text to clarify the process for an 
associated person 
• 
Updated wording on the medical devices used 
in the study 
• 
Included wording regarding the responsible 
person for compliance with local regulatory 
requirements relating to the reporting of device 
deficiencies  
• 
In line with GSK reporting 
processes 
• 
Provides clarity on what is 
considered a medical 
device 


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Section # and 
Name 
Description of Change 
Brief Rationale 
7.4.5.4 Seizures  
• 
Updated statistics regarding seizures following 
CAB administration 
• 
Provides the most up to 
date information 
7.4.7.3 Time Period 
for Collecting 
Pregnancy 
Information 
• 
Additional text regarding women who become 
pregnant whilst on LA and the collection of 
unbound CAB and extra testing during 
pregnancy, this is updated through the 
pregnancy appendix  
• 
In line with updated  
requirements to ensure 
clinical oversight of 
pregnant subjects 
7.4.7.4 Action to be 
Taken if Pregnancy 
Occurs 
• 
Additional text to clarify the additional samples 
to be collected in case of pregnancy. 
• 
In line with updated 
requirements to ensure 
clinical oversight of 
pregnant subjects. 
11.1 Appendix 1: 
Abbreviations and 
Trademarks 
• 
Added new abbreviations and trademarks used 
throughout the protocol. 
• 
Not applicable 
11.6.5. Evaluating 
AEs and SAEs 
• 
Added language regarding Medical Device 
deficiency reporting  
• 
In line with Medical Device 
Reporting requirement. 
11.8.3  Informed 
Consent Process 
• 
Updated medical device text to now use the 
term ‘’associated person’’ and ‘’authorization 
letter’’ 
• 
In line with GSK reporting 
processes 
11.11.3 
Background 
(Removed)  
• 
Removed this section as pregnancy outcome 
details were no longer current. 
• 
Safety information update. 
11.11.3.1 
Cabotegravir 
• 
Updated animal reproduction data changed in 
line with CAB IB, to ensure the most up to date 
data is used 
• 
Updated text regarding the ongoing DTG birth 
outcomes study to provide the most up to date 
data 
• 
Removal of outdated text 
• 
Clarification requested by 
Korean Reg Agency to 
align with IB exposure 
range 
• 
Safety information update 
11.11.4.3 Overall 
Benefit: Risk 
Conclusion  
 
• 
Pregnancy appendix summary updated 
• 
In line with updated 
requirements to ensure 
clinical oversight of 
pregnant subjects. 
11.11.4.1 Exposure 
• 
Additional text to clarify the additional samples 
to be collected in case of pregnancy. 
11.11.5 Study 
Assessments and 
Procedures: 
specific 
assessments for 
pregnant 
participants 
11.11.5.1. Safety 
Assessment  
• 
Mentioned that samples will be obtained for 
HIV-1 RNA and Clinical chemistry from the 
pregnant participants electing to continue the 
study 
• 
Additional safety 
assessments for pregnant 
participants 
11.11.5.2. 
Pharmacokinetics 
• 
Added the details on PK sample collections 
separately for CAB and RPV, and unbound  
concentrations. 
• 
Provided the detailed 
information 
11.12.1 Definition 
of Device 
deficiency 
 
• 
Updated definition of Device Deficiency 
• 
In line with GSK reporting 
processes 
 
11.12.2 Recording 
and Follow-Up of 
• 
Updated AE, SAE and Device Deficiency 
recording 


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Section # and 
Name 
Description of Change 
Brief Rationale 
AE and/or SAE and 
Device Deficiencies 
11.12.4 Reporting 
of Medical Device 
Deficiencies for 
Associated Person 
• 
Updated medical device text to now use the 
term ‘’associated person’’ and ‘’authorization 
letter’’  
• 
Included examples of who is an ‘’associated 
person’’ 
• 
In line with the current 
process of using an 
authorization letter if an 
associated person is 
impacted by a medical 
device in study  
• 
Informs investigators of 
who is considered an 
‘’associated person’’ 
11.13 Appendix 13 
Thigh PK sub study 
• 
Included the Appendix: Vastus Lateralis Muscle 
(Thigh) PK sub study amendment. The 
appendix includes all of the relevant information 
for the sub study. 
• 
ATLAS2M Thigh PK Sub-
study implementation. 
General Updates  
• 
Additional minor clarifications and corrections to 
typographical errors/formatting to protocol text 
have been added  
• 
Text clarifications and 
formatting 
 


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TABLE OF CONTENTS 
 
 
Page 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 4 
1. 
SYNOPSIS ............................................................................................................. 16 
1.1. 
Rationale .................................................................................................... 16 
1.2. 
Objectives and Endpoints ........................................................................... 17 
1.3. 
Overall Design ............................................................................................ 19 
1.3.1. 
207966 (ATLAS-2M) Study Design Schematic ............................ 21 
1.3.2. 
Number of Participants ................................................................ 21 
1.4. 
Treatment Groups and Duration ................................................................. 22 
1.4.1. 
Screening Phase (Up to 35 days) ................................................ 22 
1.4.2. 
Maintenance Phase (Day 1 up to Week 100) ............................... 22 
1.4.2.1. 
Patients randomized to LA dosing from current 
ART SOC therapy:...................................................... 23 
1.4.2.1.1. 
IM injections every 4 weeks (Q4W 
from SOC): ............................................. 24 
1.4.2.1.2. 
IM injections every 8 weeks (Q8W 
from SOC): ............................................. 24 
1.4.2.2. 
Participants transitioning from ATLAS and 
currently receiving CAB LA + RPV LA Q4W ............... 25 
1.4.2.2.1. 
IM injections every 4 weeks (Q4W 
from ATLAS Q4W): ................................. 26 
1.4.2.2.2. 
IM injections every 8 weeks (Q8W 
from ATLAS Q4W): ................................. 26 
1.4.3. 
Extension Phase .......................................................................... 26 
1.4.4. 
Long-Term Follow-Up Phase ....................................................... 27 
1.4.5. 
Dose Modifications: ..................................................................... 29 
2. 
INTRODUCTION .................................................................................................... 29 
2.1. 
Study Rationale .......................................................................................... 30 
2.2. 
Background ................................................................................................ 30 
2.3. 
Benefit/Risk Assessment ............................................................................ 33 
2.3.1. 
Risk Assessment ......................................................................... 33 
2.3.1.1. 
Other Clinically Relevant Information .......................... 50 
2.3.2. 
Benefit Assessment ..................................................................... 50 
2.3.3. 
Overall Benefit:Risk Conclusion ................................................... 50 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 51 
4. 
STUDY DESIGN .................................................................................................... 54 
4.1. 
Overall Design ............................................................................................ 54 
4.2. 
Treatment Groups and Duration ................................................................. 56 
4.2.1. 
Screening Phase (Up to 35 days) ................................................ 56 
4.2.2. 
Maintenance Phase (Day 1 up to Week 100) ............................... 57 
4.2.2.1. 
Patients randomized to LA dosing from current 
ART SOC therapy:...................................................... 58 
4.2.2.1.1. 
IM injections every 4 weeks (Q4W 
from SOC): ............................................. 59 


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4.2.2.1.2. 
IM injections every 8 weeks (Q8W 
from SOC): ............................................. 59 
4.2.2.2. 
Participants transitioning from ATLAS and 
currently receiving CAB LA + RPV LA Q4W ............... 60 
4.2.2.2.1. 
IM injections every 4 weeks (Q4W 
from ATLAS Q4W): ................................. 60 
4.2.2.2.2. 
IM injections every 8 weeks (Q8W 
from ATLAS Q4W): ................................. 60 
4.2.3. 
Extension Phase .......................................................................... 61 
4.2.4. 
LTFU Phase – IM Regimen Only ................................................. 62 
4.2.5. 
Dose Modifications: ..................................................................... 63 
4.2.6. 
Independent Data Monitoring Committee ..................................... 63 
4.3. 
Type and Number of Participants ................................................................ 64 
4.4. 
Scientific Rationale for Study Design .......................................................... 64 
4.5. 
Dose Justification ........................................................................................ 66 
4.5.1. 
Oral Lead-In Phase ...................................................................... 66 
4.5.2. 
Long Acting Injectable for Maintenance Phase ............................ 69 
4.5.2.1. 
CAB LA Q8W ............................................................. 73 
4.5.2.1.1. 
CAB PK Profile Following 
Transition to Q8W Regimen .................... 73 
4.5.2.2. 
CAB LA Q4W ............................................................. 76 
4.5.3. 
RPV LA ........................................................................................ 78 
4.5.3.1. 
RPV LA Q8W ............................................................. 79 
4.5.3.1.1. 
RPV PK Profile Following 
Transition to Q8W Regimen .................... 80 
4.5.3.2. 
RPV LA Q4W ............................................................. 83 
5. 
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA ............. 85 
5.1. 
Inclusion Criteria ......................................................................................... 85 
5.2. 
Exclusion Criteria ........................................................................................ 88 
5.3. 
Additional Eligibility Criteria ......................................................................... 92 
5.4. 
Screening/Baseline/Run-in Failures ............................................................ 93 
5.5. 
Withdrawal/Stopping Criteria....................................................................... 93 
5.5.1. 
Liver Chemistry Stopping Criteria ................................................ 96 
5.5.1.1. 
Liver Chemistry Stopping Criteria, Participant 
Management and Follow-Up ....................................... 97 
5.5.1.2. 
Liver Event Adjudication Committee ........................... 98 
5.5.1.3. 
Liver Chemistry Stopping Criteria – Restart ................ 98 
5.5.1.4. 
General Guidance Restart .......................................... 99 
5.5.1.4.1. 
Drug Restart ........................................... 99 
5.5.1.4.2. 
Drug Restart Following Transient 
Resolving Liver Events Not 
Related to IP ......................................... 100 
5.5.2. 
QTc Stopping Criteria ................................................................ 101 
5.5.3. 
Virologic Failure ......................................................................... 102 
5.5.4. 
Definition of Protocol-Defined Confirmed Virologic Failure ......... 102 
5.5.5. 
Managing Virologic Failure ........................................................ 102 
5.5.5.1. 
HIV-1 RNA Blips ....................................................... 102 
5.5.5.2. 
Suspected Virologic Failure ...................................... 103 
5.5.5.3. 
Confirmed Virologic Failure ...................................... 103 
5.6. 
Participant and Study Completion ............................................................. 104 


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6. 
STUDY TREATMENT .......................................................................................... 105 
6.1. 
Investigational Product and Other Study Treatment .................................. 105 
6.1.1. 
Formulations of CAB + RPV ...................................................... 106 
6.1.1.1. 
Cabotegravir Tablets (CAB) ...................................... 106 
6.1.1.2. 
Rilpivirine Tablets (RPV)........................................... 106 
6.1.1.3. 
Cabotegravir Injectable Suspension (CAB LA) ......... 106 
6.1.1.4. 
Rilpivirine Injectable Suspension (RPV LA) .............. 106 
6.2. 
Treatment Assignment .............................................................................. 107 
6.3. 
Dosage and Administration ....................................................................... 107 
6.4. 
Blinding ..................................................................................................... 110 
6.5. 
Packaging and Labeling ............................................................................ 110 
6.6. 
Preparation/Handling/Storage/Accountability ............................................ 110 
6.6.1. 
Dosing Considerations for CAB LA + RPV LA ............................ 111 
6.7. 
Compliance with Study Treatment Administration ..................................... 112 
6.8. 
Protocol Permitted Substitutions ............................................................... 113 
6.8.1. 
Oral Bridging .............................................................................. 113 
6.9. 
Interruption of Study Treatment and Visit/Dosing Windows ....................... 113 
6.9.1. 
IM Dosing .................................................................................. 113 
6.9.1.1. 
IM injections every 4 weeks (Q4W): ......................... 114 
6.9.1.2. 
IM injections every 8 weeks (Q8W): ......................... 115 
6.9.1.3. 
IM injections every 4 weeks (Q4W) (Q4W from 
ATLAS Q4W): ........................................................... 116 
6.9.1.4. 
IM injections every 8 weeks (Q8W) (Q8W from 
ATLAS Q4W): ........................................................... 116 
6.9.2. 
Oral Dosing ................................................................................ 116 
6.10. 
Discontinuation of Study Treatment .......................................................... 117 
6.11. 
Treatment of Study Treatment Overdose .................................................. 117 
6.12. 
Treatment after the End of the Study ........................................................ 118 
6.13. 
Concomitant Medications and Non-Drug Therapies .................................. 118 
6.13.1. 
Permitted Medications and Non-Drug Therapies ........................ 119 
6.13.2. 
Prohibited Medications and Non-Drug Therapies ....................... 119 
6.13.2.1. Concurrent with CAB and/or RPV ............................. 120 
6.13.2.2. Concurrent with either CAB LA or RPV LA ............... 121 
6.13.2.3. Prohibited Medications for Participants 
Receiving HAART during the Long-Term 
Follow-Up Phase ...................................................... 121 
6.14. 
Medical Devices ........................................................................................ 121 
7. 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 122 
7.1. 
Time and Events Table ............................................................................. 122 
7.1.1. 
Time and Events Table for CAB LA + RPV LA Q4 Weekly 
Administration ............................................................................ 123 
7.1.2. 
Time and Events Table for CAB LA + RPV LA Q8 Weekly 
Administration ............................................................................ 131 
7.2. 
Screening and Critical Baseline Assessments .......................................... 137 
7.2.1. 
Screening Assessments ............................................................ 137 
7.2.2. 
Baseline Assessments ............................................................... 138 
7.3. 
Efficacy ..................................................................................................... 139 
7.3.1. 
Plasma HIV-1 RNA .................................................................... 139 
7.3.2. 
Lymphocyte Subsets, CD4+ and CD8+ ..................................... 139 
7.3.3. 
HIV Associated Conditions ........................................................ 139 
7.4. 
Safety ....................................................................................................... 140 


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7.4.1. 
Clinical Evaluations .................................................................... 140 
7.4.2. 
Laboratory Assessments ........................................................... 141 
7.4.3. 
Adverse Events (AE) and Serious Adverse Events (SAEs) ........ 144 
7.4.3.1. 
Time period and Frequency for collecting AE 
and SAE information ................................................. 144 
7.4.3.2. 
Method of Detecting AEs and SAEs ......................... 144 
7.4.3.3. 
Follow-up of AEs and SAEs ...................................... 145 
7.4.3.4. 
Prompt Reporting of Serious Adverse Events 
and Other Events ..................................................... 145 
7.4.3.5. 
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs .............. 148 
7.4.3.6. 
Regulatory Reporting Requirements for SAEs .......... 148 
7.4.3.7. 
Cardiovascular and Death Events ............................ 149 
7.4.3.8. 
Death Events ............................................................ 149 
7.4.3.9. 
Medical Device Deficiencies ..................................... 150 
7.4.3.9.1. 
Time period for Detecting Medical 
Device Deficiencies .............................. 150 
7.4.3.9.2. 
Follow-up of Medical Device 
Deficiencies .......................................... 150 
7.4.3.9.3. 
Prompt Reporting of Medical 
Device Deficiencies to the 
Sponsor ................................................ 150 
7.4.3.9.4. 
Regulatory Reporting 
Requirements for Device 
Deficiencies .......................................... 151 
7.4.4. 
Toxicity Management ................................................................. 151 
7.4.4.1. 
Treatment Interruption Due to an Adverse 
Event ........................................................................ 151 
7.4.4.2. 
Grade 1 or Grade 2 Toxicity/Adverse Event ............. 152 
7.4.4.3. 
Grade 3 Toxicity/Adverse Event ............................... 152 
7.4.4.4. 
Grade 4 Toxicity/Adverse Event ............................... 153 
7.4.5. 
Specific Toxicities/Adverse Event Management ......................... 153 
7.4.5.1. 
Liver Chemistry Stopping and Follow-up 
Criteria ...................................................................... 153 
7.4.5.2. 
Diarrhea ................................................................... 153 
7.4.5.3. 
Hypertriglyceridemia/ Hypercholesterolemia ............. 154 
7.4.5.4. 
Seizures ................................................................... 154 
7.4.5.5. 
Creatine Phosphokinase (CPK) Elevation ................ 155 
7.4.5.6. 
Lipase Elevations and Pancreatitis ........................... 155 
7.4.5.7. 
Decline in Renal Function ......................................... 156 
7.4.5.7.1. 
Proximal Renal Tubule 
Dysfunctions (PRTD) ............................ 157 
7.4.5.8. 
Proteinuria ................................................................ 157 
7.4.5.9. 
QTc Prolongation ..................................................... 157 
7.4.5.10. Injection Site Reactions (ISRs) ................................. 158 
7.4.5.11. Allergic reaction ........................................................ 158 
7.4.5.12. Abacavir Hypersensitivity Reaction (ABC HSR) ........ 158 
7.4.5.12.1. Essential Patient Information ................ 159 
7.4.5.12.2. Reporting of Hypersensitivity 
Reactions ............................................. 160 
7.4.5.13. Rash Without ABC HSR Symptoms ......................... 160 
7.4.6. 
Suicidal Risk Monitoring ............................................................. 162 


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7.4.7. 
Pregnancy ................................................................................. 162 
7.4.7.1. 
Pregnancy testing ..................................................... 162 
7.4.7.2. 
Rationale for Continued Use in Pregnancy ............... 163 
7.4.7.3. 
Time Period for Collecting Pregnancy 
Information ............................................................... 163 
7.4.7.4. 
Action to be Taken if Pregnancy Occurs ................... 164 
7.4.8. 
Physical Exams ......................................................................... 165 
7.4.9. 
Vital Signs .................................................................................. 165 
7.4.10. 
Electrocardiogram (ECG) ........................................................... 165 
7.5. 
Pharmacokinetics ..................................................................................... 165 
7.5.1. 
PK Sample Collection ................................................................ 166 
7.5.2. 
Rationale of PK Sampling Strategy ............................................ 168 
7.5.3. 
Sample Analysis ........................................................................ 168 
7.5.3.1. 
CAB Sample Analysis ............................................... 168 
7.5.3.2. 
RPV Sample Analysis ............................................... 168 
7.6. 
Genetics ................................................................................................... 168 
7.7. 
Viral Genotyping and Phenotyping ............................................................ 168 
7.7.1. 
HIV-1 Polymerase Viral Genotyping and Phenotyping ............... 169 
7.7.2. 
HIV-1 Exploratory Analysis ........................................................ 169 
7.8. 
Value Evidence and Outcomes ................................................................. 169 
7.8.1. 
Value Evidence and Outcomes Endpoints (Secondary) ............. 171 
7.8.2. 
Value Evidence and Outcomes Endpoints (Exploratory) ............ 171 
7.8.3. 
Guidance for administering the different versions of 
HIVTSQc, Preference and Reason for Switch 
Questionnaires in ATLAS-2M ..................................................... 172 
8. 
DATA MANAGEMENT ......................................................................................... 173 
9. 
STATISTICAL CONSIDERATIONS AND DATA ANALYSES ............................... 174 
9.1. 
Sample Size Considerations ..................................................................... 174 
9.1.1. 
Rationale for non-inferiority margin ............................................ 174 
9.1.2. 
Assumption for Snapshot Proportion with HIV-RNA 50 
c/mL at Week 48 (Primary Endpoint) ......................................... 175 
9.1.3. 
Assumption for Response Rate at Week 48 (Secondary 
Endpoint) ................................................................................... 175 
9.1.4. 
Sample Size Sensitivity .............................................................. 175 
9.1.5. 
Sample Size Re-estimation or Adjustment ................................. 177 
9.2. 
Data Analysis Considerations ................................................................... 177 
9.2.1. 
Analysis Populations .................................................................. 177 
9.2.1.1. 
Intent-to-Treat Exposed (ITT-E) ................................ 177 
9.2.1.2. 
Per-Protocol Population (PP) .................................... 177 
9.2.1.3. 
PK Population ........................................................... 177 
9.2.1.4. 
Safety Population ..................................................... 178 
9.2.2. 
Treatment Comparisons ............................................................ 178 
9.2.2.1. 
Primary Comparison of Interest ................................ 178 
9.2.2.2. 
Other Comparisons of Interest .................................. 178 
9.2.3. 
Planned Analyses ...................................................................... 178 
9.2.3.1. 
Week 24 data analyses ............................................ 179 
9.2.3.2. 
IDMC analyses ......................................................... 179 
9.3. 
Key Elements of Analysis Plan ................................................................. 179 
9.3.1. 
Primary Analyses ....................................................................... 179 
9.3.2. 
Secondary Analyses .................................................................. 181 


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9.3.2.1. 
Key Secondary Efficacy Analysis .............................. 181 
9.3.2.2. 
Other Secondary Endpoint Analyses ........................ 181 
9.3.3. 
Pharmacokinetic Analyses ......................................................... 182 
9.3.4. 
Population PK Analysis: ............................................................. 183 
9.3.5. 
Pharmacokinetic/Pharmacodynamic Analyses ........................... 183 
9.3.6. 
Viral Genotyping/Phenotyping Analyses .................................... 183 
9.3.7. 
Health Outcomes Analyses ........................................................ 183 
9.3.8. 
Genetic Analyses ....................................................................... 184 
9.3.9. 
Other Analyses .......................................................................... 184 
10. REFERENCES ..................................................................................................... 185 
11. APPENDICES ...................................................................................................... 189 
11.1. 
Appendix 1: Abbreviations and Trademarks .............................................. 189 
11.2. 
Appendix 2: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Version 2.1, March 2017 ............................ 193 
11.3. 
Appendix 3: Liver Safety – Required actions, Follow up 
Assessments and Study Treatment Restart Guidelines ............................ 217 
11.3.1. 
VSLC Guidelines for Drug Restart after stop for Liver 
criteria ........................................................................................ 217 
11.3.2. 
VSLC Decision Process for Drug Restart Approval or 
Disapproval ................................................................................ 217 
11.3.3. 
Medical monitor, GCSP Physician and PI actions for 
Restart following VSLC decision ................................................ 219 
11.3.3.1. Medical Monitor and GCSP Physician Actions .......... 219 
11.3.3.2. PI Actions: ................................................................ 220 
11.4. 
Appendix 4: CDC Classification for HIV-1 Infection (2014) ........................ 221 
11.5. 
Appendix 5: Genetic Research ................................................................. 223 
11.6. 
Appendix 6: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events ............................................. 226 
11.6.1. 
Definition of Adverse Events ...................................................... 226 
11.6.2. 
Definition of Serious Adverse Events ......................................... 227 
11.6.3. 
Definition of Cardiovascular Events ........................................... 229 
11.6.4. 
Recording of AEs and SAEs ...................................................... 229 
11.6.5. 
Evaluating AEs and SAEs .......................................................... 230 
11.6.6. 
Reporting of SAEs to GSK ......................................................... 231 
11.7. 
Appendix 7: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 233 
11.7.1. 
Collection of Pregnancy Information .......................................... 235 
11.8. 
Appendix 8: Study governance Considerations ......................................... 236 
11.8.1. 
Regulatory and Ethical Considerations, Including the 
Informed Consent Process ........................................................ 236 
11.8.2. 
Financial Disclosure ................................................................... 236 
11.8.3. 
Informed Consent Process ........................................................ 237 
11.8.4. 
Data Protection .......................................................................... 237 
11.8.5. 
Independent Data Monitoring Committee ................................... 238 
11.8.6. 
Quality Control (Study Monitoring) ............................................. 238 
11.8.7. 
Data Quality Assurance ............................................................. 238 
11.8.8. 
Source Documents .................................................................... 239 
11.8.9. 
Study and Site Closure .............................................................. 239 
11.8.10. Records Retention ..................................................................... 240 


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11.8.11. Provision of Study Results to Investigators, Posting of 
Information on Publically Available Clinical Trials 
Registers and Publication .......................................................... 241 
11.9. 
Appendix 9: Country-Specific Requirements ............................................. 242 
11.9.1. 
Study Duration ........................................................................... 242 
11.10. Appendix 10: COVID-19 Pandemic and Clinical Trial Continuity ............... 243 
11.10.1. Changes to Study Visits and Study Procedures ......................... 243 
11.10.2. Changes to Informed Consent ................................................... 244 
11.10.3. Permissible Use of Antiretroviral Therapy .................................. 244 
11.10.4. Direct-To-Patient (DTP) Shipment of Oral Study IP ................... 246 
11.10.5. COVID-19 Experimental Agents ................................................ 247 
11.10.6. COVID-19 Specific Data Capture ............................................... 247 
11.10.6.1. Capturing COVID-19 Specific Protocol 
Deviations ................................................................ 247 
11.10.6.2. Capturing COVID-19 Specific AEs and SAEs ........... 247 
11.11. Appendix 11: Information and Guidance for Managing Pregnant 
Participants ............................................................................................... 250 
11.11.1. Collection of Pregnancy Information .......................................... 250 
11.11.2. Introduction ................................................................................ 250 
11.11.3. Benefit/Risk Assessment ........................................................... 251 
11.11.3.1. Cabotegravir ............................................................. 251 
11.11.3.2. Rilpivirine .................................................................. 254 
11.11.4. Clinical Considerations .............................................................. 254 
11.11.4.1. Exposure .................................................................. 254 
11.11.4.2. Use of Supplements with CAB + RPV LA ................. 256 
11.11.4.2.1. Oral Cabotegravir Only ......................... 256 
11.11.4.3. Overall Benefit: Risk Conclusion ............................... 256 
11.11.5. Study Assessments and Procedures: specific 
assessments for pregnant participants ....................................... 257 
11.11.5.1. Safety Assessments ................................................. 257 
11.11.5.2. Pharmacokinetics ..................................................... 258 
11.11.6. References ................................................................................ 258 
11.12. Appendix 12: Device Deficiencies: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting in Medical Device 
Studies ..................................................................................................... 260 
11.12.1. Definition of Device Deficiency ................................................... 260 
11.12.2. Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies ............................................................................... 260 
11.12.3. Reporting of Medical Device Deficiencies for participants .......... 261 
11.12.4. Reporting of Medical Device Deficiencies for Associated 
Person ....................................................................................... 262 
11.13. Appendix 13: Vastus Lateralis Muscle (Thigh) PK sub-study 
Amendment .............................................................................................. 263 
11.13.1. Sub-study Amendment Background ........................................... 263 
11.13.2. Sub-study Amendment rationale ................................................ 265 
11.13.3. Sub-study Amendment: Objectives and Endpoints .................... 266 
11.13.4. Sub-study Amendment Design .................................................. 268 
11.13.4.1. Sub-study Amendment: Inclusion and 
Exclusion Criteria ..................................................... 269 
11.13.4.1.1. Sub-study Inclusion Criteria .................. 269 
11.13.4.1.2. Sub-study Exclusion Criteria ................. 269 
11.13.4.2. Screening Phase (Gluteal IM) ................................... 273 


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11.13.4.3. Thigh injections Phase (16 weeks) ........................... 273 
11.13.4.4. Return to Gluteal Injection Phase ............................. 274 
11.13.4.5. Sub-study completion ............................................... 275 
11.13.4.6. Sub-study Amendment Withdrawal/Stopping 
Criteria ...................................................................... 276 
11.13.4.6.1. Sub-study Amendment Specific 
Virologic Failure Guidance .................... 276 
11.13.4.6.2. Sub-study Amendment HIV-1 
RNA Blips Guidance ............................. 276 
11.13.4.6.3. Sub-study Amendment Specific 
Withdrawal Criteria - Pregnancy ........... 276 
11.13.5. Sub-study: Time and Events table ............................................. 277 
11.13.5.1. Sub-study: Time and Events Table for CAB LA 
+ RPV LA Q4 Weekly Administration ........................ 277 
11.13.5.2. Sub-study: Time and Events Table for CAB LA 
+ RPV LA Q8 Weekly Administration ........................ 282 
11.13.5.3. Sub-study: Value Evidence and Outcomes ............... 286 
11.13.5.4. Sub-study: Pharmacokinetics sample collection ....... 287 
11.13.6. Sub-study Amendment: Study Treatment .................................. 287 
11.13.6.1. Sub-study Amendment: Investigational Product 
and Other Study treatment ....................................... 287 
11.13.6.2. Sub-study Dosage and Administration ...................... 287 
11.13.6.3. Oral Bridging during the Sub-study ........................... 288 
11.13.7. Sub-study Data Management .................................................... 288 
11.13.8. Sub-study Statistical Considerations and Data Analyses ........... 288 
11.13.8.1. Statistical Hypotheses .............................................. 288 
11.13.8.2. Sample Size Considerations ..................................... 289 
11.13.8.3. Data Analysis Considerations ................................... 291 
11.13.8.3.1. Analysis Populations............................. 291 
11.13.8.3.2. Planned Analyses ................................. 291 
11.13.8.4. Key Elements of Analysis Plan ................................. 291 
11.13.8.4.1. Primary Analysis ................................... 291 
11.13.8.4.2. Secondary and Exploratory 
Analyses ............................................... 292 
11.13.9. Sub-study Amendment Pharmacokinetics .................................. 292 
11.14. Appendix 14: Protocol Amendment History ............................................... 294 
 


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1. 
SYNOPSIS 
Protocol Title: A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-inferiority, 
Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting 
Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 4 
Weeks in HIV-1-infected Adults who are Virologically Suppressed. 
Short Title: Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting 
Cabotegravir Plus Long-acting Rilpivirine administered every 8 weeks in Virologically 
Suppressed HIV-1-infected Adults. 
1.1. 
Rationale 
The 207966 (ATLAS-2M) study is being conducted to establish if human 
immunodeficiency virus type 1 (HIV-1) infected adult participants with current viral 
suppression (HIV-1 RNA 50 c/mL) remain suppressed upon administration of a two-
drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine 
(RPV) administered every 8 weeks (Q8W; every 2 months).  This study is designed to 
demonstrate the non-inferior antiviral activity of CAB LA 600 mg + RPV LA 900 mg 
administered every 8 weeks compared with CAB LA 400 mg + RPV LA 600 mg 
administered every 4 weeks (Q4W; monthly) over a 48-week treatment period.  ATLAS-
2M will also provide comparative data on antiviral activity, safety, tolerability, and 
patient satisfaction through Week 152.   
Two groups of participants with demonstrated virologic suppression will be enrolled into 
ATLAS-2M including participants who at Screening are 1) receiving oral standard of 
care triple antiretroviral therapy (SOC) or 2) receiving a two drug IM regimen of Q4W 
CAB LA + RPV LA.  The majority of participants in ATLAS-2M will rollover from the 
ongoing 201585 (ATLAS) trial and additional participants on SOC will also be included 
in order to support a targeted total sample size of approximately 1020 participants.  
Participants entering on SOC treatment consisting of a stable antiretroviral (ARV) 
regimen containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an 
integrase inhibitor (INI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or a 
protease inhibitor (PI), will therefore either enter as new study participants or will 
rollover from the ongoing ATLAS trial.  All participants entering on Q4W CAB LA + 
RPV LA will be rolled over from the ATLAS trial.     
ATLAS is a Phase III, randomized, multicenter, parallel-group, non-inferiority, open-
label study evaluating the efficacy, safety, and tolerability of switching to CAB LA + 
RPV LA from current INI- NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected 
adults who are virologically suppressed.  ATLAS participants randomized to the SOC, 
“current antiretroviral” treatment arm, consisting of 2 nucleoside reverse transcriptase 
inhibitors (NRTIs) plus a third agent (INI, NNRTI, or a PI), or the CAB LA + RPV LA 
Q4W arm, who successfully complete Week 52 (at minimum) of ATLAS, and remain 
virologically suppressed (HIV-1 RNA <50 c/mL), will be eligible to enter ATLAS-2M.    
Eligible participants entering ATLAS-2M on oral SOC (either from ATLAS or new 
participants) will be randomized (1:1) to the CAB LA + RPV LA Q4W or Q8W regimen 


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beginning with 4 weeks of oral lead-in with CAB + RPV to confirm tolerability prior to 
IM dosing with CAB LA and RPV LA.  Eligible participants entering from ATLAS on 
the CAB LA+ RPV LA Q4W regimen will be randomized (1:1) to either continue Q4W 
injections or transition to Q8W injections in ATLAS-2M (without the oral lead-in).  
All participants who successfully complete Week 100 of CAB LA + RPV LA treatment 
in the Maintenance Phase will continue to have access to their randomized CAB LA + 
RPV LA regimen in the Extension Phase through Week 152 and 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 their assigned CAB LA + RPV LA regimen is 
terminated.   
1.2. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To demonstrate the non-inferior antiviral 
activity of CAB LA + RPV LA every 8 
weeks (every two months) compared to 
CAB LA + RPV LA every 4 weeks 
(monthly) over 48 weeks 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 Week 48 (Intent-to-
Treat Exposed [ITT-E] population) 
Secondary 
To demonstrate the antiviral and 
immunologic activity of CAB LA + RPV 
LA every 8 weeks compared to CAB LA + 
RPV LA every 4 weeks 
Proportion of participants with plasma HIV-1 
RNA <50 c/mL (c/mL) at Week 24, Week 
48,Week 96, and Week 152 using the FDA 
Snapshot algorithm (Intent-to-Treat Exposed 
[ITT-E] population) 
Proportion of participants with protocol-
defined confirmed virologic failure (CVF) 
through Week 24, Week 48, Week 96, and 
Week 152 
Proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL as per FDA 
Snapshot algorithm at Week 24, Week 96, 
and Week 152 
Absolute values and changes from Baseline 
in viral load and CD4+ cell counts over time 
including Week 48, Week 96, and Week 152 


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Objectives 
Endpoints 
To evaluate the safety and tolerability of 
CAB LA + RPV LA every 8 weeks 
compared to CAB LA + RPV LA every 4 
weeks 
Incidence and severity of AEs and laboratory 
abnormalities over time including Week 24, 
Week 48, Week 96, and Week 152 
Proportion of participants who discontinue 
treatment due to AEs over time including 
Week 24, Week 48, Week 96, and Week 152 
Change from Baseline in laboratory 
parameters over time including Week 
48,Week 96, and Week 152 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure  
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV 
through Week 24, Week 48,Week 96, and 
Week 152 
To characterize CAB and RPV 
concentrations and population 
pharmacokinetics and identify important 
determinants of variability 
Plasma PK parameters for CAB LA and RPV 
LA (when evaluable, Ctrough, concentrations 
post dose [~Cmax], and area under the curve 
[AUC]) 
Demographic parameters including, but not 
limited to, age, sex, race, body weight, body 
mass index, and relevant laboratory 
parameters will be evaluated as potential 
predictors of inter- and intra-participant 
variability for pharmacokinetic parameters 
To assess preference for CAB LA + RPV 
LA every 8 weeks or CAB LA + RPV LA 
every 4 weeks LA compared to oral 
antiretroviral (ARV)  
To assess preference for CAB LA+ RPV 
LA every 8 weeks compared to CAB LA + 
RPV LA every 4 weeks  
Preference for CAB LA + RPV LA every 8 
weeks and CAB LA + RPV LA every 4 
weeks compared to oral ARV and preference 
for CAB LA + RPV LA every 8 weeks 
compared to CAB LA + RPV LA every 4 
weeks will be assessed using a preference 
questionnaire at week 48 (or Withdrawal).  
To assess patient reported health-related 
quality of life, treatment satisfaction, 
injection tolerability, and treatment 
acceptance.   
 
Change from Baseline (Day 1) in HRQoL at 
Week 24, and Week 48 (or Withdrawal) 
Change from baseline (Day 1) in total 
“treatment satisfaction” score, and individual 
item scores of the HIV Treatment 
Satisfaction Status Questionnaire (HIVTSQs) 
at Week 24, 48, and 152 (or Withdrawal) 


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Objectives 
Endpoints 
Change in treatment satisfaction over time 
using the HIV Treatment Satisfaction Change 
Questionnaire HIVTSQc at Week 48 (or 
Withdrawal). 
Change from Week 8 in Dimension scores 
(“Bother of ISRs”, “Leg movement”, 
“Sleep”, and “Injection Acceptance”) and 
individual item scores assessing pain during 
injection, anxiety before and after injection, 
willingness to be injected in the future and 
overall satisfaction with mode of 
administration over time will be assessed 
using the Perception of iNjection 
questionnaire (PIN) at Weeks 8, 24, 48, and 
152 (or Withdrawal)  
Change from Baseline (Day 1) in treatment 
acceptance at Week 24, Week 48 and Week 
152 (or Withdrawal) will be assessed using 
the “General acceptance” dimension of the 
Chronic Treatment Acceptance (ACCEPT) 
questionnaire 
 
1.3. 
Overall Design 
Study 207966 (Antiretroviral Therapy as Long Acting Suppression every 2 Months-
ATLAS-2M) is a Phase III, randomized, open-label, active-controlled, multicenter, 
parallel-group, non-inferiority study designed to assess the antiviral activity and safety of 
CAB LA + RPV LA administered every 4 weeks compared to CAB LA + RPV LA 
administered every 8 weeks in approximately 1020 adult HIV-1 infected participants.   
Two groups of patients who fulfill eligibility requirements will be randomized (1:1) to 
receive CAB LA + RPV LA Q4W, or CAB LA + RPV LA Q8W regimen for at least 100 
weeks:  
Group 1: Patients randomized from current ART SOC therapy 
Patients randomized from current ART SOC therapy, including those enrolled to the 
“current ART” arm of the ATLAS study following completion of the Week 52 visit (at 
minimum), will begin oral therapy with CAB 30 mg + RPV 25 mg once daily at Day 1 
for 28 days (3 days) to determine individual safety and tolerability prior to receiving 
CAB LA + RPV LA Q4W, or CAB LA + RPV LA Q8W.  For patients on SOC 
transitioning from the ATLAS trial, eligibility for ATLAS-2M can be determined once 


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the final central lab results from ATLAS are available and safety parameters have been 
reviewed. 
Group 2: Patients currently receiving CAB LA + RPV LA Q4W 
Patients currently receiving CAB LA + RPV LA Q4W within ATLAS will be 
randomized at Day 1 to either continue Q4W administration or transition to Q8W 
administration of CAB LA + RPV LA.  Eligible patients include those originally 
randomized to Q4W in the Maintenance phase of ATLAS and those who transitioned 
from SOC to the Q4W regimen within the Extension Phase of ATLAS.  The first 
injection visit for ATLAS-2M can be performed once the final central lab results from 
ATLAS are available and safety parameters have been reviewed, and the ATLAS 
Week 52 visit (at minimum) has been completed.  Participants will continue to receive 
CAB LA + RPV LA Q4W injections as scheduled within the ATLAS trial until their 
eligibility for ATLAS-2M can be fully evaluated and the participant is re-randomized 
(Q4W or Q8W).  If determined to be ineligible for ATLAS-2M, those participants can 
elect to continue participation in ATLAS or withdraw from the ATLAS study. 
Participants in ATLAS-2M who successfully complete Week 100 (without meeting study 
defined withdrawal criteria) will be given the option to continue to receive their 
randomized treatment (CAB LA + RPV LA administered Q4W or Q8W) in the Extension 
Phase through Week 152 and until the study treatment is either locally approved and 
commercially available within the local sector (including through local 
public/government health sectors), the participant no longer derives clinical benefit, the 
participant meets a protocol-defined reason for discontinuation or until development of 
either CAB LA + RPV LA Q4W and/or Q8W is terminated.  Alternatively, participants 
can choose to complete study participation and enter the 52-week Long-Term Follow-Up 
(LTFU) Phase of the study. 
Any participant who receives at least one dose of CAB LA and/or RPV LA and 
discontinues the CAB LA + RPV LA regimen for any reason will enter a 52-week LTFU 
Phase (please refer to Section 1.4.4 of the synopsis for additional details).  Those 
participants must remain on suppressive highly active antiretroviral therapy (HAART) for 
at least 52 weeks after the last dose of CAB LA and/or RPV LA. 
In order to achieve balance across the treatment arms, randomization will be stratified by 
prior CAB + RPV Exposure: 0 weeks, 1-24 weeks, >24 weeks.  The primary endpoint for 
the study is the proportion of participants with HIV-RNA greater than or equal to 
50 c/mL (Virologic Failure) at Week 48 as per Food and Drug Administration (FDA) 
Snapshot algorithm using the Intent-to-Treat Exposed (ITT-E) population.  The 
proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA 
Snapshot algorithm (Missing, Switch or Discontinuation = Failure, ITT-E population) is a 
key secondary endpoint comparison.   
The sample size of 1020 provides 85% power to demonstrate non-inferiority in the 
primary endpoint at Week 48 using a 4% margin, assuming a true 3% failure rate for 
Q8W CAB LA + RPV LA and a 2% failure rate for the Q4W CAB LA + RPV LA arm 
and a 2.5% one-sided alpha level (using unpooled Z test statistic).   


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1.3.1. 
207966 (ATLAS-2M) Study Design Schematic 
 
Screening Phase
¥ Maintenance Phase
† Extension Phase
ATLAS Q4W 
ATLAS SOC Arm + 
additional SOC 
Patients:  PI, NNRTI, 
or INI Based 
Regimen with 2 
NRTI backbone
Wk96
Q8W CAB LA + RPV LA
Wk 48
1o Endpoint
Q4W CAB LA + RPV LA 
Randomize 
1:1
Q8W CAB LA + RPV LA 
Oral CAB
+ RPV
Oral CAB
+ RPV
Q4W CAB LA + RPV LA
CAB LA + RPV LA
Q4W or Q8W
Wk 100
Day 1
Wk 4b
Wk 4a
2o Endpoint
Randomize 
1:1
Wk 152
2o Endpoint
 
 
1.3.2. 
Number of Participants 
The target population to be enrolled is HIV-1 infected virologically suppressed (HIV-1 
RNA <50 c/mL) patients on stable antiretroviral therapy (ART) including participants 
who have completed, at minimum, Week 52 of the ATLAS study. 
It is anticipated that approximately 1020 participants will be enrolled into ATLAS-2M.  
In addition to participants rolled over from the ATLAS study, additional participants on 
SOC treatment will be screened to supplement enrollment such that the study can be 
appropriately powered.  A 15% screen failure rate, for additional patients randomized 
from SOC treatment is anticipated.  Participants will be enrolled from multiple countries 
which may include those countries actively participating in the ATLAS study including 
Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, 
South Korea, Spain, Sweden, and the United States.  
Randomization will be stratified by prior CAB + RPV exposure: 0 weeks, 1-24 weeks, 
>24 weeks.  A goal of this study is to enroll populations who are underrepresented in 


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clinical studies including approximately 25% women.  To provide sufficient data to 
determine whether either gender is correlated with treatment response, sites are expected 
to take into account gender in their screening strategies.  
1.4. 
Treatment Groups and Duration 
1.4.1. 
Screening Phase (Up to 35 days) 
Informed consent must be obtained prior to any study procedures, including any 
Screening assessment. 
Participants will be involved in a Screening period of up to 35 days and may be re-
screened once.  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. 
For participants transitioning from the ATLAS study, eligibility to transition to ATLAS-
2M at Week 52 (at the earliest) will be determined once the final central lab results from 
ATLAS, following (at minimum) completion of the ATLAS Week 48 visit are available 
and safety parameters have been reviewed.  Separate Screening Labs will be utilized to 
inform eligibility for ATLAS-2M; however, in some occasions and upon consultation 
with the Medical Monitor, individual lab results and safety data from the final visit of the 
ATLAS study can be considered towards informing eligibility for the ATLAS-2M study 
as long as all other Screening and eligibility criteria are met.     
1.4.2. 
Maintenance Phase (Day 1 up to Week 100) 
There are two ways in which study participants may transition to the LA regimen, either 
directly from oral SOC or from Q4W dosing from ATLAS.  
The Table and Figure below describe the CAB LA + RPV LA dosing regimens in 
ATLAS-2M based on the mode of transition. 
CAB LA + RPV LA Dosing Regimens in ATLAS-2M 
Participants Transitioning from Oral Standard of Care (SOC) 
Regimen 
CAB LA 
RPV LA 
Q4W 
CAB LA: 
Week 4b: 600 mg (Loading Dose) 
Week 8 & Q4W thereafter: 400 mg   
RPV LA: 
Week 4b: 900 mg (Loading Dose) 
Week 8 & Q4W thereafter: 600 mg 
Q8W 
CAB LA: 
Week 4b, Week 8, & Q8W thereafter: 
600 mg 
RPV LA: 
Week 4b, Week 8, & Q8W thereafter: 
900 mg 


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Participants Transitioning from ATLAS Q4W 
Regimen 
CAB LA 
RPV LA 
Q4W 
CAB LA: 
Day 1 & Q4W thereafter: 400 mg 
RPV LA: 
Day 1 & Q4W thereafter: 600 mg 
Q8W 
CAB LA: 
Day 1 & Q8W thereafter: 600 mg   
RPV LA: 
Day 1 & Q8W thereafter: 900 mg 
All participants entering ATLAS-2M from an oral SOC regimen will receive a 4-week oral lead-in of CAB+RPV prior to 
receiving IM injections, except for ATLAS subjects transitioning from Q4W to Q8W injections.  These participants 
previously established safety and tolerability of CAB + RPV within the ATLAS study. 
 
ATLAS-2M Treatment Schematic 
Screening Phase
Maintenance Phase and Extension Phase
From ATLAS 
on Q4W
From ATLAS
on SOC
-or-
new SOC 
patients
(PI, NNRTI, or INI  
Regimen + 2 NRTI)
Q8W
Wk 24
Q4W 
Randomize 
1:1
Q8W 
Oral CAB
+ RPV
Oral CAB
+ RPV
Q4W 
Day 1
Wk 4b
Wk 4a
Randomize 
1:1
Wk 12
Wk 8
Wk 16
CAB 600mg/RPV 900mg
CAB 400mg/RPV 600mg
Wk 20
… continued to 
end of study
treatment
 
 
1.4.2.1. 
Patients randomized to LA dosing from current ART SOC therapy: 
All participants randomized from current ART SOC therapy (including those 
transitioning from SOC in ATLAS and new study participants) will begin oral therapy 
with CAB 30 mg + RPV 25 mg once daily at Day 1 for 4 weeks to determine individual 
safety and tolerability prior to administration of CAB LA + RPV LA.  The oral lead-in 
period is part of the Maintenance Phase and will therefore be included within the Week 
48, 96, and 152 planned analyses.  
The final dosing of current daily oral ART regimen should occur the day prior to 
randomization to avoid overlap of treatment regimens however, if the participant takes 


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current ART prior to coming into the clinic, randomization and initiation of oral CAB 
and RPV should continue as planned for Day 1.  At the Week 4a visit, safety assessments 
(including e.g., clinical chemistries) will be performed as per the Time and Events Table 
to determine individual safety and tolerability prior to the initial administration of CAB 
LA + RPV LA.  Dosing of CAB LA + RPV LA Q4W or Q8W will initiate at the Week 
4b visit once safety labs from Week 4a are available and have been reviewed. 
Subjects receiving oral SOC treatment and randomized to Q4W injections will receive 
loading doses of CAB LA 600 mg + RPV LA 900 mg on Week 4b followed by 
maintenance injections of CAB LA 400 mg + RPV LA 600 mg every 4 weeks thereafter.   
Subjects receiving oral SOC treatment and randomized to Q8W injections will receive 
doses of CAB LA 600 mg + RPV LA 900 mg on Week 4b and Week 8 followed by 
identical maintenance dose injections every 8 weeks thereafter. 
All injections should be planned as single injections per drug. 
1.4.2.1.1. IM injections every 4 weeks (Q4W from SOC): 
Week 4b visit only - CAB LA 600 mg + RPV LA 900 mg, each given as 1 X 3 mL IM 
injection 
Week 8 visit and Q4W thereafter - CAB LA 400 mg IM + RPV LA 600 mg IM every 4 
weeks for 100 weeks, each given as 1 X 2 mL IM injection 
At Week 4b, participants will return to the clinic, take the last oral dose (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 with IM 
CAB LA + RPV LA at Week 4b can be performed once central lab results are available 
and safety parameters are reviewed from the Week 4a visit.   
The second and third IM injections with CAB LA 400 mg and RPV LA 600 mg will be 
performed at Week 8 and Week 12.  There will be a -7-day dosing window for the second 
and third IM injections such that the second injection occurs within the window of Week 
7 and Week 8 but no later than Week 8 and the third injection occurs within the window 
of Week 11 and Week 12 but no later than Week 12.  Subsequent injections with CAB 
LA 400 mg and RPV LA 600 mg will occur every 4 weeks (7 days) thereafter.  In 
addition, starting after the Week 16 injection, the interval between injection visits will be 
limited to a maximum of 5 weeks.  The Medical Monitor must be contacted to discuss 
individual participant case management if the length of time between injections exceeds 
or is projected to exceed 5 weeks. 
1.4.2.1.2. IM injections every 8 weeks (Q8W from SOC): 
Week 4b visit – CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM 
injection 
Week 8 visit- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM 
injection 


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Week 16 visit and Q8W thereafter - CAB LA 600 mg + RPV LA 900 mg IM, every 8 
weeks for 100 weeks, each given as 1 X 3 mL IM injection 
At the Week 4b visit, subjects will return to the clinic, take their last oral dose (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 
with IM CAB LA + RPV LA at Week 4b can be performed once central lab results are 
available and safety parameters are reviewed from the Week 4a visit.   
The second loading injection will be administered at Week 8 (CAB LA 600 mg + RPV 
LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring 
every 8 weeks thereafter.  There will be a -7-day dosing window for the second and third 
IM injections such that the second injection occurs within the window of Week 7 and 
Week 8 but no later than Week 8 and third injection occurs within the window of Week 
15 and Week 16 but no later than Week 16.  Subsequent injections with CAB LA 600 mg 
and RPV LA 900 mg will occur every 8 weeks (7 days).  Starting after the Week 16 
injection, the interval between injection visits will be limited to a maximum of 9 weeks.  
If the length of time between injections exceeds, or is projected to exceed 9 weeks, the 
Medical Monitor must be contacted to discuss individual participant case management.   
1.4.2.2. 
Participants transitioning from ATLAS and currently receiving CAB LA 
+ RPV LA Q4W 
Subjects receiving Q4W injections within ATLAS and randomized to receive Q4W 
injections in ATLAS-2M, will continue receiving maintenance injections Q4W as 
scheduled and will not require a loading dose on Day 1. 
Subjects receiving Q4W injections within ATLAS and randomized to receive Q8W 
injections in ATLAS-2M will receive doses of CAB LA 600 mg + RPV LA 900 mg on 
Day 1 one month after their last Q4W maintenance dose in order to align with day of 
study randomization.  Subjects will not require an intermediate dose at Week 4 and will 
receive their next Q8W maintenance injections at Week 8 and Q8W thereafter.   
Participants transitioning from the ATLAS study and on CAB LA + RPV LA Q4W 
treatment will be randomized at Day 1 to either continue Q4W administration or 
transition to Q8W administration of CAB LA + RPV LA.  The first injection visit for the 
ATLAS-2M study can be performed once the final central lab results from the ATLAS 
study are available and safety parameters have been reviewed.  Screening labs 
determining eligibility for ATLAS-2M can be collected at Week 48 (at minimum) for 
participants originally randomized to the Q4W arm within ATLAS.  Screening labs for 
participants who recently transitioned from SOC to Q4W injections within the ATLAS 
Extension Phase may be obtained at ATLAS Week 56b (after completion of the CAB + 
RPV Oral lead-in period) or at a subsequent ATLAS visit after receiving one set or a 
short course of Q4W injections.  The transition from the final ATLAS to ATLAS-2M 
Day 1 dosing must occur 4 weeks (7 days) from the final injections received in ATLAS.  
Dosing for participants transitioning from CAB LA + RPV LA Q4W in ATLAS is as 
follows: 


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1.4.2.2.1. IM injections every 4 weeks (Q4W from ATLAS Q4W): 
Starting at Day 1, all injections will continue with the maintenance dose of CAB LA   
400 mg and RPV LA 600 mg administered every 4 weeks (7 days).  In addition, the 
time between injection visits will be limited to a maximum of 5 weeks.  The Medical 
Monitor must be contacted if the length of time between injections exceeds or is 
projected to exceed 5 weeks. 
1.4.2.2.2. IM injections every 8 weeks (Q8W from ATLAS Q4W): 
Participants transitioning from ATLAS and randomized to receive CAB LA + RPV LA 
Q8W injections will initiate Q8W dosing at the Day 1 visit as follows:  
Day 1- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Week 8 and Q8W 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 Week 8 (CAB LA 600 mg + RPV LA 
900 mg, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring 
every 8 weeks thereafter.  There will be a -7-day dosing window for the second and third 
IM injections such that the second injection occurs within the window of Week 7 and 
Week 8 but no later than Week 8 and third injection occurs within the window of Week 
15 and Week 16 but no later than Week 16.  Subsequent injections with CAB LA 600 mg 
and RPV LA 900 mg will occur every 8 weeks (7 days).  Starting after the Week 16 
injection, the interval between injection visits will be limited to a maximum of 9 weeks.  
If the length of time between injections exceeds, or is projected to exceed 9 weeks, the 
Medical Monitor must be contacted to discuss individual participant case management.   
The primary study analysis will consist of data collected through the Week 48 visit.  A 
single repeat of HIV-1 RNA for any participant with a HIV-1 RNA 50 c/mL at Week 
48, Week 96, or Week 152 must be performed.  The retest should be scheduled as soon as 
possible (but no later than 4 weeks from the Week 48, Week 96, or Week 152 visits, 
respectively) and will inform the Week 48,Week 96, or Week 152 virological endpoint, 
respectively.   
1.4.3. 
Extension Phase 
Participants who successfully complete 96 Weeks of CAB LA + RPV LA treatment in 
the Maintenance Phase will continue to have access to their randomized treatment Q4W 
or Q8W CAB LA + RPV LA in the Extension Phase through Week 152 and until study 
treatment is either locally approved and commercially available within the local sector 
(including through local public/government health sectors), the participant no longer 
derives clinical benefit, the participant meets a protocol-defined reason for 
discontinuation or until development of either CAB LA + RPV LA Q4W and/or Q8W is 
terminated.  For participants randomized to Q4W arm, dosing visits will continue to 
occur every 4 weeks with CAB LA 400mg and RPV LA 600 mg.  For participants 
randomized to the Q8W arm, dosing visits will continue to occur every 8 weeks with 


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CAB LA 600 mg and RPV LA 900 mg.  Safety and efficacy assessments will be 
conducted as per the Time and Events Schedule.  
Participants choosing to not enter the Extension phase can complete their study 
participation at the Week 100 visit and enter into the LTFU Phase as required.  
Participants who choose to continue on to the Extension Phase will need to be assessed 
for eligibility and will continue on their current CAB LA + RPV LA regimen while 
eligibility is being confirmed.  A single repeat of HIV-1 RNA for any participant with a 
HIV-1 RNA 50 c/mL and < 400 c/mL at Week 96 or Week 152 must be performed.  
The retest should be scheduled as soon as possible (but no later than 4 weeks from the 
Week 96 or Week 152 visit).  Participants with HIV-1 RNA <50 c/mL upon retest are 
eligible to enter the Extension Phase.  Participants with HIV-1 RNA ≥400 c/mL at 
Week 96 are not eligible to enter the Extension Phase, will not be allowed a repeat to 
determine eligibility, and will therefore be withdrawn from the study treatment.  
Eligibility to enter the Extension Phase for any participants with a retest HIV-1 RNA > 
50 c/mL and <400 c/mL will require approval by the study Medical Monitor.   
Participants not eligible to enter the Extension Phase or choosing not to participate in the 
Extension Phase will end their study treatment and enter the LTFU Phase. 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. 
1.4.4. 
Long-Term Follow-Up Phase 
• 
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 before CAB LA + 
RPV LA marketed product is locally available must enter the LTFU Phase.   
Participants must remain on suppressive HAART for at least 52 weeks after the 
last dose of CAB LA and/or RPV LA in order to prevent selective pressure on 
HIV and the potential for selection of resistant mutants.  Investigators must 
discuss the choice of the follow-up HAART regimen with the Medical 
Monitor prior to initiating the new regimen with the participant.  HAART 
therapy should be initiated within 4 weeks (+7 days) after the last Q4W 
injection, or within 8 weeks (+7 days) after the last Q8W injection.  The 
LTFU Phase will begin the day of the last CAB LA and/or RPV LA dose and 
continue for 52 weeks..  Upon discontinuation from the Maintenance or 
Extension Phase, these participants will complete Withdrawal assessments  (see 
Section 5.5) and will then enter into the LTFU Phase as per the Time and Events 
Schedule (Section 7.1).   
 
• Where the CAB LA + RPV LA marketed product is locally available, only 
participants that discontinue the CAB LA + RPV LA regimen for safety-related 
reasons included in Section 5.5, must enter the LTFU Phase. Participants must 
remain on suppressive HAART for at least 52 weeks after the last dose of CAB 
LA and/or RPV LA in order to prevent selective pressure on HIV and the 
potential for selection of resistant mutants.  Investigators must discuss the 
choice of the follow-up HAART regimen with the Medical Monitor prior to 


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initiating the new regimen with the participant.  HAART therapy should be 
initiated within 4 weeks ( 7 days) after the last Q4W injection, or within 8 
weeks ( 7 days) after the last Q8W injection.  The LTFU Phase will begin the 
day of the last CAB LA and/or RPV LA dose and continue for 52 weeks.  These 
participants will complete Withdrawal assessments prior to entering  into the 
LTFU Phase 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.  
• NOTE: Participants transitioning to CAB+RPV LA marketed product or 
alternative HAART (except due to safety-related reasons) do not need to enter the 
LTFU Phase. 
Long term Follow up phase requirement  
Marketed product locally 
available 
Subject WD due to safety-
related reasons 
LTFU phase required? 
No 
Yes 
Yes 
No  
Yes 
Yes 
Yes 
No 
No, but Safety FU visit 
required to assess potential 
safety issues occurred after 
the last injection 
 
Participants will be assessed with clinic visits at months 3, 6, 9, and 12 during the 
Follow-Up Phase.  Female participants of child bearing potential must continue to use 
adequate contraception methods (see Study Procedures Manual for list of accepted forms 
of contraception) for the entire year of follow up.   
In order to assure that participants have access to HAART during the LTFU Phase, GSK 
may supply HAART regionally or reimbursement will be provided as needed during this 
phase.  The LTFU Phase may be modified 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. 
This phase is considered study participation and participants will be followed on study 
during this time.  Additional withdrawal assessments are not required for participants 
who do not complete the LTFU Phase.   


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1.4.5. 
Dose Modifications: 
No dose reductions, modifications, or changes in the frequency of any components of 
each regimen will be allowed during the study beyond what is allowed within the 
protocol or directly approved by the study Medical Monitor.  Protocol waivers or 
exemptions are not allowed.  Therefore, adherence to the study design requirements is 
essential and required for study conduct. 
In exceptional circumstances, and in consultation with the Medical Monitor, Investigators 
may provide oral CAB and/or RPV as a short-term “bridging” strategy for participants 
who have begun CAB LA + RPV LA.  Should a participant need “oral bridging”, sites 
must contact the Medical Monitor for guidance on treatment strategies prior to a missed 
CAB LA + RPV LA dose.  Should a participant not notify the site in advance, the 
Medical Monitor must be contacted for further treatment guidance. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM), which is available on 
the online Study Web Portal.  The SPM will provide the site personnel with 
administrative and detailed technical information. 
2. 
INTRODUCTION 
Current HIV treatment guidelines recommend first-line antiretroviral (ARV) regimens 
consisting of two nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) 
as a “backbone” combined with a third agent from the non-nucleoside reverse 
transcriptase inhibitor (NNRTI), protease inhibitor (ritonavir-boosted) (PI/RTV), or 
integrase strand transfer inhibitor (INSTI) classes [BHIVA, 2016; DHHS, 2016; EACS, 
2017; IAS USA, 2016]. While these regimens are highly efficacious and generally well 
tolerated, there is growing concern about long-term toxicities, and great interest from 
patients and clinicians in unique regimens that might avoid such toxicities, and to provide 
effective long-term antiretroviral therapy ART with the most streamlined and convenient 
regimens possible. 
 
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 


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avoid known NRTI-associated adverse drug reactions and long-term toxicities.  In 
addition, while there are no currently approved two-drug regimens to maintain 
suppression, simplifying treatment has long been a goal to increase treatment compliance 
and improve the quality of life for 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, 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 96 
efficacy data from study 200056 (LATTE-2) demonstrated that 94% of patients on the 
CAB LA + RPV LA Q8W dosing arm and 87% of patients on the Q4W dosing arm 
maintained virologic suppression (HIV-1 RNA <50 c/mL), with both regimens being 
well tolerated.  LATTE-2 results justify further evaluation of CAB LA + RPV LA dosing 
regimens.  Study 201585 (ATLAS) is an ongoing Phase III study conducted to establish 
if human immunodeficiency virus type 1 (HIV-1) infected adult participants with current 
viral suppression on a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) 
plus a third agent, remain suppressed upon switching to CAB LA + RPV LA Q4W.  The 
current study, 207966 (ATLAS-2M) is designed to demonstrate the non-inferior antiviral 
activity of CAB LA 600 mg + RPV LA 900 mg every 8 weeks (Q8W, every 2 months) 
compared to CAB LA 400 mg + RPV LA 600 mg administered every 4 weeks (Q4W, 
monthly) for 48 weeks. This study will also provide important long-term comparative 
antiviral activity, safety, tolerability of these regimens through Week 152 of the 
Extension Phase of the study. Additionally, eligible participants (HIV-1 RNA <50 c/mL 
at Week 96) will be given an option to continue their randomized CAB LA + RPV LA 
regimen (Q4W or Q8W) in the Extension Phase of the study. 
2.2. 
Background 
It is estimated that 36.7 million people are currently living with HIV/Acquired 
Immunodeficiency Syndrome (AIDS) and that the worldwide epidemic continues to grow 
at a rate of two million new infections and cause 1.1 million deaths per year [UNAIDS, 
2016].  Chronic HIV infection in adults continues to be characterized by increased 
development of resistant virus, increasing transmission of resistant virus and issues 
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 


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therapy requires a need for continuous improvement on the durability, tolerability and 
convenience of all antiretroviral classes. 
A study by the Antiretroviral Therapy Cohort Collaboration [ART-CC, 2013] found that 
of more than 21,000 patients in a European and North American cohort on their first 
combination antiretroviral therapy (cART) regimen (either PI or NNRTI-based), 51% 
modified or interrupted their first cART regimen during a median of 28 months of 
follow-up with one third of interruptions occurring within the first 6 months of starting 
therapy.  Forty percent of all treatment interruptions were due to the secondary side 
effects or toxicities of cART, 17% were due to the desire for simplification of the 
regimen and 14% were due to patient choice. These observations have led to numerous 
“switch” ART studies, designed to understand the efficacy, safety, and tolerability of 
switching patients from one regimen to another. 
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].   
The 200056 study (GlaxoSmithKline Document Number 2013N168152_05, Study 
[LATTE-2]) is an ongoing Phase 2b study designed to assess the induction of virologic 
suppression with CAB 30 mg daily + two NRTIs, followed by a maintenance period 
where subjects are randomized (1:2:2) to continue on oral CAB 30 mg + two NRTIs or 
switch to an IM injection of CAB LA + RPV LA administered Q4W or Q8W.  A total of 
309 participants were enrolled and treated. 
During the Induction Phase there was a rapid and sustained decline in HIV-1 RNA, with 
91% of participants (282/309) achieving HIV-1 RNA <50 c/mL through 20 weeks of 
therapy.  There was a single participant (with known compliance issues) with confirmed 
virologic failure during the Induction period.  Virologic testing revealed no treatment 
emergent phenotypic or genotypic resistance in this participant. 
The primary endpoint for 200056 was the Week 32 proportion of participants with HIV-1 
RNA <50 c/mL (Snapshot, Intent-to-Treat Maintenance Exposed population [ITT-ME]). 
Following virologic suppression on three drug oral therapy in the Induction Phase, 286 
participants qualified to enter randomization at the Day 1 visit, and were subsequently 
randomized 2:2:1 onto once every 4 weeks intramuscular (IM) injections with CAB LA + 
RPV LA every 4 weeks (Q4W), once every 8 weeks (Q8W) IM injections with CAB LA 
+ RPV LA or continuation of oral CAB + NRTIs, respectively.  Through 32 weeks of 
two-drug maintenance therapy, 95% (Q8W) and 94% (Q4W) of participants on injectable 
dosing were virologic successes, compared to 91% of participants continuing three drug 


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oral CAB + NRTIs, meeting pre-specified criteria for comparability between the dosing 
arms.   
Week 48 was a secondary endpoint for 200056, and permitted the evaluation of the two-
drug long-acting combinations’ ability to maintain the virologic suppression 
demonstrated at Week 32.  At Week 48, 92% (Q8W) and 91% (Q4W) of participants 
receiving injectable dosing had a sustained virologic response (HIV-1 RNA <50 c/mL) 
compared to 89% of participants continuing oral CAB + 2 NRTIs.  Week 96 efficacy data 
from study 200056 (LATTE-2) demonstrated that 94% of patients on the CAB LA + 
RPV LA Q8W dosing arm and 87% of patients on the Q4W dosing arm maintained 
virologic suppression (HIV-1 RNA <50 c/mL), with both regimens being well tolerated.  
At Week 48, 10 subjects met virologic nonresponse criteria (Q8W, n=8; Q4W, n=1; oral 
CAB +2 NRTIs, n=1).  For the Q8W IM arm, 4 subjects with virologic nonresponse at 
Week 48 (HIV-1 RNA >50 c/mL) were re-suppressed with HIV-1 RNA <50 c/mL at 
Week 96 without a change in therapy.  Of 5 Q8W subjects with virologic nonresponse at 
Week 96, two had HIV-1 RNA 50 c/mL at Week 96 (one of which had HIV-1 50 c/mL 
at Week 48), one discontinued due to protocol-defined virologic failure at Week 4, one 
withdrew consent due to intolerability of injections at Week 8, and one withdrew due to 
investigator discretion at Week 48 while not suppressed (and subsequently confirmed as a 
protocol-defined virologic failure).  One of the two subjects with HIV-1 RNA >50 c/mL 
at Week 96 remained on the study and had HIV-1 levels <50 c/mL at the next scheduled 
visit.  Through 96 weeks, no subjects in the Q4W arm failed for virologic reasons.  The 
Q4W subject with virologic nonresponse at Week 48 (HIV-1 RNA, 59 c/mL) remained 
on the study beyond Week 48 and had subsequent viral re-suppression with HIV-1 
<50 c/mL at Week 96.  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.  Through Week 96, the proportion 
of AEs leading to withdrawal during the study Maintenance Period was low across all 
arms (Q8W IM: n=2, 2%; Q4W IM: n=8, 7%; Oral CAB; n=1, 2%), with only one 
additional AE leading to withdrawal since the Week 48 analysis.   
Long-acting two class therapy consisting of CAB LA + RPV LA as an IM regimen has 
the benefit of being a NRTI-sparing regimen for long-term treatment of HIV infection 
which will avoid known NRTI-associated adverse drug reactions and long-term 
toxicities.  Additionally, a two-drug combination therapy with CAB LA plus RPV LA 
may offer a better tolerability and resistance profile, as well as improved adherence and 
treatment satisfaction in virologically suppressed participants improving the quality of 
life for patients with living with HIV.   
The primary objective of ATLAS-2M is to demonstrate the non-inferior antiviral activity 
of CAB LA 600 mg + RPV LA 900 mg every 8 weeks (Q8W, every 2 months) compared 
to CAB LA 400 mg + RPV LA 600 mg administered every 4 weeks (Q4W, monthly) for 
48 weeks.   ATLAS-2M will also evaluate long-term antiviral and immunologic effects, 
safety and tolerability, and viral resistance of the Q8W and Q4W regimens for a 
minimum of 100 weeks.  In addition, ATLAS-2M will assess patient reported health-


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related quality of life, treatment satisfaction, injection tolerability, and treatment 
acceptance of the Q8W and Q4W regimens.   
2.3. 
Benefit/Risk Assessment 
Summaries of findings from both clinical and non-clinical studies conducted with oral 
and LA CAB and LA RPV can be found in the current Investigator’s Brochures. 
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. 
 


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Drug Induced Liver 
Injury (DILI) 
 
Less than 1% of  participants in the CAB 
program to date have developed transaminitis 
(elevated liver transaminases characterised by 
predominant alanine aminotransferase (ALT) 
elevation).  In most participants, transient 
transaminitis was explained by acute hepatitis C 
infection (majority) and other systemic 
infections.  In a small number of participants, 
there was not an alternative explanation, 
suggesting a mild form of drug induced liver 
injury (DILI) without hepatic dysfunction, which 
resolved upon withdrawal of treatment with 
CAB.  
 
• Exclusion criteria as described in Section 5.2 
will prohibit participants with significant liver 
impairment based on screening liver chemistry 
including transaminases (ALT and Aspartate 
aminotransferase [AST]) as well on prior 
medical history. Participants with a history of 
chronic liver disease with ongoing 
inflammation and/or fibrosis will have 
additional confirmatory assessments to confirm 
suitability for entry into the study.  
 
• A 4-week oral lead- in Phase is being 
implemented in this study, where all 
participants will receive oral CAB prior to the 
administration of IM CAB to assess individual 
safety and tolerability  
 
• Liver transaminases (ALT and AST) will be 
monitored throughout this study (refer to Time 
& Events Table, Section 7.1) and the liver 
chemistry stopping criteria will be adopted as 
described in Section 5.5.1.1 of this protocol. 
Participants will be withdrawn from CAB 
treatment where no compelling alternative 
cause is identified and DILI is suspected. 
 
 


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• Participants who develop ALT ≥3 times the 
upper limit of normal (ULN) while on study 
must consult with Medical Monitor prior to 
initiation or continuation of CAB LA + RPV 
LA.   
Injection Site Reactions 
(ISRs) 
 
Clinical, experience to date has demonstrated 
ISRs occur in the majority of exposed 
participants treated with CAB LA but are 
generally mild (Grade 1) or moderate (Grade 2) 
and include events of pain, tenderness, erythema, 
or nodule formation of several days duration 
(median duration for individual events <1 week). 
ISRs may occur more than once in an individual 
participant receiving multiple injections.  
Although some Grade 3 ISRs were reported, 
overall ISRs have been well tolerated and have 
not to date been associated with an excess of 
participants’ withdrawal.  
None of the ISRs reported to date have been 
serious.   
• Administration advice will be given to 
minimize risk of poor administration technique 
giving rise to injection site reactions.  Advice 
on care, monitoring, natural course, and 
treatment of ISRs is given in study 
documentation  
 
• Advice will be given to participants on care of 
injection site on day/days immediately post 
administration, use of analgesia, compresses 
where appropriate. 
 
• 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  
 


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• Significant ISRs may be photographed and 
referred to a dermatologist for specialist advice. 
Hypersensitivity 
Reactions (HSR) 
 
Hypersensitivity reactions have been reported as 
uncommon occurrences with integrase inhibitors, 
including the closely related compound 
dolutegravir, and were characterized by rash, 
constitutional findings, and sometimes, organ 
dysfunction, including liver injury.  
While there have been no clinical cases of 
hypersensitivity to CAB to date, there is a 
theoretical risk of systemic or severe 
hypersensitivity reactions with or without hepatic 
symptoms associated with use of IM CAB.  The 
long exposures anticipated after IM CAB 
injection may complicate the management of a 
drug hypersensitivity reaction, were it to occur. 
 
• The risk of developing a hypersensitivity 
reaction post administration of IM CAB will 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.  
 
• Clinical assessments, laboratory tests (including 
liver transaminases) and vital signs will be 
performed throughout this study (refer to Time 
& Events Table, Section 7.1). Results from 
these assessments may aid early detection of 
HSR.  
 
• Oral CAB will be withdrawn immediately for 
cases with suspected HSR during the oral CAB 
lead-in phase and 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. 


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Effects in pregnancy seen 
in non-clinical studies 
In animal reproduction studies, CAB when 
administered to rats at > 30 times the systemic 
exposure at the maximum recommended oral 
human dose (MRHD) of 30 mg during 
organogenesis through delivery, had adverse 
effects on labor and delivery that may be related 
to a delay in the onset of parturition, resulting in 
increased fetal mortality (stillbirths) and neonatal 
deaths immediately after birth. 
A delay in the onset of parturition, increased 
stillbirths and neonatal deaths were observed in a 
rat pre- and postnatal development study at 
greater than 30 times the exposure at the 
recommended human dose (RHD). No evidence 
of adverse developmental outcomes was observed 
with oral cabotegravir in rats or rabbits (greater 
than 30 times or similar to (approximately 0.7 
times) the exposure at the RHD, respectively) 
given during organogenesis. 
The clinical significance of these finding in 
humans is unknown.  
For pregnant participants remaining in the study, 
refer to Appendix 11 for additional data regarding 
CAB and pregnancy.  
• Pregnant females are excluded from enrollment 
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 
• Participants who become pregnant during the 
study may remain in the study provided all 
protocol defined pregnancy related assessments, 
procedures and documentation are completed, 
and a pregnancy specific ICF addendum is 
signed by the participant. Details regarding 
management of pregnant participants are found 
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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). 
 
Potential effects in 
females exposed to 
dolutegravir during 
conception and early 
pregnancy 
A preliminary analysis of an ongoing birth 
outcome surveillance study in Botswana 
involving women exposed to dolutegravir (DTG), 
a different molecule in the same integrase class of 
medications as CAB, identified four cases (as of 
May 2018) of neural tube defects in 426 infants 
born to mothers who were exposed to DTG-
containing regimens from the time of conception. 
In the same study, no infant born to a woman 
who started DTG during pregnancy had a neural 
tube defect, out of 2,824 women. A causal 
relationship of these events to the use of DTG has 
not been established. The incidence of neural 
tube defects in the general population ranges 
• Pregnant females are excluded from enrollment 
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 long term follow up phases of 
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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from 0.5-1 case per 1,000 live births. As neural 
tube defects occur within the first 4 weeks of fetal 
development (at which time the neural tubes are 
sealed) this potential risk would concern women 
exposed to DTG at the time of conception and in 
early pregnancy.  
Recently updated data (April 2020) for this birth 
outcome study showed that among women who 
were on DTG when they became pregnant, 
7/3591 neural tube defects (NTD) occurred 
(0.19%). In comparison, NTDs were identified in 
21/19,361 (0.11%) women delivering on any 
non-DTG antiretrovirals. There was not a 
significant difference in the number of neural 
tube defects between births to women taking 
DTG and those taking other non-DTG 
antiretroviral treatments (0.09% difference). 
The clinical relevance of either of these findings 
in relation to CAB use is unknown 
periods despite discontinuation of CAB LA 
• Participants who become pregnant during the 
study may remain in the study, provided all 
protocol defined pregnancy related assessments, 
procedures and documentation are completed 
and a pregnancy specific ICF addendum is 
signed by the participant. Details regarding 
management of pregnant participants is found 
in Appendix 11. 
Development of 
Resistance following 
discontinuation of CAB 
LA 
Residual concentrations of CAB would remain in 
the systemic circulation of participants who stop 
CAB LA treatment for prolonged periods (more 
than 1 year, in some subjects, GlaxoSmithKline 
Document Number 2016N269422_00) after last 
injection (e.g., for tolerability issues or treatment 
• After participants stop CAB LA, Oral HAART 
regimens will be prescribed within 4 weeks 
after the last Q4W dose or within 8 weeks after 
the last Q8W dose, and following consultation 
with the medical monitor.  This would be 
anticipated to result in continued suppression or 


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failure).  Participants discontinuing CAB LA 
regimen may be at risk for developing HIV-1 
resistance to CAB many weeks after 
discontinuing injectable therapy.  
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 a minimum of 52 weeks from the 
time of the last LA administration. 
 
Drug-Drug Interactions 
(DDIs) 
For a complete listing of permitted and prohibited 
concurrent medications for CAB and CAB LA, 
refer to Section 6.13 
CAB and CAB LA should not be co-administered 
with the following medicinal products, as 
significant decreases in CAB plasma 
concentrations may occur (due to UGT enzyme 
induction), which may result in loss of 
therapeutic effect of CAB. 
- the anticonvulsants carbamazepine, 
oxcarbazepine, phenobarbital, phenytoin 
- the antimycobacterials rifampicin, 
rifapentine, rifabutin 
- St John’s wort (Hypericum perforatum) 
Oral CAB administration only:  Antacid products 
• All participants will be informed of prohibited 
medications throughout the study and updates 
provided as needed via the informed consent. 


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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 
discontinuing injectable therapy.  
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, 2 hour post dose PK 
samples will be obtained at a few early 
timepoints for determination of CAB 
concentration and possible pharmacokinetic 
correlation with safety parameters such as ECG 
changes and virologic response.  Additionally, 
an unscheduled PK sample may be drawn 
approximately 2 hours post dosing for future 
evaluation of CAB concentrations. 


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


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None of the ISRs was serious and no clinical 
significant complications were reported 
 
study. 
 
• Complications of ISRs such as infections 
(abscess, cellulitis) and collections of fluid 
requiring drainage will be monitored  
• Significant ISRs may be photographed and 
referred to a dermatologist for specialist advice. 
Rash 
 
Some observations of rash with oral RPV have 
been reported in clinical studies executed to date 
(the majority are Grade 1 or 2).  
Severe skin and hypersensitivity reactions have 
been reported during the postmarketing 
experience, including cases of Drug Reaction with 
Eosinophilia and Systemic Symptoms (DRESS), 
with oral RPV containing regimens.  While some 
skin reactions were accompanied by constitutional 
symptoms such as fever, other skin reactions were 
associated with organ dysfunctions, including 
elevations in hepatic serum biochemistries. 
• In this study, RPV LA administration will be 
preceded by an oral RPV lead in to evaluate 
safety and tolerability in individual participants. 
• Participants with a Grade 1 or 2 rash will be 
allowed to continue treatment  , 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 background regimen) and be 
withdrawn from the study. 
 
• All rash events should be assessed with special 
attention to systemic symptoms, laboratory 
abnormalities, or mucosal involvement.  Close 
clinical follow-up, including follow-up of 
laboratory abnormalities, and appropriate 
medical intervention, including referral to 


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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 7.4.5.13 for additional guidance on 
management of rash events. 
Development of 
Resistance 
 
Residual concentrations of RPV LA can remain in 
the systemic circulation of participants who 
stopped treatment (e.g., for tolerability issues or 
treatment failure) for prolonged periods (months to 
more than a year, in some subjects, 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 4 weeks after 
the last Q4W dose or within 8 weeks after the 
last Q8W 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 a minimum of 52 weeks from the 
time of the last LA administration. 
Drug-Drug Interactions 
(DDIs) 
For a complete listing of permitted and prohibited 
concurrent medications for RPV and RPV LA, 
refer to Section 6.13 
RPV 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 
• All participants will be informed of prohibited 
medications throughout the study and updates 
provided as needed via informed consent. 


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may result in loss of therapeutic effect of RPV LA. 
- the anticonvulsants carbamazepine, 
oxcarbazepine, phenobarbital, phenytoin 
- the antimycobacterials rifampicin, rifapentine, 
rifabutin 
- the glucocorticoid systemic dexamethasone, 
except as a single dose treatment 
- St John’s wort (Hypericum perforatum). 
Of note, evidence to date indicates that clinically 
relevant DDIs with RPV LA and other 
antiretrovirals are unlikely to occur.  
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, 


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lansoprazole, omeprazole, pantoprazole, 
rabeprazole; 
Participants discontinuing a LA regimen may be at 
risk for developing DDIs many weeks after 
discontinuing injectable therapy.   


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Inadvertent 
Intravenous Injection 
(Accidental 
Maladministration) 
As with any intramuscular injection, it is possible 
that RPV LA can be inadvertently administered 
intravenously instead of intramuscularly possibly 
resulting in higher than expected concentrations of 
RPV shortly after injection and lower 
concentrations thereafter.  This could be due to 
administrator error, improper injection technique 
and / or improper needle length used based on 
body type.   
In addition, HIV-1 viral suppression may not be 
effective following accidental intravenous 
maladministration. 
Systemic reactions following RPV LA injections 
have been observed in clinical trials. These occur 
infrequently (in less than 0.5% of participants) and 
typically begin to resolve within minutes of the 
injection, however some participants  required 
supportive care. Where timely PK data was 
available, high RPV PK plasma concentrations 
have been observed which may have resulted from 
an accidental partial IV injection of RPV 
• Training will be provided to all sites on proper 
injection technique.   
• Should IM maladministration be suspected at 
any time (e.g., suspected under or overdose or 
inadvertent IV dosing), post dose ECG 
monitoring and vital signs or any other 
supportive testing may be obtained at the 
discretion of the investigator, and the medical 
monitor notified 
• Laboratory samples for safety parameters and 
HIV-1 RNA will be closely monitored in all 
participants.  Additionally, 2-hour post dose PK 
samples will be obtained at a few early 
timepoints for determination of RPV 
concentration and possible pharmacokinetic 
correlation with safety parameters such as ECG 
changes and virologic response. Additionally, an 
unscheduled PK sample may be drawn 
approximately 2  hours post dosing for future 
evaluation of RPV concentrations. 


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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 dosed Q4W has demonstrated 
sustained antiviral activity in studies 200056, 
201584 and 201585 however the efficacy of 
Q8Wdosing remains under evaluation.    
Doses of the CAB LA and RPV LA have been 
selected to achieve exposures that are expected to 
maintain virologic efficacy on the basis of 
available data with the oral and LA formulations. 
 
• 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 throughout the 
Maintenance Phase for determination of CAB 
and RPV concentration and possible 
pharmacokinetic correlation with virologic 
response. 


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Due to administration error, it is possible that a 
participant could receive an inadequate dose of 
CAB LA or RPV LA.  Sub-therapeutic 
concentrations of either CAB LA or RPV LA 
could lead to virologic failure and possibly the 
development of viral resistance.   
 


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2.3.1.1. 
Other Clinically Relevant Information 
Additional details concerning safety observations from clinical studies and for which a 
causal association has not been established or which are of minimal clinical significance 
may be found in the Investigator’s Brochures .   
 
Adverse Events of Special Interest: 
 
Seizure 
Several cases of seizure have occurred during the cabotegravir program. These cases 
have had alternative explanations for their occurrence. Overall, there is not convincing 
evidence that cabotegravir exposure may be causally associated with seizure or with 
reduction of seizure threshold, due to the low frequency of reports, the confounders 
present in the cases received to date and lack of any pre-clinical signal or identified 
plausible mechanism. However, seizure and seizure-like events are considered as AEs of 
special interest for CAB.  Subjects with an unstable or poorly controlled seizure disorder 
will be excluded from study participation. All cases of prior seizure history should be 
discussed with the Medical Monitor prior to enrolment. Report any cases of seizure or 
seizure like events immediately. 
2.3.2. 
Benefit Assessment 
The antiviral activity against HIV-1 of CAB has been well established through Phase 2 
and Phase 3 studies. RPV 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. Participants randomized to receive CAB LA+ 
RPV LA Q4W or Q8W weekly dosing will not need to take concomitant daily oral 
therapy.  Adherence in these participants is expected to be improved and will be directly 
observed during IM injections. Efficacy of this two-drug regimen, as IM agents, has been 
demonstrated through Week 96 of the ongoing 200056, 201584 and 201585 studies. 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 Q4W 
and Q8W 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. 


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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To demonstrate the non-inferior antiviral 
activity of CAB LA + RPV LA every 8 
weeks (every two months) compared to 
CAB LA + RPV LA every 4 weeks 
(monthly) over 48 weeks 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 Week 48 (Intent-to-
Treat Exposed [ITT-E] population) 
Secondary 
To demonstrate the antiviral and 
immunologic activity of CAB LA + RPV 
LA every 8 weeks compared to CAB LA + 
RPV LA every 4 weeks 
Proportion of participants with plasma HIV-1 
RNA <50 c/mL (c/mL) at Week 24, Week 
48, Week 96, and Week 152 using the FDA 
Snapshot algorithm (Intent-to-Treat Exposed 
[ITT-E] population) 
Proportion of participants with protocol-
defined confirmed virologic failure (CVF) 
through Week 24, Week 48, Week 96, and 
Week 152 
Proportion of participants with HIV-RNA 
greater than or equal to 50 c/mL as per FDA 
Snapshot algorithm at Week 24, Week 96, 
and Week 152 
Absolute values and changes from Baseline 
in viral load and CD4+ cell counts over time 
including Week 48,Week 96, and Week 152 
To evaluate the safety and tolerability of 
CAB LA + RPV LA every 8 weeks 
compared to CAB LA + RPV LA every 4 
weeks 
Incidence and severity of AEs and laboratory 
abnormalities over time including Week 24, 
Week 48, Week 96, and Week 152 
Proportion of participants who discontinue 
treatment due to AEs over time including 
Week 24, Week 48, Week 96, and Week 152 
Change from Baseline in laboratory 
parameters over time including Week 48, 
Week 96, and Week 152 


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Objectives 
Endpoints 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure  
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV 
through Week 24, Week 48, Week 96, and 
Week 152 
To characterize CAB and RPV 
concentrations and population 
pharmacokinetics and identify important 
determinants of variability 
Plasma PK parameters for CAB LA and RPV 
LA (when evaluable, Ctrough, concentrations 
post dose [~Cmax], and area under the curve 
[AUC]) 
Demographic parameters including, but not 
limited to, age, sex, race, body weight, body 
mass index, and relevant laboratory 
parameters will be evaluated as potential 
predictors of inter- and intra-participant 
variability for pharmacokinetic parameters 
To assess preference for CAB LA + RPV 
LA every 8 weeks or CAB LA + RPV LA 
every 4 weeks LA compared to oral 
antiretroviral (ARV)  
To assess preference for CAB LA+ RPV 
LA every 8 weeks compared to CAB LA + 
RPV LA every 4 weeks 
Preference for CAB LA + RPV LA every 8 
weeks or CAB LA + RPV LA every 4 weeks 
compared to oral ARV and preference for 
CAB LA + RPV LA every 8 weeks 
compared to CAB LA + RPV LA every 4 
weeks will be assessed using a preference 
questionnaire at week 48 (or Withdrawal). 
To assess patient reported health-related 
quality of life, treatment satisfaction, 
injection tolerability, and treatment 
acceptance. 
Change from Baseline (Day 1) in HRQoL at 
Week 24, and Week 48 (or Withdrawal) 
Change from baseline (Day 1) in total 
“treatment satisfaction” score, and individual 
item scores of the HIV Treatment 
Satisfaction Status Questionnaire (HIVTSQs) 
at Week 24, 48, and 152 (or Withdrawal) 
Change in treatment satisfaction over time 
using the HIV Treatment Satisfaction Change 
Questionnaire HIVTSQc at Week 48 (or 
Withdrawal). 
Change from Week 8 in Dimension scores 
(“Bother of ISRs”, “Leg movement”, 
“Sleep”, and “Injection Acceptance”) and 
individual item scores assessing pain during 
injection, anxiety before and after injection, 
willingness to be injected in the future and 
overall satisfaction with mode of 


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Objectives 
Endpoints 
administration over time will be assessed 
using the Perception of iNjection 
questionnaire (PIN) at Weeks 8, 24, 48 and 
152 (or Withdrawal)  
Change from Baseline (Day 1) in treatment 
acceptance at Weeks 24,  48 and 152 (or 
Withdrawal) will be assessed using the 
“General acceptance” dimension of the 
Chronic Treatment Acceptance (ACCEPT) 
questionnaire 
Exploratory 
To evaluate the antiviral and immunologic 
effects, safety and tolerability, and viral 
resistance of CAB LA + RPV LA for all 
participants in the Extension Phase. 
Proportion of participants with plasma HIV-1 
RNA <50 c/mL over time 
Proportion of participants with confirmed 
virologic failure over time 
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB and RPV 
in over time 
Incidence and severity of AEs and laboratory 
abnormalities over time 
Proportion of participants who discontinue 
treatment due to AEs over time 
Absolute values and changes in laboratory 
parameters over time 
Incidence of disease progression (HIV-
associated conditions, acquired 
immunodeficiency syndrome [AIDS] and 
death) 
To explore the effect of patient 
characteristics on virologic and 
immunologic responses to CAB LA+ RPV 
LA every 8 weeks compared to CAB LA + 
RPV LA every 4 weeks 
Proportion of participants by patient 
subgroup(s) (e.g., by age, gender, BMI, race, 
HIV-1 subtype, Baseline CD4+, type of oral 
treatment [NNRTI, PI, or INSTI], duration 
prior CAB LA and RPV LA exposure [0 
weeks, 1-24 weeks, > 24 weeks]) with HIV-
RNA greater than or equal to 50 c/mLover 
time including Week 48 Week 96, and Week 
152 using the Snapshot algorithm for the 


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Objectives 
Endpoints 
ITT-E population 
Change from Baseline in CD4+ cell counts 
by subgroups at Week 48, Week 96, and 
Week 152 
To explore relationship(s) between plasma 
concentrations of CAB and RPV and 
pharmacodynamic endpoints. 
Relationship between plasma CAB and RPV 
concentrations and virologic, immunologic 
responses, and/or occurrence of adverse 
events [AEs] over time. 
To assess reason for switching using a 
single question.  
To assess reason for continuation using a 
single question 
 
For patients randomized from oral SOC, the 
reasons for willingness to switch ART at 
baseline (Day 1) will be assessed 
For patients randomized from CAB LA + 
RPV LA every 4 weeks in ATLAS, the 
reasons for willingness to continue long-
acting ART at baseline (Day 1) will be 
assessed 
To assess preference for CAB LA + RPV 
LA every 8 weeks or every 4 weeks 
compared to daily oral for participants 
receiving oral bridging during the 
Maintenance and/or Extension phases 
Preference for CAB LA + RPV LA every 8 
weeks or every 4 weeks compared to daily 
oral for participants receiving oral bridging 
during the Maintenance and/or Extension 
phases will be assessed using a preference 
questionnaire at Week 152  or Withdrawal  
4. 
STUDY DESIGN 
4.1. 
Overall Design 
Study 207966 (Antiretroviral Therapy as Long Acting Suppression every 2 Months-
ATLAS-2M) is a Phase III, randomized, open-label, active-controlled, multicenter, 
parallel-group, non-inferiority study designed to assess the antiviral activity and safety of 
CAB LA + RPV LA administered every 4 weeks compared CAB LA + RPV LA 
administered every 8 weeks in approximately 1020 adult HIV-1 infected patients.   
Two groups of patients who fulfill eligibility requirements will be randomized (1:1) at 
Day 1 to receive CAB LA + RPV LA Q4W, or CAB LA + RPV LA Q8W regimen for at 
least 100 weeks:  
Group 1: Patients randomized from current ART Standard of Care (SOC) therapy 
Patients randomized from current ART SOC therapy, including those enrolled to the 
“current ART” arm of the ATLAS study following completion of the Week 52 visit (at 


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minimum), will begin oral therapy with CAB 30 mg + RPV 25 mg once daily at Day 1 
for 28 days (3 days) to determine individual safety and tolerability prior to receiving 
CAB LA + RPV LA Q4W, or CAB LA + RPV LA Q8W.  For patients on SOC 
transitioning from the ATLAS trial, eligibility for ATLAS-2M can be determined once 
the final central lab results from ATLAS are available and safety parameters have been 
reviewed. 
Group 2: Patients currently receiving CAB LA + RPV LA Q4W 
At Day 1, patients entering ATLAS-2M from ATLAS and currently receiving CAB LA + 
RPV LA Q4W (including both those who were originally randomized to Q4W in the 
Maintenance phase of ATLAS and those who transitioned from SOC to the Q4W 
regimen within the Extension Phase of ATLAS) will be randomized 1:1 to either 
continue Q4W administration or transition to Q8W administration of CAB LA + RPV 
LA.  The first injection visit for ATLAS-2M can be performed once the final central lab 
results from ATLAS are available and safety parameters have been reviewed, and the 
ATLAS Week 52 visit (at minimum) has been completed.  Participants will continue to 
receive CAB LA + RPV LA Q4W injections as scheduled within the ATLAS trial until 
their eligibility for ATLAS-2M can be fully evaluated and the participant is re-
randomized (Q4W or Q8W).  If determined to be ineligible for ATLAS-2M, those 
participants can elect to continue participation in ATLAS or withdraw from the ATLAS 
study.  
Participants in ATLAS-2M who successfully complete Week 100 (without meeting study 
defined withdrawal criteria) will be given the option to continue to receive their 
randomized treatment (CAB LA + RPV LA administered Q4W or Q8W) in the Extension 
Phase through Week 152 and until the study treatment is either locally approved and 
commercially available within the local sector (including through local 
public/government health sectors), the participant no longer derives clinical benefit, the 
participant meets a protocol-defined reason for discontinuation or until development of 
either CAB LA + RPV LA Q4W and/or Q8W is terminated.  Alternatively, participants 
can choose to complete study participation and enter the 52-week LTFU Phase of the 
study. 
 
Any participant who receives at least one dose of CAB LA and/or RPV LA and 
discontinues the CAB LA + RPV LA regimen for any reason will enter a 52-week LTFU 
Phase.  Those participants must remain on suppressive highly active antiretroviral therapy 
(HAART) for at least 52 weeks after the last dose of CAB LA and/or RPV LA. 
In order to achieve balance across the treatment arms, randomization will be stratified by 
prior CAB + RPV Exposure: 0 weeks, 1-24 weeks, >24 weeks.  The primary endpoint for 
the study is the proportion of participants with HIV-RNA greater than or equal to 
50 c/mL (Virologic Failure) at Week 48 as per Food and Drug Administration (FDA) 
Snapshot algorithm using the Intent-to-Treat Exposed (ITT-E) population.  The 
proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA 
Snapshot algorithm (Missing, Switch or Discontinuation = Failure, ITT-E population) is a 
key secondary endpoint comparison.   


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The sample size of 1020 provides 85% power to demonstrate non-inferiority in the 
primary endpoint at Week 48 using a 4% margin, assuming a true 3% failure rate for 
Q8W CAB LA + RPV LA and a 2% failure rate for the Q4W CAB LA + RPV LA arm 
and a 2.5% one-sided alpha level.   
Figure 1 
207966 (ATLAS-2M) Study Design Schematic 
 
 
Screening Phase
¥ Maintenance Phase
† Extension Phase
ATLAS Q4W 
ATLAS SOC Arm + 
additional SOC 
Patients:  PI, NNRTI, 
or INI Based 
Regimen with 2 
NRTI backbone
Wk96
Q8W CAB LA + RPV LA
Wk 48
1o Endpoint
Q4W CAB LA + RPV LA 
Randomize 
1:1
Q8W CAB LA + RPV LA 
Oral CAB
+ RPV
Oral CAB
+ RPV
Q4W CAB LA + RPV LA
CAB LA + RPV LA
Q4W or Q8W
Wk 100
Day 1
Wk 4b
Wk 4a
2o Endpoint
Randomize 
1:1
Wk 152
2o Endpoint
N=1020, randomized 1:1 to each arm and stratified by prior CAB + RPV Exposure 
# SOC Patients not transitioning from the ATLAS study must be on uninterrupted current regimen 
(either the initial or second cART regimen) for at least 6 months prior to Screening. Documented 
evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to 
Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening.  No 
history of virologic failure.  No evidence of viral resistance based on the presence of any 
resistance-associated major INI, or NNRTI mutation (except K103N) from prior genotype assay 
results. No current or prior history of etravirine use. 
†Optional Extension Phase to continue randomized CAB LA + RPV LA Q4W or Q8W at Wk 100 
¥Participants who withdraw from IM regimen must go into 52 week long term follow up phase if 
randomized regimen is not yet locally approved and commercially available.  
4.2. 
Treatment Groups and Duration 
4.2.1. 
Screening Phase (Up to 35 days) 
Informed consent must be obtained prior to any study procedures, including any 
Screening assessment. 
Participants will be involved in a Screening period of up to 35 days and may be re-
screened once.  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. 
For participants transitioning from the ATLAS study, eligibility to transition to ATLAS-
2M at Week 52 (at the earliest) will be determined once the final central lab results from 
ATLAS, following (at minimum) completion of the ATLAS Week 48 visit are available 


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and safety parameters have been reviewed.  Separate Screening Labs will be utilized to 
inform eligibility for ATLAS-2M; however, in some occasions and upon consultation 
with the Medical Monitor, individual lab results and safety data from the final visit of the 
ATLAS study can be considered towards informing eligibility for the ATLAS-2M study 
as long as all other Screening and eligibility criteria are met.     
4.2.2. 
Maintenance Phase (Day 1 up to Week 100) 
There are two ways in which study participants may transition to the LA regimen, either 
directly from oral SOC or from Q4W dosing from ATLAS.  
Table 1 and Figure 2 describe the CAB LA + RPV LA dosing regimens in ATLAS-2M 
based on the mode of transition. 
Table 1 
CAB LA + RPV LA Dosing Regimens in ATLAS-2M 
Participants Transitioning from Oral Standard of Care (SOC) 
Regimen 
CAB LA 
RPV LA 
Q4W 
CAB LA: 
Week 4b: 600 mg (Loading Dose) 
Week 8 & Q4W thereafter: 400 mg   
RPV LA: 
Week 4b: 900 mg (Loading Dose) 
Week 8 & Q4W thereafter: 600 mg 
Q8W 
CAB LA: 
Week 4b, Week 8, & Q8W thereafter: 
600 mg 
RPV LA: 
Week 4b, Week 8, & Q8W thereafter: 
900 mg 
Participants Transitioning from ATLAS Q4W 
Regimen 
CAB LA 
RPV LA 
Q4W 
CAB LA: 
Day 1 & Q4W thereafter: 400 mg 
RPV LA: 
Day 1 & Q4W thereafter: 600 mg 
Q8W 
CAB LA: 
Day 1 & Q8W thereafter: 600 mg   
RPV LA: 
Day 1 & Q8W thereafter: 900 mg 
All participants entering ATLAS-2M from an oral SOC regimen will receive a 4-week oral lead-in of CAB+RPV prior to 
receiving IM injections, except for ATLAS subjects transitioning from Q4W to Q8W injections.  These participants 
previously established safety and tolerability of CAB + RPV within the ATLAS study. 
 


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Figure 2 
ATLAS-2M Treatment Schematic 
Screening Phase
Maintenance Phase and Extension Phase
From ATLAS 
on Q4W
From ATLAS
on SOC
-or-
new SOC 
patients
(PI, NNRTI, or INI  
Regimen + 2 NRTI)
Q8W
Wk 24
Q4W 
Randomize 
1:1
Q8W 
Oral CAB
+ RPV
Oral CAB
+ RPV
Q4W 
Day 1
Wk 4b
Wk 4a
Randomize 
1:1
Wk 12
Wk 8
Wk 16
CAB 600mg/RPV 900mg
CAB 400mg/RPV 600mg
Wk 20
… continued to 
end of study
treatment
 
 
4.2.2.1. 
Patients randomized to LA dosing from current ART SOC therapy: 
All participants randomized from current ART SOC therapy (including those 
transitioning from SOC in ATLAS and new study participants) will begin oral therapy 
with CAB 30 mg + RPV 25 mg once daily at Day 1 for 4 weeks to determine individual 
safety and tolerability prior to administration of CAB LA + RPV LA.  The oral lead-in 
period is part of the Maintenance Phase and will therefore be included within the planned 
analyses. 
The final dosing of current daily oral ART regimen should occur the day prior to 
randomization to avoid overlap of treatment regimens however, if the participant takes 
current ART prior to coming into the clinic, randomization and initiation of oral CAB 
and RPV should continue as planned for Day 1.  At the Week 4a visit, safety assessments 
(including e.g., clinical chemistries) will be performed as per the Time and Events Table 
to determine individual safety and tolerability prior to the initial administration of CAB 
LA + RPV LA.  Dosing of CAB LA + RPV LA Q4W or Q8W will initiate at the Week 
4b visit once safety labs from Week 4a are available and have been reviewed. 
Subjects receiving oral SOC treatment and randomized to Q4W injections will receive 
loading doses of CAB LA 600 mg + RPV LA 900 mg on Week 4b followed by 
maintenance injections of CAB LA 400 mg + RPV LA 600 mg every 4 weeks thereafter.   
Subjects receiving oral SOC treatment and randomized to Q8W injections will receive 
doses of CAB LA 600 mg + RPV LA 900 mg on Week 4b and Week 8 followed by 
identical maintenance dose injections every 8 weeks thereafter. 
All injections should be planned as single injections per drug. 


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4.2.2.1.1. IM injections every 4 weeks (Q4W from SOC): 
Week 4b visit only - CAB LA 600 mg + RPV LA 900 mg, each given as 1 X 3 mL IM 
injection 
Week 8 visit and Q4W thereafter - CAB LA 400 mg IM + RPV LA 600 mg IM every 
4 weeks for 100 weeks, each given as 1 X 2 mL IM injection 
At Week 4b, participants will return to the clinic, take the last oral dose (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 injections with IM CAB 
LA + RPV LA at Week 4b can be performed once central lab results are available and 
safety parameters are reviewed from the Week 4a visit.   
The second and third IM injections with CAB LA 400 mg and RPV LA 600 mg will be 
performed at Week 8 and Week 12.  There will be a -7-day dosing window for the second 
and third IM injections such that the second injection occurs within the window of 
Week 7 and Week 8 but no later than Week 8 and the third injection occurs within the 
window of Week 11 and Week 12 but no later than Week 12.  Subsequent injections with 
CAB LA 400 mg and RPV LA 600 mg will occur every 4 weeks (7 days) thereafter.  In 
addition, starting after the Week 16 injection, the interval between injection visits will be 
limited to a maximum of 5 weeks.  The Medical Monitor must be contacted to discuss 
individual participant case management if the length of time between injections exceeds 
or is projected to exceed 5 weeks. 
4.2.2.1.2. IM injections every 8 weeks (Q8W from SOC): 
Week 4b visit – CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM 
injection 
Week 8 visit- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM 
injection 
Week 16 visit and Q8W thereafter - CAB LA 600 mg + RPV LA 900 mg IM, every 8 
weeks for 100 weeks, each given as 1 X 3 mL IM injection 
At the Week 4b visit, subjects will return to the clinic, take their last oral dose (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 injections with 
IM CAB LA + RPV LA at Week 4b can be performed once central lab results are 
available and safety parameters are reviewed from the Week 4a visit.   
The second loading injection will be administered at Week 8 (CAB LA 600 mg + RPV 
LA 900 mg, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring 
every 8 weeks thereafter.  There will be a -7-day dosing window for the second and third 
IM injections such that the second injection occurs within the window of Week 7 and 
Week 8 but no later than Week 8 and third injection occurs within the window of Week 
15 and Week 16 but no later than Week 16.  Subsequent injections with CAB LA 600 mg 
and RPV LA 900 mg will occur every 8 weeks (7 days).  Starting after the Week 16 


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injection, the interval between injection visits will be limited to a maximum of 9 weeks.  
If the length of time between injections exceeds, or is projected to exceed 9 weeks, the 
Medical Monitor must be contacted to discuss individual participant case management.   
4.2.2.2. 
Participants transitioning from ATLAS and currently receiving CAB LA 
+ RPV LA Q4W 
Subjects receiving Q4W injections within ATLAS and randomized to receive Q4W 
injections in Study 207966 will continue receiving maintenance injections Q4W as 
scheduled and will not require a loading dose on Day 1. 
Subjects receiving Q4W injections within ATLAS and randomized to receive Q8W 
injections in Study 207966 will receive doses of CAB LA 600 mg + RPV LA 900 mg on 
Day 1, one month after their last Q4W maintenance dose, in order to align with Day 1 of 
study randomization.  Subjects will not require an intermediate dose at Week 4 and will 
receive their next Q8W maintenance injections at Week 8 and Q8W thereafter.   
Participants transitioning from the ATLAS study and on CAB LA + RPV LA Q4W 
treatment will be randomized at Day 1 to either continue Q4W administration or 
transition to Q8W administration of CAB LA + RPV LA.  The first injection visit for the 
ATLAS-2M study can be performed once the final central lab results from the ATLAS 
study are available and safety parameters have been reviewed.  Screening labs 
determining eligibility for ATLAS-2M can be collected at Week 48 (at minimum) for 
participants originally randomized to the Q4W arm within ATLAS.  Screening labs for 
participants who transitioned from SOC to Q4W injections within the ATLAS Extension 
Phase may be obtained at ATLAS Week 56b (following the CAB + RPV Oral lead-in 
period) or at subsequent ATLAS visits after receiving one set or a short course of Q4W 
injections.  The transition from the final ATLAS to ATLAS-2M Day 1 dosing must occur 
4 weeks (7 days) from the final injections received in ATLAS  
Dosing for participants transitioning from CAB LA + RPV LA Q4W in ATLAS is as 
follows: 
4.2.2.2.1. IM injections every 4 weeks (Q4W from ATLAS Q4W): 
Starting at Day 1, all injections will continue with maintenance doses of CAB LA 400 mg 
and RPV LA 600 mg administered every 4 weeks (7 days).  In addition, the time 
between injection visits will be limited to a maximum of 5 weeks.  The Medical Monitor 
must be contacted if the length of time between injections exceeds or is projected to 
exceed 5 weeks. 
4.2.2.2.2. IM injections every 8 weeks (Q8W from ATLAS Q4W): 
Participants transitioning from ATLAS and randomized to receive CAB LA + RPV LA 
Q8W injections will initiate Q8W dosing at the Day 1 visit as follows:  
Day 1- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Week 8 and Q8W thereafter- CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 
3 mL IM injection 


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The second loading injection will be administered at Week 8 (CAB LA 600 mg + RPV 
LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring 
every 8 weeks thereafter.  There will be a -7-day dosing window for the second and third 
IM injections such that the second injection occurs within the window of Week 7 and 
Week 8 but no later than Week 8 and third injection occurs within the window of 
Week 15 and Week 16 but no later than Week 16.  Subsequent injections with CAB LA 
600 mg and RPV LA 900 mg will occur every 8 weeks (7 days).  Starting after the 
Week 16 injections, the interval between injection visits will be limited to a maximum of 
9 weeks.  If the length of time between injections exceeds, or is projected to exceed 9 
weeks, the Medical Monitor must be contacted to discuss individual participant case 
management.   
The primary study analysis will consist of data collected through the Week 48 visit.  A 
single repeat of HIV-1 RNA for any participant with a HIV-1 RNA 50 c/mL at Week 
48, Week 96, or Week 152 must be performed.  The retest should be scheduled as soon as 
possible (but no later than 4 weeks from the Week 48,  96 or 152 visits, respectively) and 
will inform the Week 48, 96, or 152 virological endpoint, respectively.   
4.2.3. 
Extension Phase 
Participants who successfully complete 96 Weeks of CAB LA + RPV LA treatment in 
the Maintenance Phase will continue to have access to their randomized treatment Q4W 
or Q8W CAB LA + RPV LA in the Extension Phase through Week 152 and until study 
treatment is either locally approved and commercially available within the local sector 
(including through local public/government health sectors), the participant no longer 
derives clinical benefit, the participant meets a protocol-defined reason for 
discontinuation or until development of either CAB LA + RPV LA Q4W and/or Q8W is 
terminated.  For participants randomized to Q4W arm, dosing visits will continue to 
occur every 4 weeks with CAB LA 400 mg and RPV LA 600 mg.  For participants 
randomized to the Q8W arm, dosing visits will continue to occur every 8 weeks with 
CAB LA 600 mg and RPV LA 900 mg.  Safety and efficacy assessments will be 
conducted as per the Time and Events Schedule.  
Participants choosing to not enter the Extension phase can complete their study 
participation at the Week 100 visit and enter into the LTFU Phase as required.  
Participants who choose to continue on to the Extension Phase will need to be assessed 
for eligibility and will continue on their current CAB LA + RPV LA regimen while 
eligibility is being confirmed.  A single repeat of HIV-1 RNA for any participant with a 
HIV-1 RNA 50 c/mL and < 400 c/mL at Week 96, or Week 152 must be performed.  
The retest should be scheduled as soon as possible (but no later than 4 weeks from the 
Week 96 or Week 152 visit).  Participants with HIV-1 RNA <50 c/mL upon retest are 
eligible to enter the Extension Phase.  Participants with HIV-1 RNA ≥400 c/mL at 
Week 96 are not eligible to enter the Extension Phase, will not be allowed a repeat to 
determine eligibility, and will therefore be withdrawn from the study.  Eligibility to enter 
the Extension Phase for any participants with a retest HIV-1 RNA >50 c/mL and <400 
c/mL will require approval by the study Medical Monitor.   


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Participants not eligible to enter the Extension Phase or choosing not to participate in the 
Extension Phase will end their study treatment and enter the LTFU Phase. Sites may be 
reimbursed for up to a one-month supply of antiretroviral medication to facilitate 
transition to non-study ART for participants that do not qualify for the Extension Phase. 
4.2.4. 
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 before CAB LA + 
RPV LA marketed product is locally available must enter the LTFU Phase. 
Participants must remain on suppressive HAART for at least 52 weeks after the 
last dose of CAB LA and/or RPV LA in order to prevent selective pressure on 
HIV and the potential for selection of resistant mutants.  Investigators must 
discuss the choice of the follow-up HAART regimen with the Medical 
Monitor prior to initiating the new regimen with the participant.  HAART 
therapy should be initiated within 4 weeks ( 7 days) after the last Q4W 
injection or within 8 weeks ( 7 days) after the last Q8W injection.  The 
LTFU will begin the day of the last CAB LA and/or RPV LA dose and continue 
for 52 weeks.  These participants will complete Withdrawal assessments and will 
then enter into the LTFU Phase as per the Time and Events Schedule.  In addition, 
for participants who withdraw during the LTFU Phase, the final visit will be 
considered the study withdrawal visit. 
• Where the CAB LA + RPV LA marketed product is locally available, only 
participants that discontinue the CAB LA + RPV LA regimen for safety-related 
reasons included in Section 5.5 must enter the LTFU Phase. Participants must 
remain on suppressive HAART for at least 52 weeks after the last dose of CAB 
LA and/or RPV LA in order to prevent selective pressure on HIV and the 
potential for selection of resistant mutants.  Investigators must discuss the 
choice of the follow-up HAART regimen with the Medical Monitor prior to 
initiating the new regimen with the participant.  HAART therapy should be 
initiated within 4 weeks ( 7 days) after the last Q4W injection or within 8 
weeks ( 7 days) after the last Q8W injection.  The LTFU Phase will begin the 
day of the last CAB LA and/or RPV LA dose and continue for 52 weeks.  These 
participants will complete Withdrawal assessments and will then enter into the 
LTFU Phase as per the Time and Events Schedule.  In addition, for participants 
who withdraw during the LTFU Phase, the final visit will be considered the study 
withdrawal visit.  
• NOTE: Participants transitioning to CAB+RPV LA marketed product or 
alternative HAART (except due to safety-related reasons) do not need to enter the 
LTFU Phase however 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 will be assessed with clinic visits at months 3, 6, 9, and 12 during the LTFU 
Phase.  Female participants of child bearing potential must continue to use adequate 
contraception methods (see Study Procedures Manual for list of accepted forms of 
contraception) for the entire year of follow up.   


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In order to assure that participants have access to HAART during the LTFU Phase, GSK 
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. 
This phase is considered study participation and participants will be followed on study 
during this time.  A withdrawal visit is not required for participants who do not complete 
the LTFU Phase.  The participants’ last on study visit will be considered as their 
withdrawal visit. 
4.2.5. 
Dose Modifications: 
No dose reductions, modifications, or changes in the frequency of any components of 
each regimen will be allowed during the study beyond what is allowed within the 
protocol or directly approved by the study Medical Monitor.  Protocol waivers or 
exemptions are not allowed.  Therefore, adherence to the study design requirements is 
essential and required for study conduct. 
In exceptional circumstances, and in consultation with the Medical Monitor, Investigators 
may provide oral CAB and/or RPV as a short-term “bridging” strategy for participants 
who have begun CAB LA + RPV LA (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 10 in Section 11.10 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. 
4.2.6. 
Independent Data Monitoring Committee 
An Independent Data Monitoring Committee (IDMC) will be instituted to ensure external 
objective medical and/or statistical review of efficacy and safety in order to protect the 
ethical interests and well-being of subjects and to protect the scientific validity of this 
study.  
The IDMC will evaluate accumulating efficacy, tolerability, safety and PK of CAB LA + 
RPV LA Q8W at predetermined times during the study.  An interim futility analysis will 
be performed for the IDMC to evaluate the efficacy of CAB LA + RPV LA Q8W prior to 
the final analysis.  Full details of the methods, timing, decision criteria, and operating 
characteristics will be pre-specified in the IDMC Charter. 


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The interim futility analysis will be performed with the intent of having approximately 
50% of participants reaching Week 24 and providing sufficient lead time to allow the 
IDMC to review the data prior to any participants reaching the Week 52 visit.  A futility 
rule based on Bayesian posterior predictive probability approach will be applied to assess 
the probability that the CAB LA + RPV LA Q8W injectable regimen demonstrates non-
inferiority to the CAB LA + RPV LA Q4W regimen, given the partial data set.  The 
sponsor will remain blinded to this analysis. 
In addition, the IDMC may also monitor the incidence of participants meeting Confirmed 
Virologic Failure (CVF) criteria through Week 48 to ensure that participants are not 
being sub-optimally treated in the CAB LA + RPV LA Q8W arm. 
Full details of the analyses, estimated timing, and the decision criteria that will be used to 
determine regimen performance will be pre-specified in the IDMC Charter. 
4.3. 
Type and Number of Participants 
The target population to be enrolled is HIV-1 infected virologically suppressed (HIV-1 
RNA <50 c/mL) patients on stable antiretroviral therapy (ART) including participants 
who have completed at minimum, Week 52, of the 201585 (ATLAS) study. 
It is anticipated that approximately 1020 participants will be enrolled into ATLAS-2M.  
In addition to participants rolled over from the ATLAS study, additional participants on 
SOC treatment will be screened to supplement enrollment such that the study can be 
appropriately powered (See Section 9.1).  A 15% screen failure rate, for additional 
patients randomized from SOC treatment is anticipated.  Participants will be enrolled 
from multiple countries which may include those countries actively participating in the 
ATLAS study including Argentina, Canada, France, Germany, Italy, Mexico, Russia, 
South Africa, South Korea, Spain, Sweden, and the United States.  
Randomization will be stratified by prior CAB + RPV Exposure: 0 weeks, 1-24 weeks, 
>24 weeks.  A goal of this study is to enroll populations who are underrepresented in 
clinical studies, including approximately 25% women.  To provide sufficient data to 
determine whether either gender is correlated with treatment response, sites are expected 
to take into account gender in their screening strategies.  
4.4. 
Scientific Rationale for Study Design 
The design of this study (1:1 randomized, open-label, active-controlled, multicenter, 
parallel group, non-inferiority study) is well established for confirming the non-
inferiority of an investigational agent compared with an active comparator and is 
generally accepted by regulatory authorities as rigorous proof of antiviral activity. The 
primary endpoint, proportion of participants defined as virologic failures by the FDA 
Snapshot algorithm is recommended in the FDA’s 2015 guidance document (FDA, 2015) 
for assessing efficacy in Switch Trials.  The key secondary endpoints, proportion with 
plasma HIV-1 RNA <50 c/mL at Week 48,Week 96, and Week 152, 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 CAB LA + RPV LA Q4W and Q8W regimens. 


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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_05) 
clinical trial evaluated a different simplification approach and served as proof of concept 
for ATLAS-2M.  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 subjects 
maintained virologic suppression (HIV-1 RNA <50 c/mL) compared to 84% of subjects 
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 have been 
progressed into Phase 3 for further clinical development, respectively.  The CAB LA + 
RPV LA Q4W regimen is currently under evaluation in the ongoing Phase 3 201584 and 
201585 studies.  
The open-label design best suits the objectives of this study.  A double-dummy design 
could not be undertaken given the logistical challenges of blinding each regimen.  
Because 2 injections of each investigational product are administered at every visit, a 
double-dummy design would require all subjects to chronically receive 4 injections per 
Q4W visit (2 active and 2 placebo), which could be intolerable for patients. In addition, 
the volume of CAB LA and RPV LA injections will differ significantly between Q8W 
and Q4W IM injections (3 mL vs 2 mL each), it would not be logistically feasible to 
blind site staff nor patients from the study treatments being administered.  
Participants randomized to receive CAB LA + RPV LA Q8W IM administration will be 
required to participate in clinic visits approximately every 8 weeks while participants 
randomized to receive Q4W IM administration will be required approximately monthly 
clinical visits. Importantly, secondary objectives of this study are to understand the 
acceptability, tolerability, and patient reported preferences to these novel injectable 
regimens.  An unblinded study design supports collection of participant preference data 
in a way that would not be possible if a double-blind, double-dummy design were 
implemented. If the Q8W arm were required to receive blinded placebo injections every 
month, the value of comparing safety, tolerability, and convenience of Q8W compared to 
Q4W administrations would be limited and include overly burdensome visit requirements 
for those randomized to Q8W administration.  Additionally, the perceived value for 
participants to transition from the ATLAS study to ATLAS-2M for potential 
randomization to the Q8W regimen would also be limited and may result in loss of 


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patients with prior Q4W experience, thereby limiting the ability to compare experience of 
Q4W and Q8W regimens within individual patients.   
Due to the complexities, lack of feasibility and limitations of blinding CAB LA and RPV 
LA injections for Q8W compared to Q4W administration, this Phase 3b study is planned 
as open label.   
To maintain the integrity of the trial, data aggregated by actual treatment group will not 
be made available to members of the Study Team in advance of the first planned sponsor 
analysis when all subjects have completed Week 24 (see Section 9.2.3.1) and will not be 
shared with Investigators until the primary analysis at Week 48.  In addition, central 
randomization will be used to ensure that selection bias is avoided (see Section 6.2).  
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.  
4.5. 
Dose Justification 
4.5.1. 
Oral Lead-In Phase 
Participants entering the study from oral SOC will receive oral CAB 30 mg + RPV 25 mg 
once daily during the 4-week oral lead-in phase to confirm tolerability prior to receiving 
CAB LA + RPV LA injectable treatment.  Data from study LAI116181 
[GlaxoSmithKline Document Number 2011N130484_00] have demonstrated that there is 
no clinically relevant drug-drug interaction following repeat oral administration of CAB 
with RPV.  Oral RPV 25 mg once daily, the approved oral dose of RPV, has been 
administered in combination  with oral CAB to HIV-infected participants in Phase 2b 
studies LAI116482 [(LATTE); GlaxoSmithKline Document Number 2014N216014_00] 
(CAB 10, 30, or 60 mg once daily) and 200056 [LATTE-2] (CAB 30 mg, oral lead-in 
phase).  The CAB 30mg oral dose was selected based on observed safety and efficacy 
from the LATTE-2 study for use during the oral lead phase of Phase 3 studies 201585 
[ATLAS] and 201584 [FLAIR] which are evaluating Q4W dosing of CAB LA + RPV 
LA.  The present study will also use CAB 30 mg once daily with RPV 25 mg once daily 
during the oral lead-in phase.    
CAB demonstrated good short-term safety/tolerability and antiviral activity as 
monotherapy following oral administration of 5 mg and 30 mg once daily.  LAI116482 
(LATTE)  Phase IIb, dose-ranging study (randomized 1:1:1: to CAB 10 mg, 30 mg, or 60 
mg) evaluating the long-term efficacy and safety of a two-drug, two-class, once daily 
combination of CAB + RPV in HIV-infected, treatment-naïve adult participants.  
Following a 24-week phase of induction of virologic suppression using CAB + 2 NRTIs, 
the regimen was simplified to oral CAB + RPV once daily at Week 24 and continued for 
an additional 72-weeks (total comparative study duration of 96 weeks; Margolis, 2015).  
The results of this study also informed the Phase IIb study 200056 (LATTE-2) with 
intramuscular CAB LA and RPV LA.   
Comparable efficacy, safety, and tolerability were observed across all three CAB doses at 
the early dose selection and confirmation visits at Week 16 and 24 in LATTE.  The 


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proportion of participants who achieved the primary endpoint of HIV-1 RNA <50 c/mL 
(Missing, Switch, Discontinuation=Failure [MSDF] algorithm) at Week 48 (24 weeks on 
Maintenance) remained consistently high across the CAB dose arms (≥80%) with a low 
rate of confirmed virologic failure (Table 2).  Across all dose arms, CAB achieved 
similar efficacy at Week 24 of Induction when co-administered with 2 NRTIs and at 
Week 96 when co-administered with RPV 25 mg once daily (72 weeks on Maintenance).  
Rates of virologic suppression through Week 96 (Maintenance) on the two-drug regimen 
remained similar to that attained through Week 24 (Induction) on three-drug ART.   
Table 2 
Proportion (95% CI) of Participants with Plasma HIV-1 RNA <50 c/mL 
at Key Visits - Snapshot (MSDF) Analysis (ITT-E Population) in 
LATTE 
Visit 
CAB 10 mg 
N=60 
CAB 30 mg 
N=60 
CAB 60 mg 
N=61 
CAB 
Subtotal 
N=181 
EFV 600 mg
N=47 
Week 16 
n (%) 
54 (90) 
50 (83) 
53 (87) 
157 (87) 
46 (74) 
95%CI 
Proportion 
(82, 98) 
(74, 93) 
(78, 95) 
(82, 92) 
(63, 85) 
Week 24 
n (%) 
52 (87) 
51 (85) 
53 (87) 
156 (86) 
46 (74) 
95%CI 
Proportion 
(78, 95) 
(76, 94) 
(78, 95) 
(81, 91) 
(63, 85) 
Week 48 
n (%) 
48 (80) 
48 (80) 
53 (87) 
149 (82) 
44 (71) 
95%CI 
Proportion 
(70, 90) 
(70, 90) 
(78, 95) 
(77, 88) 
(60, 82) 
Week 96 
n (%) 
41 (68) 
45 (75) 
51 (84) 
137 (76) 
39 (63) 
95%CI 
Proportion 
(57,80) 
(64,86) 
(74, 93) 
(69, 82) 
(51, 75) 
CAB was administered with 2 NRTIs through Week 24 (Induction Phase) of LATTE. 
95% CIs are normal approximation confidence intervals.   
 
CAB was well tolerated across all doses studied and none of the doses met pre-defined 
safety stopping criteria.  A good safety and tolerability profile with a low discontinuation 
rate due to AEs was observed in all three dose arms with no significant dose-dependent 
trends in safety parameters.   
Although CAB 30 mg was already selected based on short-term efficacy and safety 
through Week 24, the observed durability of viral suppression through 96 weeks across 
all doses, provided further support for CAB 30 mg dose selection in Phase 3 and the 


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present study.  In addition, the 30 mg dose achieves CAB plasma trough concentrations 
that are greater than mean CAB plasma concentrations observed following CAB LA 
dosing which allows an adequate assessment of safety and tolerability prior to 
transitioning to the long-acting, Maintenance Phase of the study (Table 3). 
CAB has low risk of causing or being a victim of drug-drug interactions, and therefore, 
the selected 30 mg dose can be safely used with most common concomitant medications 
without dose adjustment.  CAB exposures are not impacted by the presence of food; 
however, given that it will be co-administered with RPV which requires food for optimal 
absorption, the recommended intake of oral CAB in the Phase 3 studies is with food at 
the same time as RPV.   
Overall, the efficacy and safety data from the LATTE study, CAB exposure following 
LA administration, and limited drug-drug interaction potential, support selection of the 
CAB 30 mg dose for once daily administration with the approved dose of RPV 25 mg 
once daily during the oral lead-in phase of this study.   


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Table 3 
Summary of CAB Pharmacokinetic Parameters Following Repeat 
Oral Administration in HIV-Infected Subjects  
 
Study 
 
Once  
Daily  
Dose 
 Phase 
Plasma CAB PK Parameter 
(Geometric mean [95%CI] (CVb%) 
AUC(0-) 
(g.h/mL) 
Cmax 
(g/mL) 
C or C0 
(g/mL) 
Tmaxa 
(h) 
LAI116482 
(LATTE) 
 
10 mg 
tab 
(n=14) 
Induction 
Phase 
+2 NRTIs 
45.7 
[38.2, 54.6] 
(32) 
2.77 
[2.3, 3.3] 
(33) 
1.35b 
[1.2, 1.5] 
(45) 
1.0 
(0.9 – 8.0) 
Maintenance 
Phase 
+RPV 25 mg 
--- 
--- 
1.34c 
[1.1, 1.6} 
(58) 
--- 
30 mg 
tab 
(n=12) 
Induction 
Phase 
+2 NRTIs 
134 
[110, 163] 
(32) 
7.49 
[6.3, 8.9] 
(28) 
4.20d 
[3.8, 4.7] 
(40) 
2.0 
(1.0 – 8.0) 
 
Maintenance 
Phase 
+RPV 25 mg 
--- 
--- 
3.93e 
[3.5, 4.4] 
(44) 
--- 
60 mg 
tab 
(2x30 
mg) 
(n=9) 
Induction 
Phase 
+2 NRTIs 
195 
[138, 277] 
(48) 
11.5 
[8.8, 15.0] 
(36) 
7.93f 
[7.2, 8.8] 
(39) 
2.0 
(1.0 – 8.0) 
 
Maintenance 
Phase 
+RPV 25 mg 
--- 
--- 
8.22g 
[7.4, 9.1] 
(37) 
--- 
200056 
LATTE-2 
Day 1, 
predose 
30 mg 
tab 
(n=246) 
Induction 
Phase 
+2NRTIs 
--- 
--- 
4.22 
[4.0, 4.4} 
(43)] 
--- 
a. median (range) 
b. n=57 
c. n=50 
d. n=53 
e. n=51 
f. 
n=55 
g. n=49 
 
4.5.2. 
Long Acting Injectable for Maintenance Phase 
The safety and efficacy of a 2-drug regimen with CAB and RPV for maintenance of 
virologic suppression was established in LATTE, as detailed in Section 4.5.1, and 
informed the Phase 2b study (LATTE-2) with CAB LA and RPV LA.  Study 200056 
(LATTE-2) is an ongoing, Phase 2b dose-ranging study evaluating the long-term efficacy 
and safety of a two-drug, two-class combination of CAB LA + RPV LA given every 
4 weeks (Q4W) or every 8 weeks (Q8W), as compared to an oral three-drug regimen, for 


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maintenance of virologic suppression in HIV-infected, treatment-naive adults.  The first 
phase of the LATTE-2 study was a 20-week Induction Phase (16 weeks of oral CAB + 2 
NRTIs, 4 weeks of CAB + 2 NRTIs + oral RPV).  Participants who were eligible to 
continue into the Maintenance Phase were then randomized (2:2:1) to receive IM 
injections of CAB LA every 4 weeks (800 mg Day 1 then 400 mg Q4W) or every 8 
weeks (800 mg Day 1, 600 mg Week 4, 600 mg Week 8, then 600 mg Q8W) in 
combination with IM RPV LA every 4 weeks (600 mg Day 1 then 600 mg Q4W) or 
every 8 weeks (900 mg Day 1, 900 mg Week 8, then 900 mg Q8W), respectively, or to 
continue on their triple ART regimen.  
The Q4W dosing strategy was selected for further investigation in Phase 3 based on 
observed efficacy, safety, and tolerability at Week 48.  Both Q4W and Q8W regimens 
were continued throughout the Maintenance Phase as planned, and Week 96 results 
(Table 4) were supportive of further evaluation of the Q8W regimen in the present study.  
Moreover, LATTE-2 was amended to permit subjects to remain on their randomized LA 
regimen (either Q4W or Q8W) during the Extension Phase (post Week 96), and those 
subjects randomized to the oral comparator arm were allowedtransition to either LA 
regimen at Week 96.  Forty-four subjects were transitioned from the oral comparator arm 
to LA treatments in the Extension Phase; 34 (77%) opted for the Q8W regimen and 10 
(23%) for the Q4W regimen.  Initial LA injections were administered at Week 100 
following a 4-week oral lead-in where 2 NRTIs were discontinued and RPV 25 mg once 
daily was added to CAB 30 mg once daily.   
Table 4 
Summary of Study Outcomes (<50 copies/mL) at Weeks 48 and 96 – 
Snapshot (MSDF) Analysis (ITT-ME Population) in LATTE-2 
Endpoint 
(Week) 
Outcome  
Q8W IM 
N=115 
n (%) 
Q4W IM 
N=115 
n (%) 
CAB 30 mg+ 
ABC/3TC 
N=56 
n (%) 
Subtotal IM 
N=230 
n (%) 
W48 
Virologic Success, n (%) 
106 (92)  
105 (91) 
50 (89) 
211 (92) 
Virologic Failure, n (%) 
8 (7)  
1 (<1) 
1 (2) 
9 (4) 
W96 
Virologic Success, n (%) 
108 (94) 
100 (87) 
47 (84) 
208 (90) 
Virologic Failure, n (%) 
5 (4) 
0 
1 (2) 
5 (2) 
 
Observed pharmacokinetic data for both CAB LA regimens in LATTE-2 are presented in 
Figure 3 and summarized in Table 5. 


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Figure 3 
Observed Mean (SD) Concentration-Time Data following CAB LA 
Q8W and Q4W and C following 30 mg PO QD through Week 48 
(200056, LATTE-2) 
Week
0 1
4
8
12
16
20
2425
28
32
32
36
4041
44
48
48
Plasma CAB ( g/mL)
0.1
1
10
800mg IM LD, 600mg IM W4, W8 and Q8W
800mg IM LD, 400mg IM Q4W
30mg PO QD
PA-IC90 (0.166 g/mL)
10mg PO QD C  (LATTE, 1.35 g/mL)
 
Both predose and 2h post injection concentrations are shown at Time Zero, Week 32, and 
Week 48. 


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Table 5 
Summary of CAB PK Parameters Following Repeat Dose 
Administration of CAB LA to Healthy and HIV-infected Subjects 
Population 
Study 
CAB LA 
Regimen 
Dosing 
Interval 
Plasma CAB PK Parameter 
(Geometric mean [95%CI] (CVb%) 
AUC(0- ) 
(g•h/mL) 
Cmax 
(g/mL) 
C  
(g/mL) 
Tmaxa 
(day post 
last dose) 
Healthy 
Subjects 
LAI115428 
800 mg IM/ 
400 mg IM 
Q4W 
(n=10) 
D1-W4 
1252 
[836, 1873] 
(61) 
2.74 
[1.72 4.35] 
(72) 
1.78 
[1.35, 2.36] 
(41) 
6 
(6 – 28) 
W4-W8 
2010 
[1619, 2494] 
(31) 
3.79 
[2.89, 4.99] 
(40) 
2.60 
[2.20, 3.07] 
(24) 
6 
(2 – 28) 
W8-W12 
2182 
[1798, 2647] 
(28) 
4.03 
[3.05, 5.30] 
(40) 
2.69 
[2.21, 3.27] 
(28) 
6 
(2 – 28) 
W12-W16 
2473 
[2063, 2965] 
(26) 
4.41 
[3.55, 5.48] 
(31) 
3.27 
[2.71, 3.94] 
(27) 
6 
(2 – 13) 
HIV 
Infected 
Subjects 
200056 
LATTE2 
800 mg IM/ 
400 mg IM 
Q4W 
(n=115) 
W24-W28 
(n=97) 
1858b 
[1719, 2007] 
(37) 
3.50  
[3.2, 3.8] 
(39) 
2.35c 
[2.2, 2.5] 
(32) 
6.9 
(0 – 29) 
W40-W44 
(n=95) 
2017d  
[1847, 2203] 
(41) 
3.50e  
[3.3, 3.8] 
(37) 
2.56f   
[2.4, 2.7] 
(32) 
6.9  
(0 – 28) 
800 mg IM/ 
600 mg IM 
Q8W 
(n=115) 
W24-W32 
(n=98) 
3037g 
[2786, 3310] 
(42) 
3.55 
[3.2, 3.9] 
(56) 
1.43h 
[1.3, 1.6] 
(54) 
6.9  
(0 – 59) 
W40-W48 
(n=104) 
3027i  
[2762, 3322] 
(47) 
3.33  
[3.1, 3.6] 
(47) 
1.49  
[1.4, 1.6] 
(42) 
7.0  
(0 –  57) 
a. 
median (range) 
b. 
n=84 
c. 
n=108 
d. 
n=80 
e. 
n=98 
f. 
n=86 
g. 
n=100 
h. 
n=93  
i. 
n=112 
 
The CAB LA population PK model was updated to include data from CAB LA pre-
exposure prophylaxis (PrEP) Study 201120 (ÉCLAIR; GlaxoSmithKline Document 
Number 2016N269422_00) and Study 200056 (LATTE-2), increasing the original model 
from 93 subjects to 416 subjects receiving CAB LA single or repeat IM injections.  
Modeling and simulation was used to enable simplification and alignment of loading dose 
strategy used in LATTE-2 for both Q4W and Q8W CAB LA and RPV LA dosing 
regimens, resulting in selection of optimized Q4W and Q8W LA dosing regimens for use 
in Phase 3 studies (Q4W) and the present study (Q4W and Q8W) as discussed in Section 
4.5.2.1 and Section 4.5.2.2. 


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4.5.2.1. 
CAB LA Q8W 
The CAB LA 600mg Q8W regimen is predicted to achieve concentrations above 
1.35 g/mL, the geometric mean C following oral CAB 10 mg once daily which was 
shown to be efficacious in the LATTE study.  The lower bound of the 90% prediction 
interval is approximately 0.166 g/mL, indicating that 95% of subjects on this regimen 
should remain above the PA-IC90 throughout dosing (Figure 4).  The CAB LA Q8W 
regimen consists of identical 600 mg doses administered at Day 1, Week 4, and Q8W 
thereafter.   
Figure 4 
Simulated* Median (90% Prediction Interval [PI]) CAB Plasma 
Concentrations versus Time for the Optimized CAB LA Q8W 
Regimen (600 mg IM Day 1, Week 4, Q8W Thereafter)^ 
 
*Note: current simulations based on interim plasma concentration dataset 
^Study Time and Events include a 4-week oral lead in for subjects transitioning to Q8W from oral SOC.  
Therefore, Day 1 (time zero) = date of first injections in 207966 
4.5.2.1.1. CAB PK Profile Following Transition to Q8W Regimen 
There are two ways in which study participants may transition to the Q8W regimen, 
either directly from oral SOC or directly from Q4W dosing from ATLAS.  Figure 4 
shows the predicted plasma CAB PK profile for SOC participants directly transitioning to 
Q8W dosing following completion of the oral lead-in phase.  The majority of participants 
receiving Q4W injections will have received injections for more than 1 year and will 
have achieved steady-state CAB concentrations within ATLAS well before transitioning 
to Q8W dosing in ATLAS-2M.  Figure 5 shows the predicted plasma CAB PK profile for 


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participants directly transitioning to Q8W dosing from Q4W dosing who have achieved 
steady-state plasma CAB concentrations.  Other participants, however, may have only 
received a short course of Q4W injections in ATLAS and will have not yet achieved 
steady-state plasma CAB concentrations prior to transitioning to Q8W dosing.  Figure 6 
shows the predicted plasma CAB PK profile for participants directly transitioning to 
Q8W dosing from a short course of Q4W dosing who have not achieved steady-state 
plasma CAB concentrations.   
Figure 5 
Predicted Median (90% PI) CAB Profile following Steady State CAB 
LA Q4W Administration in ATLAS prior to Transitioning to Q8W on 
Day 1 of ATLAS-2M assuming 20% of participants are female. 
  
 
 


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Figure 6 
Predicted Median (90% PI) CAB Profile following a Short Course of 
CAB LA Q4W Administration in ATLAS prior to Transitioning to Q8W 
on Day 1 of ATLAS-2M assuming 20% of participants are female. 
 
 
Figure 7 simultaneously shows the median predicted plasma CAB PK profile following 
transition to Q8W dosing from oral SOC, a short course of Q4W, or long-term Q4W 
dosing.  Regardless of route of transition (oral or IM) or prior length of IM dosing (short 
course or steady-state), plasma CAB concentrations are predicted to be safe and 
efficacious during the transition period and all participants are expected to achieve 
comparable target concentrations at Week 48.  In addition, Figure 7 demonstrates that 
participants transitioning from Q4W dosing (regardless of short course or long-term 
Q4W dosing), do not require an intermediate dose at Week 4 as plasma CAB 
concentrations are above Q8W targets and thus can commence Q8W dosing starting from 
the first Q8W dose at Day 1.  


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Figure 7 
Predicted CAB Profiles for CAB LA Q8W after Transition from Oral 
Lead In or CAB LA Q4W (assumes 20% female population) 
Time (Weeks)
-16
-12
-8
-4
0
4
8
16
24
32
40
48
Predicted Median CAB (ug/mL)
0
1
2
3
4
5
6
7
8
Q8W from oral lead-in (SOC in ATLAS, 600mg IM W4)
Q8W from short course Q4W (SOC to Q4W in ATLAS, 600mg IM D1)
Q8W from steady state Q4W (Q4W in ATLAS, 600mg IM D1)
Geometric mean Ctau 10mg PO (LATTE, 1.35ug/mL, ~8x PA-IC90)
 
400mg
600mg  
A one-week delay in CAB LA dosing for the Q8W regimen at steady state is predicted to 
result in ~92% rather than 95% of subjects achieving trough concentrations above the 
PA-IC90, which is considered acceptable. 
4.5.2.2. 
CAB LA Q4W 
There are two ways in which study participants may transition to the Q4W regimen, 
either directly from oral SOC or directly from Q4W dosing from ATLAS.  Figure 8 
shows the predicted plasma CAB PK profile for SOC participants directly transitioning to 
Q4W dosing following completion of the oral lead-in phase.  Former ATLAS participants 
receiving Q4W injections and randomized to the Q4W dosing arm of ATLAS-2M will 
continue receiving Q4W injections as scheduled. 
The CAB LA 400 mg Q4W regimen is predicted to achieve trough concentrations above 
4x PA-IC90 in 98% of participants at steady-state and 88% is predicted to achieve trough 
concentrations above the geometric mean trough following the 10 mg oral dose in 
LATTE of 1.35 g/mL (8x PA-IC90).  The lower bound of the PI remains approximately 
at or above 4x PA-IC90 throughout dosing (Figure 8).  The CAB LA Q4W regimen 


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consists of a 600 mg loading dose on Day 1 followed by a 400 mg maintenance dose at 
Week 4 and Q4W thereafter.   
Figure 8 
Simulated* Median (90% Prediction Interval [PI]) CAB Plasma 
Concentrations versus Time for the Optimized CAB LA Q4W 
Regimen (600 mg IM Day 1, then 400 mg IM Q4W thereafter^) 
 
* Note: current simulations based on interim plasma concentration dataset 
^Study Time and Events include a 4-week oral lead in.  Therefore, Day 1 (time zero) = date of first 
injections in 207966 
Medium dashed line at 1.35 g/mL corresponds to the geometric mean Ctrough concentration following 
oral CAB 10 mg once daily (LATTE) and is equivalent to 8x PA-IC90  
Dotted line at 0.664 g/mL corresponds to 4x PA-IC90  
Long dashed line at 0.166 g/mL corresponds to the PA-IC90. 
 
At steady state, a one-week delay in dosing of the Q4W regimen results in approximately 
15% reduction in median CAB trough.  With this delay, 95% are predicted to remain 
above 4x PA-IC90, and 79% are predicted to remain above the 10 mg oral trough 
concentrations.  Therefore, a 1-week delay is the maximum allowed per the protocol.   


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4.5.3. 
RPV LA 
Observed PK data for both RPV LA Q4W and Q8W regimens in LATTE-2 are presented 
in Figure 9 and Table 6.  The RPV LA population PK model has been updated to include 
data from LATTE-2 and from Phase 1 studies in healthy volunteers. 
Figure 9 
Observed Mean (SD) Plasma Concentration-Time Data following 
RPV LA Q8W and Q4W through Week 48 and Day 1 C following RPV 
25 mg PO QD (LATTE-2) 
Week
0 1
4
8
12
16
20
2425
28
32
32
36
4041
44
48
48
Plasma RPV (ng/mL)
10
100
1000
900mg IM Q8W
600mg IM Q4W
25mg PO QD
PA-IC90 (12ng/mL)
25mg PO QD (LATTE, 70ng/mL)
 
Both predose and 2 hr post injection concentrations are shown at Time Zero, Week 32, 
and Week 48. 


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Table 6 
Summary of RPV PK Parameters following Repeat Dose RPV LA 
Administration with CAB LA in Healthy and HIV-infected Subjects  
Study/ 
Population 
RPV LA 
Regimen 
Dosing 
Interval 
(from 1st 
RPV IM 
dose) 
Plasma RPV PK Parameter 
(Geometric mean [95%CI] (CVb%) 
AUC(0- ) 
(g•h/mL) 
Cmax 
(g/mL) 
C  
(g/mL) 
Tmaxa 
(day post last 
dose) 
LAI115428/ 
Healthy 
Subjects 
1200 mg IM/ 
900 mg IM 
(+ CAB LA 
200 mg IM) 
(n=9) 
D1-W4 
52762 
[36468, 76335] 
(51) 
109 
[74.2, 159] 
(53) 
61.6 
[39.3, 96.6] 
(64) 
6 
(1.8 – 20) 
W4-W8 
74420 
[57323, 96615] 
(35) 
168 
[128, 222] 
(37) 
79.1 
[57.2, 109] 
(44) 
6 
(2 – 13) 
1200 mg IM/ 
600 mg IM 
(+ CAB LA 
400 mg IM) 
(n=10) 
D1-W4 
52703 
[42917, 64721] 
(29) 
108 
[87.6, 133] 
(30) 
64.0 
[50.6, 80.9] 
(34) 
6 
(2 – 28) 
W4-W8 
63656 
[50186, 80741] 
(34) 
126 
[101, 158] 
(32) 
78.9 
[60.3,103] 
(39) 
9.5 
(2 – 27) 
200056 
(LATTE2)/ 
HIV 
Infected 
Subjects 
600 mg IM 
Q4W 
(n=115) 
W24-W28 
(n=96) 
61309b  
[56724, 66264] 
(37) 
111  
[103, 120] 
(40) 
77.2c  
[72, 83] 
(35) 
6.0 
(0 – 29) 
W40-W44 
(n=94) 
71106d 
 [65354, 77366] 
(39)] 
127 
[118, 136] 
(36) 
92.1e  
[87, 98] 
(32) 
6.0 
(0 – 28) 
900 mg IM 
Q8W 
(n=115) 
W24-W32 
(n=97) 
96196f  
[87286, 106015] 
(48) 
104 
[95, 114] 
(47) 
49.3g  
[46, 53] 
(41) 
7.0 
(0 – 57) 
W40-W48 
(n=104) 
116160h  
[108189, 124719] 
(35) 
121 
[111, 131] 
(42) 
63.2i  
[59,  68] 
(35) 
6.0 
(0 – 59) 
a. 
median (range) 
b. 
n=84 
c. 
n=104 
d. 
n=80 
e. 
n=102 
f. 
n=86 
g. 
n=101 
h. 
n=92 
i. 
n=100 
 
4.5.3.1. 
RPV LA Q8W 
The RPV LA Q8W regimen for this study (ATLAS-2M) was selected based on safety 
and efficacy data from study 200056 (LATTE-2) and supported by modeling and 
simulation of pharmacokinetic data obtained following administration RPV LA 
administration in healthy subjects (Phase 1 studies C158, and LAI115428 
[GlaxoSmithKline Document Number 2011N112455_03]) and in HIV-infected subjects 
(Phase 2 study LATTE-2), the majority of the data coming from 200056 (LATTE-2).  
 


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The RPV LA 900 mg Q8W regimen is predicted to achieve median (90% PI) steady-state 
C of 54 ng/mL (23 – 112 ng/mL) (Figure 10).  With this regimen, 100% of subjects 
remain above the RPV PA-IC90 during the whole dose interval at steady-state.  These 
data are similar to the observed Week 32 median steady-state C in LATTE-2 for Q8W 
which was also 54 ng/mL and the mean C was 58 ng/mL.  The RPV LA Q8W regimen 
consists of identical 900 mg doses administered at Day 1, Week 4, and Q8W thereafter.  
With the second RPV LA dose administered 4 weeks after the first dose, the anticipated 
median RPV C at Week 4 (prior to second injection) is 40 ng/mL (versus 30 ng/mL 
observed prior to second injection at Week 8 in LATTE-2, where the RPV LA dose at 
Week 4 was not included), with >92% of subjects above the RPV PA-IC90 of 12 ng/mL. 
Figure 10 
Simulated* Median (90% PI) RPV Plasma Concentrations versus 
Time Profile for the Optimized RPV LA Q8W regimen (900 mg IM Day 
 
* Note: current simulations based on interim plasma concentration dataset 
^Study Time and Events include a 4 week oral lead in for subjects transitioning to Q8W from oral SOC.  
Therefore, Day 1 = date of first injections for Study 207966 
4.5.3.1.1. RPV PK Profile Following Transition to Q8W Regimen 
As previously described, there are two ways in which study participants may transition to 
the Q8W regimen, either directly from oral SOC or directly from Q4W dosing from 
ATLAS.  Figure 10 shows the predicted plasma RPV PK profile for SOC participants 
directly transitioning to Q8W dosing following completion of the oral lead-in phase.   


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Participants may also transition to RPV LA Q8W in ATLAS-2M following RPV LA 
Q4W, treatment for a minimum of 52 weeks in ATLAS or following a shorter duration of 
RPV LA Q4W treatment following transition from oral SOC after Week 52 in ATLAS.  
Figure 11 shows the predicted plasma RPV PK profile for participants directly 
transitioning to Q8W dosing from Q4W dosing who have achieved steady-state plasma 
RPV concentrations.   
Figure 11 
Simulated Median (90% PI) RPV Profile following Steady State RPV 
LA Q4W Administration in ATLAS prior to Transitioning to Q8W on 
Day 1 of ATLAS-2M 
 
Figure 12 shows the predicted median (90% PI) profile for subjects switching to RPV LA 
Q8W after having a short course of 4 RPV LA Q4W injections.  In this setting, switching 
immediately to RPV LA 900 mg 8-weekly injections keeps the median C above 2x the 
RPV PA-IC90 and 100% of subjects remain above the RPV PA-IC90 during the whole 
dose interval. Figure 13 shows that (until steady-state is reached), the median predicted 
C for those transitioning from Q4W to Q8W is higher than the predicted C for those 
transitioning from oral to Q8W, despite not having the extra RPV LA 900 mg IM 
injection 4 weeks after the first injection on the Q8W regimen.  This therefore justifies 


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the simplified RPV LA dosing regimen (without injection at Week 4) for those subjects 
that are already on a Q4W regimen. 
Therefore, regardless of the length of time that they are already on RPV LA Q4W 
treatment, such subjects transitioning to RPV LA Q8W will receive RPV LA 900 mg IM 
Q8W from Day 1 of ATLAS-2M. 
Figure 12 
Simulated Median (90% PI) RPV Plasma Concentration versus Time 
Profile for Subjects Switching from a Short Course Q4W Regimen in 
ATLAS to a Q8W regimen (RPV LA on Day 1 and Q8W thereafter^) 
 


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Figure 13 
Simulated Median RPV Plasma Concentration versus Time Profile 
for Subjects Switching Either from an Oral Regimen or from a Q4W 
Regimen to a Q8W regimen 
 
At steady-state, a one-week delay in dosing for the Q8W regimen is predicted to result in 
a median steady-state C that is approximately 11% lower (48 ng/mL) than for dosing 
that is administered on schedule, with >99% of subjects still remaining above the RPV 
PA-IC90.  This supports allowance of some flexibility in the dosing regimen in ATLAS-
2M, similar to what is currently practiced in the LATTE-2 study. 
4.5.3.2. 
RPV LA Q4W 
The RPV LA Q4W regimen for ATLAS-2M was selected based on LATTE-2 safety and 
efficacy data as described above and supported by modeling and simulation of 
pharmacokinetic data as described above.  The Q4W dose regimen consists of a RPV LA 
900 mg dose on Day 1, and RPV LA 600 mg every 4 weeks thereafter.  This regimen is 
also studied in the Phase 3 studies ATLAS and FLAIR.  
There are two ways in which study participants may transition to the Q4W regimen, 
either directly from oral SOC or directly from Q4W dosing from ATLAS.  Figure 14 
shows the predicted plasma RPV PK profile for SOC participants directly transitioning to 


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Q4W dosing following completion of the oral lead-in phase.  Former ATLAS participants 
receiving Q4W injections and randomized to the Q4W dosing arm of ATLAS-2M will 
continue receiving Q4W injections as scheduled. 
The predicted median (90% PI) steady-state C for the proposed regimen is 84 ng/mL 
(41 – 161 ng/mL, Figure 14).  With this regimen, >99% of participants remain above the 
5th percentile of steady state trough values following oral RPV 25 mg (corresponding to 
2x the PA-IC90).  With a loading dose of 900 mg RPV LA on Day 1, the anticipated 
median RPV C at Week 4 is 40 ng/mL, with >92% of participants above the RPV PA-
IC90. 
Figure 14 
Simulated* Median (90% PI) RPV Plasma Concentrations versus 
Time Profile for the RPV LA Q4W regimen (900 mg IM Day 1, then 
600 mg IM Q4W thereafter^) 
 
* Note: current simulations based on interim plasma concentration dataset 
^Study Time and Events include a 4-week oral lead in.  Therefore, Day 1 = day of first injections for Study 207966  
 
At steady-state, a one-week delay in dosing for the Q4W regimen is predicted to result in 
a median steady-state C that remains above the median trough for oral RPV 25 mg once 
daily.  This supports allowance of some flexibility in the dosing regimen, as also 
practiced in LATTE-2 and the Phase 3 studies FLAIR and ATLAS. 


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5. 
SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA 
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 Investigator’s Brochures 
(IB) for CAB and RPV and Edurant product label. 
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. 
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: 


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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.  
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 


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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.   
Participants receiving oral standard of care (SOC) treatment for HIV-1 (not 
participating in ATLAS Trial) 
5. Must be on uninterrupted current regimen (either the initial or second ARV 
regimen) for at least 6 months prior to Screening.  Any prior switch, 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).  
Acceptable stable (initial or second) ARV regimens prior to Screening include 2 
NRTIs plus:  
• INI (either the initial or second cART regimen)  
• NNRTI (either the initial or second cART regimen) 
• Boosted PI (or atazanavir [ATV] unboosted) (must be either the initial 
cART regimen or one historical within class switch is permitted due to 
safety/tolerability) 
 
The addition, removal, or switch of a drug(s) that has been used to treat HIV 
based on antiretroviral properties of the drug constitutes a change in ART with the 
following limited exceptions:  
 
• Historical changes in formulations of ART drugs or booster drugs will not 
constitute a change in ART regimen if the data support similar exposures 
and efficacy, and the change must have been at least 3 months prior to 
Screening. 
 
• Historical perinatal use of an NRTI when given in addition to an ongoing 
HAART will not be considered a change in ART regimen. 
 
• 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.   
 
6. Documented evidence of at least two plasma HIV-1 RNA measurements 
<50 c/mL in the 12 months prior to Screening: one within the 6 to 12-month 
window, and one within 6 months prior to Screening;  
 
7. Plasma HIV-1 RNA <50 c/mL at Screening;  
Participants transitioning from 201585 (ATLAS) 
8. Must have been on CAB LA 400 mg + RPV LA 600 mg Q4W or “Current ART” 


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regimen through at minimum Week 52 of the ATLAS study as per ATLAS 
protocol dosing requirements and until Day 1 of the ATLAS-2M study.  Any 
disruptions in dosing during ATLAS must be discussed with the Medical Monitor 
for a final determination of eligibility. 
9. 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 for patients not transitioning 
from 201585 (ATLAS) 
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, any plasma HIV-1 RNA 
measurement >200 c/mL, or 2 or more plasma HIV-1 RNA measurements 
50 c/mL 
3. Any drug holiday during the window between initiating first HIV ART and 6 
months prior to Screening, except for brief periods (less than 1 month) where all 
ART was stopped due to tolerability and/or safety concerns 
4. Any switch 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)  
5. A history of use of any regimen consisting of only mono or dual HIV-1 therapy 
(even if only for peri-partum treatment).   
6. Participants who are currently participating in or anticipate to be selected for any 
other interventional study with the exception of the 201585 (ATLAS) study. 
Participants transitioning from 201585 (ATLAS) 
7. During participation in ATLAS, consecutive (2 or more sequential) plasma HIV-1 


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RNA measurements 50 c/mL 
8. During participation in ATLAS, any HIV-1 RNA measurement 200 c/mL 
9. More than two total measurements of plasma HIV-1 RNA 50 c/mL during 
participation in the ATLAS trial will require direct approval by the ATLAS-2M 
Medical Monitor and Study virologist for study participation. 
Exclusionary medical conditions- for all participants 
10. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed 
during the study 
11. Any evidence of a current Center for Disease Control and Prevention (CDC) 
Stage 3 disease [CDC, 2014] , except cutaneous Kaposi’s sarcoma not requiring 
systemic therapy, and CD4+ counts <200 cells/L are not exclusionary. 
12. Participants with moderate to severe hepatic impairment 
13. 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 
14. 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 
15. 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, 
subjects may be rescreened once following completion of antibiotic therapy for 
primary or early latent secondary syphilis.  
16. 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 
17. The participant has a tattoo or other dermatological condition overlying the 
gluteus region which may interfere with interpretation of injection site reactions 


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18. 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) and positive for HBV DNA are excluded 
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for 
anti-HBs (past and/or current evidence) are immune to HBV and are not 
excluded. 
19. Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not 
be excluded, however Investigators must carefully assess if therapy specific for 
HCV infection is required; participants who are anticipated to require HCV 
treatment within 12 months must be excluded.  (HCV treatment on study may be 
permitted post Week 52, following consultation with the medical monitor) 
20. 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 Week 52 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 ]) 
21. Unstable liver disease (as defined by any of the following:  presence of ascites, 
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, 
or persistent jaundice or cirrhosis), known biliary abnormalities (with the 
exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable 
chronic liver disease per investigator assessment) 
22. History of liver cirrhosis with or without hepatitis viral co-infection. 
23. Ongoing or clinically relevant pancreatitis 
24. 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 
25. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell 


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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 
26. Any condition which, in the opinion of the Investigator, may interfere with the 
absorption, distribution, metabolism or excretion of the study drugs or render the 
participant unable to receive study medication 
27. 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 
28. 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. 
Exclusionary Laboratory Values or Clinical Assessments at Screening (a single repeat to 
determine eligibility is allowed) 
29. Any evidence of primary resistance based on the presence of any major known 
INI or NNRTI resistance-associated mutation, except for K103N, (IAS, 2015) by 
any historical resistance test result. 
Note: Prior genotypic resistance testing is not required but if available it 
must be provided to GSK, 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 
30. Any verified Grade 4 laboratory abnormality. A single repeat test is allowed 
during the Screening phase to verify a result  
31. 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 
32. Participant has estimated creatine clearance <50mL/min per 1.73m2 via Chronic 
Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method 
33. Alanine aminotransferase (ALT) 3 × ULN 


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Concomitant Medications 
34. Exposure to an experimental drug (with the exception of those in the ATLAS 
study including CAB, CAB LA, and RPV LA) 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; 
35. 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.  
36. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening 
37. 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.  
38. Use of medications which are associated with Torsade de Pointes.  (See SPM for 
a list of relevant medications) 
39. Current or prior history of etravirine (ETR) use 
40. Current use of tipranavir/ritonavir or fosamprenavir/ritonavir 
41. Participants receiving any prohibited medication and who are unwilling or unable 
to switch to an alternate medication.  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 
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. 


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Participation in other interventional studies or non-interventional studies that require any 
type of assessment outside the local standard of care practices is generally not permitted, 
however for eligible subjects in South Africa only, co-enrolment in the AIDS Clinical 
Trial Group ACTG interventional study (A5392) could be exceptionally permitted after 
review and approval by the Medical Monitor. 
 
5.4. 
Screening/Baseline/Run-in Failures 
Screen failures are defined as participants who consent to participate in the clinical trial 
but are never subsequently randomized.  In order to ensure transparent reporting of screen 
failure participants, meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, and respond to queries from Regulatory authorities, a minimal 
set of screen failure information is required including Demography, Screen Failure 
details, Eligibility Criteria, and Serious Adverse Events. 
A single repeat of a procedure / lab parameter is allowed to determine eligibility (unless 
otherwise specified). 
Participants are allowed to re-screen for this study one time.  This will require a new 
participant number. 
5.5. 
Withdrawal/Stopping Criteria 
Participants permanently discontinuing study treatments prior to the Week 100 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 the CAB LA + RPV LA marketed product is locally 
available are considered withdrawn from the study treatments but are not considered 
withdrawn from the study because they will enter the Long Term Follow-up Phase. 
Participants who enter the Extension Phase but permanently discontinue participation in 
the Extension Phase when the CAB LA + RPV LA marketed product is locally available 
must enter the Long Term Follow-up Phase if they withdraw from the study due to 
safety-related reasons only. 
The 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. 


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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.  
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. 
After completing 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. When CAB LA + RPV LA marketed product is locally 
available, entering the LTFU phase is only required if the subject withdraws due to 
safety-related reasons.  
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 Time 
and Events Table (Section 7.1) 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 4 weeks of the last Q4W LA injection or within 8 
weeks of the last Q8W LA injection received) during which withdrawal 
assessments according to the Time and Events Table (Section 7.1) 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 Week 52,Week 100, or Week 156 (Q4W 
arm) visits, HIV-1 RNA will only be assessed if the last HIV-RNA measurement from 
Week 48,Week 96, or Week 152 was 50 copies per mL (i.e. retest for viral load blip). 
This will ensure that only the Week 48, Week 96. and Week 152 viral load assessments 
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 Week 100 
visit will be recorded as the Week 100 visit such that the participant can be considered a 
completer, consistent with the definition of study completer in Section 5.6. 


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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. 
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 5.5.4 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 5.5.1); 
• 
Renal toxicity are 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 
• 
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. 


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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 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. Please refer to Section 11.5 for additional guidance for sample destruction 
request. 
5.5.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. 
IP will be stopped if any of the following liver chemistry criteria are met: 
• 
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin, bilirubin fractionation 
required). 
• 
NOTE: serum bilirubin fractionation should be performed if testing is available.  If 
testing is unavailable, sites should evaluate the presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver 
injury.  If testing is unavailable and a participant meets the criterion of total bilirubin 
2xULN, then the event meets liver stopping criteria. 
• 
ALT 8xULN. 


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• 
ALT ≥3xULN (if Baseline ALT is <ULN) with symptoms or worsening of acute 
hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, or eosinophilia, OR; 
• 
ALT ≥3x Baseline ALT with symptoms or worsening of acute hepatitis or 
hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, or eosinophilia; 
• 
ALT ≥5xULN and <8xULN that persists ≥2 weeks (with bilirubin <2 ULN & no 
signs or symptoms of acute hepatitis or hypersensitivity). 
• 
ALT ≥5xULN but <8xULN and cannot be monitored weekly for >2 weeks. 
5.5.1.1. 
Liver Chemistry Stopping Criteria, Participant Management and Follow-
Up 
Participants who develop ALT ≥5xULN must be followed weekly until resolution or 
stabilization (ALT <5xULN on 2 consecutive evaluations). 
When any of the liver chemistry stopping criteria is met, do the following: 
• 
Immediately hold IP.  If on LA therapy, do not administer another injection until 
approval is received from the ViiV Safety and Labelling Committee. 
• 
Report the event to the Medical Monitor within 24 hours of learning its occurrence. 
• 
Complete the liver event eCRF and SAE eCRF, where applicable. 
• 
Complete the liver imaging and/or liver biopsy eCRFs if these tests are performed. 
• 
Perform liver event follow up assessments (described below), and monitor the 
participant until liver chemistries resolve, stabilize, or return to Baseline values as 
described below. 
• 
Make every reasonable attempt to have participants return to clinic within 24 hours 
for repeat liver chemistries, liver event follow-up assessments (see below), and close 
monitoring. 
• 
A specialist or hepatology consultation is recommended. 
• 
Monitor participants twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilize or return to within Baseline values. 
Make every attempt to carry out the liver event follow-up assessments described below: 
• 
Viral hepatitis serology including: 
• 
Hepatitis A immunoglobulin M (IgM) antibody; 
• 
Hepatitis B surface antigen (HBsAg) and Hepatitis B Core Antibody (IgM); 
• 
Hepatitis C RNA; 
• 
Hepatitis E IgM antibody; 
• 
Cytomegalovirus IgM antibody; 


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• 
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. 
• 
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. 
5.5.1.2. 
Liver Event Adjudication Committee 
A liver safety panel will be used to evaluate all participants who meet liver stopping 
criteria.  Uniform sets of data and standards for adjudication will be applied across cases 
to inform outcomes.  Full details of the analysis, timing, and the decision criteria will be 
pre-specified in an Adjudication Committee Charter.  
5.5.1.3. 
Liver Chemistry Stopping Criteria – Restart  
Participants who meet liver toxicity stopping criteria should not be retreated with 
investigational product unless an exemption has been approved by the ViiV Safety and 
Labeling Committee (VSLC).  The guideline for Restart approved by the VSLC, which is 
maintained as a separate document must be followed. 


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5.5.1.4. 
General Guidance 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 (see 
Section 5.5.1), study drug must be stopped. Participants who meet liver chemistry 
stopping criteria should not be retreated with investigational product unless an 
exemption has been approved by the VSLC.  The guideline for Restart approved 
by the VSLC, which is maintained as a separate document must be followed. 
• If the restart is approved by the VSLC in writing, the participant must be provided 
with a clear description of the possible benefits and risks of drug administration, 
including the possibility of recurrent, more severe liver injury or death.  
• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• The participant must also provide signed informed consent specifically for the IP 
restart. Documentation of informed consent must be recorded in the study chart. 
• Study drug must be administered at the dose specified by the VSLC. 
• Participants approved by the VSLC for restart of IP must return to the clinic once 
a week for liver chemistry tests for a minimum of one month and thereafter for as 
long as clinically indicated and then laboratory monitoring may resume as per 
protocol. Longer durations of close monitoring may be required for long acting 
IP. 
5.5.1.4.1. 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. 
 
If participant meets liver chemistry stopping criteria do not restart the participant with 
study treatment unless: 
 
• ViiV Healthcare Safety and Labelling Committee (VSLC) approval is granted, 


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• Ethics and/or IRB approval is obtained, if required, and 
 
• Separate consent for treatment restart is signed by the participant. 
Refer to Section 11.3 for full guidance. 
 
Background 
• Restarts should be limited to cases in which there is clear evidence that the 
underlying cause of the liver event is not related to study drug.  
• For long-acting agents, a restart may actually be continuation of therapy rather 
than a true re-start due to the timeframe between dose administration relative to 
decision making on allowing a restart. 
• If protocol defined stopping criteria for liver chemistry elevations are met 
(Section 11.3), study drug must be stopped. Subjects who meet liver chemistry 
stopping criteria should not be retreated with investigational product unless an 
exemption has been approved by the VSLC.  The algorithm for restart is 
described in Section 11.3 and summarised in Figure 8. 
• If the restart is approved by the VSLC in writing, the subject must be provided 
with a clear description of the possible benefits and risks of drug administration, 
including the possibility of recurrent, more severe liver injury or death.  
• Ethics Committee or Institutional Review Board approval of drug restart must be 
obtained, as required. 
• The subject must also provide signed informed consent specifically for the IP 
restart. Documentation of informed consent must be recorded in the study chart. 
• Study drug must be administered at the dose specified by the VSLC. 
• Subjects approved by the VSLC for restart of IP must return to the clinic once a 
week for liver chemistry tests for a minimum of one month and thereafter for as 
long as clinically indicated and then laboratory monitoring may resume as per 
protocol. Longer durations of close monitoring may be required for long-acting 
IP. 
Refer to Section 11.3 for full guidance. 
 
5.5.1.4.2. 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: 


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• 
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 VSLCParticipants 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. 
5.5.2. 
QTc Stopping Criteria 
A participant who has a QTc interval >550 msec considered causally related to IP will be 
withdrawn from the study.  The QTc should be based on averaged QTc values of 
triplicate electrocardiograms obtained over a brief (e.g., 5 to 10 minute) recording 
period.   
If an alternative cause of the QT prolongation is determined (e.g., participant receiving 
drug known to cause prolonged QT or TdP), the IP may be restarted (or continued) after 
consultation and agreement with the Medical Monitor. RPV and RPV LA should not be 
administered to 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.   


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5.5.3. 
Virologic Failure 
Only plasma HIV-1 RNA values determined by the central laboratory will be used to 
assess virologic failure.  
5.5.4. 
Definition of Protocol-Defined Confirmed Virologic Failure 
For the purposes of clinical management in this study, CVF is defined as:  
Rebound as indicated by two consecutive plasma HIV-1 RNA levels 200 c/mL after 
prior suppression to <200 c/mL. 
5.5.5. 
Managing Virologic Failure 
Following study entry, no changes, or intensification of ART will be permitted prior to 
protocol-defined virologic failure, outside of the planned protocol regimens.  Only 
plasma HIV-1 RNA values determined by the central laboratory will be used to assess 
virologic failure.  Baseline plasma HIV-1 RNA is the assessment completed on study 
Day 1.  The definition of confirmed virologic failure does not apply to participants in the 
LTFU Phase.  These participants will be followed for the emergence of viral resistance.  
 
Inadequate adherence is a common cause for virologic failure, and should be explored as 
a first step in the management of study participants (e.g., at the first indication of 
inadequate virologic response or rebound). Upon notification that a participant’s HIV-1 
RNA plasma level qualifies him/her as a suspected virologic failure, the Investigator 
should query the participant regarding intercurrent illness, recent immunization, or 
interruption of oral therapy. 
5.5.5.1. 
HIV-1 RNA Blips 
HIV-1 RNA “blips” are not usually associated with subsequent virologic failure [DHHS, 
2016].  Although the implications of persistent HIV-1 RNA levels between the lower 
level of detection and <200 c/mL are unclear, the risk of emerging resistance is believed 
to be relatively low.   
Participants with transient increases in HIV-1 RNA (‘blips’ HIV-1 RNA <200 c/mL) are 
not considered suspected virologic failures and do not require a change in therapy.   
Participants who have a HIV-1 RNA ≥50 c/mL and <200 c/mL at the key analysis 
timepoints (Week 48, Week 96, and Week 152) must return to the clinic as soon as 
possible (but no later than 4 weeks after the date of the Week 48, 96, or 152 visit, 
respectively) for a repeat HIV-1 RNA test such that the result falls within the same 
analysis window. 
In order to better characterize HIV-1 RNA ‘blips,’ if there is a known reason / 
explanation for the blip (e.g., immunization, allergies, etc.), the study team should be 
notified of the reason and case context. 


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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 
5.5.5.2. 
Suspected Virologic Failure 
Upon notification that a participant’s HIV-1 RNA plasma level meets the definition of 
virologic failure, the Investigator should confirm the definition is met by initiating a 
repeat of the HIV-1 RNA assessment. 
The following guidelines should be followed for scheduling confirmatory HIV-1 RNA 
testing in an effort to avoid false-positive results: 
• 
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. 
• 
If therapy is interrupted* due to toxicity management, non-compliance, or other 
reasons, confirmatory testing should be scheduled 2 to 4 weeks following resumption 
of full dose of all IP. 
• 
The participant should have received full dose of IP for at least 2 weeks at the time 
confirmatory plasma HIV-1 RNA testing is done. 
*Note:  treatment interruption guidelines above may not apply for participants on CAB 
LA + RPV LA treatment.  The study team should be contacted to discuss any treatment 
interruptions for participants meeting the definition of virologic failure. 
In addition, the Investigator should query the participant regarding intercurrent illness, 
recent immunization, or interruption of therapy. 
Sites should contact the Medical Monitor to discuss individual participants, 
whenever necessary. 
5.5.5.3. 
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 


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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. 
5.6. 
Participant and Study Completion 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition.  
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 Week 100 (with or without Week 100 study treatment) 
and did not enter the Extension Phase; 
• 
Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including Week 100, and entered and completed the Extension 
Phase (defined as remaining on study until commercial supplies of CAB LA + RPV 
LA Q4W or Q8W regimen become locally available or development of CAB LA + 
RPV LA is terminated). 
 
Participants who withdraw from CAB LA + RPV LA and go into the LTFU Phase will be 
considered to have prematurely withdrawn from the study treatment. 
 
Safety Follow Up visit: 
 
In addition to the 52-week Follow-Up phase required for participants who receive one or 
more injections with CAB LA or RPV LA, an in-clinic or telephone Follow-Up visit will 
be conducted as described below  


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1. Where marketed CAB + RPV LA is locally available:  Safety Follow Up Visit 
is required for subjects completing the study, (may or may not be transitioning 
to CAB + RPV LA marketed product). It should be conducted approximately 
2-4 weeks after the last dose of IP to assess HIV associated conditions, AEs, 
Concomitant medications, ISR AEs after the last injection and the plan to 
transition to marketed product. This visit may be conducted by telephone. 
Ensure relevant eCRF forms (including the Conclusion Visit) are updated / 
completed. 
 
2. Where marketed CAB + RPV LA is not yet locally available:  
a. Safety Follow Up Visit should be conducted approximately 2-4 weeks 
after the last dose of IP and may be conducted by telephone. Ensure 
relevant eCRF forms (including the Conclusion Visit) are updated / 
completed.  This visit is only required if the subject: 
i. has ongoing AEs or Lab abnormalities in the last on-study visit  
AND 
ii. is not planning to attend additional study visits after the last IP 
injection (ie. Withdrawal visit, Long Term Follow up  visits) where 
the ongoing AEs/Lab abnormalities can be assessed. 
b. Safety Follow Up Visit is not required if the subject completes 
Withdrawal visit as scheduled and/or is willing to enter Long Term Follow 
Up phase. Note: If the first study visit after the last injection is scheduled 
more than 3 months after the last dose of IP, please consult the MM to 
advise if Safety Follow Up is still required. 
 
6. 
STUDY TREATMENT 
6.1. 
Investigational Product and Other Study Treatment 
The term ‘study treatment’ is used throughout the protocol to describe any combination 
of products received by the participant as per the protocol design.  Study treatment 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. 
Investigational product (IP) in this protocol refers to the investigational study drugs Oral 
Cabotegravir, Cabotegravir LA, Oral Rilpivirine and Rilpivirine LA.  These will be 
supplied by GlaxoSmithKline/ViiV Healthcare and Janssen Pharmaceuticals, 
respectively.  
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.  


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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. 
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 


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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. 
6.2. 
Treatment Assignment 
Informed consent must be obtained prior to any study procedures, including Screening 
visit activities. Participants will be assigned to study treatment in accordance with the 
randomization schedule. The randomization schedule, including stratification, will be 
generated using the GSK validated randomization software RANDALL NG. The 
randomization schedule is comprised of a series of blocks, with equal treatment 
allocation within each block, which are shared across centers via central randomization. 
Given the open-label study design, central randomization was used to eliminate selection 
bias due to foreknowledge of randomized treatment.  With central randomization, 
knowledge at a site of the randomized treatment group for previous subjects does not 
predict which treatment group will be assigned to the next randomized subject.  
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.  A unique treatment number will be assigned 
for each participant participating in the study. Participants will be randomized in a 1:1 
ratio to CAB LA + RPV LA Q4W or to CAB LA + RPV LA Q8W in accordance with 
the computer generated randomization schedule.  
Participants who successfully complete 100 weeks of treatment and have a viral load 
<50 c/ml at Week 96 (or upon retest by Week 100) will be given the opportunity to enter 
the Extension Phase in which they will continue to receive their CAB LA + RPV LA 
regimen.  In addition, RAMOS NG will facilitate the initial supply and subsequent 
resupply of IP to study sites. 
6.3. 
Dosage and Administration 
Participants will be randomly assigned to receive treatment with CAB LA + RPV LA 
either Q4W or Q8W.  Patients transitioning from oral standard of care therapy will 
initiate their randomized treatment regimen with Oral CAB 30 mg + RPV 25 mg once 
daily for 4 to 5 weeks during the Oral Phase, followed by CAB LA + RPV LA IM 
injections initiating at Week 4b.  Patients transitioning from the ATLAS study and on 
CAB LA + RPV LA Q4W treatment will be randomized at Day 1 to either continue Q4W 


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administration or transition to Q8W administration of CAB LA + RPV LA.  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 Table 7 Figure 8 below. 


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Table 7 
Dosage and Administration 
Maintenance Phase and Extension Phase (Day 1 to End of Study+) 
Q4W  Arm - Transitioning from SOC 
Oral Lead-In 
Day 1 to Week 4b 
(2 tablets once daily) 
• Take 1 tablet CAB 30 mg once daily. 
• Take 1 tablet RPV 25 mg once daily. 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injections (Loading Dose) – Week 4b 
Week 4b 
(two 3mL injections once) 
• Receive last dose of oral CAB + RPV regimen 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection  
Maintenance Injections – every 4 Weeks (Q4W) following Week 4b 
Week 8 to End of Study+ 
(two 2 mL injections every 4 
weeks) 
• Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
• Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
Q8W Arm-Transitioning from SOC 
Oral Lead-In 
Day 1 to Week 4b 
(2 tablets once daily) 
• Take 1 tablet CAB 30 mg once daily. 
• Take 1 tablet RPV 25 mg once daily. 
Should be taken together once daily at approximately the same 
time each day, with a meal. 
First Injections (Loading Doses) – Week 4b 
Week 4b 
(two 3 mL injections once) 
• Receive last dose of oral CAB + RPV regimen 
• Receive CAB LA 600 mg given as 1 X 3 mL IM injection 
• Receive RPV LA 900 mg given as 1 X 3 mL IM injection  


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Maintenance Injections – every 8 Weeks (Q8W) following Week 8 
Week 8 to End of Study+ 
(two 3mL injections every 8 
weeks) 
• 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 
Q4W Arm – Continuing Q4W injections from ATLAS  
Day 1 to End of Study+ 
(two 2 mL injections every 4 
weeks) 
• Receive CAB LA 400 mg given as 1 X 2 mL IM injection 
• Receive RPV LA 600 mg given as 1 X 2 mL IM injection 
Q8W Arm- Transitioning from ATLAS Q4W 
Day 1 to End of Study+ 
(two 3 mL injections every 8 
weeks) 
• 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 Q4W or Q8W CAB LA + RPV LA regimen (or 
complete trial participation) at Week 100.  If the participant decides not to continue participation in the study, any 
arrangements for off-study ART should be made in advance of the Week 100 visit. 
^See Section 6.6.1 for Dosing Considerations for CAB LA + RPV LA 
6.4. 
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 Week 24 preliminary analysis. The Week 24 results 
will be restricted to only those study team members and GSK/ViiV Healthcare senior 
management who need to be involved in the analysis and interpretation of the results for 
reporting to regulatory authorities. Public presentation of the Week 24 analysis will not 
be done prior to Week 48 analysis complete. 
6.5. 
Packaging and Labeling 
The contents of the label will be in accordance with all applicable regulatory 
requirements. 
6.6. 
Preparation/Handling/Storage/Accountability 
• The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment. 
• Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study treatments 


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must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized site staff. 
• 
In accordance with local regulatory requirements, the investigator, institution, or the 
head of the medical institution (where applicable) is responsible for study treatment 
accountability, reconciliation, and record maintenance (i.e. receipt, reconciliation and 
final disposition records).  The amount of IP dispensed and/or administered to study 
participants, the amount returned by study participants, and the amount received 
from and returned to GSK must be documented. 
• 
Further guidance and information for the final disposition of unused study treatment 
are provided in the Study Reference Manual.  
• 
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff.  Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or 
GSK study contact. 
• 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK. 
• 
Product accountability records must be maintained throughout the course of the 
study. 
IP accountability will be evaluated using pill counts of unused IP for patients receiving 
oral treatment (oral CAB, oral RPV).  This assessment will be conducted, when the 
participant completes oral CAB and RPV lead-in treatment in the Maintenance or 
Extension 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. 
Please refer to Appendix 10 in Section 11.10 for study management information during 
the COVID-19 pandemic. 
6.6.1. 
Dosing Considerations for CAB LA + RPV LA 
Vials of CAB LA and RPV LA are each supplied as a suspension and need no further 
dilution or reconstitution.  Since RPV LA requires refrigeration, sites should allow the 
vial to come to approximately room temperature prior to injecting. The vials should be 
gently inverted a few times to re-suspend sediments and allow bubbles to subside, and 
then use a syringe to withdraw the required volume of suspension for IM injection.   
All injections must be given intramuscularly in the gluteus medius.  Sites may use their 
discretion as to where in the gluteus muscle each injection is given according to 
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approximately 2 cm from one another, from the site of any previous injection or any 
injection site reaction.  The time and location of injection will be captured in the eCRF.   
IM injections should be administered at a 90 degree angle into the gluteus medius muscle 
using a needle of appropriate gauge and length (In most participants, a 1.5” 23 gauge 
needle for CAB LA and a 1.5” 23 gauge needle for RPV LA is recommended).  The 
needle should be long enough to reach the muscle mass and prevent study drug from 
seeping into subcutaneous tissue, but not so long as to involve underlying nerves, blood 
vessels, or bone.  Variable needle lengths and/or needles with different gauge (CAB LA: 
21 to 25 gauge; RPV LA: 21 to 23 gauge) are permitted if needed to accommodate 
individual body types.  Longer needle lengths may be required for participants with 
higher body mass indexes (BMIs, example > 30), to ensure that injections are 
administered intramuscularly as opposed to subcutaneously.  BMI, needle gauge and 
length used will be collected in the eCRF.  Additional details of the injection device used 
by sites for IM administration including, but not limited to functional performance, may 
also be collected within the eCRF. 
At the Week 4b visit, participants transitioning from oral SOC should be dosed with the 
IM regimen within 2 hours of taking the last oral regimen dose where possible.  
Should IM maladministration be suspected at any time (e.g., suspected under or overdose 
or inadvertent IV dosing), the investigator may consider requesting the participant stay 
onsite for approximately 2-3 hours post dose for safety monitoring and notifying the 
Medical Monitor.  An ECG or any other supportive testing may be obtained at the 
discretion of the investigator.  Additionally, a PK sample may be drawn approximately 
2 hours post dosing for future evaluation of CAB and RPV plasma concentrations. 
Additional dosing instructions and considerations can be found in the SPM. 
6.7. 
Compliance with Study Treatment Administration 
When participants are dosed at the site, they will receive study treatment directly from 
the investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the participant’s eCRF.  The dose of study 
treatment and study participant identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study treatment.  
When participants self-administer oral study treatments at home, compliance with CAB + 
RPV dosing will be assessed through querying the participant during the site visits and 
documented in the source documents and CRF.  IP accountability will be evaluated using 
pill counts of unused IP (CAB and RPV tablets).  This assessment will be conducted each 
time the participant receives a new (refill) supply of oral study medication, completes the 
oral lead-in or any oral bridging phase.  A record of the number of CAB and RPV tablets 
dispensed to and taken by each participant must be maintained and reconciled with study 
treatment and compliance records.  Treatment start and stop dates will also be recorded in 
the eCRF.  
Due to the long acting nature of the CAB LA and RPV LA it will be imperative that the 
participant is compliant with dosing instructions.  As part of the screening and participant 
selection process, it is imperative that Investigators discuss with potential participants the 


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long-term commitments for the trial, and the importance of adhering to treatment 
regimens.  Sites are to have plans in place for adherence counselling for both treatment 
arms of the study for the duration of the study including the LTFU Phase.  In addition, 
Investigators must have plans in place to perform visit reminders, utilizing patient 
trackers provided by the study team as needed, and to verify the participant’s contact 
information at each visit.  Investigators should contact patients directly in the event that a 
participant misses any scheduled visit.  
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 the medical monitor, Investigators may provide daily oral 
CAB 30 mg and RPV 25 mg as a short-term “bridging” strategy for participants who 
have begun CAB LA + RPV LA.  In certain circumstances (e.g., prior to steady state 
dosing and following a >4 week oral bridge) repeating the loading doses of CAB IM and 
RPV IM may be required.  Participants who withdraw during an oral treatment 
period must be initiated on HAART therapy within 24 hours after the last oral 
treatment with CAB + RPV.  Should a participant require “oral bridging”, sites must 
contact the study Medical Monitor for guidance with treatment and dosing strategies prior 
to a missed CAB LA + RPV LA dose.  
Please refer to Appendix 10 in Section 11.10 for study management information during 
the COVID-19 pandemic. 
6.9. 
Interruption of Study Treatment and Visit/Dosing Windows 
IP may be interrupted at the discretion of the Investigator in the event of an AE, 
according to the severity of the AE. 
If one or more antiretroviral medications is held due to toxicity or adverse events, all 
antiretroviral medications must be held to reduce the risk of development of resistance 
taking into account both the length of the planned interruption and the pharmacokinetic 
half-life of each antiretroviral of the regimen, in a way to minimize the risk of 
development of resistance. 
It is important to note that keeping to the participant’s visit schedule is a very 
important component to the study.   
Note: All decisions regarding dose interruption / resumption must be discussed with 
the Medical Monitor in advance. 
6.9.1. 
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 


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levels which exert selective pressure on HIV.  This time period will vary by ART agent 
and is dependent upon effective concentration, inhibitory concentration, and half-life.  
Plasma concentrations of both LA drugs may be measurable for more than one year 
following IM injections. Any interruption in IM dosing should be discussed with the 
Medical Monitor.  Investigators should ensure that the participant initiates alternative 
highly active ART to minimize the risk of developing resistance as concentrations of 
CAB and RPV decline over time. 
IM dosing is expected to occur during the week in which the participant’s projected visit 
falls (as according to the date of the first injection).  The first injections for participants 
from ATLAS on CAB LA + RPV LA Q4W will occur at Day 1.  The first injections for 
participants transitioning from oral SOC are administered at Week 4b (can be performed 
as soon as lab results from Week 4a become available and should be performed where 
possible within 2 weeks of visit 4a), and the second injections are given at Week 8. 
Between the Week 4a and 4b visits, participants must continue daily treatment with oral 
CAB and RPV tablets.   
Since the first injection visit (Day 1 or 4b) will determine the future injection visit 
schedule for participants, planning for the first injection visit date (within allowed visit 
windows) should take into consideration the availability of the participants to adhere to 
future visit windows (planned vacations, business trips, etc.). 
CAB LA + RPV LA dosing for participants transitioning from SOC treatment is as 
follows: 
All injections should be planned as single injections per drug. 
6.9.1.1. 
IM injections every 4 weeks (Q4W): 
Week 4b only - CAB LA 600 mg + RPV LA 900 mg, each given as 1 X 3 mL IM 
injection 
Week 8 and Q4W thereafter - CAB LA 400 mg IM + RPV LA 600 mg IM every 4 weeks 
for 100 weeks, each given as 1 X 2 mL IM injection 
At Week 4b, participants transitioning from SOC will return to the clinic, take the last 
dose of 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 with IM CAB LA + RPV LA at Week 4b can be performed once central 
lab results are available and safety parameters are reviewed from the Week 4a visit.   
The second and third IM injections with CAB LA 400 mg and RPV LA 600 mg will be 
performed at Week 8 and Week 12.  There will be a -7 day dosing window for the second 
and third IM injections such that the second injection occurs within the window of Week 
7 and Week 8 but no later than Week 8 and the third injection occurs within the window 
of Week 11 and Week 12 but no later than Week 12.  Subsequent injections with CAB 
LA 400 mg and RPV LA 600 mg will occur every 4 weeks (7 days) thereafter.  In 
addition, starting after the Week 16 injection, efforts should be made to limit time 
between injection visits to a maximum of 5 weeks.  The Medical Monitor must be 


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contacted if the length of time between injections exceeds or is projected to exceed 5 
weeks. 
6.9.1.2. 
IM injections every 8 weeks (Q8W): 
Week 4b – CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM 
injection 
Week 8 - CAB LA 600 mg + RPV LA 900 mg IM, each given as 1 X 3 mL IM injection 
Week 16 and Q8W thereafter - CAB LA 600 mg + RPV LA 900 mg IM, every 8 weeks 
for 100 weeks, each given as 1 X 3 mL IM injection 
At Week 4b, subjects 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 with IM 
CAB LA + RPV LA at Week 4b can be performed once central lab results are available 
and safety parameters are reviewed from the Week 4a visit.   
The second loading injection will be administered at Week 8 (CAB LA 600 mg + RPV 
LA 900 mg, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring 
every 8 weeks thereafter.  The dosing window for the second injection allows 
administration between Week 7 and Week 8, but preferably not later than Week 8.  After 
Week 16, a dosing window (7 days) for injections is allowed, but not preferred. Starting 
at the Week 16 injection, the interval between injection visits should be limited to a 
maximum of 9 weeks.  If the length of time between injections exceeds, or is projected to 
exceed 9 weeks, the Medical Monitor must be contacted to discuss individual subject 
case management 
Participants transitioning from ATLAS and currently receiving CAB LA + RPV LA 
Q4W 
Patient transitioning from the ATLAS study and on CAB LA + RPV LA Q4W treatment 
will be randomized at Day 1 to either continue Q4W administration or transition to Q8W 
administration of CAB LA + RPV LA.  The first injection visit for the ATLAS-2M study 
can be performed once the final central lab results from the ATLAS study are available 
and safety parameters have been reviewed.  For participants who received three or more 
Q4W CAB LA + RPV LA injections within ATLAS, the transition from ATLAS to 
ATLAS-2M Day 1 dosing must occur 4 weeks (7 days) from the final injections 
received in ATLAS.  For those who received less than three Q4W injections within 
ATLAS, this transition to ATLAS-2M Day 1 injections must occur within 4 weeks (-7 
days) from the final ATLAS injections 
Dosing for participants transitioning from CAB LA + RPV LA Q4W in ATLAS is as 
follows: 


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6.9.1.3. 
IM injections every 4 weeks (Q4W) (Q4W from ATLAS Q4W): 
Starting at Day 1, all injections will continue with the maintenance dose of CAB LA 
400 mg and RPV LA 600 mg administered every 4 weeks (7 days).  In addition, efforts 
should be made to limit time between injection visits to a maximum of 5 weeks.  The 
Medical Monitor must be contacted if the length of time between injections exceeds or is 
projected to exceed 5 weeks. 
6.9.1.4. 
IM injections every 8 weeks (Q8W) (Q8W from ATLAS Q4W): 
Participants transitioning from ATLAS and receiving CAB LA + RPV LA Q8W 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 
Week 8 and Q8W 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 Week 8 (CAB LA 600 mg + RPV LA 
900 mg, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) every 8 weeks 
thereafter.  The dosing window for the second injection allows administration between 
Week 7 and Week 8, but preferably not later than Week 8.  After Week 16, a dosing 
window (7 days) for injections is allowed, but not preferred. Starting at the Week 16 
injection, the interval between injection visits should be limited to a maximum of 
9 weeks.  If the length of time between injections exceeds, or is projected to exceed 
9 weeks, the Medical Monitor must be contacted to discuss individual subject 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. 
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. 
6.9.2. 
Oral Dosing 
The Week 4a Visit during the Oral Lead-in Phase for participants transitioning from SOC 
is expected to occur 4 weeks (3 days) after to the Day 1 Baseline visit.  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 


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site staff becoming aware of resumption in therapy, if therapy was resumed without prior 
approval. 
Visits for participants in LTFU are expected to occur as projected according to the last 
injection.   
6.10. 
Discontinuation of Study Treatment 
Participants unable to manage drug toxicity or tolerate investigational product (IP, either 
formulations of CAB or RPV) must have IP discontinued.  Any participant receiving at 
least one dose of CAB LA and /or RPV LA who discontinues IP / Withdraw will initiate 
treatment with HAART enter the LTFU Phase for 52 weeks of follow-up (see Section 
4.2.4). 
When the CAB+RPV LA marketed product is locally available participants must enter 
the LTFU Phase if withdrawing for safety related reasons only.  see Section 5.5. 
 
6.11. 
Treatment of Study Treatment Overdose 
For participants receiving Oral CAB, any tablet intake exceeding a total daily dose of    
30 mg will be considered an overdose.  For participants receiving oral RPV, any dose 
exceeding a total daily dose of 25 mg will be considered an overdose.  
For CAB LA and RPV LA, any single dose in excess of the studied doses will be 
considered an overdose. 
Should IM maladministration, specifically overdose or inadvertent IV dosing, be 
suspected at any time, the participant will stay onsite for approximately 2-3 hours post 
dose for safety monitoring and an ECG will be performed at 2 hours post dose.  The 
Medical Monitor will be notified in the event of a suspected maladministration.  
In the event of suspected maladministration, additional PK samples will be drawn at 
2 hours post dosing for evaluation of CAB and RPV concentrations. 
For the purposes of this study, an overdose is not an AE (refer to Section 11.6.1 ) unless 
it is accompanied by a clinical manifestation associated with the overdose.  If the clinical 
manifestation presents with serious criteria, the event is a SAE (see Section 11.6.2). 
If an overdose occurs and is associated with an adverse event requiring action, all study 
medications must be temporarily discontinued until the adverse event resolves.  
The Investigator should use clinical judgement in treating overdose, as 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 


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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 and oral RPV, and 52 weeks for CAB LA 
and RPV LA 
3. Obtain a plasma sample for pharmacokinetic (PK) analysis if possible within 2 days 
from the date of the last dose of study 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. 
6.12. 
Treatment after the End of the Study 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition, whether or not GSK is providing 
specific post-study treatment.  Participants who have successfully completed 100 weeks 
of treatment will continue to have access to both CAB LA and RPV LA in the Extension 
Phase through Week 152 and 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. 
6.13. 
Concomitant Medications and Non-Drug Therapies 
Participants must be advised to notify their Investigator of any current or proposed 
concomitant medication, whether prescribed or over-the-counter, because of the potential 
for interactions between such treatments and the study medications.  Concomitant 
medications (prescription and non-prescription) will be permitted during the course of the 
study at the investigator’s discretion (except for prohibited medications described in 
Section 6.13.2) and should be administered only as medically necessary during the study.  
All concomitant medication, blood products, and vaccines taken during the study will be 
recorded in the eCRF.  The minimum requirement is that the drug name, route, and the 
dates of administration are to be recorded. 
 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
 


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6.13.1. 
Permitted Medications and Non-Drug Therapies 
Chemoprophylaxis for HIV-associated conditions is encouraged, if appropriate, at the 
discretion of the participant and their physician.  All concomitant medications, blood 
products, and vaccines taken during the study will be recorded in the eCRF with dates of 
administration. 
Because non-HIV vaccines may cause a temporary increase in the level of plasma HIV-1 
RNA, it is recommended that a vaccine, if necessary, be given during or immediately 
after a scheduled visit after all laboratory tests have been drawn.  This approach will 
minimize the risk of non-specific increases in the level of plasma HIV-1 RNA at the next 
scheduled assessment. 
Other IM injectables (with exceptions below) are permitted but must be administered 
away from the site of IP administration (should be spaced 2 cm or more away from site of 
IP injection). 
Antacid and H2 Antagonist Use: 
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. 
RPV oral administration only:  Antacid products must be taken at least 2 hours before 
or at least 4 hours after RPV.  H2-Receptor antagonists (e.g. cimetidine, famotidine, 
nizatidine, ranitidine) may cause significant decreases in RPV plasma concentrations.  
H2-receptor antagonists should only be administered at least 12 hours before or at least 4 
hours after RPV.  RPV should not be co-administered with proton pump inhibitors, such 
as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole. 
RPV:  Administration of clarithromycin, erythromycin and telithromycin is not 
recommended with RPV due to possible increase in plasma concentration of RPV due to 
CYP3A enzyme inhibition.  Where possible, alternatives such as azithromycin should be 
considered.  Please refer to the local rilpivirine prescribing information for guidance 
regarding other drugs that are prohibited, should be used with caution, require dose 
adjustment, or increased clinical monitoring if taken with rilpivirine. 
Drugs with a known risk of Torsade des Pointes (TdP) should be used with caution when 
on rilpivirine (see SPM for list of drugs associated with TdP). 
6.13.2. 
Prohibited Medications and Non-Drug Therapies 
The following concomitant medications or therapies are not permitted at any time during 
the study: 


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• HIV immunotherapeutic vaccines are not permitted at any time during the 
study.  
• Other experimental agents, antiretroviral drugs not otherwise specified in the 
protocol, cytotoxic chemotherapy, or radiation therapy may not be 
administered (see Exclusion Criteria #35-36, 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 patients with acute viral 
hepatitis (James, 2009). 
• Chronic use of systemic (oral or parenteral) glucocorticoids must be avoided 
due to their immunosuppressive effect; however, short treatment courses with 
oral prednisone/ prednisolone/methylprednisolone (e.g. adjunctive treatment 
of Pneumocystis pneumonia with ≤ 21 days of tapering prednisone) are 
allowed.  A single dose of systemic dexamethasone is permitted (more than a 
single dose in a treatment course may cause significant decrease in RPV 
plasma concentration and is prohibited). Topical, inhaled or intranasal use of 
glucocorticoids will be allowed.   
• Hepatitis C infection therapy is prohibited during the Maintenance Phase 
before the Week 48 primary endpoint, and interferon-based HCV therapy or 
use of any drugs that have a potential for adverse drug:drug interactions with 
study treatment is prohibited throughout the entire study.  
For information on concurrent therapies and interactions suspected to be relevant to other 
antiretroviral therapy in the regimen, please consult the local prescribing information. 
6.13.2.1. 
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 CAB 
CAB is a potent inhibitor of OAT1 and OAT3 transport in vitro, however, no clinically 
significant interaction risk is expected for most drugs that are substrates of these 
transporters.  Monitoring may be required for drugs with a narrow therapeutic index and 
dependent on OAT1 and OAT3 transport (e.g. methotrexate) with concomitant CAB 


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administration.  Refer to the current Investigator’s Brochure (Section 4.3.6.1 and Section 
6.4) for additional information.  
Concurrent with RPV 
In addition, participants must discontinue the following (or change to an allowable 
alternative) while receiving treatment with oral RPV: 
• 
proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, 
pantoprazole, rabeprazole; 
• 
systemic dexamethasone (more than a single dose) 
If the participant cannot discontinue use or change to an allowable alternative while 
receiving treatment with RPV, the participant should not be randomized into the study. 
6.13.2.2. 
Concurrent with either CAB LA or RPV LA 
In addition, for participants receiving CAB LA and RPV LA, use of anticoagulation 
agents for greater than 14 days is prohibited, with the exception of the use of 
anticoagulation for deep vein thrombosis (DVT) prophylaxis (e.g., postoperative DVT 
prophylaxis) or the use of low dose acetylsalicylic acid (≤325 mg). Systemic 
anticoagulation (including prophylaxis doses) on the day of an IM injection should be 
avoided. 
Note: Any prohibited medications that decrease cabotegravir or rilpivirine concentrations 
should be discontinued for a minimum of four weeks or a minimum of three half-lives 
(whichever is longer) prior to the first dose and any other prohibited medications should 
be discontinued for a minimum of two weeks or a minimum of three half-lives 
(whichever is longer) prior to the first dose. 
6.13.2.3. 
Prohibited Medications for Participants Receiving HAART during the 
Long-Term Follow-Up Phase 
For participants  taking HAART during the Long-Term Follow-Up Phase, refer to local 
prescribing information for details regarding concurrent therapies. 
6.14. 
Medical Devices 
The medical devices to be used in this study are: vial adaptor, syringe and needle. 
Instructions for medical device use are provided in the Study Reference Manual. 
All device deficiencies, (including malfunction, use error and inadequate labelling) shall 
be documented, and reported by the investigator throughout the clinical investigation (see 
Section 11.2) and appropriately managed by the sponsor. 
 


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7. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the Time and Events Table, are essential and required for study conduct. 
This section lists the procedures and parameters of each planned study assessment.  The 
exact timing of each assessment is listed in the Time and Events Table (Section 7.1). 
The following points must be noted:  
• If assessments are scheduled for the same nominal time, THEN the assessments 
should occur in the following order: 
1. 12-lead ECG 
2. vital signs 
3. blood draws   
Note: The timing of the assessments should allow the blood draw to occur at the 
exact nominal time. 
• The timing and number of planned study assessments, including safety, 
pharmacokinetic, pharmacodynamic/biomarker assessments may be altered 
during the course of the study based on newly available data (e.g., to obtain data 
closer to the time of peak plasma concentrations) to ensure appropriate 
monitoring.  
• The IRB/IEC will be informed of any safety issues that require alteration of the 
safety monitoring scheme or amendment of the Informed Consent Form.  
 
Please refer to Appendix 10 in Section 11.10 for study management information during 
the COVID-19 pandemic. 
7.1. 
Time and Events Table 
Note:  While some assessments included in the Time and Events Table are conducted less 
frequently following the primary endpoint (Week 48), IM injections for participants 
during the Extension Phase will continue to be administered Q4W or Q8W based on 
original study randomization assignment. 
All patients will be randomized at Day 1 to initiate either Q4 weekly or Q8 weekly 
administration of IM CAB LA + RPV LA. Only participants randomized from oral SOC 
treatment will participate in the Day 1 to Week 4 Oral CAB + Oral RPV lead-in 
treatment. 
 


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7.1.1. 
Time and Events Table for CAB LA + RPV LA Q4 Weekly Administration 
Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments.y 
(Maintenance) 
Withdrawal Assessments 
(Extension) 
Long-Term Follow-up z 
Day 1 
Week 
Week 4A (Oral 
Lead-in Only)b 
Week 4B 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Q4W 
56-92 
Q8W 
56-92 
96 
100 
Q4W After 
Week 100 
Q8W After 
Week 96 
152 
Written 
informed 
consentaa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Verification 
(Inclusion/Ex
clusion 
Criteria) 
X 
 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xc 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
Historyd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular 
risk 
assessmentd 
X X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication 
History/ 
Prior ART 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments.y 
(Maintenance) 
Withdrawal Assessments 
(Extension) 
Long-Term Follow-up z 
Day 1 
Week 
Week 4A (Oral 
Lead-in Only)b 
Week 4B 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Q4W 
56-92 
Q8W 
56-92 
96 
100 
Q4W After 
Week 100 
Q8W After 
Week 96 
152 
Syphilis 
serology + 
Reflex Rapid 
Plasma 
Reagin 
(RPR) 
X X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom 
Directed 
Physical 
Exam and 
Medical 
Assessmente 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight, 
Height and 
BMIf 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
Vital Signs: 
BP, HR, 
Temperature)g 
X X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
12-lead ECG 
h 
(triplicate at Day 
1 pre-dose) 
X X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
CDC HIV-1 
stage 
X X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments.y 
(Maintenance) 
Withdrawal Assessments 
(Extension) 
Long-Term Follow-up z 
Day 1 
Week 
Week 4A (Oral 
Lead-in Only)b 
Week 4B 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Q4W 
56-92 
Q8W 
56-92 
96 
100 
Q4W After 
Week 100 
Q8W After 
Week 96 
152 
HIV 
Associated 
Conditions 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs, SAEs, 
device 
deficiencies, 
Concomitant 
Medicationsi 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ISR 
Assessment 
for IM 
injections 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Columbia 
Suicide 
Severity 
Rating Scale 
(eC-SSRS) j 
X X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
 
 
 
 
X 
 
 
Clinical 
chemistry 
and 
Hematology 
X X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
Pregnancy 
Testingk 
S U 
S 
U 
S 
U 
S 
U 
S 
U 
S 
U 
S 
U 
S 
S 
U 
S 
S 
S 
U 
S 
S 
S 
S 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments.y 
(Maintenance) 
Withdrawal Assessments 
(Extension) 
Long-Term Follow-up z 
Day 1 
Week 
Week 4A (Oral 
Lead-in Only)b 
Week 4B 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Q4W 
56-92 
Q8W 
56-92 
96 
100 
Q4W After 
Week 100 
Q8W After 
Week 96 
152 
HIV-1 RNA 
and sample 
for storage 
(S)l 
X X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
S 
 
X 
X 
S 
 
X 
X 
X 
X 
CD4+ cell 
count 
X X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
 
 
X 
X 
X 
X 
CD8+ cell 
count 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
Urinalysism 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
Fasting Lab 
Assessment:  
Glucose, 
Cholesterol 
(Total, HDL 
and LDL) and 
Triglyceridesn 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Xo 
 
Hepatitis B 
(HBsAg), 
Anti-HBc, and 
Anti-HBsAG,  
Hepatitis C  
(anti-HCV Ab) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PT/PTT/INR  
X X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PBMCsp 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
Genetics 
sampleq 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments.y 
(Maintenance) 
Withdrawal Assessments 
(Extension) 
Long-Term Follow-up z 
Day 1 
Week 
Week 4A (Oral 
Lead-in Only)b 
Week 4B 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Q4W 
56-92 
Q8W 
56-92 
96 
100 
Q4W After 
Week 100 
Q8W After 
Week 96 
152 
PK 
samplingr 
(S)=Storage 
only 
 
 
 
X 
X 
S 
X 
S 
X 
S 
X 
S 
X 
S 
X 
 
S 
S 
 
S 
X 
S 
 
 
X 
X 
S 
Oral CAB 
and Oral 
RPV 
Dispensations 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP 
accountability 
(Pill Counts)s 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IM treatment 
administratio
n when 
transitioning 
from SOCt 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
IM treatment 
administration 
when 
transitioning 
from CAB + 
RPV LA Q4W 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Patient Reported Outcomesu 
HAT-QoL 
(short-form) 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments.y 
(Maintenance) 
Withdrawal Assessments 
(Extension) 
Long-Term Follow-up z 
Day 1 
Week 
Week 4A (Oral 
Lead-in Only)b 
Week 4B 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Q4W 
56-92 
Q8W 
56-92 
96 
100 
Q4W After 
Week 100 
Q8W After 
Week 96 
152 
HIV TSQs 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
HIV TSQc v 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
ACCEPT 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
Reason for 
Switch or 
Reason for 
continuation w 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Preference 
Questionnaires x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
PIN 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
 
Safety Follow Up Visit (for subjects completing the study, may or may not be transitioning to CAB + RPV LA marketed product) and 
Safety Follow Up Visit (for subjects withdrawing from the study) are required as described in Section 5.6. 
 
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.   Participants transitioning from the 201585 (ATLAS) study must reach 
ATLAS Week 48 (at minimum) prior to initiating Screening procedures for ATLAS-2M and must reach ATLAS Week 52 (at minimum) prior to 
randomization in ATLAS-2M.  
b. 
Visits Week 4a is part of the CAB + RPV Oral Lead-in period and is required only for participants transitioning from current SOC to CAB LA + RPV LA. 
c. 
Confirmation of eligibility to continue the Maintenance Phase and eligibility to enter the Extension Phase.  
d. 
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. 


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e. 
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.   
f. 
Height collected at Baseline Day 1 only. 
g. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
h. 
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. For participants 
transitioning from ATLAS, the pre-dose Week 48 ECG can also serve as the ATLAS-2M Screening ECG.  ECG pre-dose will be performed in triplicate at 
Day 1.  A 2-hour post-dose ECG will also be performed at Days 1 and Week 48 for participants receiving CAB LA + RPV LA with an allowable window of 
30 minutes. 
i. 
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. 
j. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  The eC-SSRS will preferably 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. 
k. 
Women of childbearing potential only.  SR=serum, UR=urine.  Pregnancy events will be captured starting at Day 1 following initial exposure to study drug.  
Urine pregnancy test performed at Day 1 prior to administration of study drug, at Week 4b, and at study visits when other blood draws are not required in 
order to limit needle sticks.  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. Pregnant participants who remain in the study do not need pregnancy testing during the 
study, for the duration of their pregnancy. Pregnant participants remaining in the study have additional assessments required, as described in Appendix 11. 
l. 
Week 48, Week 96, and Week 152 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. 
m. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; and urine phosphate. Urine phosphate 
results from visit 4a are not required by protocol to inform the safety review at visit 4b prior to receipt of initial CAB LA + RPV LA injections. 
n. 
An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
o. 
Only collect if the Withdrawal visit occurs at Week 48 Week 96, or Week 152. 
p. 
Whole blood/PBMC collection samples may be used for virologic analyses.  PBMCs will be collected at baseline Day 1, Week 48, Week 96, Week 152 or 
Withdrawal if prior to Week 152. 
q. 
Genetics sample should be collected only for patients who did not participate in the 201585(ATLAS) study (sample was previously collected and stored). 
Informed consent for genetic research must be obtained before sample collection.  Sample may be collected at any visit after signing informed consent, but 
preferably at the Day 1 visit.   
r. 
One blood sample for CAB and RPV each to be collected at each PK timepoint.  At Day 1, for participants from the ATLAS Q4W arm, PK samples are to 
be collected pre-dose relative to IM administration.  At Week 4b, for participants randomized from SOC, Pre dose PK samples are to be collected: AFTER 
review of the PK diary to ensure that the samples are taken 20/28 hours after previous oral dose (diaries to be given at Day 1 or W4a); PRIOR to the final 
oral dose of CAB + RPV; PRIOR to the first IM injection. Trough plasma PK samples of CAB and RPV will be obtained for every pregnant woman at every 
study visit during the pregnancy for both Q4W and Q8W regimens. See Appendix 11. 
s. 
Only for Participants entering CAB + RPV Oral Treatment 
t. 
Participants switching to CAB LA + RPV LA will take final dose of oral lead-in regimen in the clinic at the Week 4b visit and begin injections.  If possible, 
injections should be spaced approximately 2 cm from one another and from the site of any previous injection and or any injection site reaction.  Bring RPV 


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LA to approximately room temperature prior to injecting.  Time and location of injection (right or left) as well as needle length used will be collected in the 
eCRF. The first injection can be performed as soon as central lab results become available and safety parameters are reviewed.   
u. 
All Patient Report Questionnaires/Surveys will be administered via paper instrument (in exceptional circumstances the questionnaires could be completed 
via telephonic interview, please refer to COVID19 appendix for additional details)  at the beginning of the visit before any other assessments are conducted 
and prior to administration of the eC-CSSRS.  During the Maintenance phase conduct questionnaires/surveys (HAT-QoL, HIV TSQs, HIV TSQc, ACCEPT, 
PIN and Preference) at W48 or upon Withdrawal only if occurring at or prior to Week 48. During the Extension phase conduct questionnaires/surveys (HIV 
TSQs, ACCEPT, “Reason for Oral Bridging and Preference questionnaire ” and PIN) at W152 or upon Withdrawal only if occurring at or prior to Week 152 
v. 
The HIV-TSQc is to be administered to all participants transitioning from ATLAS and new participants transitioning from oral SOC.  For participants 
transitioning from ATLAS, the version of the HIV-TSQc instrument to be administered will be based on the initial randomization arm at ATLAS Day 1.  
w. 
For patients randomized to oral SOC at Day 1 in ATLAS or new patients on SOC, the reasons for willingness to switch ART will be assessed at Day 1.  For 
patients randomized to CAB LA + RPV LA Q4W in ATLAS, the reasons for willingness to continue long-acting ART in ATLAS-2M will be assessed at 
Day 1. 
x. 
During Maintenance phase Preference Questionnaire (injection to injection/oral to injection) will be administered to all participants at W48 or upon WD if at 
or prior to W48. “Reason for Oral Bridging and Preference questionnaire ” questionnaire at Week 152 or upon WD visit if occurred at or before Week 152, 
will be administered only to participants who received oral bridging during the Maintenance and/or Extension Phases. 
y. 
Refer to Section 5.5 of the protocol for additional information on performing withdrawal assessments.  HIV-1 RNA will be collected as Storage sample only 
if withdrawal assessments coincide with Week 52  Week 100 or Week 156 (as per Section 5.5)  
z. 
Participants receiving one or more injections with CAB LA and/or RPV LA will be assessed with clinic visits at months 3, 6, 9 and 12 during the Long-Term 
Follow-Up Phase 
aa. 
After discussion of risk/benefit, a pregnancy specific ICF addendum must be signed by pregnant participants who wish to remain in the study 
 
Note: BP – Blood pressure, HR – Heart Rate, HDL – High Density Lipoprotein, LDL – Low Density Lipoprotein, PT Prothrombin Time, 
PTT Partial Thromboplastin Time, INR International normalized ratio 


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7.1.2. 
Time and Events Table for CAB LA + RPV LA Q8 Weekly Administration 
Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments y 
(Maintenance) 
WD assessemnts (Extension) 
Long-Term Follow-up z 
Day 1 
Week 
 
Week 4A (Oral 
lead-in ONLY) 
b
Week 4B 
(Oral lead-in 
ONLY) b
8 
9 
16 
24 
32 
40 
41 
48 
56 
64 
72 
80 
88 
96 
100 
Q8W After 
Week 96 
152 
Written informed 
consentaa 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Verification 
(Inclusion/ 
Exclusion Criteria) 
X 
 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xc 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
Historyd  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular risk 
assessmentd 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication History/ 
Prior ART history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Syphilis serology + 
reflex Rapid Plasma 
Reagin (RPR) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom Directed 
Physical Exam and 
Medical Assessmente 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight, Height and 
BMIf 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
 
 
Vital Signs 
 (BP, HR, 
Temperature)g 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments y 
(Maintenance) 
WD assessemnts (Extension) 
Long-Term Follow-up z 
Day 1 
Week 
 
Week 4A (Oral 
lead-in ONLY) 
b
Week 4B 
(Oral lead-in 
ONLY) b
8 
9 
16 
24 
32 
40 
41 
48 
56 
64 
72 
80 
88 
96 
100 
Q8W After 
Week 96 
152 
12-lead ECG h 
(triplicate at Day 1 pre-
dose) 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
 
CDC HIV-1 stage 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV Associated 
Conditions 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs, SAEs, device 
deficiency, 
Concomitant 
Medications 
Xi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ISR Assessment 
for IM injection 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Columbia Suicide 
Severity Rating Scale 
(eC-SSRS) j 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
 
Clinical chemistry and 
Hematology 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Testingk 
S 
U 
S 
U 
S 
 
S 
S 
S 
S 
 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
HIV-1 RNA and sample 
for storage (S)l 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
S 
X 
X 
X 
X 
CD4+ cell count 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CD8+ cell count 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
 
Urinalysism 
 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
 
Fasting Labs 
Glucose, Cholesterol 
(Total, HDL and LDL) 
and Triglyceridesn 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
Xo 
 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments y 
(Maintenance) 
WD assessemnts (Extension) 
Long-Term Follow-up z 
Day 1 
Week 
 
Week 4A (Oral 
lead-in ONLY) 
b
Week 4B 
(Oral lead-in 
ONLY) b
8 
9 
16 
24 
32 
40 
41 
48 
56 
64 
72 
80 
88 
96 
100 
Q8W After 
Week 96 
152 
Hepatitis B (HBsAg), 
Anti-HBc, and Anti-
HBsAG,  
Hepatitis C  
(anti-HCV Ab) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PT/PTT/INR  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PBMCs p 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
 
Genetics sample q 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK sampling when 
transitioning from SOC 
r 
(S)=Storage only 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
S 
S 
S 
S 
S 
X 
S 
 
X 
X 
S 
PK sampling when 
transitioning from CAB 
+ RPV Q4W r 
(S)=Storage only 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
S 
S 
S 
S 
S 
X 
S 
 
X 
X 
S 
Oral CAB and Oral 
RPV Dispensation s 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP accountability (Pill 
Counts) 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IM treatment 
administration when 
transitioning from SOC 
t 
 
 
 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
 
 


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Procedure 
Screening Visit a 
Maintenance Phase 
 
Extension 
Phase 
Withdrawal Assessments y 
(Maintenance) 
WD assessemnts (Extension) 
Long-Term Follow-up z 
Day 1 
Week 
 
Week 4A (Oral 
lead-in ONLY) 
b
Week 4B 
(Oral lead-in 
ONLY) b
8 
9 
16 
24 
32 
40 
41 
48 
56 
64 
72 
80 
88 
96 
100 
Q8W After 
Week 96 
152 
IM treatment 
administration when 
transitioning from CAB 
+ RPV Q4W 
 
X 
 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
 
 
 
 
Patient Reported Outcomes u 
HAT-QoL (short-form) 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
HIV TSQs 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
HIV TSQc v 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
ACCEPT 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
Reason for Switch or 
Reason for continuation 
w 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Preference 
Questionnairesx 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
PIN  
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
Safety Follow Up Visit (for subjects completing the study, may or may not be transitioning to CAB + RPV LA marketed product) and 
Safety Follow Up Visit (for subjects withdrawing from the study) are required as described in Section 5.6. 
 
bb. 
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.  Participants transitioning from the 201585 (ATLAS) study must reach 
ATLAS Week 48 (at minimum) prior to initiating Screening procedures for ATLAS-2M and must reach ATLAS Week 52 (at minimum) prior to 
randomization in ATLAS-2M.  


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cc. 
Visits Weeks 4A and 4B are part of the CAB + RPV Oral Lead-in period and are required only for participants transitioning from current SOC to CAB LA + 
RPV LA. 
dd. 
Confirmation of eligibility to continue the Maintenance Phase, and eligibility to enter the Extension Phase.  
ee. 
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. 
ff. 
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.   
gg. 
Height collected at Baseline Day 1 only. 
hh. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
ii. 
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. For participants 
transitioning from ATLAS, the pre-dose Week 48 ECG can also serve as the ATLAS-2M Screening ECG.  ECG pre-dose will be performed in triplicate at 
Day 1.  A 2-hour post-dose ECG will also be performed at Days 1 and Week 48 for participants receiving CAB LA + RPV LA with an allowable window of 
 30 minutes. 
jj. 
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. 
kk. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  The eC-SSRS will preferably 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. 
ll. 
Women of childbearing potential only.  SR=serum, UR=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. Pregnant participants who remain in the study do not need pregnancy testing during the study, for the duration of 
their pregnancy. Pregnant participants remaining in the study have additional assessments required, as described in Appendix 11. 
mm. 
Week 48, Week 96, and Week 152 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. 
nn. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; and urine phosphate.  Urine phosphate 
results from visit 4a are not required by protocol to inform the safety review at visit 4b prior to receipt of initial CAB LA + RPV LA injections. 
oo. 
An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
pp. 
Only collect if the Withdrawal visit occurs at Week 48, Week 96, or Week 152. 
qq. 
Whole blood/PBMC collection samples may be used for virologic analyses.  PBMCs will be collected at baseline Day 1, Week 48, Week 96, Week 152, or 
Withdrawal if prior to Week 152. 
rr. 
Genetics sample should be collected only for patients who did not participate in the 201585(ATLAS) study (sample was previously collected and stored). 
Informed consent for genetic research must be obtained before sample collection.  Sample may be collected at any visit after signing informed consent, but 
preferably at the Day 1 visit. 


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ss. 
One blood sample for CAB and RPV each to be collected at each PK timepoint.  At Day 1, for participant from the ATLAS Q4W arm, PK samples are to be 
collected pre-dose relative to IM administration. injection. At Week 4b, for participants randomized from SOC, Pre dose PK samples are to be collected: 
AFTER review of the PK diary to ensure that the samples are taken 20/28 hours after previous oral dose (diaries to be given at Day 1 or W4a); PRIOR to the 
final oral dose of CAB + RPV; and PRIOR to the first IM injection.  At Week 9 and 41, the PK samples should be collected 3 to 10 days after the Week 8 
and Week 40 visits, respectively. Trough plasma PK samples of CAB and RPV will be obtained for every pregnant woman at every study visit during the 
pregnancy for both Q4W and Q8W regimens. See Appendix 11. 
tt. 
Only for Participants entering CAB + RPV Oral Treatment  
uu. 
Participants switching to CAB LA + RPV LA will take final dose of oral lead-in regimen in the clinic at the Week 4b visit and begin injections.  If possible, 
injections should be spaced approximately 2 cm from one another and from the site of any previous injection and or any injection site reaction.  Bring RPV 
LA to approximately room temperature prior to injecting.  Time and location of injection (right or left) as well as needle length used will be collected in the 
eCRF.  The first injection can be performed as soon as central lab results become available and safety parameters are reviewed.   
vv. 
All Patient Report Questionnaires/Surveys will be administered via paper instrument at the beginning of the visit before any other assessments are conducted 
and prior to administration of the eC-CSSRS (in exceptional circumstances, the questionnaires could be completed via telephonic interview, please refer to 
COVID19 appendix for additional details)  . During the Maintenance phase, conduct questionnaires/surveys (HAT-QoL, HIV TSQs, HIV TSQc, ACCEPT, 
PIN, and Preference) at W48 or upon Withdrawal only if occurring at or prior to Week 48. During the Extension phase, conduct questionnaires/surveys (HIV 
TSQs, ACCEPT, “Preference and Reason for OB” and PIN) at W152 or upon Withdrawal only if occurring at or prior to Week 152 
ww. 
The HIVTSQc is to be administered to all participants transitioning from ATLAS and new participants transitioning from oral SOC. For participants 
transitioning from ATLAS, the version of the HIV-TSQc instrument to be administered will be based on the initial randomization arm at ATLAS Day 1 
xx. 
For patients randomized to oral SOC at Day 1 in ATLAS or new patients on SOC, the reasons for willingness to switch ART will be assessed at Day 1.  For 
patients randomized to CAB LA + RPV LA Q4W in ATLAS, the reasons for willingness to continue long-acting ART in ATLAS-2M will be assessed at 
Day 1. 
yy. 
During Maintenance phase Preference Questionnaire (injection to injection/oral to injection) will be administered to all participants at W48 or upon WD if 
prior to W48. “Preference and Reason for OB” questionnaire at Week 152 or upon WD visit if occurred at or before Week 152, will be administered only to 
participants who received oral bridging during the Maintenance and/or Extension Phases. 
zz. 
Refer to Section 5.5 of the protocol for additional information on performing withdrawal assessments.  HIV-1 RNA will be collected as Storage sample only 
if withdrawal assessments coincide with Week 52 or Week 100 (as per Section 5.5) 
aaa. 
Participants receiving one or more injections with CAB LA and/or RPV LA will be assessed with clinic visits at months 3, 6, 9 and 12 during the Long-Term 
Follow-Up Phase 
bbb. 
After discussion of risk/benefit, a pregnancy specific ICF addendum must be signed by pregnant participants who wish to remain in the study 
Note: BP – Blood pressure, HR – Heart Rate, HDL – High Density Lipoprotein, LDL – Low Density Lipoprotein, PT Prothrombin Time, 
PTT Partial Thromboplastin Time, INR International normalized ratio 
 


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7.2. 
Screening and Critical Baseline Assessments 
Written informed consent must be obtained from each potentially eligible participant by 
study site personnel prior to the initiation of any Screening procedures as outlined in this 
protocol. The consent form must have been approved by the Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC). After signing an informed consent, 
participants will complete Screening assessments to determine participant eligibility. 
Each participant being screened for study enrolment evaluation will be assigned a 
participant number at the Screening visit. This number will be given sequentially in 
chronological order of participant presentation according to a numeric roster provided by 
GSK. 
7.2.1. 
Screening Assessments 
Eligibility criteria must be carefully assessed at the Screening visit. Physical 
examinations should be conducted as part of normal routine clinical care. Background 
information to be collected at Screening includes demography and prior ART history. 
Eligible participants may be randomly assigned immediately as soon as all Screening 
assessments are complete and the results are available and documented. All participants 
will complete the screening period of approximately 14 days prior to Baseline (Day 1) 
during which all clinical and laboratory assessments of eligibility must be performed and 
reviewed. The Screening period may be extended to 35 days to accommodate availability 
of all Screening assessment results, completion of source document verification to satisfy 
the Inclusion and Exclusion Criteria, and scheduling. All Screening results must be 
available prior to randomization.  
All information about the participant’s current regimen must be available for 
review by the Principal Investigator or designee prior to randomization.  Source 
documents from other medical facilities must be located/received during the 14 day 
(up to 35 days) screening period and under no circumstances may the participant be 
randomized in the absence of source documentation even if there are delays in 
receipt of this information. 
Any available prior genotypic resistance testing must be provided to GSK, after screening 
and before randomization according to guidance in the SPM, to provide direct evidence 
of no pre-existing exclusionary resistance mutations. The lack of exclusionary resistance 
mutations must be confirmed by the study virologist, which will be provided before the 
screening window closes. Details on use of RAMOS for tracking historic resistance 
report availability and submission to ViiV Healthcare Virology for evaluation are 
described in the SPM. Details regarding baseline or prior resistance data must be noted in 
the source documentation. 
Participants infected with HBV will not be enrolled in the study.  Evidence of HBV 
infection is based on the results of testing at Screening for hepatitis B surface antigen 
(HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs), 
and HBV DNA.  HBV DNA will only be performed for participants with positive anti-
HBc and negative HBsAg and negative anti-HBs (past and/or current evidence).  


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Participants with an anticipated need for HCV therapy during the study must not be 
enrolled into this study, as HCV therapy currently includes the prohibited medication 
interferon.  The length of this study should be considered when assessing the potential 
need for therapy. 
All participants will be screened for syphilis. Participants with untreated syphilis 
infection, defined as a positive RPR without clear documentation of treatment, are 
excluded.  Participants with a serofast RPR result despite history of adequate therapy and 
no evidence of re-exposure may enrol after consultation with the Medical Monitor. 
Participants with a positive RPR test who have not been treated may be rescreened at 
least 30 days after completion of antibiotic treatment for syphilis. 
The eCSSRS (see Section 7.4.6) assessed at the Screening visit will assess the 
participant’s lifetime risk (any suicidal ideation, behavior, etc. occurring over the 
participant’s lifetime).  A positive alert (indicating some risk) is not necessarily 
exclusionary, rather a means to assess overall risk. 
Participants who meet all entry criteria are randomized and assigned a randomization 
number. A single repeat of a procedure/lab parameter is allowed to determine eligibility 
(unless otherwise specified).  Participants not meeting all inclusion and exclusion criteria 
at initial screen may be rescreened and receive a new participant number one time unless 
they were excluded for reason of having exclusionary historic genotypic resistance.  
Participants who are randomized into the trial and subsequently withdrawn from the 
study for any reason may not be rescreened. 
7.2.2. 
Baseline Assessments 
At Day 1 and prior to randomization, any changes to the eligibility parameters must be 
assessed and any results required prior to randomization (e.g., Day 1 urine pregnancy test 
for women of childbearing potential) must be available and reviewed. The following 
demographic parameters will be captured: year of birth, sex, race and ethnicity. 
Medical/medication/family history will be assessed as related to the inclusion/exclusion 
criteria listed in Section 5.  
HIV-1 genotypic resistance testing and plasma HIV-1 RNA measurement results from 
Screening must be available prior to the Baseline visit. 
Baseline information to be collected at Day 1 includes general medical history and 
current medical conditions. Laboratory and health outcomes assessments will also be 
assessed.  Questionnaire/surveys are recommended to be administered at the beginning of 
the visit before any other assessments are conducted, in the order specified.  For 
participants who agree to the optional assessment, a whole blood sample for genetic 
research should be collected at Day 1 (if not already collected during participation in the 
ATLAS study). 
In addition to a full routine medical history at Baseline, more detailed information will be 
collected for some disease processes such as: 


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• Cardiovascular medical history/risk factors (as detailed in the eCRF) will be 
assessed at Baseline and assessments will include height, weight, blood pressure, 
smoking status and history, pertinent medical conditions (e.g., hypertension, 
diabetes mellitus), and family history of premature cardiovascular disease.  In 
addition, medical history/risk factors for renal disease such as nephropathy, renal 
failure, and nephrolithiasis will be assessed. 
• history of illicit drug use [e.g., cocaine, heroin, and methamphetamine use]); 
• intravenous drug use history; 
• gastrointestinal disease (e.g., GI bleeding, PUD, etc.); 
• metabolic (e.g., Type I or II diabetes mellitus); 
• psychiatric (e.g., depression); 
• renal (e.g., nephrolithiasis, nephropathy, renal failure); and, 
• neurologic disorders 
Procedures conducted as part of the participant’s routine clinical management [e.g., 
laboratory assessments] and obtained prior to signing of informed consent may be 
utilized for Screening or baseline purposes provided the procedure meets the protocol-
defined criteria and has been performed in the timeframe of the study.  Where possible 
local lab results should be confirmed by submission of samples to the central lab.  
7.3. 
Efficacy 
7.3.1. 
Plasma HIV-1 RNA 
Plasma for quantitative HIV-1 RNA will be collected according to the Time and Events 
schedule (Section 7.1).  Methods to be used may include but are not limited to the Abbott 
RealTime HIV-1 Assay lower limit of detection (LLOD) 40 c/mL.  In some cases, (e.g., 
where the HIV-1 RNA is below the lower limit of detection for a given assay) additional 
exploratory methods will be used to further characterize HIV-1 RNA levels. 
7.3.2. 
Lymphocyte Subsets, CD4+ and CD8+ 
Lymphocyte subsets will be collected for assessment by flow cytometry (total 
lymphocyte counts, percentage and absolute CD4+ and CD8+ lymphocyte counts, ratios) 
according to Time and Events schedule (Section 7.1) and Laboratory Assessments 
(Section 7.4.2). 
7.3.3. 
HIV Associated Conditions 
HIV-associated conditions will be recorded as per Time and Events schedule 
(Section 7.1).  HIV-associated conditions will be assessed according to the 2014 CDC 
Revised Classification System for HIV Infection (see Section 11.4).   


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7.4. 
Safety 
7.4.1. 
Clinical Evaluations 
The following clinical evaluations will be performed according to the Time and Events 
schedule: 
• Monitoring and recording of all AEs and SAEs.  Additional information on the 
Time Period and Frequency of Detecting AEs and SAEs is provided in Section 
7.4.3.1. 
• Physical exams should be conducted as part of normal routine clinical care.  
Abnormalities noted during any exam must be recorded in the eCRF (e.g., in the 
current medical conditions or AE logs). 
• Height and weight will be measured and recorded.  Height collected on the Day 1 
(Baseline) only. 
• Vital signs will include systolic and diastolic blood pressure and heart rate 
collected after resting for about 5 minutes.  Temperature will also be collected. 
• Past medical history, family history, social history, medication history.  Targeted 
history on cardiovascular risk (smoking history, family and personal history). 
• HIV-associated conditions will be recorded. 
• Electrocardiogram:  A 12-lead ECG will be performed in a semi-supine position 
after 5 minutes of rest.  On Day 1 (Baseline) of the Maintenance Phase, ECGs 
should be performed in triplicate prior to first dose.  An ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals is preferred, and these calculated numbers can be used for reporting 
purposes.  Otherwise, an appropriately qualified ECG reader must interpret the 
results.  The same interpreter should assess all ECGs for each participant for the 
site.  Regardless, each ECG should be reviewed by a qualified ECG reader.  The 
qualified ECG reader will make the non-calculated ECG interpretations.  The 
same QT correction formula must be used for each individual participant to 
determine eligibility for and discontinuation from the study.  This formula may 
not be changed or substituted once the participant has been enrolled. 
• Regular monitoring of hematology, blood chemistry, 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 
Time and Events Schedule (Section 7.1). 
o Participants who are enrolled in the study and have a positive pregnancy 
test during the course of the study, will be allowed to remain in the study, 


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provided a pregnancy specific ICF addendum is signed by the participant. 
No IP can be continued (oral or LA) in any pregnant participant until the 
benefit/risk assessment is discussed with the participant and the pregnancy 
specific ICF addendum has been signed. See details in Appendix 11. 
o Pregnant participants who remain in the study do not need pregnancy 
testing during the study, for the duration of their pregnancy. 
• 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 
Time and Events Schedule (see Section 7.1 and Suicidal Risk Monitoring Section 
7.4.6). 
Any appropriately qualified site personnel (e.g., Investigator, sub-Investigator, or study 
coordinator/nurse) can perform assessments. 
7.4.2. 
Laboratory Assessments 
All protocol required laboratory assessments, as defined in the Time and Events Schedule 
(see Section 7.1), must be performed by the central laboratory.  Laboratory assessments 
must be conducted in accordance with the Central Laboratory Manual and Protocol Time 
and Events Schedule.  Laboratory requisition forms must be completed and samples must 
be clearly labeled with the participant number, protocol number, site/centre number, and 
visit date.  Details for the preparation and shipment of samples will be provided by the 
central laboratory.  Reference ranges for all safety parameters will be provided to the site 
by the central laboratory. 
• 
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.  


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• 
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 subject 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 11.2 “Division of AIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events”). 
For fasting laboratory assessments, an overnight fast is preferred; however, a minimum of 
a 6 hour fast is acceptable. 
Table 8 includes lab parameters to be assessed as per the Time and Events Schedule (see 
Section 7.1).  In addition to the protocol-specified laboratory assessments the study 
Medical Monitor, in collaboration with the site investigator, may request additional 
central laboratory assessments be performed to support safety profiling and case 
management of individual study participants. 


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Table 8 
Safety Laboratory Assessments 
Hematology 
Platelet count  
Automated WBC differential: 
RBC count 
Neutrophils 
WBC count (absolute)  
Lymphocytes 
Hemoglobin 
Monocytes 
Hematocrit 
Eosinophils 
MCV 
Basophils 
Clinical Chemistry 
BUN 
Potassium 
AST  
Total bilirubina 
Creatinine 
Chloride 
ALT  
Albumin  
Glucosec 
Total CO2 
Alkaline phosphatase 
Creatine phosphokinase 
Sodium 
Lipase 
Phosphate 
Creatinine clearanceb 
Fasting Lipid Paneld 
Total cholesterol 
HDL cholesterol 
LDL cholesterol 
Triglycerides 
Other Tests 
Plasma HIV-1 RNAe 
CD4+ and CD8+ cell counts [CD4/CD8 ratio]f 
Peripheral Blood Mononuclear Cells (PBMCs):  Day 1, Week 48, Week 96, Week 152 Withdrawal only 
Hepatitis B (HBsAg), anti-HBc, anti-HBsAg, and hepatitis C antibody (Screening)g 
Syphilis serology + Reflex Rapid Plasma Reagin (RPR) (Screening and Baseline) 
Prothrombin Time (PT)/International Normalized Ratio (INR)/ Partial Thromboplastin Time (PTT) 
Pregnancy test for women of childbearing potentialh 
Urinalysis, urine albumin/creatinine ratio, and urine protein/creatinine ratio, urine phosphate 
Genetics Sample  
Follicle stimulating hormone (FSH) and estradiol (only for instances when postmenopausal status is questionable) 
MCV = mean corpuscular volume, RBC = red blood cells, WBC = white blood cells, BUN = Blood urea nitrogen, 
AST=aspartate aminotransferase, ALT = alanine aminotransferase, CO2 = carbon dioxide, HDL = high density 
lipoprotein, LDL = low density lipoprotein, HBsAg= hepatitis B virus surface antigen, PT/INR = prothrombin 
time/international normalized ratio. 
a) Direct bilirubin will be reflexively performed for all total bilirubin values >1.5 × ULN. 
b) Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) [Levey, 2009]. 
c) 
For fasting glucose assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments. 
d) For fasting lipids assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable 
for participants with afternoon appointments. 
e) For participants meeting virologic withdrawal criteria, plasma samples will be analyzed in attempt to obtain 
genotype/phenotype data. 
f) 
CD8+ cells will only be reported at Baseline, Day 1, Weeks 4b, 24, 48, 96 and 152. 
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 Time and Events Table (Section 
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7.4.3. 
Adverse Events (AE) and Serious Adverse Events (SAEs) 
The investigator and their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE.  
Please refer to Appendix 10 in Section 11.10 for study management information during 
the COVID-19 pandemic. 
Reporting for medical device deficiencies are covered in Section 11.2 
7.4.3.1. 
Time period and Frequency for collecting AE and SAE information 
• Any SAEs assessed as related to study participation (e.g., protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK 
product will be recorded from the time a participant consents to participate in 
the study up to and including any follow-up contact.  
• All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
• AEs will be collected from the start of Study Treatment until the final follow-
up contact, at the timepoints specified in the Time and Events Table (Section 
7.1). 
• All AEs and SAEs associated with medical device deficiencies for associated 
person (iespouse, caregiver, site staff…) will be collected. The associated 
person will be provided with a safety reporting information and authorization 
letter. 
• Medical occurrences that begin prior to the start of study treatment but after 
obtaining informed consent may be recorded on the Medical History/Current 
Medical Conditions section of the eCRF. 
• The method of recording, evaluating and assessing causality of AEs and SAEs 
plus procedures for completing and transmitting SAE reports to GSK are 
provided in Section 11.6, Appendix 6  
• Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, 
at any time after a participant has been discharged from the study, and he/she 
considers the event reasonably related to the study treatment or study 
participation, the investigator must promptly notify GSK. 
7.4.3.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.  Appropriate questions include: 
• “How are you feeling?”  
• “Have you had any (other) medical problems since your last visit/contact?” 


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• “Have you taken any new medicines, other than those provided in this study, 
since your last visit/contact?” 
7.4.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  All SAEs, and non-serious AEs of special 
interest (as defined in Section 7.4.5) will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the participant is lost to follow-
up (as defined in Section 5.5). Further information on follow-up procedures is given in 
Section 11.6, Appendix 6). 
7.4.3.4. 
Prompt Reporting of Serious Adverse Events and Other Events 
SAEs, pregnancies, and liver function abnormalities meeting pre-defined criteria will be 
reported promptly by the investigator to the medical monitor as described in Table 9 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 9. 
Criteria for liver chemistry stopping and follow-up criteria are in Section 5.5.1. 


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Table 9 
Reporting of Serious Adverse Events and Other Events 
 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Evente 
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 


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Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Evente 
Time Frame 
Documents 
Time Frame 
Documents 
ALT≥5×ULN that 
persists ≥2 weeks  
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
ALT ≥8×ULN  
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
ALT ≥3×ULN (if 
baseline ALT is <ULN) 
or ALT ≥3 fold increase 
from baseline value 
with appearance or 
worsening of symptoms 
of hepatitis or 
hypersensitivity 
24 hoursc 
Liver Event eCRFd 
24 hours  
Updated Liver Event 
eCRFd 
a. 
Additional details and time frames for reporting supplementary information for cardiovascular and death events 
are provided in Section 7.4.3.7 and Section 7.4.3.8, respectively. 
b. 
ABC HSR eCRF only required if event meets one of the ICH E2A definitions of seriousness. 
c. 
GSK must be contacted at onset of liver chemistry elevations to discuss participant safety. 
d. 
Liver event documents (i.e., “Liver Event eCRF” and updates, “Liver Imaging eCRF” and/or “Liver Biopsy eCRF”, 
as applicable) should be completed as soon as possible. 
e. 
Please refer to Section 11.12 (Appendix 12) for additional details around Medical Device Deficiencies reporting 
requirements.  
SAE reporting to GSK via electronic data collection tool 
• Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool. 
• If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the Medical Monitor. 
• Site will enter the serious adverse event data into the electronic system as soon as it 
becomes available. 
• After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) will be taken off-line to prevent the entry of new data or changes to 
existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, the site can report this information on a paper SAE form or to the 
Medical Monitor by telephone. 
• Contacts for SAE receipt can be found  in the Study Reference Manual. 
• The investigator will be required to confirm review of the SAE causality by ticking 
the ‘reviewed’ box at the bottom of the eCRF page within 72 hours of submission of 
the SAE. 
The method of recording, evaluating, and follow-up of AEs and SAEs plus procedures 
for completing and transmitting SAE reports to the medical monitor are provided in the 
SPM.  Procedures for post study AEs/SAEs are provided in the SPM.  Primary and 


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secondary Medical Monitor/SAE contact information is provided in the Study Reference 
Manual . 
7.4.3.5. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
Disease related events (DREs) or outcomes listed in the CDC Classification System for 
HIV-1 Infections (Appendix 4) can be serious/life threatening and will be recorded on the 
HIV-Associated Conditions eCRF page if they occur. However, these individual events 
or outcomes, as well as any sign, symptom, diagnosis, illness, and/or clinical laboratory 
abnormality that can be linked to any of these events or outcomes are not reported to 
GSK as AEs and SAEs even though such event or outcome may meet the definition of an 
AE or SAE.  However, if any of the following conditions applies, then the event must be 
recorded and reported as an AE or SAE (According to severity) ):  
• The investigator determines that the event or outcome qualifies as an SAE 
under part ‘other situations’ of the SAE definition (see Section 11.6.2), or 
• The event is, in the investigator’s opinion, of greater intensity, frequency, 
or duration than expected for the individual participant, or 
• The investigator considers that there is a reasonable possibility that the 
event was related to treatment with the investigational product, or 
• Death occurring for any reason during a study, including death due to a 
disease-related event, will always be reported promptly. 
• Lymphomas and invasive cervical carcinomas are excluded from this 
exemption; they must be reported as SAEs even if they are considered to 
be HIV-related. 
If any of the above conditions is met, then record the 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 7.4.3.4) to GSK. 
7.4.3.6. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to GSK of SAEs related to study treatment (even 
for non- interventional post-marketing studies) is essential so that legal obligations and 
ethical responsibilities towards the safety of participants and the safety of a product under 
clinical investigation are met.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a product under clinical investigation.  GSK 
will comply with country specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC) and investigators. 


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Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
7.4.3.7. 
Cardiovascular and Death Events 
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs:   
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularisation 
This information should be recorded in the specific cardiovascular eCRF within one week 
of when the AE/SAE(s) are first reported.  The CV CRFs are presented as queries in 
response to reporting of certain CV 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. 
  
7.4.3.8. 
Death Events 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
In addition, all deaths will require a specific death data collection tool to be completed.  
The death data collection tool includes questions regarding cardiovascular (including 
sudden cardiac death) and noncardiovascular death. 


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7.4.3.9. 
Medical Device Deficiencies 
Medical devices (vial adaptor -where applicable-, syringe, and needles) are used in this 
study as the study intervention.. To fulfill 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 11.2 
NOTE: Medical device deficiencies associated with an SAE will be reported together 
with an SAE form. AEs associated with a medical device deficiency must be documented 
in the eCRF. 
7.4.3.9.1. 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 a device deficiency is considered reasonably related 
to a medical device provided for the study, the investigator will notify the sponsor within 
24 hours. 
Medical device deficiencies and any associated AE/SAEs for  associated persons (i.e, 
spouse, caregiver, site staff) will be collected. The associated person will be provided 
with safety reporting information and an authorization letter. 
The method of documenting Medical Device Incidents is provided in Section 11.2 
7.4.3.9.2. Follow-up of Medical Device Deficiencies 
Follow-up applies to all participants and associated persons, including those participants 
who discontinue study treatment or the study 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
New or updated information will be recorded on the original completed form with all 
changes signed and dated by the investigator. 
7.4.3.9.3. Prompt Reporting of Medical Device Deficiencies to the Sponsor 
Device deficiencies will be reported to the sponsor within 24 hours after the investigator 
determines that the event meets the protocol definition of a device deficiency. 
The medical device deficiency report form will be sent to the sponsor by email.  
The sponsor will be the contact for the receipt of device deficiency reports. 


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7.4.3.9.4. Regulatory Reporting Requirements for Device Deficiencies 
The investigator will promptly report all device deficiencies occurring with any medical 
device used for CAB+RPV in the study, as described in Section 11.2 in order for the 
sponsor to fulfil the legal responsibility to notify appropriate regulatory authorities and 
other entities about certain safety information relating to medical devices being used in 
clinical studies. 
The investigator, or responsible person according to local requirements (e.g., the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/IEC.  
 
7.4.4. 
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 11.2. 
“Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events”).  Additional information regarding detecting, documenting and reporting AEs 
and SAEs are available in Section 7.4.3 and Section 11.6. 
7.4.4.1. 
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. 


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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. 
7.4.4.2. 
Grade 1 or Grade 2 Toxicity/Adverse Event 
Participants who develop a Grade 1 or Grade 2 AE or toxicity may continue study drug at 
the discretion of the investigator.  Participants who choose to withdraw from the study 
due to a Grade 1 or 2 AE should have study withdrawal and follow-up evaluations 
completed. 
Participants who develop ALT ≥3 times ULN while on study must consult with 
Medical Monitor prior to initiation or continuation of CAB LA + RPV LA 
7.4.4.3. 
Grade 3 Toxicity/Adverse Event 
Participants who develop a Grade 3 AE or toxicity should be managed as follows: 
• 
If the Investigator has compelling evidence that the Grade 3 AE or toxicity has 
not been caused by IP, dosing may continue after discussion with the Medical 
Monitor. 
• 
Participants who develop a Grade 3 AE or toxicity, which the Investigator 
considers related or possibly related to the IP, should have the IP withheld and be 
rechecked each week until the AE returns to Grade 2.  Once the AE is Grade 2, 
IP may be re-started.  
• 
Should the same Grade 3 AE recur within 28 days in the same participant, the IP 
should be permanently discontinued and the participant withdrawn from study.  
• 
Participants experiencing Grade 3 AEs requiring permanent discontinuation of 
IP should be followed weekly until resolution of the AE and to have withdrawal 
study evaluations completed.  A follow-up visit should be performed 2-4 weeks 
after the last dose of IP.  Any participant receiving at least one dose of CAB LA 
and /or RPV LA who discontinue IP / Withdraw will initiate treatment with 
HAART and enter the 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 7.4.5.1).  Isolated Grade 3 lipid abnormalities do 
not require withdrawal of IP. 


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7.4.4.4. 
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 7.4.5.1).  An in-clinic follow-up 
visit will be performed approximately 2-4 weeks after the last dose of study 
medication if AEs, SAEs, or laboratory abnormalities considered potentially 
harmful to the participant are ongoing at the last on-study visit.  Isolated Grade 4 
lipid abnormalities do not require withdrawal of IP. 
7.4.5. 
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 7.4.3.3. 
7.4.5.1. 
Liver Chemistry Stopping and Follow-up Criteria 
Liver chemistry threshold stopping criteria have been designed to assure participant 
safety and to evaluate liver event etiology during administration of study drug and the 
follow-up phase. All Phase 3 participants who meet liver stopping criteria will be 
adjudicated by the ViiV Safety and Labelling Committee (VSLC) – resulting in a case 
summary, adjudication, and management plan.  The VSLC contains an external expert 
hepatologist, familiar with both DILI and cabotegravir, who will participate in this 
review.  This committee meets on a 3-weekly basis, and can be convened on an ad hoc 
basis as needed.  
7.4.5.2. 
Diarrhea 
Participants with Grade 1 or 2 diarrhea may continue study treatment without 
interruption.  Participants with diarrhea of any toxicity grade may be treated 
symptomatically with anti-motility agents; however, the recommended daily dose of the 
chosen anti-motility agent must not be exceeded.  If symptoms persist or get worse on the 


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recommended daily dose of the chosen anti-motility agent then the anti-motility agent 
must be discontinued and consultation made with the Medical Monitor. 
For participants with Grade 3 diarrhea that is unresponsive to the recommended dose of 
the anti-motility agents and for which an alternative etiology (e.g., infectious diarrhea) is 
not established, the treatment with the anti-motility agent and IP must be interrupted until 
resolution of diarrhea to Grade 2 or Baseline, after which IP and background ART may 
be resumed after discussion and agreement with the Medical Monitor.  If Grade 3 
diarrhea recurs within 28 days upon the resumption of IP, the IP should be permanently 
discontinued and the participant withdrawn from the study.  Any participant receiving at 
least one dose of CAB LA and /or RPV LA who discontinue IP / Withdraw will initiate 
treatment with HAART and enter the LTFU Phase for 52 weeks of follow up. 
If loperamide is used for treatment of diarrhea, local prescribing information should be 
followed with respect to dose and frequency of administration.  Loperamide dosing 
should not exceed local prescribing information. 
7.4.5.3. 
Hypertriglyceridemia/ Hypercholesterolemia 
Samples for lipid measurements must be obtained in a fasted state according to the Time 
and Events table (Section 7.1).  Participants who experience asymptomatic triglyceride or 
cholesterol elevations may continue to receive IP.  Clinical management of participants 
with hypertriglyceridemia/hypercholesterolemia should not be based upon non-fasting 
samples (obtained in the fed state).  A confirmatory fasting triglyceride and/or cholesterol 
level should be obtained prior to the institution of medical therapy for hyperlipidemia.  
Isolated Grade 3 and Grade 4 lipid abnormalities do not require withdrawal of IP. 
Please see the Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular 
Disease Focus Group [Dube, 2003] for full discussion of management of hyperlipidemia 
in the context of HIV therapy. 
7.4.5.4. 
Seizures 
A small number of seizure cases have been reported following CAB administration (less 
than 1% of all those receiving CAB in clinical studies).   
. These cases have had alternative explanations for their occurrence. 
ViiV Healthcare has reviewed these cases in detail and does not believe they constitute a 
reasonable likelihood of causation associated with CAB.  This assessment is supported by 
the lack of preclinical signal, class effect or known CNS mechanism, the relatively low 
frequency of seizures relative to expected rates in both healthy and HIV positive 
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 


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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. 
7.4.5.5. 
Creatine Phosphokinase (CPK) Elevation 
A Grade 3 or higher elevation in CPK should result in a repeat assessment within 2-4 
weeks to ensure the result is transient or due to exercise and will not require a change in 
study treatment.  A history regarding use of drugs known to cause increase of CPK (such 
as statins) physical activity or exercise preceding the CPK evaluation should be obtained.  
Grade 4 elevations in CPK should have a repeat assessment after the participant has 
abstained from exercise for >24 hours.  For persistent Grade 4 CPK elevations that are 
considered possibly or probably related to the IP, IP should be discontinued and the 
participant withdrawn from the study.  Any participant receiving at least one dose of 
CAB LA and /or RPV LA who discontinue IP / Withdraw will initiate treatment with 
HAART enter the LTFU Phase for 52 weeks of follow-up. 
7.4.5.6. 
Lipase Elevations and Pancreatitis 
Participants with asymptomatic Grade 1 or 2 elevations in lipase may be followed closely 
for the development of symptoms. 
Participants with asymptomatic Grade ≥3 elevations in lipase that are considered possibly 
or probably related to IP should have IP interrupted until serum lipase returns to 
Grade 2.  The lipase assay should be repeated within 2 weeks of any Grade ≥3 result.  
Participants with persistence of Grade ≥3 lipase in the absence of other diagnoses or 
reoccurrence of lipase elevation (at Grade ≥2) following reintroduction of IP should 
permanently discontinue IP. 
Participants with a confirmed diagnosis of clinical pancreatitis that is considered possibly 
or probably related to IP should have IP held.  After complete resolution of the episode, 
participants may be re-challenged with IP after discussion with the Medical Monitor, 
only if the Investigator has compelling evidence that the event was not caused by IP.  
Upon re-challenge, lipase determinations should be performed every 2 weeks for at least 
6 weeks after re-initiation of treatment.  With any elevation of lipase of Grade ≥2 or any 
recurrence of symptoms, the participant should discontinue IP and be withdrawn from 
study. 
Any participant receiving at least one dose of CAB LA and /or RPV LA who discontinue 
IP / Withdraw will initiate treatment with HAART and enter the LTFU Phase for 52 
weeks of follow up. 


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Drug Restart Following Transient Resolving Liver Events Not Related to Study Drug 
Approval by VSLC for drug restart can be considered where: 
Liver chemistries have a clear underlying cause (e.g., biliary obstruction, hypotension, 
and liver chemistries have improved to normal or are within 1.5 × baseline and 
ALT <3 × ULN). Ethics Committee or IRB approval of drug restart must be obtained, as 
required. 
If restart of drug is approved by VSLC in writing, the participant must be provided with a 
clear description of the possible benefits and risks of drug administration, including the 
possibility of recurrent, more severe liver injury or death. 
The participant must also provide signed informed consent specifically for the restart. 
Documentation of informed consent must be recorded in the study chart. 
Study drug must be administered at the dose specified by VSLC.  
Participants approved by VSLC for restarting study drug must return to the clinic once a 
week for liver chemistry tests for a minimum of one month and thereafter for as long as 
clinically indicated and then laboratory monitoring may resume as per protocol. If 
protocol defined stopping criteria for liver chemistry elevations are met, study drug must 
be stopped. 
Refer to Section 11.2, 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, 2017) Table for Grading the Severity of Adult and 
Pediatric Adverse Events, Version 2.1. [March 2017]. Available from: 
https://rsc.tech-res.com/docs/default-source/safety/daids-ae-grading-table-mar2017.pdf 
Refer to Section 11.3, Appendix 3: Liver Safety – Required actions, Follow up 
Assessments and : Liver Safety – Study Treatment Restart Guidelines for further details. 
7.4.5.7. 
Decline in Renal Function 
Participants who experience an increase in serum creatinine from Baseline of 
45 micromoles/liter (Mol/L) (or 0.5 milligrams/deciliter [mg/dL]) should return for a 
confirmatory assessment within 2 to 4 weeks.  A urinalysis and urine albumin/creatinine 
and urine total protein/albumin ratios should also be done at this confirmatory visit.  If 
the creatinine increase is confirmed, the investigator should contact the study medical 
monitor to discuss additional follow-up and medical management. 
Participants who have a decline in the estimated GFR (using the CKD-EPI method) of 
>50% from Baseline must return for a confirmatory assessment as soon as possible 
[Levey, 2009]. A urinalysis and urine albumin/creatinine and urine protein/creatinine 
ratios should also be done at this confirmatory visit. If the estimated GFR has declined by 
>50% (confirmed), then study drug should be withheld and the investigator should 
contact the study medical monitor to discuss the rationale for restarting study drugs (if 
appropriate).  Consideration for confounding factors (e.g., background therapy, other 


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medications, dehydration, concurrent conditions) should be taken into account, and a 
nephrology consult may be obtained.   
7.4.5.7.1. Proximal Renal Tubule Dysfunctions (PRTD) 
PRTD is defined as: 
Confirmed rise in serum creatinine of ≥0.5 mg/dL from Baseline AND serum phosphate 
<2.0 mg/dL; 
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. 
7.4.5.8. 
Proteinuria 
Participants with an abnormal urine microalbumin/creatinine ratio (>0.3 mg/mg, 
>300 mg/g, or >34 mg/mmol) that represents a change from Baseline and no associated 
increase in creatinine, should have a repeat spot urine microalbumin/creatinine ratio 
performed within 2-4 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.  
7.4.5.9. 
QTc Prolongation 
Participants with an average QTc interval >550 msec from three or more tracings 
separated by at least 5 minutes should have IP discontinued.  These criteria are based on 
an average QTc value of triplicate ECGs.  If an ECG demonstrates a prolonged QT 
interval, obtain 2 more ECGs over a brief period (~5-10 minutes) and use the averaged 
QTc values of the 3 ECGs to determine whether the participant should be discontinued 


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from the study.  If an alternative cause of the QT prolongation is determined (e.g., 
participant receiving drug known to cause prolonged QT or TdP), then IP may be 
restarted after consultation with, and agreement by, the Medical Monitor.  
7.4.5.10. 
Injection Site Reactions (ISRs) 
Injection site reactions will be managed through investigator assessment throughout the 
study.  All ISRs that are either serious, Grade 3 or higher, or persisting beyond 2 weeks 
must be discussed with the Medical Monitor to determine etiology and assess appropriate 
continued study participation.   
Digital photographs may be documented where possible on all participants who have an 
injection site reaction, with observable findings, that is either serious or Grade 3 or 
higher, or that 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. 
7.4.5.11. 
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. 
7.4.5.12. 
Abacavir Hypersensitivity Reaction (ABC HSR) 
The most significant toxicity associated with ABC is the well-characterized drug-related 
hypersensitivity reaction (HSR).  A detailed clinical description of this reaction 
(including the type and severity of events that can occur on re-challenge or reintroduction 
following ABC interruption for non-HSR reasons) and guidance regarding its 
management are included in the Local Country Prescribing Information for 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. 


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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. 
7.4.5.12.1. 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 
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 
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7.4.5.12.2. 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 11.6.2 
then, in addition to reporting the case as an SAE, the ABC HSR eCRF should also be 
completed within one week of the onset of the hypersensitivity reaction.  Clinically 
suspected cases of HSR to ABC that do not meet criteria as an SAE can be recorded as an 
AE. 
7.4.5.13. 
Rash Without ABC HSR Symptoms 
Including serious skin reactions such as Stevens-Johnson Syndrome, Toxic 
Epidermal Necrolysis, Erythema Multiforme or rash with significant liver 
dysfunction.  
Participants should be instructed to contact the Investigator as soon as possible if they 
develop a rash on study. 
Participants who develop rash of any grade should be evaluated for the possibility of an 
ABC HSR or a serious skin reaction such as Stevens - Johnson syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) or Erythema Multiforme.  SJS, TEN, and Erythema 
Multiforme have been reported very rarely in patients taking ABC-containing products.  
These patients generally do not have the cluster of additional symptoms (e.g., 
gastrointestinal and respiratory) that characterize the ABC HSR, but they do have 
features typical of these serious skin reactions. 
If a serious skin reaction develops, ABC (and / or all other concurrent medication(s) 
suspected in the Investigators causality assessment) should be discontinued, and the 
participant should not be re-challenged with any ABC-containing medicinal product (i.e., 
ZIAGEN, TRIZIVIR, EPZICOM, or KIVEXA). 
As many products other than abacavir also cause rash and/or serious skin reactions, all 
other medicinal products that the participant is receiving should also be reviewed and 
discontinued as appropriate. 
The following guidance is provided for clinical management of participants who 
experience rash alone in the absence of accompanying diagnosis of ABC HSR, systemic 
or allergic symptoms or signs of mucosal or target lesions. 
CAB is an analogue of DTG and mild to moderate rash is an expected adverse reaction 
for DTG-containing ART.  Episodes generally occur within the first 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 
CAB IB . 
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 


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moderate (Grade 2).  There were no Grade 4 rashes and none were serious.  Treatment-
related Grade 3 rash was reported in 0.1% of participants in the RPV group.  Treatment-
related rash led to permanent discontinuation in 0.1% of participants in the RPV group.  
No cases of erythema multiforme, SJS or TEN have been reported during clinical 
development of RPV. 
Participants with an isolated Grade 1 rash may continue study drug at the Investigator’s 
discretion.  The participant should be advised to contact the Investigator immediately if 
there is any worsening of the rash, if any systemic signs or symptoms appear, or if 
mucosal involvement develops. 
Participants may continue study drug for an isolated Grade 2 rash.  However, study drug 
(and all other concurrent medication(s) suspected in the Investigators causality 
assessment) should be permanently discontinued for any Grade ≥2 rash that is associated 
with an increase in ALT.  The participant should be advised to contact the physician 
immediately if rash fails to resolve (after more than two weeks), if there is any worsening 
of the rash, if any systemic signs or allergic symptoms develop, or if mucosal 
involvement develops. 
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 11.2, Appendix 2). 
However, if the etiology of the rash has been definitively diagnosed as being unrelated to 
study drug and due to a specific medical event or a concomitant infection or a 
concomitant non-study medication, routine management should be performed and 
documentation of the diagnosis provided.  In this situation, the study drug should be 
continued.  
Participants in the 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 Week 4b 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. 


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7.4.6. 
Suicidal Risk Monitoring 
Participants with HIV infection may occasionally present with symptoms of depression 
and/or suicidal ideation or behavior.  In addition, there have been some reports of 
depression, suicidal ideation and behavior (particularly in participants with a pre-existing 
history of depression or psychiatric illness) in some 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 Time and Events Table 
(Section 7.1).  The eC-SSRS will be conducted electronically by telephone or by 
computer/tablet connected to the internet. 
Additionally, the investigator will collect information using the Possible Suicidality-
Related AE (PSRAE) eCRF form in addition to the Adverse Event (non-serious or 
Serious Adverse Events) eCRF form on any participant that experiences a possible 
suicidality-related adverse event while participating in this study.  This may include, but 
is not limited to, an event that involves suicidal ideation, a preparatory act toward 
imminent suicidal behavior, a suicide attempt, or a completed suicide.  The investigator 
will exercise his or her medical and scientific judgment in deciding whether an event is 
possibly suicide-related.  PSRAE forms should be completed and reported to ViiV/GSK 
within one week of the investigator diagnosing a possible suicidality-related adverse 
event.  All sites should have a plan in place for managing possible risks for suicide 
related events.   
7.4.7. 
Pregnancy 
7.4.7.1. 
Pregnancy testing 
Women of childbearing potential must have a negative pregnancy test at Screening, and 
at Baseline (Day 1).  Pregnancy testing will also be conducted as per the Time and Events 
Table (Section 7.1) and at anytime during the trial when pregnancy is suspected. 


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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 11 for details. 
Pregnant participants who remain in the study do not need pregnancy testing during the 
study, for the duration of their pregnancy. 
Additionally, the Medical Monitor may request that a urine pregnancy test be performed 
in the event of a treatment interruption greater than 7 days. 
7.4.7.2. 
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 11 
The use of CAB + RPV LA during pregnancy may offer unique benefits. It is well 
documented that treatment adherence challenges to oral therapy exists both in the peri-
partum and post-partum periods with LA dosing offering a unique opportunity to 
overcome such adherence challenges. LA therapy may also help with nausea (50 % mild 
to moderate) or hyperemesis (2%) that is frequently seen, 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 cabotegravir and rilpivirine 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. 
7.4.7.3. 
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 pregnancy will 
continue to have all clinical assessments (with the exception of pregnancy test) performed 
as per the Time and Events Table (Section 7.1) ,  including the collection of additional 
PK samples for CAB and RPV. See Appendix 11 for details.  


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Pregnant participants who have received at least one dose of CAB LA or RPV LA and 
decide NOT to continue in the study during pregnancy will enter the  the LTFU Phase of 
the study and will be monitored for 52 weeks after the last LA dose. Moreover, an 
alternative oral HAART will be initiated, at the discretion of the PI and in discussion with 
the Medical Monitor and If a participant becomes pregnant within 52 weeks of the last 
dose of study drug the participant should notify the study site. 
For women who become pregnant while on LA therapy and who consent to continue with 
LA dosing, a descriptive analysis for these women will be obtained and will include but 
not be limited to VLs, CD4 cell count, CAB and RPV plasma concentrations and 
unbound [CAB] concentrations during pregnancy in addition to the first post-partum visit 
after delivery.  
7.4.7.4. 
Action to be Taken if Pregnancy Occurs 
Any pregnancy that occurs during study participation must be reported using a clinical 
trial pregnancy form.  To ensure participant safety, if a pregnancy is reported then the 
investigator should inform GSK within 24 hours of learning of the pregnancy and should 
follow the procedures outlined in Appendix 7. 
Pregnant participants who elect to continue in the study and receive  CAB + RPV LA 
must sign a pregnancy specific ICF addendum. Cabotegravir and rilpivirine are detected 
in systemic circulation for up to 12 months or longer after discontinuing injections of 
CAB + RPV LA; therefore, consideration should be given to the potential for fetal 
exposure during pregnancy and should be discussed between the study participant and the 
study PI. Participants who become pregnant during the study and elect to continue in the 
study and receive CAB+RPV LA, will have additional samples collected (including PK 
samples to monitor cabotegravir and rilpivirine exposure levels throughout the 
pregnancy, see Appendix 11) and at the time of delivery.   
The pregnancy must be followed up to determine outcome (including premature 
termination) and status of mother and child(ren).  Pregnancy complications and elective 
terminations for medical reasons must be reported as an AE or SAE.  Spontaneous 
abortions must be reported as SAEs. 
Any SAE occurring in association with a pregnancy brought to the investigator’s 
attention after the participant has completed the study and considered by the investigator 
as possibly related to the study treatment, must be promptly reported to ViiV/GSK. 
GSK’s central safety department will also forward this information to the Antiretroviral 
Pregnancy Registry.  The international registry is jointly sponsored by manufacturers or 
licensees of ARV products.  Additional information and a list of participating 
manufacturers/licensees are available from http://apregistry.com/index.htm. 
 


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7.4.8. 
Physical Exams 
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 Time and 
Events Table in Section 7.1 above.  
• A brief physical examination will include, at a minimum assessments of the 
skin, lungs, cardiovascular system, and abdomen (liver and spleen). 
• The site of IM injection administration should be assessed at every visit for 
signs of any possible reaction.  See Section 7.4.5.10 for additional information. 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
7.4.9. 
Vital Signs 
Vital signs will be measured in semi-supine position after 5 minutes rest and will include 
temperature, systolic and diastolic blood pressure and pulse rate.  These will be recorded 
as per the Time and Events Table in Section 7.1. 
7.4.10. 
Electrocardiogram (ECG) 
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 and Week 48 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 Time and Events Table for collection timepoints (Section 
7.1).  Refer to Section 5.5.2 for [QTc] withdrawal criteria and additional [QTc] readings 
that may be necessary 
7.5. 
Pharmacokinetics 
Plasma samples for determination of CAB and RPV concentrations will be collected 
throughout the Maintenance and Extension Phases of the study. Additional samples will 
be collected for storage during the LTFU Phase (blood and plasma). Samples (blood and 
plasma) for determination of RPV concentrations will be protected from light at all times, 
from sampling collection through analysis. 
 


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Pregnant participants will have additional PK samples collected during the duration of the 
pregnancy. See Appendix 11 for details. 
7.5.1. 
PK Sample Collection 
Blood samples for evaluation of CAB (2mL each) and RPV (2 mL each) plasma PK 
concentrations will be collected from all participants as described in Table 10.  
 
For participants transitioning from oral SOC, at Week 4b PK samples should be collected 
within the window of 20-28 hours after the last oral dose of CAB + RPV was taken the 
day prior to the clinic visit. Participants will take their final dose of oral CAB + RPV in 
the clinic at Week 4b after the pre-dose PK sample.  
These participants will be expected to complete a PK dosing diary card noting the date 
and time of the last three oral doses of IP prior to the scheduled clinic visits at Week 4b.  
The information from the diary card and the actual date and time of the PK samples will 
be recorded in the eCRF.  Additionally, dosing information on the clinic day, including 
dosing and the actual date and time of the PK samples, must be recorded on the eCRF.   
Plasma concentrations will be summarized and used to evaluate potential exposure-
response relationships. 
The timing of PK samples may be altered and/or PK samples may be obtained at 
additional time points to ensure thorough PK monitoring.   


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Table 10 
CAB and RPV Plasma Pharmacokinetic Sample Schedule 
Group 
Analytes 
Sample Times Relative to Dose 
Participants receiving 
CAB LA + RPV LA 
Q4W injections 
CAB and RPV 
Pre-Dose: Weeks 4b, 8, 16, 24, 32, 40, 48, 96, and 
152  
A PK sample will be taken at Withdrawal. 
PK samples for storage only: 
Pre-dose: Week 12, 20, 28, 36, 44, 52, 56, 60, 64, 
68, 72, 76, 80, 84, 88, 92, 100 
Long-term follow-up Period (off-drug; storage 
sample) 
Months 3, 6, 9, and 12 
Participants receiving 
CAB LA + RPV LA 
Q8W injections 
CAB and RPV 
Pre-Dose: Day 1*, Weeks 4b**, 8, 16, 24, 32, 40, 
48, 96, and 152  
 
1 Week Post Dose:  Week 9 and Week 41 
A PK sample will be taken at Withdrawal 
PK samples for storage only: 
Pre-dose: Weeks 56, 64, 72, 80, 88, 100 
LTFU Period (off-drug; storage sample) 
Months 3, 6, 9, and 12 
* Day 1 sample required only for those transitioning 
from ATLAS on Q4W injections. 
**Week 4b sample required only for participants 
transitioning from oral SOC and requiring oral CAB 
+ RPV Lead-in 
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 Week 4b (for participants transitioning from the 
current ART arm) should be collected 20 to 28 hours after the last oral dose of CAB and 
RPV was taken. 
If a participant withdraws from the study a PK sample should be collected as early as 
practically possible (i.e., at withdrawal visit or on the day the withdrawal decision was 
made).   
Additional details concerning handling of PK samples, labeling and shipping directions 
will be supplied in the central laboratory manual. 


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Samples for determination of RPV will be protected from light until analysed.  
7.5.2. 
Rationale of PK Sampling Strategy 
Blood sampling for CAB and RPV concentrations will be performed during the 
Maintenance Phase of the study to evaluate PK in HIV infected participants.  The 
proposed PK visits and sampling scheme at each visit presented in Section 7.1 is based on 
consideration of available PK data to support interim and final PK and 
PK/Pharmacodynamic (PD) analysis planned in this study. 
7.5.3. 
Sample Analysis 
7.5.3.1. 
CAB Sample Analysis 
Plasma CAB analysis will be performed under the control of PTS-DMPK, 
GlaxoSmithKline, the details of which will be included in the Study Reference Manual 
(SRM).  Concentrations of CAB will be determined in plasma samples using the 
currently approved bioanalytical methodology.  Raw data will be archived at the 
bioanalytical site (detailed in the SRM). 
Once the plasma has been analyzed for CAB any remaining plasma may be analyzed for 
other compound-related metabolites and the results reported under a separate GSK PTS-
DMPK, GSK protocol.  No human DNA analysis will be performed on these samples. 
7.5.3.2. 
RPV Sample Analysis 
Plasma RPV analysis will be performed under the control of Janssen R&D. 
Concentrations of RPV will be determined in plasma samples using the currently 
approved bioanalytical methodology.  Raw data will be archived at the bioanalytical site. 
Once the plasma has been analyzed for RPV any remaining plasma may be used by the 
sponsor for further exploratory work on pharmacokinetics, metabolites, plasma protein 
binding, protein analysis, and biochemistry.  No human DNA analysis will be performed 
on these samples. 
7.6. 
Genetics 
Information regarding genetic research is included in Appendix 5: Genetic Research.  
7.7. 
Viral Genotyping and Phenotyping 
Whole venous blood samples will be obtained from each participant to provide PBMCs 
and plasma for storage samples according to the Time and Events Table (see Section 7.1) 
for potential viral genotypic and phenotypic analyses. 
Details concerning the handling, labeling and shipping of these samples will be supplied 
separately. Genotypic and phenotypic analyses may be carried out by Monogram 
Biosciences using, but not limited to, their Standard PhenoSense and GenoSure testing 
methods for protease (PRO), reverse transcriptase (RT), and integrase assays. 


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7.7.1. 
HIV-1 Polymerase Viral Genotyping and Phenotyping 
Participants meeting confirmed virologic failure will have plasma samples tested for 
HIV-1 PRO and RT genotype and phenotype and HIV-1 integrase genotype and 
phenotype from samples collected at the time of meeting suspected virologic failure; 
these results will be reported to the investigator as soon as available to provide guidance 
for election of an alternative regimen. 
7.7.2. 
HIV-1 Exploratory Analysis 
Additional analyses for HIV-1 resistance may, for example, be carried out on peripheral 
blood mononuclear cell (PBMC) samples collected at Baseline and/or on stored blood 
samples from other relevant time points.  These analyses may include but are not limited 
to additional viral genotyping and/or phenotyping, as well as other virologic evaluations 
such as linkage and minority species analyses, low level HIV-1 RNA quantitation and 
measurement of viral replicative capacity. HIV-1 PRO and RT genotype and phenotype 
and HIV-1 integrase genotype and phenotype will also be determined on the last on-
treatment isolates from participants who have HIV-1 RNA 200 c/mL regardless of 
confirmatory HIV-1 RNA. 
7.8. 
Value Evidence and Outcomes 
Health outcomes assessments will be conducted according to the Time and Events Table 
(Section 7.1).  Assessments are recommended to be administered with a paper instrument 
at the beginning of the visit prior to collection of blood for analysis and other scheduled 
assessments. 
The “Preference” questionnaire will assess whether patients prefer the CAB LA + RPV 
LA injectable treatment or the daily oral ARV regimen, and assess preference for the 
CAB LA + RPV LA Q8W regimen or CAB LA + RPV LA Q4W regimen. The 
“Preference” questionnaire will include 3 questions evaluating preference of HIV 
treatment and the attributes supporting this preference.  
 
The HIV Treatment Satisfaction Questionnaire (HIVTSQ) [Woodcock, 2001 and 
Woodcock, 2006] was developed to evaluate treatments for HIV and patient satisfaction. 
The original HIVTSQ included 10 items and underwent two stages of psychometric 
validation (Woodcock, 2001, Woodcock, 2006). Recently, the HIVTSQ was adapted to 
include injectable treatment for HIV following a qualitative study with HIV patients in 
five European countries.  The adaptation of the HIVTSQ included two additional items 
related to the mode of administration (i.e., long acting intramuscular injection).  These 
are: 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are 
protected by third party copyright laws and therefore have been excluded.


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Psychometric analyses from three datasets (one from the UK, one from the USA and one 
from the LATTE-2 trial) reveal that the addition of two items in the original version of 
the HIVTSQ is suitable and does not reduce the overall validity of the questionnaire.  The 
current study will be using the HIVTSQs (status version) and the revised HIVTSQc 
(change version) of this recently developed HIVTSQ 12-item questionnaire. The 
HIVTSQ 12-item questionnaire retains the option of calculating the total score as if it 
only had the original 10 items (as the original 10 items are included in the HIV-TSQ12). 
In addition, it allows for calculation of an 11-item scale score including the 
“
” item (item-11). The “
” item (item-12) will be included in 
the questionnaire as a stand-alone item to evaluate potentially painful injectables. These 
measures will assess change in treatment satisfaction over time (in the same participants) 
and compare current satisfaction with previous treatment satisfaction, from an earlier 
time point. 
The Perception of Injection (PIN) questionnaire explores the bother of pain at the 
injection site and ISR, anxiety before and after injection, willingness to receive an HIV 
injectable treatment the following visit and satisfaction with the mode of treatment 
administration of individuals receiving injection and perceptions of individuals associated 
with receiving injections.  The PIN questionnaire was derived from the Vaccines' 
Perception of Injection (VAPI) questionnaire (Chevat, 2009), and adapted for HIV-
infected patients who will receive the CAB LA and RPV LA regimen. This measure 
contains 21 items that measure pain at injection site, local site reactions, impact on 
functioning and willingness to pursue injectable treatment outside of a clinical trial.  
Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 
always equated with the most favourable perception of vaccination, and 5 the most 
unfavourable. 
The ACCEPT questionnaire is a generic medication acceptance measure assessing how 
patients weigh advantages and disadvantages of long-term medications (Marant, 2012). 
ACCEPT may be a predictor of patients' future adherence to and/or persistence with their 
treatment. While the ACCEPT questionnaire consists of 25 items that capture six 
dimensions, we will use three questions that focus on general acceptance of study 
medication. 
The HIV/AIDS Targeted Quality of Life (HAT-QoL) instrument [Holmes, 1998] 
originally contained 42 items, grouped into nine dimensions, assessing overall function 
and well-being. For the purposes of this study, ViiV Healthcare is using a shorter version 
adapted from the original version. This shorter version contains 14 items grouped into the 
three following dimensions: “life satisfaction”, “disclosure worries” and “HIV 
medication”. All items use a ‘‘past 4 weeks’’ timeframe and a Likert response scale from 
1=‘‘all of the time’’ to 5=‘‘none of the time’’ 
The “Reason for Switch” question will contain a single item exploring the reasons why 
patients choose to switch study medication. The single item will include six possible 
response options. 
Qualitative interviews with participants and/or health care providers at study sites may be 
conducted regarding their experience with study treatment. These would be conducted 
CCI
CCI


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under a separate IRB approved consent. Participation in the interviews would be 
voluntary. 
7.8.1. 
Value Evidence and Outcomes Endpoints (Secondary) 
• The “Preference” questionnaire will assess preference for CAB LA + RPV LA  
every 8 weeks or CAB LA + RPV LA every 4 weeks compared to oral ARV 
regimen, and preference for CAB LA + RPV LA every 4 weeks compared to 
CAB LA + RPV LA every 8 weeks at Week 48 (or Withdrawal). 
• Change from Week 8 in Dimension scores (e.g., “Bother of ISRs”, “Leg 
movement”, “Sleep”, and “Injection Acceptance”) and individual item scores 
assessing pain during injection, anxiety before and after injection, willingness to 
be injected in the future and overall satisfaction with mode of administration over 
time using the Perception of iNjection questionnaire (PIN) at Weeks 24, 48, and 
Week 152 (or Withdrawal).  
• Proportion of participants considering pain and local reactions following injection 
to be extremely or very acceptable based on the acceptability score over time 
using the Perception of iNjection questionnaire (PIN). 
• Change from Baseline (Day 1) in total “treatment satisfaction” score, and 
individual item scores of the HIVTSQs at Weeks 24, 48 and 152 (or 
Withdrawal). 
• Change in treatment satisfaction over time (using the HIVTSQc) at Week 48 (or 
Withdrawal). 
• Change from Baseline (Day1) in treatment acceptance (at Weeks 24, 48 and 
152(or Withdrawal from the study) using the “General acceptance” dimension of 
the Chronic Treatment Acceptance (ACCEPT) questionnaire. 
• Change from Baseline (Day1) in HR QoL (using the HAT-QoL short form) at 
Weeks 24, and 48, (or Withdrawal). 
7.8.2. 
Value Evidence and Outcomes Endpoints (Exploratory) 
• The “Reason for Switch” question will be administered at Day 1 (Baseline) for 
patients randomized from oral SOC, to assess the reasons for willingness to 
switch ART. 
• The “Reason for Switch” question will be administered at Day 1(Baseline) for 
patients randomized from CAB LA + RPV LA every 4 weeks in ATLAS, to 
assess the reasons for willingness to continue long-acting ART. 
• A preference questionnaire will be administered to participants receiving oral 
bridging during the Maintenance and/or Extension Phases in order to explore 
preference for CAB + RPV LA Q4W or Q8W compared to daily oral HIV 
medication at W152 or upon WD visit if occurred at or before Week 152. 


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7.8.3. 
Guidance for administering the different versions of HIVTSQc, 
Preference and Reason for Switch Questionnaires in ATLAS-2M 
For the questionnaires not included below, HIVTSQs, HAT-QoL, ACCEPT and PIN, 
there only exists one version of each PRO that will be administered to all patients. 
Questionnaire Version 
Week visit 
in ATLAS-
2M 
Treatment 
Arm in 
ATLAS-
2M 
Treatment 
before 
entering 
ATLAS-2M 
Patients in 
Extension 
phase in 
ATLAS 
HIVTSQc 
Q4W 
ATLAS to 
Q4W 
ATLAS-2M 
Week 48 / 
Withdrawal 
Currently 
on Q4W 
Randomized 
at Day 1 in 
Q4W arm in 
ATLAS 
Even if 
patients 
remained in 
extension 
phase in 
ATLAS 
consider only 
the initial 
arm they 
were 
randomized 
in Day 1 in 
ATLAS  
Q4W 
ATLAS to 
Q8W 
ATLAS-2M 
Week 48 / 
Withdrawal 
Currently 
on Q8W 
Randomized 
at Day 1 in 
Q4W arm in 
ATLAS 
SOC to 
Q4W or 
Q8W 
ATLAS-2M 
Week 48 / 
Withdrawal 
Currently 
on Q4W or 
Q8W 
Any SOC 
treatment:  
Randomized 
at Day 1 in 
SOC in 
ATLAS or 
coming 
outside of 
ATLAS 
Preference 
Injection to 
Injection 
treatment 
Week 48 / 
Withdrawal 
Currently 
on Q8W  
Randomized 
at Day1 in 
Q4W arm in 
ATLAS 
Even if 
patients 
remained in 
extension 
phase in 
ATLAS 
consider only 
the initial 
arm they 
were 
randomized 
in Day 1 in 
ATLAS  
 
Oral to 
Injection 
treatment 
Week 48 / 
Withdrawal 
Currently 
on Q4W or 
Q8W 
Any SOC 
treatment:  
Randomized 
at Day 1 in 
SOC in 
ATLAS or 
coming 
outside of 
ATLAS 
Continuing 


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Questionnaire Version 
Week visit 
in ATLAS-
2M 
Treatment 
Arm in 
ATLAS-
2M 
Treatment 
before 
entering 
ATLAS-2M 
Patients in 
Extension 
phase in 
ATLAS 
Q4W from 
ATLAS 
Reason for 
Oral 
Bridging and 
Preference 
questionnaire  
Week 152 / 
Withdrawal  
Currently 
on Q4W or 
Q8W 
SOC and 
Q4W from 
ATLAS 
Not 
applicable. 
Reason for 
Switch 
 
Day 1 
Currently 
on Q4W or 
Q8W 
Any SOC 
treatment:  
Randomized 
at Day 1 in 
SOC in 
ATLAS or 
coming 
outside of 
ATLAS 
Administer 
again even if 
patients were 
administered 
the “reason 
for switch” at 
week 52 in 
ATLAS. 
Reason for 
Continuation  
 
Day 1 
Currently 
on Q4W or 
Q8W 
Randomized 
at Day 1 in 
Q4W arm in 
ATLAS 
 
8. 
DATA MANAGEMENT 
• For this study participant data will be entered into GSK defined eCRFs, 
transmitted electronically to GSK or designee and combined with data provided 
from other sources in a validated data system.   
• Management of clinical data will be performed in accordance with applicable 
GSK standards and data cleaning procedures to ensure the integrity of the data, 
e.g., removing errors and inconsistencies in the data. 
• Adverse events and concomitant medications terms will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) and an internal validated 
medication dictionary, GSKDrug.   
• eCRFs (including queries and audit trails) will be retained by GSK, and copies 
will be sent to the investigator to maintain as the investigator copy.  Participant 
initials will not be collected or transmitted to GSK according to GSK policy. 


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Please refer to Appendix 10 in Section 11.10 for study management information 
during the COVID-19 pandemic. 
9. 
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES 
The study is designed to demonstrate that the antiviral effect of Q8W dosing with CAB 
LA + RPV LA is non-inferior to Q4W dosing CAB LA + RPV LA in subjects stably 
suppressed on an oral SOC regimen or Q4W CAB LA + RPV LA regimen prior to 
randomization.  Non-inferiority in the proportion of participants with HIV-RNA 50 
c/mL at Week 48 (defined by the US FDA snapshot algorithm) can be concluded if the 
upper bound of a two-sided 95% confidence interval for the difference between the two 
treatment arms (Q8W – Q4W) is less than 4%. 
If fQ8W is the snapshot failure rate for Q8W CAB LA + RPV LA, and fQ4W is the snapshot 
failure rate for Q4W CAB LA + RPV LA then the hypotheses can be written as follows: 
H0: fQ8W – fQ4W 4%  vsH1: fQ8W – fQ4W < 4% 
9.1. 
Sample Size Considerations 
This study will randomize approximately 510 participants per arm. Assuming the true 
proportion with HIV-1 RNA 50 c/mL is 3% for the Q8W arm and 2% for the Q4W arm, 
a non-inferiority margin of 4%, and a 2.5% one-sided significance level, this sample size 
would provide at least 85% power to show non-inferiority at Week 48 (using unpooled Z 
test statistic).  With this sample size, 90% power would be achieved assuming a 1% 
treatment difference and true proportions with HIV-1 RNA 50 c/mL of 2.63% for the 
Q8W arm and 1.63% for the Q4W arm. 
With 510 subjects per arm and assuming an observed proportion HIV-RNA 50 c/mL is 
2% for Q4W, the largest observed treatment difference to achieve non-inferiority with 
respect to a 4% margin is 1.92 percentage points.  This equates approximately to 
observing an excess of 10 subjects on the Q8W arm (10 subjects on Q4W vs. 20 subjects 
on Q8W). 
This sample size of 510 participants per arm will also provide at least 90% power (using 
unpooled Z test statistic) to show non-inferiority in the proportion of participants with 
plasma HIV-1 RNA <50 c/mL (per FDA’s snapshot algorithm) at Week 48 over a range 
of true response rates, on the basis of a -10% non-inferiority margin and 2.5% one-sided 
significance level (see Figure 15).  For example, assuming true response rate for the Q8W 
arm and Q4W arm are both 92%, the power is 99% to show non-inferiority for this key 
secondary endpoint. 
9.1.1. 
Rationale for non-inferiority margin 
A non-inferiority margin of 4% has been chosen for this study because a snapshot 
proportion with HIV-1 RNA 50 c/mL at Week 48 in this range is considered clinically 
tolerable given the Q8W regimen will offer important advantages over the Q4W regimen 


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such as reduced injection frequency, and may offer better adherence and treatment 
satisfaction.  This margin is also in concordance with the current FDA Guidance for 
Industry (FDA, 2015), which is the most current regulatory guidance from either the 
European Medicines Agency (EMA) or FDA and includes specific recommendations 
regarding switch studies. 
9.1.2. 
Assumption for Snapshot Proportion with HIV-RNA 50 c/mL at 
Week 48 (Primary Endpoint) 
For the sample size calculation, assumptions regarding the true proportion with HIV 
RNA  50 c/mL for each arm were informed by data from the LATTE-2 Phase 2b study 
(Table 11).  These data suggest a rate of 2% for Q4W and a possibly higher rate in the 
neighbourhood of 3% for Q8W. 
Two important changes to the current study in relation to the LATTE-2 study were also 
considered in setting the sample size. Firstly, the loading dose schedule for Q8W has 
been modified in an attempt to optimize the pharmacokinetics of CAB LA + RPV LA. 
Secondly, a re-testing strategy (see Section 5.5.5.1) has been added to reduce the number 
of subjects counted as having HIV RNA  50 c/mL in the primary analysis at key 
timepoints because of transient blips (consistent with the FDA’s guidance for the 
Snapshot endpoint).  Through these changes, it is possible that the proportions with HIV 
RNA  50 copies/mL will be lower than that observed in the LATTE-2 study. 
Table 11 
Snapshot Analysis Outcomes for LATTE-2 Phase IIb Study of CAB 
LA + RPV LA (Intent-to-Treat Maintenance Exposed Population) 
Week 48 
Study 
Maintenance Treatment Arm 
HIV-RNA <50 
HIV-RNA 50 
LATTE-2 (ITT-ME) a 
CAB LA + RPV LA Q8W (N=115) 
92% 
8/115 (7%) 
 
CAB LA + RPV LA Q4W (N=115) 
91% 
1/115 (<1%) 
 
 Pooled LA (N=230) 
92% 
6/230 (4%) 
 
Oral CAB + 2NRTIs (N=56) 
89%  
1/56 (2%) 
Week 96 
LATTE-2 (ITT-ME) b 
CAB LA + RPV LA Q8W (N=115) 
94% 
5/115 (4%) 
 
CAB LA + RPV LA Q4W (N=115) 
87% 
0/115 (0%) 
 
 Pooled LA (N=230) 
90% 
5/230 (2%) 
 
Oral CAB + 2NRTIs (N=56) 
84%  
5/56 (2%) 
a) Participants had HIV-1 RNA <50 c/mL at Week -4 and received oral CAB 30 mg + 2 NRTIs as initial induction 
period therapy from Week -20 to Day 1. 
b) Participants had HIV-1 RNA <50 c/mL at Week 20 and switched from oral CAB 30 mg + 2 NRTIs to Oral CAB 30 
mg + RPV at Week 24. 
9.1.3. 
Assumption for Response Rate at Week 48 (Secondary Endpoint) 
Given the response rates shown in Table 11, a reasonable assumption for the true 
response rate (HIV-1 RNA <50 c/mL) for both arms is 92%. 
9.1.4. 
Sample Size Sensitivity 
Figure 15a (left panel) shows the sensitivity of the power curve for the primary 
comparison to different assumed ‘true’ proportions with HIV-RNA  50c/mLwith 510 


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randomized participants per arm based on calculations using an unpooled Z test statistic 
and asymptotic approximation.  For example, if the true rate for Q8W is 1.5 percentage 
points higher than Q4W (green line), then the study would still have over 80% power to 
meet its primary objective if the Q4W rate is less than 1.3%.   
Figure 15b (right panel) shows the impact on power to changes in the sample size 
assuming a 2% true-rate for Q4W.  Power remains at least 80% for sample sizes as low as 
425 per arm if the true Q8W rate is at most 1-percentage point inferior to Q4W. 
Figure 15 
Sensitivity of Estimated Power for Snapshot Proportion with HIV-
RNA  50 c/mL 
 
Figure 16a (left panel) shows the sensitivity of the estimated power for the secondary 
endpoint comparison of response rates (HIV-1 RNA <50 c/mL at Week 48) to different 
assumed ‘true’ response rates based on calculations using an unpooled Z test statistic and 
asymptotic approximation.  For example, if the true Q8W rate is two percentage points 
inferior to Q4W (blue line), then power is at least 90% for Q4W rates greater than 82%.   
Figure 16b (right panel) shows the impact on power to changes in the sample size 
assuming an 92% response rate for Q4W.  For example, if the true Q8W rate is 3-
percentage points inferior to Q4W (green line), then power remains at least 90% for 
sample sizes as low as 368 per arm. 


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Figure 16 
Sensitivity of Estimated Power for Snapshot Proportion with HIV-
RNA <50 c/mL 
 
9.1.5. 
Sample Size Re-estimation or Adjustment 
No sample-size re-estimation based on response data is planned for this study. 
9.2. 
Data Analysis Considerations 
9.2.1. 
Analysis Populations 
9.2.1.1. 
Intent-to-Treat Exposed (ITT-E) 
The ITT-E population will consist of all randomly assigned participants who receive at 
least one dose of study drug. Participants will be assessed according to their randomized 
treatment, regardless of the treatment they received.  The population used in the primary 
efficacy analysis will be the ITT-E population. 
9.2.1.2. 
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. 
9.2.1.3. 
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 


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RPV plasma concentration data.  Participants in this population will be included in the 
PK analysis. 
9.2.1.4. 
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. 
9.2.2. 
Treatment Comparisons 
9.2.2.1. 
Primary Comparison of Interest 
The primary analysis will be based on the ITT-E population.  The primary comparison 
will be made at a one-sided 2.5% level of significance.  Treatment with Q8W will be 
declared non-inferior to Q4W if the upper end of a two-sided 95% confidence interval for 
the difference between the two groups (Q8W – Q4W) in the proportion of participants 
with HIV-RNA 50 c/mL at Week 48 (defined by the US FDA snapshot algorithm) lies 
below 4%. 
9.2.2.2. 
Other Comparisons of Interest 
• The analysis described above will also be performed using the PP population and the 
results will be compared for consistency with the results from the ITT-E population.  
If the primary comparison on interest using the ITT-E population demonstrates non-
inferiority of Q8W compared to Q4W then the following key secondary comparisons 
will be tested: Treatment with Q8W will be declared non-inferior to Q4W with 
respect to the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48 
(defined by the US FDA snapshot algorithm) if the lower end of a two-sided 95% 
confidence interval for the difference between in rates (Q8W – Q4W) lies above
 
-10% using the ITT-E population 
• Superiority of Q8W compared to Q4Wwith respect to change from baseline 
HIVTSQs total score at Week 48 using the ITT-E population and a two-sided 5% 
level of significance 
9.2.3. 
Planned Analyses 
At least 4 analyses will be conducted to evaluate the objectives of the protocol after all 
subjects have completed their visits at Week 24, Week 48, Week 96, and Week 152 
respectively.  Further data cuts and analyses may be conducted as necessary in order to 
support regulatory submissions and publications (first publication at Week 48).  The 
Week 48 analysis will be primary and no results will be shared publicly until Week 48 
analysis is complete. Full details for the primary Week 48 analysis (and preliminary 
Week 24 analysis) will be prespecified in the RAP prior to the database freeze for the 
Week 24 analysis and sponsor review of any summary of data grouped by actual 
treatment arm.  


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9.2.3.1. 
Week 24 data analyses 
An analysis of data through Week 24 will be conducted when all subjects have completed 
their Week 24 visit, with the intent of expediting submission of results to health 
authorities. 
The analyses described in Section 9.3.2.2, Section 9.3.3 and Section 9.3.6 will be 
performed. Health outcomes analyses will not be performed. 
There is no intention to stop the study early if positive efficacy findings are seen at Week 
24 and a formal hypothesis test of non-inferiority at Week 24 will not be evaluated. The 
analysis at Week 48 is primary and will overrule the findings based on the Week 24 data.  
Therefore, no multiplicity adjustment to the primary Week 48 treatment comparisons is 
needed because of the analysis of Week 24 data. 
 
Neither investigators nor subjects will be informed of the results of the Week 24 data 
analysis.  Sponsor staff will only review aggregate data by actual treatment arm after the 
Week 24 IDMC evaluation is complete as required in the preparation of submission 
documents. 
 
9.2.3.2. 
IDMC analyses 
Independent review will be provided by an IDMC to ensure external objective medical 
and/or statistical review of efficacy and safety in order to protect the ethical interests and 
well-being of subjects and to protect the scientific validity of this study.  An ad-hoc 
review of data by the IDMC will be triggered whenever the number of confirmed 
virologic failures in the CAB LA + RPV LA Q8W arm exceeds thresholds pre-specified 
in the IDMC charter.  Further, an interim futility analysis will be performed for the 
IDMC to evaluate the efficacy and safety of CAB LA + RPV LA Q8W arm when 
approximately 50% of subjects have completed their visit at Week 24; the sponsor will 
remain blinded to this analysis.  Any additional Week 24 analyses will also be shared 
with the IDMC. Full details of the methods, timing, decision criteria and operating 
characteristics will be pre-specified in the IDMC Charter. 
Since the statistical stopping guidelines will not result in early stopping due to positive 
efficacy findings for the Q8W regimen, these planned analyses will not inflate the type I 
error rate for the primary treatment comparison at Week 48. 
9.3. 
Key Elements of Analysis Plan 
9.3.1. 
Primary Analyses 
For the primary efficacy analysis, virologic outcome for each participant in the Intent-to-
Treat Exposed population will be calculated according to the FDA’s Snapshot algorithm.  
The primary analysis at Week 48 will take place after the last participant has had their 
Week 48 viral load assessed, including a retest if required.  
As defined by the Snapshot algorithm, HIV-RNA  50 copies/mL is determined by the 
last available HIV-1 RNA measurement while the participant is on treatment within the 


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analysis visit window of interest.  In addition, participants without evaluable HIV-RNA 
data for the visit of interest and who discontinue from the maintenance phase for reasons 
not related to adverse event with HIV-1 RNA result at the time of discontinuation  
50 copies/mL or who change study treatment not permitted per protocol before the 
analysis window are classified as having HIV-RNA  50 copies/mL. 
For the primary efficacy analysis, the adjusted difference between the randomized arms 
for the proportion of participants with HIV-1 RNA 50 c/mL at Week 48 (according to 
the FDA snapshot algorithm) and its confidence interval will be calculated according to a 
stratified analysis with Cochran-Mantel Haenszel (CMH) weights.  This analysis will 
adjust for the randomization strata (rederived for analysis to correct for stratification 
errors) according to prior exposure to CAB + RPV (0 weeks, 1-24 weeks, >24 weeks).   
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 proportion 
between the two arms as follows: 
• 
If nk is the number of Q8W treated participants, mk is the number of Q4W arm 
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 
 
kdˆ
 are estimates of the differences in proportions between 
the two treatment arms, fQ8W-fQ4W, for the kth stratum. 
The corresponding two-sided 95% CI will be calculated as: 
 
using the variance estimator given by [Sato, 1989], which is consistent in both sparse data 
and large strata.  The formula for computing the Sato variance estimate will be provided 
in the RAP.  Non-inferiority will be declared if the upper bound of the two-sided 95% 
confidence interval for the difference (Q8W – Q4W) is less than 4%. 
The weighted least squares chi-squared statistic [Fleiss, 1981] will be used to assess 
evidence of treatment difference heterogeneity across strata.  strata, Following Lui and 
Kelly [Lui, 2000], 0.50 will be added to each cell in any strata for which the stratum-


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specific rate estimates of either fQ8W or fQ4W are zero or one.  Any heterogeneity found to 
be statistically significant will be explored.  Stratum-specific analyses will also be 
provided.  Investigation of heterogeneity will be confined to the primary endpoint.  Tests 
of homogeneity will be assessed at the one-sided 10% level of significance.  Full details 
will be contained in the RAP. 
On-treatment data collected from extra visits within a window will be included in the 
derivation of the Snapshot response/failure but summary tables using observed case (OC) 
datasets will only use the data captured closest to the target visit date.  Detailed 
explanations of the derivation of visit windows will be included in the RAP.  Any 
changes to the original analysis plan in the protocol will be described in the RAP and/or 
clinical study report (CSR). 
9.3.2. 
Secondary Analyses 
9.3.2.1. 
Key Secondary Efficacy Analysis 
A key secondary analysis will evaluate the proportion of participants with HIV-1 RNA 
<50 c/mL (according to the FDA’s Snapshot algorithm) at Week 48 for the ITT-E 
population.  Participants with last available HIV-1 RNA measurement less than 
50 copies/mL while the participant is on treatment within the analysis visit window of 
interest are classified as responders; participants without evaluable HIV-RNA data for the 
visit of interest or who change treatment not permitted per protocol before the analysis 
window are considered non-responders. Full details on the Snapshot algorithm for 
computation of the proportion with HIV-1 RNA < 50 copies/mL will be contained in the 
RAP.  The adjusted difference between the randomized arms for the proportions (Q8W – 
Q4W) and its confidence interval will be calculated according to a stratified analysis with 
Cochran-Mantel Haenszel (CMH) weights, as described for primary endpoint (Section 
9.3.1). 
A non-inferiority margin of -10% will be used for this secondary comparison, where if 
the lower limit of the 95% confidence interval (CI) of the difference between the rates 
(Q8W – Q4W) is greater than -10%, non-inferiority will be demonstrated. 
9.3.2.2. 
Other Secondary Endpoint Analyses 
The primary analysis (Section 9.3.1) and key secondary efficacy analysis (Section 
9.3.2.1) will be repeated at Week 96 and Week 152 with the only difference being a 
change in time point from Week 48 to Week 96 or Week 152 for determining the 
snapshot outcomes. 
For the Week 24 planned analyses, the adjusted treatment difference in proportion of 
participants with plasma HIV-1 RNA 50 c/mL (FDA Snapshot algorithm, with 95% 
confidence interval) at Week 24 will be calculated using the methodology described in 
Section 9.3.1, but no formal test of non-inferiority will be performed at this early 
timepoint. 
 


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Proportion of participants with plasma HIV-1 RNA 50 c/mL and HIV-1 RNA <50 c/mL 
(FDA Snapshot algorithm) at Week 24, Week 48,Week 96, and Week 152 respectively, 
will be summarized using the Snapshot algorithm for the ITT-E population.  Proportion 
of participants with confirmed virologic failures will also be summarized over time.  
Absolute values and change from Baseline in CD4+ lymphocyte count will be 
summarized over time including Week 48, Week 96, and Week 152.  
The proportion of participants with HIV-1 RNA 50 c/mL  based on the snapshot 
algorithm, will be summarized at Week 24, Week 48, Week 96, and Week 152 by 
duration of prior CAB + RPV exposure (0 weeks, 1-24 weeks, >24 weeks)., 
The proportion of participants with HIV-1 RNA < 50 c/mL based on snapshot algorithm, 
will be summarized at Week 48,Week 96, and Week 152 by duration of prior CAB + 
RPV exposure (0 weeks, 1-24 weeks, >24 weeks). 
An observed case dataset, with no imputation for missing data, will be the primary 
dataset used for analysis of safety endpoints.  
The proportion of participants reporting AEs will be tabulated for each treatment group. 
The following summaries of AEs will be provided: 
• Incidence and severity of all AEs 
• Incidence and severity of treatment related AEs 
• Incidence and severity of AEs leading to withdrawal 
• Incidence of SAEs 
Changes from baseline in laboratory will be summarized by visit and treatment group 
including Week 48,Week 96, and Week 152.  In addition, the number and percentage of 
participants with graded laboratory toxicities (based on DAIDS categories) will be 
summarized by treatment group.  
Further details for secondary efficacy, safety, and exploratory endpoint analyses will be 
included in the RAP. 
9.3.3. 
Pharmacokinetic Analyses 
The GSK Division of Clinical Pharmacology Modeling and Simulation (CPMS) will be 
responsible for the PK analysis of CAB.  The Division of Clinical Pharmacology 
Development at Janssen Research and Development will be responsible for conduct or 
oversight of the PK analysis for RPV.  
Actual sampling and dosing times as recorded in the eCRF will be used for analysis.   
Plasma CAB and RPV concentration data will be listed and summarized by week, day, 
and planned sampling time in both tabular and graphical forms.  A composite predose 
(C0) concentration may be estimated for purposes of PK/PD analysis.  Post hoc estimates 
of PK parameters will be determined by population PK modeling separately (see 
Population PK Analysis below). 


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9.3.4. 
Population PK Analysis: 
CAB LA and RPV LA population PK models will be constructed separately and 
individual Bayesian PK parameter estimates may be obtained, if the quality of the data 
permits.  Data from this study may be merged with previous data to support the model 
building process.  Sources of variability in pharmacokinetic parameters will be 
investigated during population modeling.  Demographic parameters including, but not 
limited to age, gender, ethnic origin, body size (weight, height, body surface area, body 
mass index), and relevant laboratory parameters will be evaluated as potential predictors 
of inter- and intra-participant variability for pharmacokinetic parameters.  Population 
pharmacokinetic modeling will be performed using the non-linear mixed effects software 
NONMEM (ICON; Hanover, MD).  Further details of population pharmacokinetic 
analyses will be described in a separate RAP.  Population PK analyses will be done under 
separate Population-PK Reporting and Analysis Plans, and post hoc PK parameters may 
be determined. 
9.3.5. 
Pharmacokinetic/Pharmacodynamic Analyses 
Relationships between various plasma CAB LA and/or RPV LA PK parameters and 
pharmacodynamic measures (e.g., HIV-1 RNA, or safety measures) may be explored 
using simple correlation analyses or population-based PK/PD approach.  Additional 
factors that may be considered include; e.g., age, weight, BMI, gender, race, Baseline 
HIV-1 RNA, HIV risk factors, CDC HIV-1 stage, and CD4+ cell count.   
Exploratory analyses will be performed to examine the relationship(s) between plasma 
concentrations of CAB and RPV and pharmacodynamic endpoints.  A population 
pharmacokinetic/pharmacodynamic modeling approach may be further applied to model 
the data using the nonlinear mixed effect modeling software, NONMEM (ICON LLC, 
Hanover, MD).  Details of the PK/PD analyses plans for CAB and / or RPV will be 
provided in separate RAPs. 
9.3.6. 
Viral Genotyping/Phenotyping Analyses 
The incidence of treatment emergent genotypic and phenotypic resistance to NRTIs and 
INIs, PIs, and NNRTIs and in particular to current antiretroviral regimen and to CAB or 
RPV will be summarized by treatment arm for subjects meeting confirmed virologic 
failure criteria.  Limited analyses will be conducted for Week 24 planned analyses. 
Details of the analyses to be performed will be specified in the reporting and analysis 
plan (RAP). 
9.3.7. 
Health Outcomes Analyses 
Details of the analyses to be performed for the endpoints described in Section 7.8 will be 
specified in the reporting and analysis plan.  Participant preference for CAB LA + RPV 
LA every 8 weeks or CAB LA + RPV LA every 4 weeks compared to oral ARV regimen, 
and preference for CAB LA + RPV LA every 4 weeks compared to CAB LA + RPV LA 
every 8 weeks will be a key secondary treatment analysis based on the ITT-E population.  
As another key secondary treatment comparison, superiority of Q8W compared to Q4W 


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with respect to change from baseline in HIVTSQs total score at Week 48 will be tested at 
a two-sided 5% significance level using a linear model based on the ITT-E population. 
9.3.8. 
Genetic Analyses 
See the full protocol for details about the Genetics Analysis Plan. 
9.3.9. 
Other Analyses 
Planned subgroup analyses include: proportion of participants by patient subgroup(s) 
(e.g., by age, gender, BMI, race, HIV-1 subtype, Baseline CD4+, type of oral treatment 
[NNRTI, PI, or INSTI], duration prior CAB LA and RPV LA exposure [0 weeks, 1-24 
weeks, >24 weeks]) with HIV-1 RNA 50 c/mL over time including Week 48,Week 96, 
and Week 152.  
In addition, stratum-specific analyses (unadjusted treatment difference and corresponding 
95% confidence interval) of the primary endpoint (proportion of participants with HIV-1 
RNA 50 c/mL) and key secondary endpoint (proportion of participants with HIV-1 
RNA <50 c/mL) at Week 48 (Week 96, and Week 152) will be performed within each of 
the following patient populations: (Group 1) those currently receiving Standard of Care 
antiretroviral therapy [no prior CAB + RPV exposure] and (Group 2) those receiving 
Q4W CAB LA + RPV LA therapy in the ongoing ATLAS study).  For Group 2, a stratum-
adjusted analysis will also be provided, with adjustment for prior CAB + RPV exposure 
(1 to 24 weeks vs. >24 weeks) using Cochran-Mantel Haenszel (CMH) weights, as 
described in Section 9.3.1. 
Changes from baseline in CD4+ lymphocyte count at Week 48, Week 96, and Week 152 
will also be summarized by subgroups.  Additional details on subgroup analyses will be 
provide in the RAP.   
Further details of exploratory analyses will be presented in the RAP. 
 


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11. 
APPENDICES 
11.1. 
Appendix 1: Abbreviations and Trademarks 
Abbreviations 
3TC 
Lamivudine, EPIVIR 
ABC 
Abacavir, ZIAGEN 
ABC/3TC 
Abacavir/lamivudine, EPZICOM, KIVEXA 
ABC/DTG/3TC 
Abacavir/dolutegravir/lamivudine, TRIUMEQ 
ACCEPT 
General acceptance” dimension of the Chronic Treatment 
Acceptance 
ADE 
Adverse device effect 
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 
Antiretrovral Pregnancy Registry 
ARV 
Antiretroviral 
ART 
Antiretroviral therapy 
ATV 
Atazanavir 
ATLAS 
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 
CD4 
Cluster of Differentiation 4 
CD8 
Cluster of Differentiation 8 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of federal regulation 
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 


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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 
DAIDS 
Division of Acquired Immunodeficiency Syndrome 
DILI 
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 
EQ-5D-5L 
European Quality of Life-5 Dimensions-5 Levels 
ETR 
Etravirine 
EU 
European Union 
EVG 
Elvitegravir 
FDA 
Food and Drug Administration 
FDC 
Fixed-dose combination 
FRP 
Females of Reproductive Potential 
FSH 
Follicle Stimulating hormone  
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 
HCP 
Health Care Provider 
HDL 
High density lipoprotein 
HDPE 
High density polyethylene 
HIV 
Human immunodeficiency virus  
HIV TSQ 
HIV treatment satisfaction questionnaire 
HLA 
Human leukocyte antigen 
HRT 
Hormone Replacment Therapy 
HSR 
Hypersensitivity reaction 
IAS 
International AIDS Society 


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IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
IDFU 
Investigational directions for use 
IDMC 
Independent data monitoring committee 
IEC 
Independent Ethics Committee 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
INH 
Isoniazid 
INI 
Integrase inhibitor 
INR 
International normalized ratio 
INSTI 
Integrase strand transfer inhibitor 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT-E 
Intent-to-treat exposed 
IUD 
Intrauterine device 
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 Defects Program 
MCV 
Mean corpuscular volume 
MedDRA 
Medical dictionary for regulatory activities 
Mg 
Milligram 
Mg/dL 
Milligram 
MSD=F 
Missing, switch, or discontinuation equals failure 
NNRTI 
Non-nucleoside reverse transcriptase inhibitor 
NRS 
Numeric Rating Scale 
NRTI 
Nucleoside reverse transcriptase inhibitor 
NTD 
Neural Tube Defect 
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 
PTCA 
Percutaneous transluminal coronary angioplasty 
QTc 
Corrected QT interval  
Q8W 
Every 8 weeks 
Q4W 
Every 4 weeks 
RAL 
Raltegravir 
RAP 
Reporting and Analysis Plan 


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RBC 
Red blood cell 
RBP 
Retinol Binding Protein 
RNA 
Ribonucleic acid 
RPR 
Rapid plasma reagin 
RPV 
Rilpivirine, Edurant 
RPV LA 
Rilpivirine long-acting 
RT 
Reverse transcriptase 
RTV 
Ritonavir 
SAE 
Serious adverse event 
SJS 
Stevens-Johnson syndrome 
SOC 
Standard of Care 
SPM 
Study Procedures 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 
VAPI 
Vaccines’ Perception of Injection 
VAS 
Visual Analog Scale 
VSLC 
ViiV Safety and Labeling Committee 
WBC 
White blood cell 
Trademark Information 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by ViiV 
Healthcare 
CABENUVA 
 
Edurant 
EPIVIR 
 
Genosure 
EPZICOM/KIVEXA 
 
InForm 
TIVICAY 
 
MedDRA 
TRIUMEQ 
 
Monogram Biosciences  
ZIAGEN 
 
NONMEN 
 
 
PhonoSense 
 
 
RAMOS NG 
 
 
RANDALL NG 
 
 
TRIZIVIR 
 
 
 
 
 
 


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11.2. 
Appendix 2: 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. 
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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11.3. 
Appendix 3: Liver Safety – Required actions, Follow up 
Assessments and Study Treatment Restart Guidelines 
11.3.1. 
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 12; Figure 
17). 
Restarts should be limited to cases in which there is clear evidence that the 
underlying cause of the liver event is not related to study drug. 
DRUG RESTART 
“Drug restart” can be approved by the VSLC for transient, defined non-drug-induced 
liver injury if no evidence of: 
• 
 immunoallergic injury /HLA association with injury 
• 
alcoholic hepatitis 
Study drug must be held while labs and evaluation are completed to assess diagnosis. 
11.3.2. 
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< 5xULN.  
• GSK Medical Monitor and GCSP Physician to review the participant’s diagnosis 
restart risk factors (Hepatotoxicity Panel consultation is available) and complete 
checklist (Table 12). 
– 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:   


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• Safety ReviewTeam Leader, Safety Development Leader, or Senior Safety 
Physician 
• MDL and PPLRequest is taken to VSLC for final decision 
Table 12 
Checklist for Phase III drug restart after well-explained liver injury 
(e.g. biliary, pancreatic, hypotensive events, congestive heart failure 
(CHF), acute viral hepatitis), and improvement of liver chemistry to 
normal or 1.5x baseline & ALT<5xULN 
 
Yes 
No 
Is 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 patients current resistance profile 
 
 
Previous drug history 
 
 
 


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Figure 17 
VSLC process for drug restart approval or disapproval 
 
Participant exhibits transient, non-drug related liver injury while 
disease condition stable or improving 
 
 
 
 
 
 
 
 
Medical Monitor and Safety Physician(s) to discuss etiology of 
liver injury and 
Have liver injuries decreased to normal or to <1.5x Baseline and ALT 
<5xULN 
Any fever, rash, eosinophilia in this 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 
 
11.3.3. 
Medical monitor, GCSP Physician and PI actions for Restart 
following VSLC decision 
11.3.3.1. 
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 (SAEs or fatalities which occur following a drug restartmust 
be immediately reported to Line Management including, VSLC Chair, VP Global 
Medical Strategy and EU Qualified Person for Pharmacovigilance.  


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11.3.3.2. 
PI Actions: 
• 
The PI must obtain Ethics Committee or Institutional Review Board approval of 
drug restart, as required.  
• 
If VSLC approves drug restart, the patient must sign a new informed consent 
containing a clear description of possible benefits and risks of drug administration 
including recurrent, more severe liver injury or possible death. 
• Targeted drug drug restart consent form must be used. 
• 
The patient’s informed consent must be recorded in the study chart, and the drug 
administered at agreed dose, as communicated by Medical Monitor. 
• 
Liver chemistries must be followed once weekly for ‘restart’ cases for a 
minimum of one month and thereafter for as long as clinically indicated following 
drug re-initiation.  If participant exhibits protocol-defined liver chemistry 
elevations, IP should be discontinued as protocol specified. 
• 
Medical Monitor and the Ethics Committee or Institutional Review Board must 
be informed of the patient’s outcome following drug rechallenge or restart. 
Drug Drug Restart Outcomes Table Template 
To be completed/updated and provided to VSLC with each event recorded across 
studies and indications 
Drug Restart Outcomes Table – Update with each event 
Protocol# Participant# Safety outcome* Drug benefit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Restart safety outcomes: 
0 = no liver chemistry elevation 
1 = recurrent liver chemistry elevation not meeting participant stopping criteria 
2 = recurrent liver chemistry elevation meeting participant stopping criteria 
3 = serious adverse event 
4 = fatality 


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11.4. 
Appendix 4: 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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11.5. 
Appendix 5: Genetic Research 
Genetic Research Objectives and Analyses 
The objectives of the genetic research are to investigate a relationship between genetic 
variants and:  
• Response to medicine, including CAB + RPV or any concomitant medicines;  
• HIV-1 susceptibility, severity and progression and related conditions.  
Genetic data may be generated while the study is underway or following completion of 
the study.  Genetic evaluations may include focused candidate gene approaches and/or 
examination of a large number of genetic variants throughout the genome (whole genome 
analyses). Genetic analyses will utilize data collected in the study and will be limited to 
understanding the objectives highlighted above.  Analyses may be performed using data 
from multiple clinical studies to investigate these research objectives. 
Appropriate descriptive and/or statistical analysis methods will be used. A detailed 
description of any planned analyses will be documented in a RAP prior to initiation of the 
analysis. Planned analyses and results of genetic investigations will be reported either as 
part of the clinical RAP and study report, or in a separate genetics RAP and report, as 
appropriate. 
Study Population 
Any participant who is enrolled in the clinical study can participate in genetic research. 
Any participant who has received an allogeneic bone marrow transplant must be excluded 
from genetic research. 
Study Assessments and Procedures 
A key component of successful genetic research is the collection of samples during 
clinical studies. Collection of samples, even when no a priori hypothesis has been 
identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.   
• A 6 mL blood sample will be taken for deoxyribonucleic acid (DNA) extraction.  
A blood sample is collected at the baseline visit, after the participant has been 
randomized and provided informed consent for genetic research. Instructions for 
collection and shipping of the genetic sample are described in the laboratory 
manual. The DNA from the blood sample may undergo quality control analyses to 
confirm the integrity of the sample.  If there are concerns regarding the quality of 
the sample, then the sample may be destroyed.  The blood sample is taken on a 
single occasion unless a duplicate sample is required due to an inability to utilize 
the original sample.  
The genetic sample is labelled (or “coded”) with the same study specific number used 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.  
In the event a participant withdraws from the study and requests destruction of their 
samples then  the site staff must document this in the site study records, complete form F-
GRD-001 and must inform ViiV/GSK via the CRA within 5 days of notification by the 
participant to trigger sample destruction requests.  
Genotype data may be generated during the study or after completion of the study and 
may be analyzed during the study or stored for future analysis.  
• If a participant withdraws consent for genetic research and genotype data has not 
been analyzed, it will not be analyzed or used for future research. 
• Genetic data that has been analyzed at the time of withdrawn consent will 
continue to be stored and used, as appropriate. 
 


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Screen and Baseline Failures 
If a sample for genetic research has been collected and it is determined that the 
participant does not meet the entry criteria for participation in the study, then the 
investigator should instruct the participant that their genetic sample will be destroyed. No 
forms are required to complete this process as it will be completed as part of the consent 
and sample reconciliation process.  In this instance a sample destruction form will not be 
available to include in the site files.  
Provision of Study Results and Confidentiality of Participant’s Genetic Data 
ViiV/GSK may summarize the genetic research results in the CSR, or separately, and 
may publish the results in scientific journals.  
ViiV/GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the 
participant, family members, insurers, or employers of individual genotyping results that 
are not known to be relevant to the participant’s medical care at the time of the 
study, unless required by law. This is due to the fact that the information generated from 
genetic studies is generally preliminary in nature, and therefore the significance and 
scientific validity of the results are undetermined.  Further, data generated in a research 
laboratory may not meet regulatory requirements for inclusion in clinical care.  
 
 


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11.6. 
Appendix 6: Definition of and Procedures for Recording, 
Evaluating, Follow-Up and Reporting of Adverse Events 
11.6.1. 
Definition of Adverse Events 
Adverse Event Definition: 
• An AE is any untoward medical occurrence in a patient or clinical investigation 
participant, temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product. 
 
Events meeting AE definition include: 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECGs, radiological scans, vital signs 
measurements), including those that worsen from baseline, and felt to be clinically 
significant in the medical and scientific judgement of the investigator. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication (overdose per se will not be reported as an 
AE/SAE unless this is an intentional overdose taken with possible suicidal/self-
harming intent.  This should be reported regardless of sequelae). 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE.  However, the signs and symptoms and/or clinical 
sequelae resulting from lack of efficacy will be reported if they fulfil the definition 
of an AE or SAE. 
 


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Events NOT meeting definition of an AE include: 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE. 
• Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
11.6.2. 
Definition of Serious Adverse Events 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease, etc.). 
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose: 
Results in death 
Is life-threatening 
NOTE: 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires hospitalization or prolongation of existing hospitalization 
NOTE: 
• In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or out-patient setting.  Complications that occur during hospitalization are 
AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 


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Results in disability/incapacity 
NOTE: 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g. sprained ankle) which may interfere or prevent everyday 
life functions but do not constitute a substantial disruption 
Is a congenital anomaly/birth defect 
Other situations: 
• Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize 
the participant or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition.  These should also be considered 
serious. 
• Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse 
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. 
 


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11.6.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 
11.6.4. 
Recording of AEs and SAEs 
AEs and SAE Recording: 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
relative to the event. 
• The investigator will then record all relevant information regarding an AE/SAE in 
the eCRF 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK, AE/SAE CRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all participant identifiers, with the exception of 
the participant number, will be blinded on the copies of the medical records prior to 
submission to GSK. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis will be 
documented as the AE/SAE and not the individual signs/symptoms. 
• Participant-completed Value Evidence and Outcomes questionnaires and the 
collection of AE data are independent components of the study. 
• Responses to each question in the Value Evidence and Outcomes questionnaire will 
be treated in accordance with standard scoring and statistical procedures detailed by 
the scale’s developer. 
• The use of a single question from a multidimensional health survey to designate a 
cause-effect relationship to an AE is inappropriate. 


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11.6.5. 
Evaluating AEs and SAEs 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE, SAE and device 
deficiency reported during the study and will assign it to one of the following categories: 
• Mild:  An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities 
• Severe:  An event that prevents normal everyday activities. - an AE that is assessed 
as severe will not be confused with an SAE. Severity is a category utilized for rating 
the intensity of an event; and both AEs and SAEs can be assessed as severe. 
• An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE. 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study treatment and 
the occurrence of each AE/SAE/device deficiency. 
• A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled 
out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the study 
treatment will be considered and investigated. 
• The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in the determination of his/her assessment. 
• For each AE/SAE/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 when an SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK.  However, it is very important 
that the investigator always make an assessment of causality for every event 
prior to the initial transmission of the SAE data to GSK. 
• The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
 
 


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Follow-up of AEs, SAEs and device deficiency 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to 
elucidate as fully as possible the nature and/or causality of the AE, SAE and device 
deficiency. 
• The investigator is obligated to assist.  This may include additional laboratory tests 
or investigations, histopathological examinations or consultation with other health 
care professionals. 
• If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK with a copy of any post-mortem 
findings, including histopathology. 
• New or updated information will be recorded in the originally completed CRF. 
• The investigator will submit any updated SAE data to GSK within the designated 
reporting time frames. 
11.6.6. 
Reporting of SAEs to GSK 
SAE reporting to GSK via electronic data collection tool 
• Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool 
• If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the Medical Monitor. 
• Site will enter the serious adverse event data into the electronic system as soon as it 
becomes available. 
• The investigator will be required to confirm review of the SAE causality by ticking 
the ‘reviewed’ box at the bottom of the eCRF page within 72 hours of submission of 
the SAE. 
• After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) will be taken off-line to prevent the entry of new data or changes to 
existing data 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, the site can report this information on a paper SAE form or to the 
Medical Monitor by telephone. 
• Contacts for SAE receipt can be found in the Study Reference Manual. 


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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 
• Initial notification via the 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 receipt can be found in the Study Reference Manual. 
 


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11.7. 
Appendix 7: Contraceptive Guidance and Collection of 
Pregnancy Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below) 
Women in the following categories are not considered WOCBP 
a. Premenarchal 
b. Premenopausal female with ONE of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s: review of participant’s 
medical records, medical examination, or medical history interview. 
c. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-hormonal highly effective contraception methods if they wish 
to continue their HRT during the study. Otherwise, they must discontinue HRT 
to allow confirmation of postmenopausal status before study enrollment. 
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 13.  
 


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Table 13 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen-containing ) hormonal contraception associated with 
inhibition of ovulation 
• oral 
• intravaginal  
• transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• injectable  
Highly Effective Methods That Are User Independent  
• Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP  and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.)  
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and 
the preferred and usual lifestyle of the participant.)  
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.  
 
Pregnancy Testing 
o WOCBP should only be included after a confirmed menstrual period and a 
negative highly sensitive serum pregnancy test  
o Additional pregnancy testing should be performed as per the study Time and 
Events Table.  
o Pregnancy testing will be performed whenever a menstrual cycle is missed or 
when pregnancy is otherwise suspected  
o Pregnancy testing will be performed and assayed in the central laboratory OR 
using the test kit provided by the central laboratory / provided by the sponsor 


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/approved by the sponsor and in accordance with instructions provided in its 
package insert]   
o If pregnancy is confirmed, please see Appendix 11for details regarding allowing 
pregnant participants to remain in the study 
11.7.1. 
Collection of Pregnancy Information 
• The Investigator will collect pregnancy information on any participant who 
becomes pregnant while participating in this study. See Appendix 11 and 11.11.1 
for information to be collected for participants who become pregnant while 
participating in this study. 
• Participants who become pregnant while in the study may remain in study and 
continue scheduled dosing with CAB + RPV LA, once a pregnancy specific ICF 
addendum is signed by the participant. See Appendix 11 for additional data and 
information regarding the management of participants who remain in the study 
while pregnant. 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 this section.  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. 
 


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11.8. 
Appendix 8: Study governance Considerations 
11.8.1. 
Regulatory and Ethical Considerations, Including the Informed 
Consent Process 
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 
11.8.2. 
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. 
11.8.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorized representative and answer all 
questions regarding the study. 
• 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 
• 
A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative. 
• 
Participants who are rescreened are required to sign a new ICF. 
• 
Participants who become pregnant while in the study and who elect to continue 
to receive CAB + RPV LA injections must sign the pregnancy specific ICF 
addendum. 
• 
If an associated persont experiences a medical device incident with an AE, the 
associated person will be provided with a safety reporting information and 
authorization letter.  
 
The ICF may contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research in accordance with SOP-GSKF-410. The 
investigator or authorized designee will explain to each participant the objectives of the 
exploratory research. Participants will be told that they are free to refuse to participate 
and may withdraw their consent at any time and for any reason during the storage period. 
A separate signature will be required to document a participant's agreement to allow any 
remaining specimens to be used for exploratory research. Participants who decline to 
participate will not provide this separate signature. 
11.8.4. 
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 


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only; participant names or any information which would make the participant 
identifiable will not be transferred. 
• 
The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant. 
• 
The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
11.8.5. 
Independent Data Monitoring Committee 
An IDMC will be utilized in this study to ensure external objective medical and/or 
statistical review of safety and/or efficacy issues in order to protect the ethical and safety 
interests of participants and to protect the scientific validity of the study.  The schedule of 
any planned interim analysis and the analysis plan for IDMC review is described in 
Section 9.2.3 and the IDMC the charter, which is available upon request.. 
11.8.6. 
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 
11.8.7. 
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. 
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  


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• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  Detailed information about study data 
collection and management process including systems used can be found in the 
study Data Management Plan. 
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years from the issue of the final Clinical Study 
Report (CSR)/ equivalent summary unless local regulations or institutional policies 
require a longer retention period. No records may be destroyed during the retention 
period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor 
11.8.8. 
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. 
11.8.9. 
Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
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 
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• Inadequate recruitment of participants by the investigator 
• Discontinuation of further study treatment development 
• If GSK determines such action is needed, GSK will discuss the reasons for 
taking such action with the investigator or the head of the medical institution 
(where applicable).  When feasible, GSK will provide advance notification to 
the investigator or the head of the medical institution, where applicable, of the 
impending action. 
• Upon completion or premature discontinuation of the study, the GSK monitor 
will conduct site closure activities with the investigator or site staff, as 
appropriate, in accordance with applicable regulations including GCP, and 
GSK Standard Operating Procedures. 
• If the study is suspended or prematurely discontinued for safety reasons, GSK 
will promptly inform all investigators, heads of the medical institutions (where 
applicable) and/or institution(s) conducting the study. GSK will also promptly 
inform the relevant regulatory authorities of the suspension or premature 
discontinuation of the study and the reason(s) for the action.   
• If required by applicable regulations, the investigator or the head of the 
medical institution (where applicable) must inform the IRB/IEC promptly and 
provide the reason for the suspension or premature discontinuation. 
11.8.10. 
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, 
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ownership of the records in the event the investigator is no longer associated 
with the site. 
11.8.11. 
Provision of Study Results to Investigators, Posting of 
Information on Publically 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. 
• 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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11.9. 
Appendix 9: Country-Specific Requirements 
11.9.1. 
Study Duration 
In this study, the Extension Phase is intended to provide access to CAB LA + RPV LA 
Q4W or Q8W based on original randomization assignment until the regimen receives 
local (by country) Regulatory approval, and becomes commercially available.  Therefore, 
the duration of the Extension Phase will vary from country to country and is dependent 
on the recruitment time for the study and the time taken to achieve local approval for 
marketing. During this time, participants will be monitored at minimum every 8 weeks to 
ensure they continue to derive clinical benefit from CAB LA + RPV LA. 


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11.10. 
Appendix 10: COVID-19 Pandemic and Clinical Trial 
Continuity 
Background 
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participants ability to attend clinic visits.  In some places, medical 
visits are occurring, and in others, research clinics are operating with only emergency 
staff. 
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in HIV-1 
treatment for participants enrolled in this clinical study, through continuous access to 
antiretroviral therapy. 
In order to maintain the scientific integrity of the study, and adhere to updated guidance 
from regulators, procedures have also been put into place to ensure that the actions taken 
to mitigate against any impact of COVID-19 are well documented in the trial database. 
A “Memo to Investigators” was issued on March 18th, 2020 and served as a record of 
approved emergency actions being taken within this clinical trial to manage issues related 
to COVID-19.  That memo continues to serve as record of approved actions which can be 
fully implemented by Investigators, in advance of this protocol guidance.  This appendix 
will remain consistent with the guidance provided within the “Memo to Investigators” 
and will also serve to provide additional protocol documentation requirements and 
procedures. 
This appendix outlines the measures which are approved for implementation within this 
clinical trial, to protect patient safety and to ensure the integrity of the clinical trial, as a 
result of COVID-19 only. These measures may be implemented in accordance with any 
requirements and expectations set out by local Independent Review Boards/Independent 
Ethics Committees (IRB/IEC) and National Competent Authorities (NCA), as necessary. 
This appendix does not apply to participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19.  
11.10.1. 
Changes to Study Visits and Study Procedures 
• Where site staff resource is constrained due to COVID-19, IM dosing visits may 
proceed with limited or no other protocol-defined assessments (e.g. lab tests, 
questionnaires, etc.). If lab tests will be missed for more than one consecutive 
visit, the medical monitor must be contacted, to provide guidance for safety 
monitoring.  
• For WOCBP, point of care pregnancy testing should be performed, prior to IM 
dosing. 
• If central laboratory testing cannot be performed at a particular visit, and 
monitoring for safety is required, tests may be performed at an appropriately 


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authorised/accredited local laboratory (or other relevant clinical facility), if this 
can be done within local restrictions on physical distancing. The site should 
proactively inform the sponsor about such instances. Local laboratory results may 
be used to inform safety decisions. Results should be retained in source records. 
• When on-site visits are reduced, it is important that the investigator continue 
collecting relevant clinical information, including adverse events, from the 
participant through alternative means, e.g. by telephone contact. 
• There may be cases where the current principal investigator (PI) of a site is 
indisposed for a period and may need to delegate parts of his/her duties 
temporarily, e.g. to a sub-investigator. Any such changes should be documented 
in the site’s source records. Any permanent changes in PI should be 
communicated to the sponsor. 
• There may also be circumstances where immediate actions are required by the 
sponsor and/or investigator, outside of what is contemplated in the protocol, in 
order to protect a study participant from immediate hazard. Any such measures 
will be carefully documented and conducted in accordance with the National 
Competent Authority (NCA)/IRB/IEC regulations. 
 
11.10.2. 
Changes to Informed Consent 
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   
Any updated informed consent form or other subject-facing materials should be provided 
to participants by e-mail, mail or courier before re-consent is obtained. Any consent 
obtained this way should be documented in source records and confirmed by way of 
normal consent procedure at the earliest opportunity when participants attend their next 
on-site study visit. 
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval. 
 
11.10.3. 
Permissible Use of Antiretroviral Therapy 
In order to minimize the risk of gaps in HIV-1 antiretroviral therapy (ART) for 
participants impacted by COVID-19 in the clinical trial, the following options can be 
considered with regards to ART dosing, in order of preference: 


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1. Where possible, and safe to do, please continue to prioritize IM dosing visits in 
order to keep the participants on the protocol-defined regimen 
 
a. Qualified healthcare professionals (HCPs) trained on study procedures can 
administer IM injections outside of the study clinic setting (e.g. home, 
nursing facility, hospital), assuming this can be done safely, without 
compromising investigational product 
preparation/handling/storage/accountability requirements and done in 
accordance with local requirements. Please seek approval by the study 
team on a case-by-case basis. 
 
 
2. If a participant is not able to attend an IM injection visit due to COVID-19 related 
restrictions, the gap in IM dosing should be covered with oral ART, until IM 
dosing can resume. Participants should be reminded of the importance of adhering 
with daily oral dosing. Two options can be approved for oral bridging therapy in 
consultation with the Medical Monitor, listed in order of preference: 
 
a. Oral CAB + RPV  
i. Investigator should request availability of oral CAB + RPV supplies, 
prior to pursuing option b. 
b. Oral standard of care (SOC) commercial ART (prescribed locally) 
 
Oral bridging with CAB + RPV 
The protocol permits oral bridging to cover planned missed injections with oral CAB + 
RPV, only until IM dosing can be resumed.  The start date of oral bridging should be 
within the dosing window for the missed IM dosing visit. This recommendation can be 
used to accommodate requests for oral dosing due to COVID-19. Oral bridging 
recommendations should be followed as per protocol Section 6.8.1. The process and 
required information for requesting oral bridging can be found in your Study Reference 
Manual.  Please continue to reach out to your study medical monitor for approval of oral 
bridging, in order to document use and to ensure expeditious shipment of oral CAB + 
RPV to your site.  
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.  In order to assure that participants have access to SOC ART during short-term 
oral bridging, GSK may allow for reimbursement of SOC ART or copayments as needed. 
Participants who use oral SOC ART as short-term oral bridging as a result of 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. 
11.10.4. 
Direct-To-Patient (DTP) Shipment of Oral Study IP  
If a participant is unable to travel to the clinic, either to receive IM injections or to be 
dispensed oral bridging, sites are encouraged to consider DTP shipments of drug, from 
the site, to the participant, to ensure access to medicines.  
• If the study site is considering DTP shipment of oral CAB + RPV investigational 
product (IP), the site must first verify if DTP IP dispensing by 
investigators/hospital pharmacies is locally permitted and whether it requires 
regulatory and/or local ethics pre-approval, or post-hoc notification. 
• The study participant should express his/her agreement for DTP shipment and the 
sharing of their personal information with any third-party couriers (as applicable), 
in accordance with local requirements.  This agreement should be documented in 
source records. 
• Oral CAB + RPV IP can be shipped at ambient temperatures via ground transport 
without a temperature monitoring device, with low risk of temperature excursions. 
Sites are encouraged to use discretion in determining the need for in-transit 
temperature monitoring based on the labelled storage requirements and the 
planned mode of transport and apply this as appropriate.  Shipment of oral CAB + 
RPV via air courier continues to require appropriate temperature monitoring.  For 
shipment conditions of oral medications other than oral CAB + RPV, please 
consult the product labelling. 
• In all cases IP accountability must be maintained, and all DTP dispensing 
documentation should be reflected in source records and dispensing logs per GCP. 


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• Please refer to your CRA or local study manager for support with the DTP 
process, ensuring reference to current sponsor guidance and arrangement of a 
courier that can support shipment of IMP directly to participants. 
 
11.10.5. 
COVID-19 Experimental Agents 
If any treatments for COVID-19 are planned for a study participant, please consult with 
the study medical monitor to ensure that relevant drug interactions are considered and to 
ensure that continued study participation remains appropriate. 
11.10.6. 
COVID-19 Specific Data Capture 
11.10.6.1. Capturing COVID-19 Specific Protocol Deviations 
In order to summarise the impact of COVID-19 in a systematic way and in line with 
regulatory authorities’ recommendations, any study-level impact around COVID-19 will 
be documented as a protocol deviation. This will include the permissible actions 
summarized in this Appendix, which are taken to protect patient safety, including the use 
of CAB + RPV or SOC ART as oral bridging as well as missed visits and assessments as 
a result of logistical challenges resulting from COVID-19. 
Although the conduct of remote visits and the continuity of antiretroviral therapy, via oral 
bridging, are being utilized to protect patient safety, these events fall outside of the intent 
of the original protocol design, may have an impact on data interpretation, and thus will 
be characterized as protocol deviations for the purposes of data summary and analysis. 
 
Any protocol deviations resulting from COVID-19 will be clearly identified as such 
within the protocol deviation description and summarised separately. 
 
 
11.10.6.2. Capturing COVID-19 Specific AEs and SAEs 
It is important for the study team to describe COVID-19 related adverse events/serious 
adverse events (AEs/SAEs) and their impact on study data and outcomes. Standardization 
of case definitions will facilitate future data analysis.  
Please use the following guidance:  
1. AEs should continue to be evaluated as to whether they meet SAE criteria as 
defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. SAEs and AEs should be submitted following usual 
study procedures and timelines.  
 
2. When an in-person clinic visit is not possible, please conduct a remote telehealth 
visit to assess for, and document any AEs/SAEs. 
3. Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released March 20, 2020, represents a time point for 


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standardized collection. We recognize definitions are likely to continue to 
evolve. When reporting both serious and non- serious adverse events (related 
to COVID-19 infection, investigators should use the following Verbatim 
terms:  
a) Suspected COVID-19 infection; or  
b) Probable COVID-19 infection; or  
c) Confirmed COVID-19 infection  
 
4. Sites should contact the study Medical Monitor for questions related to definitions 
and reporting, and decisions around impact to study drug continuation.  
 
5. A new COVID-19 infection Case Report Form will be added to the eCRF to 
collect additional details about the reported COVID-19 AE or SAE data. It is 
important to collect the correct information from each participant reporting a 
COVID-19 AE or SAE.  Therefore, please use the CRF templates to help you 
collect this information, once available. 
 
WHO Case Definition - March 20, 2020 Version (https://www.who.int/publications-
detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov)):  
Suspected case: 
A. A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or 
residence in a location reporting community transmission of COVID-19 disease 
during the 14 days prior to symptom onset;  
OR  
B. A patient with any acute respiratory illness AND in contact (see definition of 
“contact” below) with a confirmed or probable COVID-19 case (see definition of 
contact) in the last 14 days prior to symptom onset;  
OR  
C. A patient with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation.  
 
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.  
 


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Confirmed case:  
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms.  
Covid-19 Contact: 
A contact is a person who experienced any one of the following exposures during the 2 
days before and the 14 days after the onset of symptoms of a probable or confirmed case:  
1. Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes;  
2. Direct physical contact with a probable or confirmed case;  
3. Direct care for a patient with probable or confirmed COVID-19 disease without 
using proper personal protective equipment; OR  
4. Other situations as indicated by local risk assessments.  
 
Note: For confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken which led to 
confirmation. 
 
 


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11.11. 
Appendix 11: Information and Guidance for Managing 
Pregnant Participants 
11.11.1. 
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 7.4.3.  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. 
11.11.2. 
Introduction 
Pregnancy increases the risk of HIV progression, while HIV increases the risk for 
maternal complications from pregnancy and poses the risk of perinatal HIV transmission 
to the unborn fetus.  Mother to child transmission (MTCT) of HIV can occur during 
pregnancy, labor, delivery or postpartum through breastfeeding.  In the absence of any 
interventions, vertical HIV transmission rates approximate 35%, but fall below 5% with 
effective interventions [WHO, 2010].  In the United States and other developed countries, 
the risk of perinatal infection has decreased from 25% without intervention to less than 
2% with intervention [WHO, 2012].  The HIV-infected mother who breastfeeds her 
infant while taking ARVs herself or giving ARVs to her infant reduces the risk of 
transmission to about 2% after 6 months of breastfeeding, or 4% over 12 months 
[UNAIDS, 2011]. 
The 2013 WHO Guidelines thus recommend (strong recommendation, moderate-quality 
evidence) all pregnant and breastfeeding women with HIV should initiate triple ARVs 


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(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 World Health Organization recommends that they continue 
such therapy if they are responding to the ARV. 
In line with this recommendation, this study will allow those females participating in 
207966 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.  
11.11.3. 
Benefit/Risk Assessment 
Discuss with pregnant participant the benefit-risk of continuing in the study and 
continuing to receive CAB + RPV LA injections, or being withdrawn from study, as a 
result of her pregnancy. All participants who chose to stay in the study during pregnancy, 
and who choose to continue to receive CAB + RPV LA injections will need to sign a 
pregnancy specific ICF addendum. 
There is a pregnancy exposure registry that monitors pregnancy outcomes in women 
exposed to CAB + RPV LA (CABENUVA) during pregnancy. Healthcare providers are 
encouraged to register all pregnant study participants, whether or not they choose to 
remain in the study, by calling the Antiretroviral Pregnancy Registry [Antiretroviral 
Pregnancy Registry (APR) Steering Committee, 2013] at 1-800-258-4263. 
11.11.3.1. 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 


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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 1,000 mg/kg/day 
from 15 days before cohabitation, during cohabitation, and from Gestation Days 0 to 17. 
There were no effects on fetal viability when fetuses were delivered by caesarean 
although a minor decrease in fetal body weight was observed at 1,000 mg/kg/day (greater 
than 30 times the exposure in humans at the RHD). No drug-related fetal toxicities were 
observed at 5 mg/kg/day (approximately 13 times the exposure in humans at the RHD) 
and no drug-related fetal malformations were observed at any dose. 
Cabotegravir was administered orally to pregnant rabbits at 0, 30, 500, or 2,000 
mg/kg/day from Gestation Days 7 to 19. No drug-related fetal toxicities were observed at 
2,000 mg/kg/day (approximately 0.7 times the exposure in humans at the RHD). 
In a rat pre- and postnatal development study, cabotegravir was administered orally to 
pregnant rats at 0, 0.5, 5, or 1,000 mg/kg/day from Gestation Day 6 to Lactation Day 21. 
A delay in the onset of parturition and increases in the number of stillbirths and neonatal 
deaths by Lactation Day 4 were observed at 1,000 mg/kg/day (greater than 30 times the 
exposure in humans at the RHD); there were no alterations to growth and development of 
surviving offspring. In a cross-fostering study, similar incidences of stillbirths and early 
postnatal deaths were observed when rat pups born to cabotegravir-treated mothers were 
nursed from birth by control mothers. There was no effect on neonatal survival of control 
pups nursed from birth by cabotegravir-treated mothers. A lower dose of 5 mg/kg/day (13 
times the exposure at the RHD) was not associated with delayed parturition or neonatal 
mortality in rats. Studies in pregnant rats showed that cabotegravir crosses the placenta 
and can be detected in fetal tissue. 
During the pre-clinical development of CAB, there were no positive genotox findings. 
Embryo-fetal studies also showed no adverse findings including neural tube defects.  In a 
pre and postnatal study, there were some test article-related decreases in F1 pup survival 
(87.4% vs 98.9% in control) in the highest dose (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 neural tube defects (NTDs) 
with exposure to CAB + RPV LA during pregnancy, preliminary findings from an 
unscheduled analysis of a birth outcomes surveillance study conducted in Botswana 
(Tsepamo Study) and presented in May 2018 showed a higher than expected number of 
neural tube defects (NTDs) among newborns whose mothers were exposed to DTG based 


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ART at conception.  DTG is a different molecule in the same integrase class of 
medications as CAB. As of May 2018 four cases of neural tube defects were identified in 
426 infants born to mothers who were exposed to DTG-containing regimens from the 
time of conception. In the same study, no infant born to a woman who started DTG 
during pregnancy had a neural tube defect, out of 2,824 women. Updated analysis of 
interim data from the Tsepamo study became available in 2019 and more recently in 
2020. Subsequently, the study team presented an updated analysis, including data through 
to 30 April 2020, at the 23rd International AIDS Society (IAS) Meeting [Zash, 2020].  
 
The latest data from the Tsepamo study included additional data accrued between 1 April 
2019 (the cut-off for the last formal analysis) and 30 April 2020. Over this 13-month 
period, 39,200 additional births were recorded, including 1908 additional exposures to 
DTG at conception. Two additional NTDs were detected in 1908 (0.10%) deliveries to 
mothers taking DTG at conception, compared with six NTDs in 4569 (0.13%) deliveries 
in mothers taking non-DTG regimens at conception, of which five NTDs in 2999 (0.17%) 
deliveries were to mothers taking efavirenz at conception. The incidence in HIV negative 
mothers over the 13-month period was 17/30,258 (0.06%).  
As of the Tsepamo Apr 2020 analysis, seven cases of neural tube defects were reported in 
3,591 deliveries (0.19%) to mothers taking dolutegravir -containing regimens at the time 
of conception, compared with 21 cases in 19,361 deliveries (0.11%) to mothers taking 
non- dolutegravir containing regimens at the time of conception (Prevalence Difference 
0.09%; 95% CI -0.03, 0.30).  Since first analysis, the estimated prevalence of neural tube 
defects with DTG exposure at conception has decreased in magnitude from 0.94% to 
0.19%. In the same study, no increased risk of neural tube defects was reported in women 
who started dolutegravir during pregnancy. Two out of 4,448 deliveries (0.04%) to 
mothers who started dolutegravir during pregnancy had a neural tube defect, compared 
with five out of 6,748 deliveries (0.07%) to mothers who started non-dolutegravir -
containing regimens during pregnancy. 
 
A causal relationship of these events to the use of DTG has not been established.  
The incidence of neural tube defects in the general population ranges from 0.5-1 case per 
1,000 live births. There are insufficient human data on the use of CAB + RPV LA during 
pregnancy to adequately assess a drug-associated risk of miscarriage or birth defects, 
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11.11.3.2. Rilpivirine 
Animal Data 
Rilpivirine was administered orally to pregnant rats (40, 120, or 400 mg/kg/day) and 
rabbits (5, 10, or 20 mg/kg/day) through organogenesis (on Gestation Days 6 through 17, 
and 6 through 19, respectively). No significant toxicological effects were observed in 
embryo-fetal toxicity studies performed with rilpivirine in rats and rabbits at exposures 
15 (rats) and 70 (rabbits) times the exposure in humans at the RHD. In a pre- and 
postnatal development study, rilpivirine was administered orally up to 400 mg/kg/day 
through lactation. No adverse effects were noted in the offspring at maternal exposures 
up to 63 times the exposure in humans at the RHD 
Human Data 
Based on prospective reports to the APR of over 390 exposures to oral rilpivirine-
containing regimens during the first trimester of pregnancy and over 170 during 
second/third trimester of pregnancy, the prevalence of birth defects in live births was 
1.3% (95% CI: 0.4% to 3.0%) and 1.1% (95% CI: 0.1% to 4.0%) following first and 
second/third trimester exposures. 
Available data from the APR show no difference in the overall risk of birth defects for 
rilpivirine compared with the background rate for major birth defects of 2.7% in a U.S. 
reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) 
In a clinical trial, total oral rilpivirine exposures were generally lower during pregnancy 
compared with the postpartum period. Refer to the current Edurant Prescribing 
Information for additional information on rilpivirine (Edurant Prescribing Information, 
2018). 
11.11.4. 
Clinical Considerations 
11.11.4.1. Exposure 
Lower exposures with oral rilpivirine were observed during pregnancy. Cabotegravir and 
rilpivirine are detected in systemic circulation for up to 12 months or longer after 
discontinuing injections of CAB + RPV LA; therefore, consideration should be given to 
the potential for fetal exposure during pregnancy. 
With the change in volume of distribution associated with pregnancy, drug concentrations 
of CAB and RPV during pregnancy will be assessed in pregnant participants who 
contiune to receive LA therapy while on study. For these participants, plasma PK 
samples of CAB and RPV will be obtained at every study visit for Q8W and Q4W during 
the pregnancy and at the first postpartum LA injection visit. Viral load testing and 
Clinical Chemistry will also be collected at every study visit during the pregnancy and at 
the first postpartum LA injection visit. Additionally, all other scheduled assessments,  
will continue as reflected in as described in the protocol in the Time and Events Table 
(see Section 7.1) 


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Figure 18 
LTFU PK in Female and Pregnant Participants 
(LATTE-2, ATLAS) 
Weeks Post Final Injection
0
12
24
36
48
60
Plasma CAB ( g/mL)
0.01
0.1
1
10
L2 512
A 5911
L2 592
A 5487 (+HCG)
A 5485 (-HCG)
A 7224 (-HCG)
A 6595 (-HCG)
 
 


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11.11.4.2. Use of Supplements with CAB + RPV LA 
During pregnancy, additional supplements including vitamins, minerals and other 
mediations including OTC meds may be prescribed to the pregnant woman. It is 
important for all female participants who remain in the study to be aware of any potential 
DDIs that may occur with study medications and other agents used during pregnancy. 
11.11.4.2.1. 
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. 
11.11.4.3. Overall Benefit: Risk Conclusion  
All medications have AE profiles that must be assessed prior to use, allowing for an 
appropriate risk/benefit assessment.  Additional considerations when using CAB + RPV 
LA can be found in the protocol in Section 2.3. 
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 
Metropolitan Atlanta Congenital Defects Program (MACDP). 
Refer to Section 11.11.3 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, while the 207966 protocol still mandates effective contraception for all 
WOCP, if a woman does become pregnant while on study, a benefit/risk assessment 
between the treating physician and the study participant regarding whether to continue on 
study will be undertaken. Allowing women who become pregnant to stay on study will 
abrogate the need to add additional ART agents to maintain VL suppression if such a 
woman was to be withdrawn from study and LA dosing. 
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 


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withdrawal, pregnant participants will be allowed to remain in the study and continue to 
receive CAB + RPV LA injections, once the new pregnancy ICF addendum is signed by 
the participant.  
11.11.5. 
Study Assessments and Procedures: specific assessments for 
pregnant participants 
Participants who become pregnant while in the study, and who sign the informed consent 
pregnancy addendum may remain in the study and continue to receive CAB + RPV LA.  
Please note: The HIV provider is responsible for HIV care and will collaborate and share 
information with the subject’s obstetric care provider, discuss the subject’s participation 
in this study, the necessary procedures at delivery, to share HIV information, and to 
collect birth and infant outcomes from the subject’s obstetric care provider and/or the 
pediatric health provider for the infant. 
Because obstetric and/or pediatric care will not be specifically provided via this study, the 
subject must also establish appropriate obstetric and pediatric care (including prenatal 
care) per local standard of care (SoC) in parallel.  It will be necessary for the subject to 
provide a release of medical information to facilitate collection of pregnancy and 
pregnancy outcomes by the investigator 
In addition to the asssessments mentioned in this appendix, the rest of the study 
assessments will be conducted in accordance with the protocol, as described in the 
protocol in the Time and Events Table (see Section 7.1) 
11.11.5.1. Safety Assessments 
All pregnant participants who elect to remain in the study will have the following 
samples obtained at each LA injection visit throughout the pregnancy and at the first 
postpartum LA injection visit.  
• HIV-1 RNA 
• Clinical Chemistry 
Pregnancy related complications and diagnoses, and outcomes will be captured as AEs 
and SAEs as outlined in the protocol in section 7.4.3. 
Pregnancy complications (e.g., preeclampsia or eclampsia, prolonged hospitalization after 
delivery, for wound infections etc, seizures) and elective terminations for medical reasons 
must be reported as an AE or SAE.  Spontaneous abortions must be reported as an SAE. 
In the event of a pregnancy loss, after the loss is confirmed the subject may continue to 
receive CAB + RPV LA unless they meet the criteria for confirmed virologic withdrawal.  
They may continue to CAB + RPV LA until study medications are locally approved and 
commercially available or until they no longer receive benefit.  In this case the subject 
must agree to use contraception to avoid a ‘new’ pregnancy (See Appendix 7). 


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Any SAE occurring in association with the pregnancy brought to the investigator’s 
attention after the subject has completed the study and considered by the investigator as 
possibly related to the study treatment, must be promptly reported to GSK 
11.11.5.2. Pharmacokinetics 
Refer to section 7.5 in the protocol 
All pregnant participants who elect to remain in the study will have the following PK 
samples obtained at each LA injection visit throughout the pregnancy and at the first 
postpartum LA injection visit: 
• Blood samples for evaluation of total CAB (2mL each) and total RPV (2mL 
each) plasma concentrations.  
• Blood sample for evaluation of unbound CAB (9mL each) plasma PK 
concentration. 
. All PK samples will be trough levels and will be collected prior to the scheduled LA 
injection. The pre-dose trough PK sample is to be collected within 15 minutes prior to the 
LA dose, on the day of the study visit.  
For participants pregnant during the Long Term Follow Up phase, plasma concentrations 
of cabotegravir and rilpivirine will be collected as per Section 7.1 Time and Events table. 
Please refer to the SPM for PK sample collection, processing, and shipping instructions. 
The actual date and time of each PK sample collection will be recorded in the eCRF. 
11.11.6. 
References 
Antiretroviral Pregnancy Registry (APR) Steering Committee. Antiretroviral Pregnancy 
Registry International Interim Report for 1 January 1989 through 31 January 2013. 
Wilmington, NC: Registry Coordinating Center; 2013. Available from URL: 
www.APRegistry.com. 
Edurant Prescribing Information, February 2018 
UNAIDS (2011) Reference Group on Estimates, Modelling and Projections. Working 
Paper on Mother-to-Child HIV Transmission Rates for use in Spectrum, 6 June 2011. 
Available online at http://www.epidem.org/Publications/MTCTratesworkingpaper.pdf. 
World Health Organization (WHO) (2010). Antiretroviral drugs for treating pregnant 
women and preventing HIV infection in infants: Recommendations for a public health 
approach.  Available online at: 
http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf, accessed 6 Feb 
2013. 
World Health Organization (WHO) (2012). Antiretroviral Treatment as Prevention 
(TasP) of HIV and TB:  2012 Update.  June 2012, Available online at: 
http://www.who.int/hiv/pub/mtct/programmatic_update_tasp/en/index.html 


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World Health Organization (WHO) (2013). Consolidated Guidelines on the Use of 
Antiretroviral Drugs for Treating and Preventing HIV Infection. 30 June 2013.  Available 
online at: http://www.who.int/hiv/pub/guidelines/arv2013/download/en/index.html 
Zash R, Holmes L, Diseko M, Jacobson D, Mayondi G. Update on neural tube defects 
with antiretroviral exposure in the Tsepamo study, Botswana. JAIDS 2020. 
 


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11.12. 
Appendix 12: 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, and the US Food and Drug Administration (FDA) combination product 
reporting rule, 21 CFR 4, Subpart B. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements for medical devices. 
The detection and documentation procedures described in this protocol apply to all 
medical devices used in the study (see Section 6.14 for the list of medical devices). 
11.12.1. 
Definition of Device Deficiency 
Device Deficiency Definition 
• 
A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors, and inadequacy of the information supplied by 
the manufacturer. 
11.12.2. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies 
AE, SAE and Device Deficiency Recording 
• 
When adevice deficiency occurs, with or without an associated AE/SAE, it is the 
responsibility of the investigator to review all applicable documentation (e.g., 
hospital progress notes, laboratory reports, and diagnostics reports) related to the 
event. 
• 
The investigator will then record all relevant device deficiency information on the 
appropriate form. If applicable, any associated AE or SAE will be documented in 
the participant’s medical records, in accordance with the investigator’s standard 
clinical practice.There may be instances when copies of medical records for 
certain cases are requested by the sponsor. In this case, all participant identifiers, 
with the exception of the participant number, will be redacted on the copies of the 
medical records before submission to the sponsor. 
• 
The investigator will attempt to fully describe the device deficiency and provide 
details on any treatment provided.  
• 
For device deficiencies, it is very important that the investigator describe any 
corrective or remedial actions taken to prevent the deficiency’s recurrence. 
o A remedial action is any action other than routine maintenance or servicing of 
a medical device where such action is necessary to prevent the recurrence of a 
device deficiency. This includes any amendment to the device design to 


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prevent recurrence. 
Assessment of Intensity of associated AE/SAEs 
• If an AE or SAE is associated with a device deficiency, the investigator will make an 
assessment of intensity for each AE or SAE as outlined in Section 7.4.3 
Follow-up of device deficiency 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature of the device deficiency and any associated AE or 
SAE as fully as possible 
• 
New or updated information regarding the device deficiency will be recorded in the 
originally completed medical device deficiency report form. 
• 
If there is an associated SAE with the device deficiency, the investigator will submit 
any updated SAE data to GSK within 24 hours of receipt of the information. 
11.12.3. 
Reporting of Medical Device Deficiencies for participants 
Reporting to GSK  
• 
NOTE: There are additional reporting obligations for medical device deficiencies 
that are potentially related to SAEs that must fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.  
• 
Medical device deficiencies that are not related to an AE or SAE should be reported 
via email to gsk-rd.complaints@gsk.com, using the medical device deficiency report 
form.  
• 
If the medical device deficiency is related to a non-serious AE and not linked to an 
SAE, please send the medical device deficiency report form via email to gsk-
rd.complaints@gsk.com only. The eCRF for the subject should also be updated with 
AE information, as outlined in Section 7.4.3 
• 
If the device incident is linked to an SAE, please email the medical device deficiency 
report form, within 24 hours, to both uk.gsk-rd-gcsp-ctsm-admin@gsk.com (or fax 
+44(0)20 8754 7822) and gsk-rd.complaints@gsk.com. The SAE form should also 
be reported, as outlined in Section 7.4.3. The eCRF for the subject should also be 
updated with the SAE information. 
• 
GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported to 
the regulatory authorities and IRBs/IECs as required by national regulations. 
• 
Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 


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11.12.4. 
Reporting of Medical Device Deficiencies for Associated Person  
Reporting to GSK  
If an Associated Person (i.e. spouse, caregiver, site staff…) experiences a device 
deficiency, the medical device deficiency information and any associated AE/SAE 
information will be reported to GSK. The associated person will be provided with 
the safety reporting information and authorization to contact physician letter.   
If follow up is required, authorization to contact physician (or other licensed medical 
practitioner) must be signed to obtain consent.  
• 
Medical device deficiencies that are not related to an AE or SAE should be reported 
via email to gsk-rd.complaints@gsk.com, using the medical device deficiency report 
form.  
• 
If the medical device deficiency is related to a non-serious AE and not linked to an 
SAE, please send the medical device deficiency report form with details of the 
associated AE via email to gsk-rd.complaints@gsk.com only. 
• 
If the device incident is linked to an SAE, please email the medical device deficiency 
report form, within 24 hours, to both uk.gsk-rd-gcsp-ctsm-admin@gsk.com (or fax 
+44(0)20 8754 7822) and gsk-rd.complaints@gsk.com. The associated SAE form 
should also be reported to uk.gsk-rd-gcsp-ctsm-admin@gsk.com (or fax +44(0)20 
8754 7822). 
• 
GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported to 
the regulatory authorities and IRBs/IECs as required by national regulations. 
• 
Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 
 


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11.13. 
Appendix 13: Vastus Lateralis Muscle (Thigh) PK sub-study 
Amendment 
TITLE PAGE  
Parent Study Protocol Title: A Phase IIIb, Randomized, Multicenter, Parallel-group, 
Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of 
Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or 
Every 4 Weeks in HIV-1-infected Adults who are Virologically Suppressed (ATLAS-
2M), further referred to as A2M. 
 
Sub-study Protocol Amendment Title: Sub-sudy to the A2M study to Evaluate the 
Pharmacokinetics, Tolerability and Efficacy of Cabotegravir and Rilpivirine Long-Acting 
Injections Following Intramuscular Administration in the Vastus Lateralis Muscle (thigh) 
in HIV-infected Adult Participants who have Received at Least Three Years of Gluteal 
Injections in the A2M Study. 
 
11.13.1. 
Sub-study Amendment Background 
Cabotegravir/rilpivirine (CAB/RPV) long acting (LA) has been approved for the 
treatment of HIV-1 infection as a complete regimen in adults to replace the current 
antiretroviral regimen in many geographical regions of the world including the United 
States, Canada, Europe and Australia with additional countries approaching regulatory 
approval. CAB/RPV LA is administered via gluteal injections for monthly or every two 
months dosing for clinic-based administration by a Health Care Provider (HCP).  As 
more patients are experiencing this new treatment paradigm, it is becoming apparent that 
HIV stigma and issues surrounding HIV disclosure, while improved, have not totally 
been eradicated.  As more HIV infected individuals opt for LA therapy to control their 
HIV infection, many patient groups and other activist communities are requesting 
continued research and development in alternative injection sites. These measures may 
improve overall treatment compliance for patients with difficulty adhering to monthly or 
every other month office visits and may improve any residual stigma that patients may 
still be experiencing during their engagement with various healthcare systems. 
 
An ongoing Phase 1, healthy volunteer open-label study (208832) is evaluating the 
pharmacokinetics (PK) and tolerability of cabotegravir and rilpivirine long-acting 
injections following intramuscular administration in the vastus lateralis muscle (further 
referred to as thigh) in 15 study participants (n= 9 male, n=6 female; BMI (kg/m2)  
median 30.3). All subjects received a 4-week oral lead in (OLI) with daily cabotegravir 
30 mg and rilpivirine 25 mg, and after a two week wash out, 14 participants received 
single 600 mg CAB LA and 900 mg RPV LA injections. One participant was withdrawn 
after the OLI phase and before injection due to confirmed pregnancy. 
 
PK sampling for measurement of plasma CAB and RPV in this on-going Phase 1 study 
was performed at the following timepoints: D1, 2, 4, 5, 7, 8, 10, 15, 17 , 22, 28 (week 4) 
post injection with longer term PK evaluations also obtained at weeks 8, 12, 24, 36, and 
52 post the single CAB/RPV injections. Safety and tolerability data through week 12 


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demonstrated good overall tolerability with all 14 subjects receiving injections 
experiencing ISRs of limited duration (mostly pain at the injection site with a few 
subjects experiencing erythema and induration at the injection site). Of the 14 ISRs, 13 
were judged by the investigator as mild and one considered moderate (pain and erythema 
at the injection site). Additionally, one subject with mild ISR of pain also had bilateral 
hip pain after injection and a mild elevation of AST (84 UL/L) and ALT (74 UL/L). This 
subject had a confirmed diagnosis of COVID-19 infection raising the possibility that the 
constellation of signs and symptoms may be secondary to infection with SARS-COV-2. 
Overall, laboratory abnormalities were minimal with mild and transient ALT elevations 
noted for some subjects. All ALT elevations returned to baseline levels during the study 
except for one subject who continued with fluctuating ALT elevations, with the highest 
value reported for ALT of  97 UL/L and for AST of 106 UL/L.  
 
PK data through 12 weeks post injections was evaluated and considered supportive of 
further studies of thigh administration in HIV-infected individuals. When compared to 
the simulated CAB plasma concentrations following gluteal administration of CAB LA 
600 mg (accounting for covariates), observed CAB plasma concentrations following 
600 mg of CAB LA to the lateral thigh were slightly higher than the predicted at 1-week 
(~Cmax) and 4-weeks post injection but similar to the predicted at 8-weeks post 
injection. These differences may have resulted from slightly faster absorption via thigh 
administration than gluteal administration for CAB LA. RPV plasma concentrations 
following 900 mg of RPV to the lateral thigh were consistent with predictions following 
RPV gluteal administration. 
 
 
Figure 19 
Preliminary CAB Concentrations following a Single 600 mg IM 
injection to the lateral thigh (n=14) Phase 1 Study 208832 
 


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Covariates were resampled 1000 times from the participants in the thigh PK study (n=14), 
generating 1000 virtual subjects. Individual PK parameters of the virtual subjects were calculated 
using subject-specific covariates and using the population parameter estimates including residual 
variability, subject-specific NONMEM inter-individual errors (ETAs) sampled from the distributions 
that are decided by the estimated variance-covariate matrix of between-subject variability from 
the final PopPK model. Concentration-versus-time profiles of the virtual subjects were calculated 
using the individual PK parameters of the virtual subjects following a single CAB LA injection of 
600 mg. Median and 5th and 95th percentiles of the simulated concentration-versus-time profiles 
of the virtual subjects were calculated and plotted. 
 
Figure 20 
Preliminary RPV Concentrations following a Single 900 mg IM 
injection to the lateral thigh (n=14) Phase 1 Study 208832 
 
Note: the predictions are based on population PK model for IM gluteal injections 
Open black circles: observed data thigh injection Phase 1 study; Blue dotted line (upper, lower 
vertical blue line), red closed circles: geometric mean (5th, 95th percentile), median of observed 
data thigh injection Phase 1 study 
12 ng/mL: protein binding adjusted IC90  
17.3 ng/mL: observed 5th percentile Ctau 4 weeks after first IM gluteal injection in ATLAS/FLAIR 
 
 
11.13.2. 
Sub-study Amendment rationale 
Data through week 12 from the Phase 1 study, as described above, suggest well tolerated 
thigh injections with CAB and RPV PK concentrations similar between thigh and gluteal 
injections. This study provides the evidence  to evaluate thigh injections  in HIV-infected 
individuals  already receiving either  Q4W or  Q8W dosing of CAB/RPV LA. Instead of 
designing a separate study, A2M will be amended to allow an assessment of thigh 
injections as an alternative injection site than what is currently allowed in the prescribing 


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information to evaluate the PK parameters, safety, tolerability and virologic response in 
HIV-1 infected participants receiving CAB and RPV LA. 
 
This sub-study will assess the comparability of CAB and RPV PK (and other parameters) 
following gluteal and thigh injections. Absorption of CAB following injection into an IM 
site is described as a first order process with an absorption rate constant, KA LA. This 
absorption rate constant is the model parameter that is most sensitive to alterations in 
physiology and drug administration; the factors of gender, BMI and needle length all 
influence CAB absorption kinetics and are covariates for the parameter KA LA. Plasma 
trough concentration (Ctau) is the exposure parameter most associated with 
cabotegravir efficacy with an identified 5th percentile of population exposure used to 
determine efficacious regimens and interventions. Importantly, CAB has a wide 
therapeutic index where despite approximately 6-fold difference in CAB ka values across 
the population (including a 2-fold mean difference between males and females) there is 
no difference in Phase 3 efficacy.   
 
The main PK parameters of interest include Ctau, concentrations post dose [~Cmax], and 
AUC (0-Ctau). CAB and RPV PK parameter will be evaluated by comparing thigh 
injection with  gluteal injection using the ratio of the geometric mean of thigh injection to 
the geometric mean of the gluteal injection for a PK parameter within each treatment arm 
(Q8W, Q4W) and each analyte (CAB, RPV).  No formal statistical hypotheses are to be 
tested,   and the sample size was selected mainly based on the precision of the geometric 
mean ratio estimate (thigh injection vs gluteal injection) and the data sufficiency to assess 
the safety parameters within 16 weeks of thigh injection phase.  
Moreover, additional safety and tolerability data following thigh injections for both 
regimens will also be collected to better characterise the safety/tolerability profile of IM 
injections to the lateral thigh.   
 
The study’s main objective is to assess the comparability of PK  between thigh vs gluteal 
injections in HIV-1 infected participants to support at home IM strategy for LA self-
administration by demonstrating similar safety/tolerability and PK parameters between 
gluteal and thigh administration. 
 
11.13.3. 
Sub-study Amendment: Objectives and Endpoints 
Objectives 
Endpoints 
Primary Endpoint 
Pharmacokinetic 
To evaluate the PK  of monthly and every 
two months dosing of CAB LA  and RPV 
LA injections following intramuscular 
administration in the vastus lateralis (thigh) 
muscle (compared to gluteal injections) in 
HIV-1 
infected 
participants 
currently 
Plasma PK parameters for CAB LA and RPV 
LA (Ctau, concentrations post dose [~Cmax], 
and area under the curve [AUC (0-tau)]) for 
thigh injections during the thigh injection 
phase  compared with similar PK parameters 


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Objectives 
Endpoints 
enrolled in the A2M sub-study 
for gluteal injections. 
Secondary Endpoints 
Safety and tolerability 
To assess safety and tolerability of monthly 
and every two months dosing of CAB LA 
and RPV LA following intramuscular 
injections in the vastus lateral (thigh) 
muscle in HIV-1 infected participants 
currently enrolled in the A2M sub-study. 
Incidence and severity of ISRs and AEs of 
special interest during the thigh injection 
phase. 
Proportion of participants who discontinue 
treatment due to ISRs and AEs of special 
interest during the thigh injection phase.   
Virologic Efficacy 
To assess the ability to maintain virologic 
suppression (HIV-RNA < 50 copies) in 
subjects 
who 
transition 
to 
thigh 
administrations of CAB and RPV after 
receiving at least 3 years of gluteal 
injections.  
 
• Proportion 
of 
participants 
with 
plasma HIV-1 RNA <50 c/mL over 
time (including at Week 16) during 
the thigh injection phase using the 
FDA Snapshot algorithm.  
• Proportion 
of 
participants 
with 
plasma HIV-RNA ≥50 c/mL over 
time (including at Week 16) as per 
Food and Drug Administration (FDA) 
Snapshot algorithm during the thigh 
injection phase.  
• Proportion 
of 
participants 
with 
protocol-defined confirmed virologic 
failure (CVF) during the thigh 
injection phase. 
To assess viral resistance in participants 
experiencing protocol-defined confirmed 
virologic failure. 
Incidence of treatment emergent genotypic 
and phenotypic resistance to CAB, RPV 
during the thigh injection phase. 
Health Outcomes 
To assess patient reported outcomes during 
the thigh injection phase by administering 
the 
following 
health 
outcome 
measurements: Numerical Rating Scale 
(NRS) and HIVTSQ.  
• Numerical Rating Scale (NRS):  To 
assess the tolerability of injections 
during both the Thigh and Gluteal 
Injection Phase   
• HIVTSQ (both s and c versions): 


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Objectives 
Endpoints 
 
To measure levels of satisfaction and 
detect change in satisfaction when 
switching from gluteal to thigh 
injections 
 
in 
total 
“treatment 
satisfaction” score, and individual 
item scores of the HIV Treatment 
Satisfaction Questionnaire (HIVTSQ) 
during the Thigh Injection Phase as 
well as the change from thigh during 
the Return to Gluteal Phase. 
 
To assess participant’s preference of thigh 
injections during the thigh injection phase 
compared to gluteal injections. 
Preference Questionnaire:  To assess 
patient’s 
preference, 
and 
reasons 
for 
preference, for injections received during the 
Thigh Injection Phase compared with prior 
gluteal injections as well as for injections 
received during the Return to Gluteal phase 
compared with prior thigh injections. 
Exploratory Endpoints 
 
11.13.4. 
Sub-study Amendment Design 
The A2M sub-study will consist of three phases including a Screening Phase (1 injection 
interval: 4 weeks for Q4W subjects and 8 weeks for Q8W subjects), a Thigh Injection 
Phase 16 weeks of thigh injections, 4 injection intervals for Q4W and 2 injection 
intervals for Q8W) and a Return to Gluteal Injection Phase (8 weeks of gluteal injections 
for both Q4W subjects and Q8W subjects). At the conclusion of the sub-study, 
participants will have the option to continue on the A2M main study or if commercial 
access treatment is available, the participant can transition off the sub-study and 
withdraw from A2M and proceed directly to CAB/RPV LA. 
CCI


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Figure 21 
Thigh Sub-study Amendment Design 
 
NOTE: All injection visits during the sub-study should kept to the same projected visit 
schedule as in the parent study. 
11.13.4.1. Sub-study Amendment: Inclusion and Exclusion Criteria 
11.13.4.1.1. 
Sub-study Inclusion Criteria 
1. Capable of giving signed informed consent (Sub-study specific informed 
consent), which includes compliance with the requirements and restrictions listed 
in the consent form and in this protocol.  Eligible participants or their legal 
guardians (and next of kin when locally required), must sign a written Informed 
Consent Form before any protocol-specified assessments are conducted.  
Enrolment of participants who are unable to provide direct informed consent is 
optional and will be based on local legal/regulatory requirements and site 
feasibility to conduct protocol procedures. 
2. Eligible participants must have been on CAB LA + RPV LA regimen for a 
minimum of 152 weeks while on the  ATLAS2-M  study. Any disruptions in 
dosing during ATLAS2-M must be discussed with the Medical Monitor for a final 
determination of eligibility into the sub-study.   
3. Plasma HIV-1 RNA <50 c/mL at Sub-Study Screening. 
11.13.4.1.2. 
Sub-study Exclusion Criteria 
4. More than 1 plasma HIV-1 RNA measurement 50 c/mL to <200 c/mL (virologic 
blip) within 24 weeks prior to sub-study Screening visit. 


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5. Any Suspected Virologic Failure (HIV-RNA>200 c/mL) as defined in Section 
5.5.5.2 during ATLAS-2M study. 
6. Subjects planning to require oral bridging during participation in the ATLAS-2M 
sub-study. 
7. The participant has a tattoo or any dermatological condition overlying the thigh 
region which may interfere with interpretation of injection site reactions. 
8. Any condition which, in the opinion of the Investigator, may interfere with the 
absorption, distribution, metabolism or excretion of the study drugs or render the 
participant unable to receive study medication. 
 
 
Additionally, the following entry criteria detailed for the ATLAS-2M main study apply to 
the sub-study as well : 
 
A2M parent study - Inclusion criteria 
9. A female participant is eligible to participate if she is not pregnant (as confirmed 
by a negative serum human chorionic gonadotropin (hCG) test) not lactating, and 
at least one of the following conditions applies: 
a. Non-reproductive potential defined as: 
• Pre-menopausal females with one of the following: 
• Documented tubal ligation 
• Documented hysteroscopic tubal occlusion procedure with follow-up 
confirmation of bilateral tubal occlusion 
• Hysterectomy 
• Documented Bilateral Oophorectomy 
• Postmenopausal defined as 12 months of spontaneous amenorrhea [in 
questionable cases a blood sample with simultaneous follicle stimulating 
hormone (FSH) and estradiol levels consistent with menopause (refer to 
laboratory reference ranges for confirmatory levels)].  Females on 
hormone replacement therapy (HRT) and whose menopausal status is in 
doubt will be required to use one of the highly effective contraception 
methods if they wish to continue their HRT during the study.  Otherwise, 
they must discontinue HRT to allow confirmation of post-menopausal 
status prior to study enrolment.  
b. Reproductive potential and agrees to follow one of the options listed in the 
Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of 
Reproductive Potential (FRP) from 30 days prior to the first dose of study 
medication, throughout the study, for at least 30 days after discontinuation of all 


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oral study medications, and for at least 52 weeks after discontinuation of CAB LA 
and RPV LA.  
The investigator is responsible for ensuring that participants understand how to properly 
use these methods of contraception.   
 
A2M parent study - Exclusionary medical conditions- for all participants 
10. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed 
during the study 
11. Any evidence of a current Center for Disease Control and Prevention (CDC) 
Stage 3 disease [CDC, 2014] , except cutaneous Kaposi’s sarcoma not requiring 
systemic therapy, and CD4+ counts <200 cells/L are not exclusionary. 
12. Participants with moderate to severe hepatic impairment. 
13. 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. 
14. 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. 
15. 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. 
16. Unstable liver disease (as defined by any of the following:  presence of ascites, 
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, 
or persistent jaundice or cirrhosis), known biliary abnormalities (with the 
exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable 
chronic liver disease per investigator assessment). 
17. History of liver cirrhosis with or without hepatitis viral co-infection. 
18. Ongoing or clinically relevant pancreatitis. 
19. Clinically significant cardiovascular disease, as defined by history/evidence of 
congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary 
artery bypass grafting (CABG) surgery or percutaneous transluminal coronary 
angioplasty (PTCA) or any clinically significant cardiac disease. 
20. 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. 
21. Any condition which, in the opinion of the Investigator, may interfere with the 


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absorption, distribution, metabolism or excretion of the study drugs or render the 
participant unable to receive study medication. 
22. 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. 
23. 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. 
A2M parent study - Exclusionary Laboratory Values or Clinical Assessments at 
Screening (a single repeat to determine eligibility is allowed) 
24. Any verified Grade 4 laboratory abnormality. A single repeat test is allowed 
during the Screening phase to verify a result. 
25. 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. 
26. Participant has estimated creatine clearance <50mL/min per 1.73m2 via Chronic 
Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method. 
27. Alanine aminotransferase (ALT) 3 × ULN at Screening. 


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A2M parent study - Concomitant Medications 
28. Exposure to an experimental drug (with the exception of those in the ATLAS-2M 
study including CAB, CAB LA, and RPV, RPV LA) 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; 
29. 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.  
30. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of 
Screening. 
31. Use of medications which are associated with Torsade de Pointes.  (See SPM for 
a list of relevant medications). 
32. Participants receiving any prohibited medication and who are unwilling or unable 
to switch to an alternate medication.  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. 
 
11.13.4.2. Screening Phase (Gluteal IM) 
Eligibility criteria must be assessed at the Screening visit and confirmed visit prior to the 
first Thigh injection. Participants who are enrolled in the sub-study and subsequently 
withdrawn from the main A2M study for any reason may not be re-screened. Screening 
procedures should occur within 35 days prior to Day 1 for Q4W subjects and 63 days 
prior to Day 1 for Q8W subjects of the first dose in the Thigh Injection Phase. 
After the Screening visit, participants will need to return to the clinic 1 week later (for 
Q4W subjects) and 1 week and 4 weeks later (for Q8W subjects) to obtain PK sampling 
as outlined in the Sub-study Time and Event Table. 
11.13.4.3. Thigh injections Phase (16 weeks) 
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After confirming eligibility into the sub-study, participants will enter into the Thigh 
Injection Phase and receive an intramuscular injection of CAB LA (2 mL; 400 mg) on 
one lateral thigh and RPV LA (2 mL; 600 mg) into the opposite lateral thigh at the 
following visits (7 days): 
• 
Day 1  
• 
Week 4 
• 
Week 8 
• 
Week 12 
Participants will remain in the research unit for at least 2 hours after the injection for 
post-dose PK sampling and safety assessments. 
After certain visits, participants will need to return to the clinic 1 week after the injection 
for PK sampling as outlined in Time and Event Table Section 11.13.5.1.  
For participants receiving 2M (Q8W) IM injections while on ATLAS 2M: 
After confirming eligibility into the sub-study, participants will enter into the Thigh 
Injection Phase and receive an intramuscular injection of CAB LA (3 mL; 600 mg) on 
one lateral thigh and RPV LA (3 mL; 900 mg) into the opposite lateral thigh at the 
following visits: 
• Day1 
• Week 8 
 
Participants will remain in the research unit for at least 2 hours after the injection for 
post-dose PK sampling and safety assessments.  
Participants will then return to the clinic 1 week and 4 weeks after the injection for PK 
sampling as outlined in Time and Event Table Section 11.13.5.2.  
11.13.4.4. Return to Gluteal Injection Phase 
For participants receiving monthly (Q4W) IM injections while on A2M 
Participants who received CAB LA + RPV LA IM thigh injection every 4 weeks for a 
total of 16 weeks during the Thigh Injection Phase  will return to the clinic to receive an 
IM gluteal injection of CAB LA (2 mL; 400 mg) on one lateral thigh and RPV LA (2 mL; 
600 mg) into the opposite lateral thigh at the following visits (7 days): 
• Week 16 
• Week 20 
 
Q4W participants will complete 8 weeks (2 injection cycles) of CAB/RPV LA and the 
Week 24 pre-injection assessments after which the participant’s participation in the sub-
study will conclude (at week 24). The Week 24 injection will be the first injection back 
on the main study (A2M). 


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The 2 injection cycles for Q4W dosing during the Gluteal Injection Phase will correspond 
to 1 injection cycle during the Gluteal Injection Phase for the Q8W dosing participants 
thereby ensuring similar assessments for both arms (see T&E). 
For participants receiving 2M (Q8W) IM injections while on A2M: 
Participants, who received CAB LA + RPV LA IM thigh injection every 8 weeks for a 
total of 16 weeks during the Thigh Injection Phase will return to the clinic to  receive an  
IM gluteal injection of CAB LA (3 mL; 600 mg) on one lateral thigh and RPV LA (3 mL; 
900 mg) into the opposite lateral thigh at the following visits: 
• Week 16 
• Week 24 
 
Q8W participants will complete 8 weeks (1 injection cycle) of CAB/RPV LA and the 
Week 24 pre-injection assessments after which the participant’s participation in the sub-
study will conclude (at Week 24). The W24 injection will be the first injection back on 
the parent study (A2M).  
The 1 injection cycle for Q8W dosing during the Gluteal Injection Phase will correspond 
to 2 injection cycles during the Gluteal Injection Phase for the Q4W dosing participants 
thereby ensuring similar assessments for both arms (see T&E) 
11.13.4.5. Sub-study completion 
Participants are considered to have completed the study if they complete pre-dose 
assessments at sub-study Week 24 visit. 
Depending on the local availability of the marketed product in each country, after the 
sub-study is completed participants will be invited to: 
• 
Countries where CAB LA+RPV LA marketed product is not yet locally available: 
Continue in the Extension phase of the main study and complete study visits as 
per Time & Events table in Section 7.1). 
• 
Countries where CAB LA+RPV LA marketed product is locally available:  
Transition to CAB LA + RPV LA marketed product or an alternative ART as 
indicated below:  
i. After the pre-injection assessments are completed at week 24, the 
participant will receive the last gluteal injection as part of the 
main study.  
ii. Participant  will complete Safety Follow Up visit 2-4 weeks after 
the last injection (please refer to Section 5.6 of the Protocol) before 
transitioning to a marketed ART. 


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Note: If the participant has to withdraw from the study due to safety related reasons once 
CAB LA + RPV LA marketed product is locally available (see Section 5.5) the subject 
would need to complete withdrawal visit and enter in the Long Term Follow Up phase 
(see Section 4.2.4). 
11.13.4.6. Sub-study Amendment Withdrawal/Stopping Criteria 
Participants meeting Withdrawal/Stopping criteria as per Section 5.5 will discontinue 
the study treatment and be withdrawn from both A2M and the sub-study, and will  
complete assessments per T&E table in Section 7.1 and enter in the Long Term Follow-
Up phase. 
Participants who decide to discontinue their participation in the sub-study for non-safety 
reasons (refer to Section 5.5), including participants who require Oral Bridging during 
the sub-study or participants who decide to discontinue their participation in the sub-
study due to injection-site (thigh) related tolerability reasons:  
• In countries were the marketed products of CAB and RPV LA are not yet locally 
available, such patients will be allowed to transition back to the main study and 
continue with IM gluteal injections per the randomized dosing schedule. 
• In countries were the marketed products of CAB and RPV LA are locally 
available: patients will be invited to return to gluteal injections in the main study 
and receive 1 more gluteal injections (additional injections might be required if 
requested by MM) before transitioning to marketed product as described in 
Section 4.2.4 and Section 5.6 
11.13.4.6.1. 
Sub-study Amendment Specific Virologic Failure Guidance 
Refer to Section 5.5.3, Section 5.5.4 and Section 5.5.5 
11.13.4.6.2. 
Sub-study Amendment HIV-1 RNA Blips Guidance 
Refer to Section 5.5.5.1 
Participants who have a HIV-1 RNA ≥50 c/mL and <200 c/mL at any timepoing during 
the sub-study including during the Return to Gluteal Injection Phase, must return to the 
clinic as soon as possible (no later than 4 weeks) for a repeat HIV-1 RNA test. 
In case of a virologic blip occurring at the last study visit of the sub-study (Return to 
Gluteal Injection Phase), the Medical Monitor should be immediately consulted for 
further guidance.     
11.13.4.6.3. 
Sub-study Amendment Specific Withdrawal Criteria - Pregnancy 
If a subject becomes pregnant during the substudy, the subject would need to withdraw 
from the substudy and have the option to continue with gluteal injections in the main 
A2M  study after signing a  pregnancy-specific ICF addendum or be withdrawn from 
A2M. Please refer to Appendix 11 for additional information. 
 


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11.13.5. 
Sub-study: Time and Events table 
11.13.5.1. Sub-study: Time and Events Table for CAB LA + RPV LA Q4 Weekly Administration 
Procedure 
Screening Phased 
Gluteal  
administration 
Thigh Injection Phased 
Q4 Weekly thigh administration 
Return to Gluteal Injection Phased 
Q4 Weekly gluteal admin. 
 
Screening 
(Week  
-4) 
Week -3 
Day1 
Week 
1 
Week 4 
Week 8 
Week 12 
Week 
13 
Week 
16 
Week 
17 
Week 
20 
Week 
24 
IM treatment 
administrationi 
X 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
Written Inform 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Verification 
(Inclusion/Exclusio
n criteria) 
X 
 
 
 
 
 
 
 
 
 
 
 
Symptom directed 
physical exam and 
Medical 
assessmenta 
X 
 
X 
 
X 
X 
X 
 
X 
 
X 
X 
Weight and BMI  
 
 
X 
 
 
 
 
 
X 
 
 
 


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Procedure 
Screening Phased 
Gluteal  
administration 
Thigh Injection Phased 
Q4 Weekly thigh administration 
Return to Gluteal Injection Phased 
Q4 Weekly gluteal admin. 
 
Screening 
(Week  
-4) 
Week -3 
Day1 
Week 
1 
Week 4 
Week 8 
Week 12 
Week 
13 
Week 
16 
Week 
17 
Week 
20 
Week 
24 
Vital Signs, BP, 
HR, tempb 
X 
 
X 
 
 
 
 
 
X 
 
 
 
Smoking status 
X 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECGc  
X 
 
X 
 
 
 
 
 
X 
 
 
 
HIV associated 
conditions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs, SAEs, 
concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ISR assessments 
for IM  injections 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Chemistry 
and Hematology 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
X 
Pregnancy Testing, 
SERUMe 
S 
 
S 
 
S 
S 
S 
 
S 
 
U 
S 


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Procedure 
Screening Phased 
Gluteal  
administration 
Thigh Injection Phased 
Q4 Weekly thigh administration 
Return to Gluteal Injection Phased 
Q4 Weekly gluteal admin. 
 
Screening 
(Week  
-4) 
Week -3 
Day1 
Week 
1 
Week 4 
Week 8 
Week 12 
Week 
13 
Week 
16 
Week 
17 
Week 
20 
Week 
24 
HIV-1 RNA and 
sample for storage 
(S) 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
X 
CD4+ cell count 
X 
 
X 
 
X 
X 
X 
 
X 
 
 
X 
CD8+ cell count 
 
 
X 
 
 
 
 
 
X 
 
 
 
Urinalysisf 
 
 
X 
 
 
 
 
 
X 
 
 
 
Fasting lab 
assessments: 
Glucose, 
Cholesterol (Total, 
HDL and LDL) 
and triglyceridesg 
 
 
X 
 
 
 
 
 
X 
 
 
 
PBMC for storage 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 


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Procedure 
Screening Phased 
Gluteal  
administration 
Thigh Injection Phased 
Q4 Weekly thigh administration 
Return to Gluteal Injection Phased 
Q4 Weekly gluteal admin. 
 
Screening 
(Week  
-4) 
Week -3 
Day1 
Week 
1 
Week 4 
Week 8 
Week 12 
Week 
13 
Week 
16 
Week 
17 
Week 
20 
Week 
24 
PK sample collectionj 
Pre dose PK 
sampling  
X 
 
X 
 
X 
X 
X 
 
X 
 
 
 
2h Post dose PK 
sampling  
 
 
X 
 
X 
X 
X 
 
 
 
 
 
Post dose PK 
sampling (~Cmax) 
 
X 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
PROsl 
HIVTSQc 
 
 
 
 
 
 
 
 
Xk 
 
 
 
HIVTSQs 
 
 
X 
 
 
 
 
 
Xk 
 
X 
 
NRSh 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
Preference Thigh 
inj. vs Gluteal inj. 
 
 
 
 
 
 
X 
 
 
 
X 
 


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 Sub-study Footnotes: 
a. 
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.  
b. Measure vital signs after about 5 minutes of rest in a semi-supine position. 
c. 
A 12-lead ECG will be performed after resting in a semi-supine position for at least 5 minutes. ECGs will be performed pre-dose. A 2-hour post dose ECG 
will also be performed at sub-study Day1 visit. 
d. All injection visits during the sub-study should kept to the same projected visit schedule as in the parent study. 
e. 
Women of childbearing potential only. SR=serum, UR=urine. Urine pregnancy test can be performed at study visits when other blood draws are not required 
in order to limit needle sticks.  
f. 
A morning specimen is preferred. 
g. An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
h. Should be collected 30 to 60 minutes post injection 
i. 
Week 24 IM administration will not be considered part of the sub-study assessments. The  IM administration at W24 and any assessments completed after 
IM administration at this visit will be considered part of the parent study. 
j. 
PK window allowed for sample collection: For 1-week post dose sample (3 to 10 days post dose), for 4-week post dose sample (+-7 days) and for 2-hours 
post dose samples ( hour)  
k. At Week 16, HIVTSQs should be administered before HIVTSQc. 
l. 
All Patient Report Questionnaires/Surveys - except NRS - will be administered via paper instrument (in exceptional circumstances the questionnaires could 
be completed via telephonic interview, please refer to COVID19 appendix for additional details)  at the beginning of the visit before any other assessments 
are conducted. 
 
 


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11.13.5.2. Sub-study: Time and Events Table for CAB LA + RPV LA Q8 Weekly Administration 
Procedure 
Screening Phased 
Gluteal  administration 
Thigh injection phased 
Q8 Weekly thigh administration 
Return to Gluteal Injection Phased 
Q8 Weekly gluteal admin. 
Screening   
(Week -8) 
Week 
-7 
Week 
-4 
Day1 
Week 
1 
Week 
4 
Week 8 
Week 
9 
Week 
12 
Week 16 
Week 
17 
Week 24 
IM treatment 
administrationi 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Written Inform 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Verification 
(Inclusion/Exclusion 
criteria) 
X 
 
 
 
 
 
 
 
 
 
 
 
Symptom directed 
physical exam and 
Medical assessmenta 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
Weight and BMI  
X 
 
 
 
 
 
 
 
 
X 
 
 
Vital Signs, BP, HR, 
tempb 
X 
 
 
X 
 
 
 
 
 
X 
 
 
Smoking status 
X 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECGc  
X 
 
 
X 
 
 
 
 
 
X 
 
 
HIV associated 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Procedure 
Screening Phased 
Gluteal  administration 
Thigh injection phased 
Q8 Weekly thigh administration 
Return to Gluteal Injection Phased 
Q8 Weekly gluteal admin. 
Screening   
(Week -8) 
Week 
-7 
Week 
-4 
Day1 
Week 
1 
Week 
4 
Week 8 
Week 
9 
Week 
12 
Week 16 
Week 
17 
Week 24 
conditions 
AEs, SAEs, 
concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ISR assessments for 
IM  injections 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Chemistry 
and Hematology 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
Pregnancy Testing, 
SERUMe 
S 
 
 
S 
 
 
S 
 
 
S 
 
S 
HIV-1 RNA and 
sample for storage (S) 
X 
 
 
X 
 
X 
X 
 
X 
X 
 
X 
CD4+ cell count 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
CD8+ cell count 
X 
 
 
X 
 
 
 
 
 
X 
 
 
Urinalysisf 
X 
 
 
X 
 
 
 
 
 
X 
 
 
Fasting lab 
assessments: Glucose, 
Cholesterol (Total, 
HDL and LDL) and 
X 
 
 
X 
 
 
 
 
 
X 
 
 


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Procedure 
Screening Phased 
Gluteal  administration 
Thigh injection phased 
Q8 Weekly thigh administration 
Return to Gluteal Injection Phased 
Q8 Weekly gluteal admin. 
Screening   
(Week -8) 
Week 
-7 
Week 
-4 
Day1 
Week 
1 
Week 
4 
Week 8 
Week 
9 
Week 
12 
Week 16 
Week 
17 
Week 24 
triglyceridesg 
PBMC for storage 
 
 
 
X 
 
 
 
 
 
 
 
 
PK samplesj 
Pre dose PK sampling  
X 
 
 
X 
 
 
X 
 
 
X 
 
 
2h Post dose PK 
sampling   
 
 
 
X 
 
 
X 
 
 
 
 
 
Post dose PK 
sampling (~Cmax) 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
 
PROsl 
HIVTSQc 
 
 
 
 
 
 
 
 
 
Xk 
 
 
HIVTSQs 
 
 
 
X 
 
 
 
 
 
Xk 
 
X 
NRSh 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
Preference Thigh inj. 
vs Gluteal inj. 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
 


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Sub-study Footnotes: 
a. 
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.  
b. Measure vital signs after about 5 minutes of rest in a semi-supine position. 
c. 
A 12-lead ECG will be performed after resting in a semi-supine position for at least 5 minutes. ECGs will be performed pre-dose. A 2-hour post dose ECG 
will also be performed at sub-study Day1 visit. 
d. All injection visits during the sub-study should kept to the same projected visit schedule as in the parent study. 
e. 
Women of childbearing potential only. SR=serum, UR=urine. Urine pregnancy test can be performed at study visits when other blood draws are not required 
in order to limit needle sticks.  
f. 
A morning specimen is preferred. 
g. An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
h. Should be collected 30 to 60 minutes post injection 
i. 
Week 24 IM administration will not be considered part of the sub-study assessments. The  IM administration at W24 and any assessments completed after 
IM administration at this visit will be considered part of the parent study. 
j. 
PK window allowed for sample collection: For 1-week post dose sample (3 to 10 days post dose), for 4-week post dose sample (+-7 days) and for 2-hours 
post dose samples ( hour)  
k. At Week 16, HIVTSQs should be administered before HIVTSQc.  
l. 
All Patient Report Questionnaires/Surveys - except NRS - will be administered via paper instrument (in exceptional circumstances the questionnaires could 
be completed via telephonic interview, please refer to COVID19 appendix for additional details)  at the beginning of the visit before any other assessments 
are conducted. 
 
 


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11.13.5.3. Sub-study: Value Evidence and Outcomes 
Health outcomes assessments will be conducted according to the Time and Events Table 
(Section 11.13.5). Assessments are recommended to be administered with a paper 
instrument at the beginning of the visit (except for NRS which is performed after the 
injections) prior to collection of blood for analysis and other scheduled assessments. 
There will be four health outcome measurements that will be administered during the 
sub-study including Numerical Rating Scale (NRS), HIVTSQc, HIVTSQs and a 
Preference questionnaire.  
Numerical Rating Scale (NRS) 
A numeric rating scale was used to assess the level of pain experienced following 
injections with CAB + RPV. The scale contains one item and the response scale is 
ranging from 0= “no pain” to 10= “extreme pain”. The NRS was used to assess 
maximum level of pain on the day of the injection as well as maximum level of pain one 
week following injection. NRS questionnaires should be collected 30 to 60 minutes post 
injection. 
HIV Treatment Satisfaction Questionnaire (HIVTSQ) 
HIVTSQ is a self-completion measure specifically designed to measure treatment 
satisfaction in PLHIV. It explores multiple aspects of treatment satisfaction including 
side effects, treatment demands, convenience, flexibility and understanding of HIV.  
There are two versions of this questionnaire: HIVTSQs and HIVTSQc.  
HIVTSQs (status version) is needed to measure absolute level of satisfaction while the 
HIVTSQ change version (HIVTSQc) was developed to overcome ceiling effects 
associated with HIVTSQs and enhance sensitivity to change by allowing those who were 
optimally (or close to optimally) satisfied at baseline to express even greater satisfaction 
at follow up. The HIVTSQc is assessing the change in patients’ satisfaction between their 
previous and their current treatment within the same group.  
Total score for HIVTSQs ranges from 0-66 and. Higher scores indicate a greater 
satisfaction and a lower score indicate dissatisfaction. Individual score range from 0-6. 
HIVTSQc total score ranges from -33 to 33. A higher score indicate improvement in 
satisfaction with treatment; lower scores indicate a greater deterioration in satisfaction 
with treatment; a score of 0 represents no change. Individual items scores range from -3 
to 3 (-3= much less satisfied now, 3= much more satisfied now).  
Preference Questionnaire 
A preference question was used to assess patients’ preference, and reasons for preference, 
for the thigh injections compared with the gluteal injections. The “Preference” 
questionnaire will include a single item questions evaluating preference of HIV treatment 
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11.13.5.4. Sub-study: Pharmacokinetics sample collection 
Table 14 
Sub-study CAB and RPV Plasma Pharmacokinetic Sample Schedule 
Group 
Analytes 
Sample Times Relative to Dose 
Participants receiving 
CAB LA + RPV LA 
Q4W injections 
CAB and RPV 
Pre-Dose: Screening (Week -4), Day 1, Week 4, 
Week 8, Week 12, Week 16 
2 hours Post dose: Day 1, Week 4, Week 8, Week 
12 
1 Week Post dose: Week -3, Week 1, Week 13 
Participants receiving 
CAB LA + RPV LA 
Q8W injections 
CAB and RPV 
Pre-Dose: Screening (Week -8), Day 1, Week 8, 
Week 16  
2 hours Post dose: Day 1, Week 8  
1 Week Post dose: Week -7, Week 1, Week 9 
4 Week Post dose: Week -4, Week 4, Week 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.   
Additional details concerning handling of PK samples, labeling and shipping directions 
will be supplied in the central laboratory manual. 
 
11.13.6. 
Sub-study Amendment: Study Treatment 
11.13.6.1. Sub-study Amendment: Investigational Product and Other Study 
treatment 
Please refer to Sections 6.1.1.3 Cabotegravir Injectable Suspension (CAB LA) and 
Section 6.1.1.4 Rilpivirine Injectable Suspension (RPV LA) of main A2M protocol. 
11.13.6.2. Sub-study Dosage and Administration 
NOTE: All injection visits during the sub-study should kept to the same projected visit 
schedule as in the parent study. 
Participants receiving monthly (Q4W) IM injections while on A2M study who enter 
into the Thigh Injection Phase will receive an intramuscular injection of CAB LA (2 mL; 
400 mg) on one lateral thigh and RPV LA (2 mL; 600 mg) into the opposite lateral thigh 
on Day 1 of the Thigh Injection Phase. Subsequent thigh injections with CAB LA 400 mg 
and RPV LA 600 mg will occur every 4 weeks (7 days). 


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Participants who received CAB LA + RPV LA IM thigh injection every 4 weeks for a 
total of 16 weeks during the Thigh Injection Phase will return to the clinic 4 weeks later  
(7 days) to receive their first IM gluteal injection (at Week 16) of CAB LA (2mL; 
400mg) and RPV LA (2 mL; 600 mg) during the Return to Gluteal Injection Phase. The 
subsequent gluteal injection with CAB LA 400 mg and RPV LA 600 mg will occur 4 
weeks later (7 days) at Week 20. Gluteal injection administered at Week 24 visit will be 
considered part of the parent study. 
The interval between injection visits will be limited to a maximum of 5 weeks.  The 
Medical Monitor must be contacted to discuss individual participant case management if 
the length of time between injections exceeds or is projected to exceed 5 weeks. 
Participants receiving 2M (Q8W) IM injections while on A2M study who enter into the 
Thigh Injection Phase will receive  an intramuscular injection of CAB LA (3 mL; 600 
mg) on one lateral thigh and RPV LA (3 mL; 900 mg) into the opposite lateral thigh on 
day 1 of the Thigh Injection Phase. Subsequent thigh injections with CAB LA 600 mg 
and RPV LA 900 mg will occur every 8 weeks (7 days). 
Participants who received CAB LA + RPV LA IM thigh injection every 8 weeks for a 
total of 16 weeks during the Thigh Injection Phase  will return to the clinic 8 weeks later 
(at Week 16)  to receive their first IM gluteal injection of CAB LA (3mL; 600mg) and 
RPV LA (3 mL; 900 mg) during the Return to Gluteal Injection phase. The subsequent 
gluteal injection with CAB LA 600 mg and RPV LA 900 mg will 8 weeks later (7 days) 
at Week 24. Gluteal injection administered at Week 24 visit will be considered part of the 
parent study. 
The interval between injection visits will be limited to a maximum of 9 weeks.  The 
Medical Monitor must be contacted to discuss individual participant case management if 
the length of time between injections exceeds or is projected to exceed 9 weeks. 
For additional details regarding the Sub-study dosage and administration please refer to 
the Study Reference Manual. 
11.13.6.3. Oral Bridging during the Sub-study 
Given the limited number of thigh injections for both Q4W (4 injections) and Q8W (2 
injections) during the sub-study, any oral bridging will not be allowed in this sub-study. 
11.13.7. 
Sub-study Data Management 
Please refer to Section 8. 
11.13.8. 
Sub-study Statistical Considerations and Data Analyses 
11.13.8.1. Statistical Hypotheses 
The primary objective of this sub-study is to evaluate the pharmacokinetics of monthly 
and every 2 months dosing of CAB LA  and RPV LA injections following intramuscular 
administration in the vastus lateralis (thigh) muscle of HIV-1 infected participants 


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currently enrolled in the A2M study. No formal statistical hypotheses are to be tested. 
Where appropriate, an estimation approach will be taken and point estimates and 
confidence intervals will be constructed for the ratio of the geometric mean of thigh 
injection to the geometric mean of the gluteal injection. 
11.13.8.2. Sample Size Considerations 
No formal sample size calculation has been made. The sample size of 41 subjects per 
treatment arm (Q8W, Q4W) is sufficient to evaluate the geometric mean ratio (thigh 
injection vs gluteal injection) of PK parameters and to assess the safety parameters within 
16 weeks of the thigh injection phase. 
PK parameter comparisons of interest are shown in Table 15.  Each comparison (first or 
last thigh injection vs gluteal injection) will be evaluated separately by treatment arm and 
analyte (CAB, RPV). In the main study, the observed between subject coefficient of 
variation (CVb) for Week 96 trough PK concentrations among overall population ranges 
from 40% to 56%. Conservatively, assuming within subject coefficient of variation is 
56%, it is estimated that the half width of the 90% confidence interval for the geometric 
mean ratios on log-scale will be within 19%. If the point estimate of the ratio of 
geometric means is 1, then the 90% confidence interval will be approximately (0.83, 
1.21) on the original scale. 


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Table 15 
Planned Pharmacokinetic Parameter Comparisons between Thigh 
and Gluteal Injections 
Parameters (CAB and RPV) 
Q8W 
Q4W 
Cmax, Ctau (end of dosing 
intervala), AUC(0-tau) 
Thigh Injection 1: 
Gluteal Injection 
Thigh Injection 1: 
Gluteal Injection 
Thigh Injection 2: 
Gluteal Injection 
Thigh Injection 4: 
Gluteal Injection 
aDosing interval is defined in Table 16. 
 
Table 16 
Dosing Intervals for Each Treatment Arm 
Treatment 
Arm 
Dosing Interval 
Gluteal Injection 
First Thigh Injection 
Last Thigh Injection 
Q8W 
Week -8 to Day 1 
Day 1 to Week 8 
Week 8 to Week 16 
Q4W 
Week -4 to Day 1 
Day 1 to Week 4 
Week 12 to Week 16 
 
Table 17 provides probabilities of observing at least one subject with an adverse event 
(AE) at a given true AE rate across a range of sample sizes. The smaller true AE rate, the 
larger sample size is required to observe the AE with a decent probability. In the main 
study, the observed rates for injection site reaction (ISR) AEs and AEs of special interest 
(AESI) during the Maintenance phase varies, ranging from 0% to 79%. At true AE rate of 
0.5%, the sample size of 41 subjects per treatment arm can provide approximately 18% 
probability of observing at least one subject with AE in each treatment arm. In case of 
rare events (e.g. serious AEs) with 0% observed rate, the upper limit of the 1-sided 95% 
clopper-pearson confidence interval is 7.0% with the sample size of 41 subjects. 
 
Table 17 
Probability of Observing at Least One Subject with AE at a Given 
True AE Rate 
True AE 
Rate (%) 
Probability of Observing at Least One Subject with AE in N Subjects (%) 
N=10 
N=20 
N=30 
N=40 
N=50 
0.5 
4.9 
9.5 
14.0 
18.2 
22.2 
1 
9.6 
18.2 
26.0 
33.1 
39.5 
2.5 
22.4 
39.7 
53.2 
63.7 
71.8 
10 
65.1 
87.8 
95.8 
98.5 
99.5 
25 
94.4 
99.7 
100.0 
100.0 
100.0 
50 
99.9 
100.0 
100.0 
100.0 
100.0 
80 
100.0 
100.0 
100.0 
100.0 
100.0 
 


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11.13.8.3. Data Analysis Considerations 
11.13.8.3.1. 
Analysis Populations 
Pharmacokinetic Concentration Population for Thigh PK Sub-study Amendment 
The pharmacokinetic concentration population for this sub-study will consist of all 
participants who received at least one CAB and/or RPV thigh injection and provide at 
least one non-missing CAB and/or RPV plasma concentration value (non-quantifiable 
values will be considered as non-missing values) during the sub-study. 
Pharmacokinetic Parameter Population for Thigh PK Sub-study Amendment 
The pharmacokinetic parameter population for this sub-study will consist of all 
participants who received at least one CAB and/or RPV thigh injection and had at least 
one available PK parameter estimate.  
Intent-to-Treat Exposed Population for Thigh PK Sub-study Amendment  
The ITT-E population for this substudy will consist of all participants who were 
randomized in the main study and received at least one CAB and/or RPV thigh injection. 
Participants will be assessed according to their randomized treatment, regardless of the 
treatment they received. Participants in this population will be included in the efficacy 
and health outcomes analyses. 
Safety Population for Thigh PK Sub-study Amendment 
The safety population for this sub-study will consist of all participants who were 
randomized in the main study and received at least one CAB and/or RPV thigh injection. 
Participants will be assessed according to the actual treatment they received.  
Additional populations may be added and details will be provided in the RAP. 
11.13.8.3.2. 
Planned Analyses 
Only one final analysis is planned after all  subjects have completed the sub-study. 
11.13.8.4. Key Elements of Analysis Plan 
11.13.8.4.1. 
Primary Analysis 
The primary analysis is to compare the thigh injection with the gluteal injection using the 
ratio of the geometric mean of thigh injection to the geometric mean of the gluteal 
injection for a PK parameter within each treatment arm (Q8W, Q4W) and each analyte 
(CAB, RPV). The PK parameter comparisons of interest are described in Table 15 of 
Section 11.13.8.2. No formal hypothesis testings will be performed.  
Following loge-transformation, Cmax, Ctau and AUC(0-tau) will be separately analyzed by 
treatment arm and analyte using a mixed effects model with fixed effect term for type of 
injection (thigh, gluteal) and random effect term for subject. In each model, only subjects 


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with PK parameter estimates from corresponding both thigh and gluteal injections are 
included. For example, in the model for comparing Cmax between the first CAB  thigh 
injection vs gluteal CAB injection for Q8W subjects, only Q8W subjects with Cmax 
estimates from both first CAB thigh injection and CAB gluteal injection are included. 
Point estimates and their associated 90% confidence intervals will be constructed for the 
differences between the thigh injection and the gluteal injection. The point estimates and 
their associated 90% confidence intervals from the log-transformed analysis will then be 
back-transformed to provide point estimates and 90% confidence intervals for the ratios 
between the thigh injection and the gluteal injection on the original scale. 
 
11.13.8.4.2. 
Secondary and Exploratory Analyses 
The proportion of participants with HIV-1 RNA ≥50 c/mL and HIV-1 RNA <50 c/mL 
during the thigh injection phase will be summarized using FDA Snapshot algorithm for 
the ITT-E population for the substudy. Proportion of participants with protocol-defined 
confirmed virologic failures will also be summarized over time. 
The proportion of participants reporting AEs will be tabulated for each treatment group. 
The following summaries of AEs will be provided: 
• Incidence and severity of all AEs 
• Incidence and severity of treatment related AEs 
• Incidence and severity of AEs leading to withdrawal 
• Incidence of SAEs 
• ISR AEs from study drug injections at the event level and subject level, 
separately. 
• Change from baseline (latest non-missing value prior to the first thigh injection) 
in laboratory will be summarized by visit and treatment group.  
• The incidence of observed genotypic and phenotypic resistance to NRTIs and 
INIs, PIs, and NNRTIs will be summarized by treatment arm for subjects meeting 
confirmed virologic failure criteria. 
The health outcomes analyses include analyses of data collected from the following four 
questionnaires, HIVTSQ (both s and c versions), NRS and Preference between thigh and 
gluteal injections. Further details will be provided in the RAP.  
 
 
11.13.9. 
Sub-study Amendment Pharmacokinetics 
Pharmacokinetic analysis will be the responsibility of the Clinical Pharmacology 


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Modeling & Simulation Department (CPMS), GSK. Individual Plasma CAB ad RPV 
concentration-time data will be analyzed by non-compartmental methods with 
WinNonlin 5.2 or higher. Calculations will be based on the actual sampling times 
recorded during the study.  PK intervals are defined for each arm of the substudy in Table 
16, and the concentration at the end of the interval will also serve as the predose 
concentration for the subsequent interval. The following pharmacokinetic parameters will 
be determined for each interval, as data permit: maximum concentration (Cmax), time to 
Cmax (tmax), area under the plasma concentration-time curve through the end of the 
dosing interval (AUC(0- )), and concentration at the end of the dosing interval (C ).   
 
Plasma concentration data will be summarized descriptively by analyte and treatment 
regimen and presented in graphical and/or tabular form.  Parameters will be summarized 
by analyte and treatment regimen.  Cmax, AUC(0- ) and C  treatment comparisons are 
described above (see Table 15); tmax will not be compared statistically.  All 
pharmacokinetic data (both CAB and RPV) will be stored in the Archives, 
GlaxoSmithKline Pharmaceuticals, R&D.  Additional analyses including modelling, 
simulation and external validation may be performed to assist in the clinical interpretation 
of these data and will be reported separately. 
 
 
 
 
 
 
 
 


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11.14. 
Appendix 14: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 5  16-Apr-2021 
Overall Rationale for Amendment 5 
The primary purposes of this amendment are: 
• To allow participants who become pregnant to remain in the study and not be 
withdrawn due to pregnancy. Allowing pregnant participants to continue in the 
study will negate any additional and subsequent fetal exposures to new 
antiretrovirals agents that would occur if the pregnant participant was withdrawn 
from the study and placed on an oral SOC regimen. An Appendix, “Information 
and Guidance for Managing Pregnant Participants” was inserted as Appendix 11, 
and all subsequent appendices were renumbered accordingly.  
• Contraceptive methods have been updated to permit the use of progestogen-only 
implantable and injectable contraceptives without the requirement of a second 
highly effective method. 
• Removal of the optional collection of cord blood and/or breast milk after delivery. 
• Removal of the option for study treatment rechallenge following suspected drug-
induced liver injury (DILI) 
• Clarification of which participants enter the LTFU phase when CAB+RPV LA 
marketed product is locally available. 
• Clarification added: The Reason for Oral Bridgingand Preference questionnaire 
will also be administered at Withdrawal if it occurred at or before Week 152 only 
to participants who received oral bridging during the Maintenance and/or 
Extension Phases. 
• Medical Device reporting requirement added 
• Co-enrolment (Only applicable for South African participants) 
• Clinical and safety references updated 
• Removal of the reference to “randomized study treatment” in Overall design 
sections for alignment with CAB program studies and transition to marketed 
product plan. 
 
Other additional edits were made, for clarity and/or correction. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1.3 Overall 
Design 
 
Section 1.4.3 
Extension Phase 
 
Section 1.4.4. Long 
Term Follow- Up 
Phase 
New text added to clarify the Long Term Follow up 
phase requirements depending on the local 
availability of marketed product and the reason for 
stopping the study treatment. 
Transition to 
marketed product 


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Section # and 
Name 
Description of Change 
Brief Rationale 
 
Section 4.2.3 
Extension phase 
 
Section 4.2.4 LTFU 
Phase- IM 
Regimen Only 
 
Section 5.5. 
Withdrawal/Stoppin
g Criteria 
Section 2, Section 
4 and Section 7 
Safety update text added throughout the following 
sections: 
• 
Section 2.3.1, Drug Induced Liver Injury 
(DILI), updated text "All participants with 
suspected DILI identified in clinical studies 
to date were receiving oral cabotegravir " 
• 
Section 2.3.1 Risk Assessment RPV LA, 
Risk of treatment failures updated text: 
"Both IM CAB and RPV have demonstrated 
antiviral activity in large clinical studies and 
the two drug combination dosed Q4W has 
demonstrated sustained antiviral activity in 
studies 200056, 201584 and 201585 
however the efficacy of Q8Wdosing 
remains under evaluation." 
• 
Section 2.3.1.1 Other Clinically Relevant 
Information, Adverse Events of Special 
Interest, Seizure, updated text: "Several 
cases of seizure have occurred during the 
cabotegravir program. These cases have 
had alternative explanations for their 
occurrence (...) Several cases of seizure 
have occurred during the cabotegravir 
program. These cases have had alternative 
explanations for their occurrence (...) 
Report any cases of seizure or seizure like 
events immediately." 
• 
Section 2.3.2 Benefit Assessment, updated 
text “The antiviral activity against HIV-1 of 
CAB has been well established through 
Phase 2 and Phase 3” 
• 
Section 4.4 Scientific Rationale for Study 
Design, updated text “The CAB LA + RPV 
LA Q4W regimen is currently under 
evaluation in the ongoing Phase 3 201584 
and 201585 studies” 
• 
Section 4.5.1 Oral Lead-In Phase, updated 
the status of study .  LAI116482 (LATTE)  
Phase IIb 
• 
Section 7.4.3.4  Prompt Reporting of 
Serious Adverse Events and Other Events, 
updated text "Contacts for SAE receipt can 
be found at the beginning of this protocol 
on the Sponsor/Medical Monitor Contact 
General safety 
updates 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Information page in the Study Reference 
Manual." 
• 
Section 7.4.5.4 Seizures, updated text: 
"Several cases of seizure have occurred 
during the cabotegravir program. These 
cases have had alternative explanations for 
their occurrence."  
 
Section 1.3 Overall 
Design 
Section 4.1 Overall 
Design 
Removal of the reference to “randomized study 
treatment” in Overall design sections for alignment 
with CAB program studies and transition to 
marketed product plan. 
 
Transition to 
marketed product  
 
Section 2.3.1 Risk 
Assessment 
Updated section Potential Risk of Clinical 
Significance: Effects in late stage pregnancy seen 
in non-clinical studies 
Summary of Data/Rationale for Risk 
Animal reproduction studies data updated  
Mitigation Strategy updated to allow participants 
who become pregnant to remain in the study. 
 
To allow participants 
who become 
pregnant to remain in 
the study 
Section 2.3.1 Risk 
Assessment 
Added new category:  : Potential Risk of Clinical 
Significance Potential effects in females exposed to 
dolutegravir during conception and early pregnancy. 
Summary of Data/Rationale for Risk with data from 
preliminary analysis of an ongoing birth outcome 
surveillance study in Botswana involving women 
exposed to dolutegravir (DTG). 
Mitigation Strategy updated to allow participants 
who become pregnant to remain in the study.  
To allow participants 
who become 
pregnant to remain in 
the study 
Section 2.3.1 Risk 
Assessment 
Removed text from RPV risks, Rash mitigation 
strategy: Participants with a Grade 1 or 2 rash will 
be allowed to continue treatment or to be 
rechallenged , depending on the clinical judgment 
of the investigator. 
 
Removal of 
rechallenge option 
Section 3 
Objectives and 
Endpoints 
Added text in bold: Preference for CAB LA + RPV 
LA every 8 weeks or every 4 weeks compared to 
daily oral for participants receiving oral bridging 
during the Maintenance and/or Extension phases 
will be assessed using a preference questionnaire 
at Week 152  or Withdrawal 
Clarification required 
to be consistent with 
T&E table: Reason 
for OB and 
Preference 
questionnaire 
requirements at WD 
in the extension 
phase 
Section 5.3 
Additional Eligibility 
Criteria 
Added text: Participation in other interventional 
studies is generally not permitted, however for 
eligible participantsin South Africa  co-enrolment in 
the AIDS Clinical Trial Group ACTG interventional 
study (A5392) could be exceptionally permitted 
after review and approval by Medical Monitor. 
 
Co-enrolment in 
study A5392 would 
be permitted in South 
Africa on a case by 
case approval basis. 
Section 5.5 
Withdrawal/Stoppin
g Criteria 
Updated text to clarify the process for 
participantsthat discontinue participation when CAB 
LA + RPV LA is locally available  
Transition to 
marketed product  
 


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Section # and 
Name 
Description of Change 
Brief Rationale 
 
Removed text: Pregnancy (intrauterine), regardless 
of termination status of pregnancy.  
 
To allow participants 
who become 
pregnant to remain in 
the study 
Section 5.5.1. 
Removed “rechallenge” option throughout the 
sections 
 
Rechallenge option removed throughout all sections  
New text updated with the current process required 
in case of restart throughout the section: 
- 
5. 5.1.3 Liver Chemistry Stopping Criteria - 
Restart 
- 
5.5.1.4 General Guidance Restart 
- 
5.5.1.4.1 Drug Restart 
5.5.1.4.2 Drug Restart Following Transient 
Resolving Liver Events Not Related to IP 
Rechallenge option 
removed 
Section 5.6 
Participant and 
Study Completion 
Updated text to clarify the Safety Follow up visit 
requirements 
Transition to 
marketed product 
Section 6.10 
Discontinuation of 
Study Treatment 
Text added to clarify the process for participantsthat 
transition from study treatment to marketed product. 
Transition to 
marketed product 
Section 6. Study 
Treatment 
New section added: 6.14 Medical Devices 
Medical Device 
reporting requirement 
Section 7.1. Time 
and Events table 
Safety FU visit additional text added to clarify visit 
requirements 
Transition to 
marketed product 
Section 7.1 Time 
and Events Table 
Added new column to list WD assessments during 
Extension phase 
Clarification added to the pre-existing WD column 
to indicate it only refers to WD visit occurred during 
Maintenance phase 
 
Amended footnotes to clarify requirements for 
participantswho become pregnant during the study 
 
Amended footnotes to clarify the questionnaires 
required at W152 and WD visit in the Extension 
phase  
Withdrawal only if occurring at or prior to Week 152 
to Conduct questionnaires/surveys at Withdrawal 
only if occurring at or prior to Week 152. 
To clarify the WD 
and W152 
assessments in the 
extension phase and 
add PK testing in 
case of pregnancy.  
Section 7.4.1 
Clinical Evaluation 
Added text: Participants who are enrolled in the 
study and have a positive pregnancy test during the 
course of the study, will be allowed to remain in the 
study, provided a pregnancy specific ICF 
addendum is signed by the participant. No IP can 
be continued (oral or LA) in any pregnant 
participant until the benefit/risk assessment is 
discussed with the participant and the pregnancy 
specific ICF addendum has been signed. See 
details in Appendix 11. Pregnant participants who 
remain in the study do not need pregnancy testing 
during the study, for the duration of their pregnancy. 
 
To allow participants 
who become 
pregnant to remain in 
the study 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 7.4.3 
Adverse Events 
(AE) and Serious 
Adverse Events 
(SAEs) 
 
Added text througought Section 7.4.3. and Section 
7.4.3.1.  referring to the new requirement to report 
Medical Device incidents. 
 
New sections added to cover the new requirement 
to report Medical Device incidents. 
7.4.3.9 Medical Device Deficiencies:  
7.4.3.9.1 Time period for Detecting Medical Device 
Deficiencies 
7.4.3.9.2 Follow-up of Medical Device Deficiencies 
7.4.3.9.3 Prompt Reporting of Medical Device 
Deficiencies to Sponsor 
7.4.3.9.4 Regulatory Reporting Requirements for 
Medical Device Deficiencies 
 
Added Medical 
Device incidents  
reporting requirement 
Section 7.4.7 
Pregnancy 
Added text throughout all sections below to allow 
participants who become pregnant to remain in the 
study: 
Added text in Section 7.4.7.1 
Added new Section 7.4.7.2  
Amended Section 7.4.7.3  
Amended Section 7.4.7.4  
To allow participants 
who become 
pregnant to remain in 
the study 
Section 7.4.7.4  
Action to be taken if 
Pregnancy occurs 
Removed text: Additionally, there will be an optional 
umbilical cord blood collection at time of delivery 
and/or breast milk after delivery, requiring additional 
parental informed consent.  Cord blood and breast 
milk samples would be used to better understand 
the level of PK exposure to the neonate, if any.  
 
Removal of optional 
umbilical cord blood 
and/or breast milk pk 
testing 
Section 7.5. 
Pharmcokinetics 
Added text: Pregnant participants will have 
additional PK samples collected during the duration 
of the pregnancy. 
Added PK collection 
during pregnancy 
Section 7.8.2. 
Value Evidence 
and Outcomes 
endpoints 
(Exploratory) 
 
 
 
Section 7.8.3. 
Guidance for 
administering the 
different versions of 
HIVTSQc, 
Preference and 
Reason for Switch 
Questionnaires in 
ATLAS-2M 
 
Added text: A preference questionnaire will be 
administered to participants receiving oral bridging 
during the Maintenance and/or Extension Phases in 
order to explore preference for CAB + RPV LA 
Q4W or Q8W compared to daily oral HIV 
medication at W152 or upon WD visit if occurred 
at or before Week 152. 
 
Added row in the table under Preference: Reason 
for Oral Bridging and Preference questionnaire 
Added clarification of 
Preference 
questionnaires 
completion in the 
extension phase 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 11.3. 
Appendix 3 
Updated Appendix 3: Liver Safety – Required 
actions, Follow up Assessments and Study 
Treatment Restart Guidelines 
 
Removal of 
rechallenge option 
Section 11.5.  
Appendix 5 
Genetics research 
Text updated: In the event a participant withdraws 
from the study and requests destruction of their 
samples then  the site staff must document this in 
the site study records, complete form F-GRD-001 
and must inform ViiV/GSK via the CRA within 5 
days of notification by the participant to trigger 
sample destruction requests.  
 
To align with most 
recent template 
requirements 
Section 11.7. 
Appendix 7: 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Removed footer b of table 14 Highly Effective 
contraceptive Methods:  Two highly effective 
methods of contraception should be utilized from 30 
days prior to the first dose of study medication, 
throughout the study,  and for at least 52 weeks 
after discontinuation of CAB LA and RPV LA . 
Permitted 
contraceptive 
methods updated 
Section 11.7. 
Appendix 7: 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Added text throuought this section for cases of 
pregnancy during the study  
 
 
 
To allow participants 
who become 
pregnant to remain in 
the study 
Section 11.8.3. 
Informed Consent 
Process 
Text added to cover the process for participantes 
that become pregnant and wish to continue in the 
sudy. 
Text added to cover the process for a non-
participant that experiences a medical device 
incident with an AE. 
 
Informed consent 
process required for 
pregnant 
participantswho wish 
to continue 
participating in the 
study and non-
participants who 
result injured due to 
Medical device 
incident 
Section 11.8.7. 
Data Quality 
Assurance 
Text added (in bold): The sponsor or designee is 
responsible for the data management of this study 
including quality checking of the data.  Detailed 
information about study data collection and 
management process including systems used 
can be found in the study Data Management 
Plan. 
 
For clarification 
purposes 
Section 11.10.6.1. 
Capturing COVID-
19 Specific 
Protocol Deviations 
Removed text: Please refer to your study procedure 
manual for specific details on capturing protocol 
deviations as a result of COVID-19. 
 
For clarification 
purposes. 
Section 11.11.  
New appendix added: Appendix 11: Information 
and Guidance for Managing Pregnant Participants 
To allow participants 
who become 
pregnant to remain in 
the study 
Section 11.12. 
New appendix added: Appendix 12: Device 
Deficiencies: Definition and Procedures for 
Medical Device 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Recording, Evaluating, Follow-up, and Reporting in 
Medical Device Studies 
Section 11.13. 
Appendix 13: Protocol Amendment history updated 
 
 
Amendment 04 – 05-Aug-2020 
Overall Rationale for Amendment 4 
The primary reasons for protocol amendment 04 are to add a formal efficacy and safety 
secondary analysis at Week 152, allowing participants to continue treatment with 
randomized study medication through at minimum the Week 152 timepoint.  The study 
endpoints and additional assessments in support of the planned secondary analyses have 
been updated for Week 152.  Health outcomes assessments including the HIV-TSQs, 
Accept, and PIN questionnaires are included at Week 152 to gain further insight into 
participant’s long-term treatment experience with Long-acting Cabotegravir Plus Long-
acting Rilpivirine.  The Preference questionnaire will also be administered at Week 152 
only to participants who received oral bridging during the Maintenance and/or Extension 
Phases.  Additional minor clarifications to protocol language have also been 
incorporated.  


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Section # and Name 
Description of Change 
Brief Rationale 
Synopsis Section 1.1 
Rationale 
Synopsis Section 1.3 
Overall Design 
Synopsis Section 
1.4.2 Maintenance 
Phase 
Section 2.1 Study 
Rationale 
Section 4.2.2 
Maintenance Phase 
Section 4.2.3 
Extension Phase 
Section 4.4 Scientific 
Rationale for Study 
Design 
Section 6.12 
Treatment after the 
End of Study 
 Section 7.4.2-Table 
8 (Table text and 
footnote both) 
Week 152 timepoint has been added 
within multiple protocol sections. 
To enable Week 152 
safety and efficacy 
formal analyses 
Section 1.2 and 
Section 3.0 
Objectives and 
Endpoints 
Added Week 152 to secondary and 
exploratory endpoints 
Added new exploratory objective and 
Endpoint to assess patient preference 
for CAB LA + RPV LA every 8 
weeks or every 4 weeks compared to 
daily oral for participants receiving 
oral bridging during the Maintenance 
and/or Extension phases 
To enable Week 152 
safety and efficacy 
formal analyses  
 
Section 1.3.1 and 
Section  4.1 Overall 
Design, Study 
Schematic 
Added Week 152 Endpoint to Study 
Schematic 
To enable Week 152 
safety and efficacy 
formal analyses  
 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.4.3 and 
Section 4.2.3 
Extension Phase 
Text in bold was added: 
Participants who successfully 
complete 96 Weeks of CAB LA + 
RPV LA treatment in the 
Maintenance Phase will continue to 
have access to their randomized 
treatment Q4W or Q8W CAB LA + 
RPV LA in the Extension Phase 
through Week 152 and until study 
treatment is either locally approved 
and commercially available… 
Extends participant 
access to randomized 
study treatment through 
Week 152 at minimum. 
Section 1.4.4 Long-
Term Follow-Up 
Phase 
Text in bold was added: 
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 4 weeks (+7 days) 
after the last Q4W injection, or 
within 8 weeks (+7 days) after the 
last Q8W injection 
Clarification is added to 
the allowed window for 
initiation of HAART 
therapy following the last 
CAB LA + RPV LA IM 
injections received. 
Section 5.5 
Withdrawal/Stopping 
Criteria 
Text in bold was added: 
If withdrawal coincides with the 
active planned Week 52, Week 100, 
or Week 156 (Q4W arm) visits, 
HIV-1 RNA will only be assessed if 
the last HIV-RNA measurement from 
Week 48, Week 96, or Week 152 
was 50 copies per mL (i.e. retest for 
viral load blip). This will ensure that 
only the Week 48, Week 96. and 
Week 152 viral load assessments or 
required retest will be counted 
towards the primary and secondary 
efficacy endpoint windows.  
Maintains consistency 
with HIV-1 RNA 
analysis and retest 
strategy 
5.5.5.1 HIV-1 RNA 
Blips 
 
Text in bold was added: 
Participants who have a HIV-1 RNA 
≥50 c/mL and <200 c/mL at the key 
analysis timepoints (Week 48, Week 
96, and Week 152) must return to 
Incorporates similar HIV-
1 RNA retesting strategy 
for Week 152 visit that 
was utilized for prior 
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Section # and Name 
Description of Change 
Brief Rationale 
the clinic as soon as possible (but no 
later than 4 weeks after the date of 
the Week 48, 96, or 152 visit, 
respectively 
timepoints. 
6.8.1 Oral Bridging 
 
The following text was added:  
Participants who withdraw during 
an oral treatment period must be 
initiated on HAART therapy 
within 24 hours after the last oral 
treatment with CAB + RPV.   
Clarification regarding 
guidance for initiation of 
HAART therapy for 
participants withdrawing 
during oral treatment. 
7.1.1 and 7.1.2 
Time and Events 
Tables. 
Week 152 efficacy, safety, and 
Health Outcomes assessments have 
been added to support the additional 
secondary and exploratory analyses.  
T&E table footnotes are 
correspondingly updated.  
To enable Week 152 
safety and efficacy and 
Health Outcomes formal 
analyses  
 
7.4.3.5    
Disease-Related 
Events and/or 
Disease-Related 
Outcomes Not 
Qualifying as SAEs 
 
Text in bold was added: 
If any of the above conditions 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 
7.4.3.4) to GSK. 
Clarifies that disease 
related events (DREs) or 
outcomes listed in the 
CDC Classification 
System for HIV-1 
Infections are also to be 
entered on the HIV 
associated conditions 
eCRF page.  
7.5.1 PK Sample 
Collection- Table 10 
CAB and RPV 
Plasma 
Pharmacokinetic 
Sample Schedule 
Added PK Sample Collections for 
planned analysis at Week 152 
(Table 10) 
 
PK sampling added in 
support of planned Week 
152 safety and efficacy 
formal analyses 
7.8.1 Value 
Evidence and 
Outcomes Endpoints 
(Secondary) 
 
Health outcomes assessments 
including the HIV-TSQs, Accept, 
and PIN questionnaires are included 
at Week 152. 
 
Health Outcome 
Measurements added at 
Week 152 are purposed 
to gain further insight 
into participant’s long-
term treatment 
experience with Long-
acting Cabotegravir Plus 
Long-acting Rilpivirine. 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 7.8.2 (Value 
Evidence and 
Outcomes Endpoints 
(Exploratory) 
Text in bold was added: 
A preference questionnaire will be 
administered to participants 
receiving oral bridging during the 
Maintenance and/or Extension 
Phases in order to explore 
preference for CAB + RPV LA 
Q4W or Q8W compared to daily 
oral HIV medication 
Health Outcome 
Measurements added at 
Week 152 are purposed 
to gain further insight 
into participant’s long-
term treatment 
experience with Long-
acting Cabotegravir Plus 
Long-acting Rilpivirine. 
9.2.3 Planned 
Analyses 
 
 
 
 
9.3.2.2. Other 
Secondary Endpoint 
Analyses 
9.3.9 Other Analyses 
Text in bold was added: 
The number of planned analyses was 
updated to state that at least four 
analyses will be conducted to 
evaluate the objectives of the 
protocol after all participants have 
completed their visits at Week 24, 
Week 48, Week 96, and Week 152 
respectively 
Week 152 endpoints are added within 
the planned statistical analyses 
sections. 
To enable Week 152 
safety and efficacy 
formal analyses  
 
 
 


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Amendment 03  21-May-2020 
Overall Rationale for Amendment 3: 
The primary reason for protocol amendment 03 is to include information on Covid-19 
specific guidance for clinical trial continuity (participant and study management) during 
the pandemic.  This information is included within Appendix 10: COVID-19 Pandemic 
and Clinical Trial Continuity. 
 
Amendment 02  03-Jul-2018 
Overall Rationale Amendment 2: The primary reasons for amendment #2 are to: 
• Add the additional interim analysis of data when all participants have completed 
the Week 24 visit, with the intent of expediting the submission of study results to 
Health Authorities; 
• Change the objective for assessing the preference for CAB LA + RPV LA every 8 
weeks or CAB LA + RPV LA every 4 weeks LA compared to oral antiretroviral 
(ARV) and the preference for CAB LA+ RPV LA every 8 weeks compared to 
CAB LA + RPV LA every 4 weeks from an exploratory objective to a secondary 
objective.  A change to the supporting version of the Preference questionnaire 
administered to participants at Week 48 (or withdrawal) is also acknowledged;  
• Add revisions and clarifications for the administration of health outcomes 
questionnaires; 
• Extend exclusion criterion #28 to also exclude hereditary coagulation and platelet 
disorders such as haemophilia or Von Willebrand Disease; 
• Update exclusion criterion #11 to indicate that CD4+ counts ˂200 cells/L are not 
exclusionary; 
• Offer clarification that withdrawal assessments will be performed for any 
participant who withdraws prematurely from the Maintenance or Extension Phase.  
Additional guidance for participants withdrawing at Week 52 or Week 100 has 
been added;  
• Offer guidance to monitor medications that are dependent on OAT1 and OAT3 
transport upon concomitant exposure with CAB; 
• Specify that 2-hour post-dose ECG should be performed at Day 1 and Week 48 
only for participants receiving CAB LA + RPV LA as it is not required to perform 
2-hour post-dose ECG for those receiving oral CAB + RPV at Day 1; 
• Exclude language that previously indicated hormonal contraception may be 
susceptible to interaction with the study drugs.  The lack of a demonstrated 
interaction with a representative contraceptive supports use of CAB and RPV 
across a broad range of estrogen and progestin or progestin only hormonal 
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• Add minor clarifications and corrections to typographical errors/formatting to 
protocol text. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Synopsis Section 
1.4.2, and Section 
4.2.2, Maintenance 
Phase (Day1 up to 
Week 100), CAB LA 
+ RPV LA Dosing 
Regimens in 
ATLAS-2M  
Clarified for Q8W cohort 
transitioning from Oral Standard 
of Care (SOC) that CAB LA + 
RPV LA is administered at Week 
4b, Week 8, & Q8W thereafter. 
(Week 8 was added) 
Week 8 dosing for this group was 
inadvertently omitted in Amendment #1 
of the prior protocol within these 
sections and is now updated for 
consistency with the intended dosing 
administration in other sections of the 
protocol. 
Synopsis Section 
1.2, Section 3 
Objectives and 
Endpoints; 
Select secondary efficacy and 
safety endpoints have been 
updated to include Week 24 
endpoints. 
Adds the additional analysis of data 
through Week 24 with the intent of 
expediting the submission of study 
results to Health Authorities 
Synopsis Section 
1.2, Section 3 
Objectives and 
Endpoints; Section 
7.8, Value Evidence 
and Outcomes; 
Section 7.8.1, Value 
Evidence and 
Outcomes 
Endpoints 
(Secondary); 
Section 9.3.7, 
Health Outcomes 
Analyses. 
Assessment of the preference for 
CAB LA + RPV LA every 8 weeks 
or CAB LA + RPV LA every 4 
weeks LA compared to oral 
antiretroviral (ARV) and the 
preference for CAB LA+ RPV LA 
every 8 weeks compared to CAB 
LA + RPV LA every 4 weeks is 
changed from an exploratory 
objective to a secondary 
objective of ATLAS-2M.  The 
description of the Preference 
questionnaire is updated to 
reflect the revised questionnaire.  
The Preference questionnaire will 
be captured at Week 48 or 
Withdrawal if prior to Week 48. 
The version of the Preference 
questionnaire has been updated and 
re-purposed as a secondary objective 
for the ATLAS-2M trial. 
Section 4.2.4, LTFU 
Phase-IM Regimen 
Only 
Window for initiating HAART 
therapy during the LTFU Phase 
has been added: 
HAART therapy should be 
initiated within 4 weeks ( 7 
days) after the last Q4W 
injection, or within 8 weeks ( 7 
days) after the last Q8W 
injection. 
Allowable window for the initiation of 
HAART therapy ensures timely start of 
HAART during the LTFU Phase to 
approximate exposure coverage for 
CAB LA + RPV LA. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 5.2, 
Exclusionary Criteria 
Exclusion criterion #28 has been 
extended to also exclude 
hereditary coagulation and 
platelet disorders such as 
haemophilia or Von Willebrand 
Disease. 
Exclusion criterion #11 has been 
updated to indicate that CD4+ 
counts ˂200 cells/L are not 
exclusionary. 
Due to recurring intramuscular 
injections, participants with coagulation 
disorders are excluded. 
 
HIV Stage 3 disease is excluded with 
the exceptions of cutaneous Kaposi’s 
sarcoma not requiring systemic 
therapy, and CD4+ counts ˂200 
cells/L are not exclusionary. 
Section 5.5, 
Withdrawal/Stopping 
Criteria; Section 
1.4.4, Long-Term 
Follow-Up Phase 
Text has been added to provide 
additional instruction regarding 
withdrawal assessments to be 
performed for participants 
withdrawing from the 
Maintenance or Extension Phase  
Clarification has been added on when 
and how to perform withdrawal 
assessments relative to the time of 
individual participant withdrawal.   
Section 5.6 
Participant and 
Study Completion 
Text has been added to clarify 
the definition of a study 
completer: 
Randomly assigned to either 
treatment group, completed the 
randomized Maintenance Phase 
including Week 100 (with or 
without Week 100 study 
treatment) and did not enter the 
Extension Phase. 
Study completers will include those 
participants who complete Week 100 
protocol procedures and assessments 
without study treatment at Week 100 
should those participants not enter into 
the study Extension Phase. 
Section 6.1 
Investigational 
Product and Other 
Study Treatment 
IP Storage requirements have 
been updated to indicated that 
study IP is to be stored according 
to the product labeling. 
Specific IP storage and temperature 
requirements have been removed from 
the text as the storage conditions are 
subject to updates during the course of 
the trial which could lead to 
inconsistencies with the approved 
protocol.  Storage requirements will be 
incorporated in product labeling and 
supporting trial documentation which 
can be referenced separately from the 
protocol. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 6.13.2, 
Prohibited 
Medications and 
Non-Drug Therapies 
The following text is added: 
Concurrent with CAB 
CAB is a potent inhibitor of OAT1 
and OAT3 transport in vitro, 
however, no clinically significant 
interaction risk is expected for 
most drugs that are substrates of 
these transporters.  Monitoring 
may be required for drugs with a 
narrow therapeutic index and 
dependent on OAT1 and OAT3 
transport (e.g. methotrexate) with 
concomitant CAB administration.  
Refer to the current Investigator’s 
Brochure (Section 4.3.6.1 and 
Section 6.4) for additional 
information.  
Additional guidance is offered for 
monitoring of medications dependent 
on OAT1 and OAT3 transport upon 
concomitant exposure with CAB.  
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
Footnote c updated to: for Weeks 
4a and 96: Confirmation of 
eligibility to continue enter the 
Maintenance Phase and eligibility 
to enter the Extension Phase 
Clarification of text 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
 
Footnote h updated to:  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. For 
participants transitioning from 
ATLAS, the pre-dose Week 48 
ECG can also serve as the 
ATLAS-2M Screening ECG. ECG 
pre-dose will be performed in 
triplicate at Day 1. A 2-hour post-
dose ECG will also be performed 
at Days 1 and Week 48 for 
participants receiving CAB LA + 
RPV LA with an allowable 
window of  30 minutes. 
Additional guidance is provided for any 
Screening CGs overlapping with 
ATLAS Week 48 for ATLAS rollover 
participants. Language added to 
specify that 2-hour post-dose ECG 
should be performed at Day 1 and 
Week 48 only for participants receiving 
CAB LA + RPV LA as it is not required 
to perform 2 hour post-dose ECG for 
those receiving oral CAB + RPV at Day 
1.  


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
Footnote r updated to: 
One blood sample for CAB and 
RPV each to be collected at each 
PK timepoint.  PK samples are to 
be collected pre-dose relative to 
IM administration. At Week 4b, 
Pre-dose samples are to be 
collected after review of PK diary 
provided at Day 1 and prior to the 
final oral dose of CAB + RPV for 
participants randomized from 
SOC.  PK window allowed for 
sample collection is 3 to 10 days 
for 1 wk post dose sample (Visits 
9 and 41). 
Clarification of timing for pre-dose PK 
sample collection at Week 4b for 
participants randomized from oral 
SOC. 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
Footnote u updated to: All Patient 
Report Questionnaires/Surveys 
will be administered via paper 
instrument at the beginning of the 
visit before any other 
assessments are conducted and 
prior to administration of the eC-
SSRS.  Conduct 
questionnaires/surveys upon 
Withdrawal only if occurring at or 
prior to Week 48. 
Clarification that all patient reported 
questionnaires are to be administered 
together at the beginning of the visit 
prior to all other assessments.   
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
 
Footnote v updated to: 
Clarification that versions of the 
HIV-TSQc are to be administered 
to all participants transitioning 
from ATLAS and new participants 
transitioning from oral SOC. For 
participants transitioning from 
ATLAS, the version of the HIV-
TSQc instrument to be 
administered will be based on the 
initial randomization arm at 
ATLAS Day 1 
Distinct versions of the HIVTSQc have 
been developed for all participants 
including those transitioning from 
ATLAS and new participants 
transitioning from oral SOC 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
Footnote w updated to: 
For patients randomized to oral 
SOC at Day 1 in ATLAS or new 
patients on SOC, the reasons for 
willingness to switch ART will be 
assessed at Day 1.  For patients 
randomized to CAB LA + RPV LA 
Q4W in ATLAS, the reasons for 
willingness to continue long-
acting ART in ATLAS-2M will be 
assessed at Day 1. 
Additional clarification on 
administration of Reason for Switch 
and Reason for Continuation for patient 
groups. 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
Footnote X updated to: 
Preference Questionnaire will be 
administered to all participants.  
The version of the Preference 
questionnaire has been revised under 
Protocol Amendment #2 and will be 
administered to all study participants. 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
Footnote Y has been added: Refer 
to Section 5.5 of the protocol for 
additional information on 
performing withdrawal 
assessments.  HIV-1 RNA will be 
collected as Storage sample only 
if withdrawal assessments 
coincide with Week 52 or Week 
100 (as per Section 5.5.) 
Reference to Section 5.5. for 
withdrawal assessments has been 
added to ensure appropriate sample 
collections are performed. 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms and 
throughout protocol 
 
Footnote Z and throughout 
protocol, Month 1 of the Long-
Term Follow-Up (LTFU) visit has 
been removed such that 
participants receiving one or more 
injections with CAB LA and/or 
RPV LA will be assessed with 
clinic visits at a withdrawal visit, 
and months, 3, 6, 9 and 12 during 
the Long-Term Follow-Up Phase 
Withdrawal assessments conducted 
during withdrawal visit will serve as the 
first set of follow-up assessments for 
the LTFU Phase, followed by planned 
visits at months 3, 6, 9, and 12 
following the last CAB LA + RPV LA 
injections received. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 
7.4.3.1:.Time period 
and Frequency for 
collecting AE and 
SAE information 
The following text has been 
removed: 
During the Extension Phase, AEs 
leading to Withdrawal and all 
SAEs will be recorded. 
Clarification and to add consistency 
with other text that all AEs will be 
collected from the start of study 
treatment until the final follow-up 
contact 
Section 7.4.10, 
Electrocardiogram 
(ECG) 
The following text has been 
added: At Day 1 and Week 48 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 
Adds clarification that the 2 hour post-
dose ECG is only for those participants 
receiving CAB LA  RPV LA at Day 1, 
and specifies the allowable window for 
conduct of the ECG. 
Section 7.8.3 
Guidance for 
administering the 
different versions of 
HIVTSQc, 
Preference and 
Reason for Switch 
Questionnaires in 
ATLAS-2M 
Section 7.8.3 has been added 
including a table to guide 
administration of Evidence and 
Outcomes instruments 
Additional guidance towards Value 
Evidence and Outcomes instruments 
has been added to assist investigative 
staff with administration of different 
versions of these patient 
questionnaires. 
Section 9.2.2.1: 
Primary Comparison 
of Interest 
Treatment with Q8W will be 
declared non-inferior to Q4W if 
the upper end of a two-sided 95% 
confidence interval for the 
difference between the two 
groups (Q8W – Q4W) in the 
proportion of participants with 
HIV-RNA 50 c/mL at Week 48 
(defined by the US FDA snapshot 
algorithm) lies below 4%. 
Section 9.2.2.1 Primary Comparison of 
Interest erroneously referred to a non-
inferiority declaration of the Q8W 
regimen relative to the Q4W regimen if 
the difference in the proportion of 
participants with HIV-RNA 50 c/mL 
between the two groups lies below 5% 
rather than the intended update to 4%.   
 
Section 9.2.3.1  
Week 24 data 
analyses 
Section 9.2.3.1 has been added 
to describe the additional 
analyses of early data through 
Week 24. 
Adds the additional analysis of data 
through Week 24 with the intent of 
expediting the submission of study 
results to Health Authorities 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Appendix 7: 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Footnote b from Table 14 has 
been modified to exclude 
language indicating that 
hormonal contraception may be 
susceptible to interaction with the 
study drugs. 
 
Hormonal contraception may be 
susceptible to interaction with the study 
drug, which may reduce the efficacy of 
the contraceptive method. In this case  
b. Two highly effective methods 
of contraception should be 
utilized from 30 days prior to the 
first dose of study medication, 
throughout the study, and for at 
least 52 weeks after 
discontinuation of CAB LA and 
RPV LA. 
CAB and RPV have demonstrated no 
impact on the pharmacokinetics of 
commonly used combined estrogen 
and progestin containing oral 
contraceptives.  Neither CAB nor RPV 
induce or inhibit UGT or CYP enzymes 
which are the predominant metabolic 
routes of elimination for these products. 
The interaction has only been studied 
with levonorgestrel/ethinyl estradiol for 
CAB and norethindrone/ethinyl 
estradiol for RPV. The lack of a 
demonstrated interaction with a 
representative contraceptive supports 
use of CAB and RPV across a broad 
range of estrogen and progestin or 
progestin only hormonal 
contraceptives. 
General Updates 
Additional minor clarifications and 
corrections to typographical 
errors/formatting to protocol text 
have been added. 
Text clarifications and formatting 
 
Amendment 01 14-Sep-2017 
Overall Rationale for Amendment #1: The primary purpose of protocol amendment #1 
is to revise the study sample size to randomize approximately 1020 participants including 
510 participants per arm based on a non-inferiority margin of 4% between the CAB LA + 
RPV LA Q8W and Q4W arms.  Assuming the true proportion with HIV-RNA >=50 
c/mL is 3% for the Q8W arm and 2% for the Q4W arm, the revised sample size will 
provide at least 85% power to show non-inferiority at Week 48.  Additional minor 
clarifications and corrections have been added to the protocol text. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Synopsis Short Title 
Protocol short title updated to be 
consistent with short title of title 
page. 
Short title consistency 
General Updates 
throughout protocol 
Update of noninferiority margin 
and corresponding study 
participant size and statistical 
powering. 
Increase of sample size to 1020 
participants to support 4% non-
inferiority margin and 85% power 
assuming a true 3% failure rate for 
Q8W arm and 2% failure rate for the 
Q4W arm. 
Section 4.2.6 
Independent Data 
Monitoring 
Committee 
 
Clarification of IDMC analysis 
Clarification added that IDMC will focus 
evaluation of efficacy, tolerability, 
safety, and PK on accumulating CAB 
LA + RPV LA Q8W data 
Section 5.5 
Withdrawal/Stopping 
Criteria. 
Bullet # 4 under reasons 
participants must be 
discontinued from study 
treatment updated to: “ 
“Participant requires substitution 
of ART”. 
Dose modification of CAB or RPV is not 
an available option to participants.  
Section 5.6 
Participant and 
Study Completion 
Text updated to: In addition to 
the 52-week Follow-Up phase 
required for participants who 
receive one or more injections 
with CAB LA or RPV LA, an in-
clinic Follow-Up visit will be 
conducted approximately 4 
weeks after the last dose of 
study medication for participants 
who withdraw during the oral 
lead-in phase 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. 
Clarification of required procedures for 
Long-term Follow-up Phase and follow-
up visit for participants with ongoing 
AEs, SAEs, or laboratory abnormalities. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 6.1 
Investigational 
Product and other 
Study Treatment 
Text updated to: 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.  
 
Clarification that HAART selected 
during Long-Term Follow-Up Phase will 
not be provided as clinical trial material 
and removal of reference to current 
ART. 
Section 6.9 
Interruption of Study 
Treatment and 
Visit/Dosing 
Windows 
Text updated to: 
IP may be interrupted at the 
discretion of the Investigator in 
the event of an AE, according to 
the severity of the AE. 
 
Removal of reference to current ART 
Section 6.9.1.1: IM 
injections every 4 
weeks (Q4W) 
Text updated to: The first 
injection visit with IM CAB LA + 
RPV LA at Week 4b can be 
performed once central lab 
results are available and safety 
parameters are reviewed from 
the Week 4a visit.   
Text updated to indicate first injections 
received at Week 4b rather than Day 1 
for consistency with Time and Events 
Table.  
Section 6.13.2.3:  
Prohibited 
Medications for 
Participants 
Receiving HAART 
during the Long-
Term Follow-Up 
Phase 
Text updated to: For participants 
taking HAART during the Long-
Term Follow-Up Phase, refer to 
local prescribing information for 
details regarding concurrent 
therapies. 
 
Clarification that local prescribing 
information should be referenced for 
HAART taken during Long-Term 
Follow-Up Phase regarding prohibited 
concurrent therapies. 
Section 7.1, Time 
and Events Table 
for Q4W and Q8W 
arms. 
Text added to footnote q, for 
genetics sample. Sample may be 
collected at any visit after signing 
informed consent, but preferably 
at the Day 1 visit. 
Footnotes added to Preference 
and HIVTSQc questionnaires. 
Adds flexibility to when genetic sample 
for genetic research can be obtained. 
 
 
Added clarification for intended 
administration of questionnaires to 
participant groups.  


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Section # and 
Name 
Description of Change 
Brief Rationale 
 
eCSSRS questionnaire removed 
from study Extension Phase. 
 
Removal of reference to 
collection of Health Outcomes 
data via electronic site pads for 
footnote “u” 
 
Suicidality assessment tool 
administered through study Week 96 or 
withdrawal. 
 
Collection of Health Outcomes data will 
be performed via paper instruments. 
Section 7.4.3.4: 
Prompt Reporting of 
Serious Adverse 
Events and Other 
Events 
Table 9: Reporting 
of Serious Adverse 
Events and Other 
Events 
Text updated to: Suspected ABC 
HSR in participants receiving Oral 
SOC during the Long-Term Follow-
Up Phaseb 
 
Initial report of pregnancy and 
completion of Pregnancy 
Notification Form has been updated 
to within 24 hours of identification of 
a Pregnancy event.  Follow-up 
Pregnancy form (and SAE if 
required) has been updated to 
within 24 hours of investigator 
awareness of pregnancy outcome. 
 
Clarification for reporting suspected 
ABC HSR adverse event is relevant 
only during the Long-Term Follow-Up 
Phase for participants returning to Oral 
Standard of Care 
 
Reporting timelines and documentation 
requirements have been updated to 
reflect current Sponsor requirements. 
 
Section 7.4.5.7.1 
Proximal Renal 
Tubule Dysfunctions 
(PRTD) 
Text removal: ). If a participant in 
the current ART arm is also 
receiving TDF, then a dose 
adjustment may be considered if 
restarting study drug unless 
participants met renal toxicity 
stopping criteria (see Section 
7.4.5.7) 
Removal of reference to current ART 
therapy dose adjustments. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 7.8 Value 
Evidence and 
Outcomes 
Removal of reference to 
collection of Health Outcomes 
data via electronic site pads. 
Collection of Health Outcomes data will 
be performed via paper instruments. 
Section 9 Statistical 
Considerations and 
Data Analyses 
Updates to sample size, analysis 
considerations, and planned 
analysis within Section 9.1-
Section 9.3. have been added 
Updates to statistical section required 
based on change of noninferiority 
margin from 5% to 4%, corresponding 
increase in study participant size, 
impact on sample size sensitivity 
analysis. 
Additional details for subgroup and 
stratum-specific analysis plan are 
included.  
General Updates 
Additional minor clarifications 
and corrections to typographical 
errors/formatting to protocol text 
have been added. 
Text clarifications and formatting 
 

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  207966
Official Title of Study: A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-
inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-
acting Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 
4 Weeks in HIV-1-infected Adults who are Virologically Suppressed (ATLAS-2M), 
further referred to as A2M.
NCTID: NCT03299049
Sub-study Protocol Amendment Title: Sub-sudy to the A2M study to Evaluate the 
Pharmacokinetics, Tolerability and Efficacy of Cabotegravir and Rilpivirine Long-Acting 
Injections Following Intramuscular Administration in the Vastus Lateralis Muscle (thigh) 
in HIV-infected Adult Participants who have Received at Least Three Years of Gluteal 
Injections in the A2M Study. 
NCTID: NCT05896761
Date of Document: 23 September 2022
The sub-study was added to the protocol of the main study via an amendment. Details of 
the sub-study can be found in the protocol section 11.13 Appendix 13: Vastus Lateralis 
Muscle (Thigh) PK sub-study Amendment. A separate record has been created on 
ClinicalTrials.gov for the sub-study. 


 
C O N FI D E N TI A L  
 
T h e Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s  
 
2 0 7 9 6 6  
 
1  
 
Di visi o n  
: W orl d wi de  De vel o p me nt  
I nf or m ati o n T y pe 
: Re p orti n g a n d A nal ysis Pla n  ( R A P) 
Title  
: Re p orti n g a n d A nal ysis Pla n f or Pr ot oc ol 2 0 7 9 6 6: St u d y 
E val uati n g t he Efficac y, Safet y, a n d T olera bilit y of L o n g -
acti n g Ca b ot e gra vir Pl us L o n g -acti n g Ril pi viri ne 
a d mi nistere d e ver y 8 wee ks i n Vir ol o gicall y S u p presse d 
HI V -1 -i nf ecte d A d ults  
C o m p o u n d N u m ber  : G S K 1 2 6 5 7 4 4  
Effecti ve D ate  
: 0 8 -Se p -2 0 2 2  
 
Descri pti o n:  
•  
T he p ur p ose of t his R A P is t o descri be t he pla n ne d a nal ys es a n d o ut p ut t o b e 
i ncl u de d i n t he T hi g h P K S u b -st u d y Cli nical St u d y Re p ort f or Pr ot oc ol 
2 0 7 9 6 6 . Re p orti n g det ails pertai ni n g t o t he pri mar y W ee k 4 8 a n d t he earlier 
a nal ys es ( Wee k 2 4 I D M C, Wee k 2 4, Wee k 9 6 a n d Wee k 1 5 2) ha ve b ee n 
retai ne d f or c o m plete n ess.   
•  
T his versi o n of t he R A P i ncl u des a me n d me nts t o t he ori gi n all y a p pr o ve d R A P.  
 
A ut h or(s)  
A ut h or  
D ate  
Le a d  
 
0 8 -Se p -2 0 2 2  
Statistics Lea der  (D e v Bi ostats Stats De v ) 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o p yri g ht 2 0 2 2  t he Gla x o S mit h Kli ne gr o u p of c o m pa nies. All ri g hts r eser ve d.  
U na ut h orise d c o p yi n g or use of t his i nf or mati o n is pr o hi bite d.
P P D


 
C O N FI D E N TI A L  
 
T h e Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s  
 
2 0 7 9 6 6  
 
2  
 
R A P Te a m R e vie w C o nfir m ati o n s 
( Met h o d: E-mail)  
Re vie w er  
D ate  
 
1 6 -Se p -2 0 2 2  
Cli nical De vel o p me nt Lea d, C A B Treat me nt  ( Vii V Healt hcare) 
 
1 5 -Se p -2 0 2 2  
 ( Vii V Healt hcare)  
 
1 4 -Se p -2 0 2 2  
Pri nci pal  Pr o gra m mer  (I nfecti o us Diseas es, Bi ost atistics 
Pr o gra m mi n g)  
 
 ( C M O G C S P S E R M) 
1 9 -Se p -2 0 2 2  
 
2 3 -Se p -2 0 2 2  
 Cli nical P har m ac ol o g y M o delli n g a n d Si m ulati o n  
( C P M S) 
  
1 6 -Se p -2 0 2 2  
Cli nical De vel o p me nt Ma na ger ( Tra nslati o nal Me dici ne, Vii V 
Sci Me d Offic e)  
 
 ( Vii V 
Healt hcare)  
9 -Se p -2 0 2 2  
 
1 9 -Se p -2 0 2 2  
 Ca b ote gra vir Gl o bal Healt h O utc o mes  
Cli nic al St atistics a n d Cli nic al Pr o gr a m mi n g Li ne A p pr o v als:  
( Met h o d: Vee v a Va ult  T M F e Si g n at ure)  
A p pr o ver  
 
 (I nfecti o us Diseases, Bi ostatistics ) 
 
 (I nfecti o us Diseases, Bi ostatistics  
Pr o gra m mi n g)  
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


CONFIDENTIAL 
 
 
 
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TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 8 
1.1. 
RAP Amendments ...................................................................................... 10 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION ................................................ 12 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan .......................... 12 
2.2. 
Study Objective(s) and Endpoint(s)............................................................. 12 
2.2.1. 
Thigh PK Sub-study Objectives and Endpoints ............................ 14 
2.3. 
Study Design .............................................................................................. 16 
2.4. 
Statistical Hypotheses / Statistical Analyses ............................................... 18 
3. 
PLANNED ANALYSES .......................................................................................... 19 
3.1. 
IDMC Analyses ........................................................................................... 19 
3.2. 
Final Analyses ............................................................................................ 20 
4. 
ANALYSIS POPULATIONS ................................................................................... 21 
4.1. 
Protocol Deviations ..................................................................................... 23 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 24 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 24 
5.2. 
Baseline Definitions .................................................................................... 24 
5.3. 
Multicentre Studies ..................................................................................... 24 
5.4. 
Examination of Covariates, Other Strata and Subgroups ............................ 25 
5.4.1. 
Covariates and Other Strata ........................................................ 25 
5.4.2. 
Examination of Subgroups ........................................................... 25 
5.5. 
Multiple Comparisons and Multiplicity ......................................................... 29 
5.5.1. 
Primary Comparison of Interest ................................................... 29 
5.5.2. 
Other Comparisons of Interest ..................................................... 29 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 30 
6. 
STUDY POPULATION ANALYSES ....................................................................... 31 
6.1. 
Overview of Planned Study Population Analyses ........................................ 31 
6.2. 
Prior and Concomitant Medications ............................................................ 32 
7. 
EFFICACY ANALYSES .......................................................................................... 35 
7.1. 
Primary Efficacy Analyses .......................................................................... 35 
7.1.1. 
Endpoint / Variables ..................................................................... 35 
7.1.2. 
Summary Measure ...................................................................... 35 
7.1.3. 
Population of Interest ................................................................... 35 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 35 
7.1.5. 
Statistical Analyses / Methods ..................................................... 35 
7.1.5.1. 
Statistical Methodology Specification .......................... 35 
7.2. 
Secondary Efficacy Analyses ...................................................................... 38 
7.2.1. 
Endpoints..................................................................................... 38 
7.2.2. 
Summary Measure ...................................................................... 39 
7.2.3. 
Population of Interest ................................................................... 39 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 39 


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7.2.5. 
Statistical Analyses / Methods ..................................................... 39 
7.2.5.1. 
Statistical Methodology Specification .......................... 39 
7.3. 
Exploratory Efficacy Analyses ..................................................................... 42 
8. 
SAFETY ANALYSES ............................................................................................. 44 
8.1. 
Adverse Events Analyses ........................................................................... 44 
8.1.1. 
Analyses for Injection Site Reaction Adverse Events from 
Study Drug Injection .................................................................... 44 
8.2. 
Adverse Events of Special Interest Analyses .............................................. 44 
8.3. 
Clinical Laboratory Analyses ....................................................................... 46 
8.4. 
Other Safety Analyses ................................................................................ 46 
9. 
PHARMACOKINETIC ANALYSES ......................................................................... 47 
9.1. 
Endpoint / Variables .................................................................................... 47 
9.1.1. 
Drug Concentration Measures ..................................................... 47 
9.2. 
Overview of Planned Analyses ................................................................... 47 
9.3. 
Statistical Analyses / Methods .................................................................... 48 
10. POPULATION PHARMACOKINETIC ANALYSES ................................................. 50 
11. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES ................................. 50 
11.1. 
Overview of Planned Analyses ................................................................... 50 
11.2. 
Statistical Analyses / Methods .................................................................... 52 
12. HEALTH OUTCOMES ANALYSES ........................................................................ 53 
12.1. 
Endpoint / Variables .................................................................................... 53 
12.1.1. 
Main Study ................................................................................... 53 
12.1.2. 
Sub-study .................................................................................... 53 
12.2. 
Summary Measure ..................................................................................... 54 
12.3. 
Population of Interest .................................................................................. 54 
12.4. 
Analysis of Reason for switch will be based on a subset of Intent-to-
Treat Exposed population who either were randomized to SOC arm 
in ATLAS or did not participate in ATLAS study (i.e. SOC 
population).Strategy for Intercurrent (Post-Randomization) Events ............. 54 
12.5. 
Statistical Analyses / Methods .................................................................... 54 
12.5.1. 
Statistical Methodology Specification ........................................... 54 
13. VIROLOGY ............................................................................................................ 57 
14. REFERENCES ....................................................................................................... 59 
15. APPENDICES ........................................................................................................ 60 
15.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 60 
15.1.1. 
Exclusions from Per Protocol Population ..................................... 60 
15.2. 
Appendix 2: Schedule of Activities .............................................................. 63 
15.2.1. 
Protocol Defined Schedule of Events for Q4W Arm in Main 
Study ........................................................................................... 64 
15.2.2. 
Protocol Defined Schedule of Events for Q8W Arm in Main 
Study ........................................................................................... 72 
15.2.3. 
Protocol Defined Schedule of Events for Q4W Arm in Sub-
study ............................................................................................ 79 


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15.2.4. 
Protocol Defined Schedule of Events for Q8W Arm in Sub-
study ............................................................................................ 84 
15.3. 
Appendix 3: Assessment Windows ............................................................. 88 
15.3.1. 
Definitions of Assessment Windows for Analyses ........................ 88 
15.3.2. 
Definitions of Assessment Windows for Analyses other 
than Health Outcome and PK ...................................................... 89 
15.3.3. 
Assessment Window for Phase Conclusion ................................. 95 
15.3.4. 
Assessment Window for Health Outcome Data ........................... 95 
15.3.4.1. PIN / HAT-QoL / HIVTSQs / HIVTSQc / 
ACCEPT / Preference in Main Study .......................... 95 
15.3.4.2. Reasons for Continuation/Switch in Main Study ......... 97 
15.3.4.3. HIVTSQs/HIVTSQc/Preference in Sub-study ............. 97 
15.3.4.4. Tolerability of Injections (NRS) in Sub-study ............... 97 
15.3.5. 
Assessment Window for PK Concentration Data ......................... 98 
15.3.5.1. Maintenance and Extension Phase 
Assessments .............................................................. 98 
15.3.5.2. Long-term Follow-up Phase Assessments .................. 99 
15.3.5.3. Sub-study Assessments ............................................. 99 
 15.3.6. Multiple Assessments within an Assessment Window................ 100 
15.4. 
Appendix 4: Study Phases and Treatment State ....................................... 101 
15.4.1. 
Study Phases ............................................................................ 101 
15.4.2. 
Treatment State ......................................................................... 106 
15.4.2.1. Treatment States for AE Data ................................... 107 
15.4.3. 
Study Period .............................................................................. 108 
15.5. 
Appendix 5: Data Display Standards & Handling Conventions .................. 110 
15.5.1. 
Reporting Process ..................................................................... 110 
15.5.2. 
Reporting Standards .................................................................. 110 
15.5.3. 
Reporting Standards for Pharmacokinetic .................................. 111 
15.6. 
Appendix 6: Derived and Transformed Data ............................................. 112 
15.6.1. 
General ...................................................................................... 112 
15.6.2. 
Study Population ........................................................................ 114 
15.6.3. 
Efficacy ...................................................................................... 117 
15.6.4. 
Safety ........................................................................................ 120 
15.6.5. 
Pharmacokinetic ........................................................................ 127 
15.6.6. 
Health Outcomes ....................................................................... 130 
15.6.7. 
Virology ..................................................................................... 136 
15.7. 
Appendix 7: Reporting Standards for Missing Data ................................... 140 
15.7.1. 
Premature Withdrawals .............................................................. 140 
15.7.2. 
Handling of Missing Data ........................................................... 140 
15.7.2.1. Handling of Missing and Partial Dates ...................... 141 
15.7.2.2. Handling of Missing data for Statistical Analysis ....... 142 
15.8. 
Appendix 8: Values of Potential Clinical Importance ................................. 144 
15.9. 
Appendix 9: Snapshot Algorithm Details ................................................... 145 
15.10. Appendix 10: Variables Defined for Time to Event Analysis ...................... 151 
15.11. Appendix 11: Identification of Adverse Events of Special Interest ............. 155 
15.12. Appendix 12: Identification of COVID-19 Adverse Events ......................... 178 
15.13. Appendix 13: IDMC ................................................................................... 179 
15.13.1. Adhoc CVF IDMC Analyses ....................................................... 179 
15.13.2. Week 24 IDMC Analyses ........................................................... 179 
15.14. Appendix 14: Abbreviations & Trademarks ............................................... 180 
15.14.1. Abbreviations ............................................................................. 180 
15.14.2. Trademarks ............................................................................... 182 


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15.15. Appendix 15: List of Data Displays............................................................ 183 
15.15.1. Data Display Numbering ............................................................ 183 
15.15.2. Mock Example Shell Referencing .............................................. 183 
15.15.3. Deliverables ............................................................................... 184 
15.15.4. List of Data Displays for Week 24 IDMC and Week 24 
Planned Analyses ...................................................................... 184 
15.15.4.1. Study Population Tables ........................................... 185 
15.15.4.2. Efficacy Tables ......................................................... 186 
15.15.4.3. Efficacy Figures ........................................................ 189 
15.15.4.4. Safety Tables ........................................................... 190 
15.15.4.5. Safety Figures .......................................................... 192 
15.15.4.6. Pharmacokinetic Tables ........................................... 193 
15.15.4.7. Pharmacokinetic Figures .......................................... 194 
15.15.4.8. Virology Tables ......................................................... 195 
15.15.4.9. ICH Listings .............................................................. 196 
15.15.4.10. Non-ICH Listings ..................................................... 198 
15.15.5. List of Data Displays for Week 48/96/End-of-Study 
Planned Analyses ...................................................................... 201 
15.15.5.1. Study Population Tables ........................................... 201 
15.15.5.2. Efficacy Tables ......................................................... 208 
15.15.5.3. Efficacy Figures ........................................................ 216 
15.15.5.4. Safety Tables ........................................................... 218 
15.15.5.5. Safety Figures .......................................................... 232 
15.15.5.6. Pharmacokinetic Tables ........................................... 236 
15.15.5.7. Pharmacokinetic Figures .......................................... 238 
15.15.5.8. Pharmacokinetic / Pharmacodynamic Tables ........... 241 
15.15.5.9. Pharmacokinetic / Pharmacodynamic Figures .......... 242 
15.15.5.10. Health Outcomes Tables ......................................... 245 
15.15.5.11. Health Outcomes Figures ........................................ 253 
15.15.5.12. Virology Tables ....................................................... 255 
15.15.5.13. ICH Listings ............................................................. 257 
15.15.5.14. Non-ICH Listings ..................................................... 263 
15.15.6. List of Data Displays for Week 152 Planned Analyses ............... 268 
15.15.6.1. Study Population Tables ........................................... 268 
15.15.6.2. Efficacy Tables ......................................................... 272 
15.15.6.3. Efficacy Figures ........................................................ 277 
15.15.6.4. Safety Tables ........................................................... 279 
15.15.6.5. Safety Figures .......................................................... 288 
15.15.6.6. Pharmacokinetic Tables ........................................... 290 
15.15.6.7. Pharmacokinetic Figures .......................................... 292 
15.15.6.8. Pharmacokinetic / Pharmacodynamic Figures .......... 295 
15.15.6.9. Health Outcomes Tables .......................................... 297 
15.15.6.10. Health Outcomes Figures ........................................ 302 
15.15.6.11. Virology Tables ....................................................... 303 
15.15.6.12. ICH Listings ............................................................. 305 
15.15.6.13. Non-ICH Listings ..................................................... 308 
15.15.7. List of Data Displays for Sub-study Analysis .............................. 312 
15.15.7.1. Study Population Tables ........................................... 312 
15.15.7.2. Efficacy Tables ......................................................... 315 
15.15.7.3. Efficacy Figures ........................................................ 318 
15.15.7.4. Safety Tables ........................................................... 319 
15.15.7.5. Safety Figures .......................................................... 327 


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15.15.7.6. Pharmacokinetic Tables ........................................... 328 
15.15.7.7. Pharmacokinetic Figures .......................................... 330 
15.15.7.8. Health Outcomes Tables .......................................... 332 
15.15.7.9. Virology Tables ......................................................... 335 
15.15.7.10. ICH Listings ............................................................. 337 
15.15.7.11. Non-ICH Listings ..................................................... 340 
15.16. Appendix 16: Example Mock Shells for Data Displays .............................. 342 
 
 


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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol: 
Revision Chronology: 
2017N326521_00 
17-JUL-2017 
Original 
2017N326521_01 
14-SEP-2017 
The primary purpose of protocol amendment # 1 is to revise 
the study sample size to randomize approximately 1020 
participants including 510 participants per arm based on a 
non-inferiority margin of 4% between the CAB LA + RPV LA 
Q8W and Q4W arms. 
2017N326521_02 
03-Jul-2018 
The primary reasons for amendment #2 are to: 
• 
Add the additional interim analysis of data when all 
subjects have completed the Week 24 visit, with the 
intent of expediting the submission of study results 
to Health Authorities; 
• 
Change the objective for assessing the preference 
for CAB LA + RPV LA every 8 weeks or CAB LA + 
RPV LA every 4 weeks LA compared to oral 
antiretroviral (ARV) and the preference for CAB 
LA+ RPV LA every 8 weeks compared to CAB LA + 
RPV LA every 4 weeks from an exploratory 
objective to a secondary objective.  A change to the 
supporting version of the Preference questionnaire 
administered to participants at Week 48 (or 
withdrawal) is also acknowledged;  
• 
Add revisions and clarifications for the 
administration of health outcomes questionnaires; 
• 
Extend exclusion criterion #28 to also exclude 
hereditary coagulation and platelet disorders such 
as haemophilia or Von Willebrand Disease; 
• 
Update exclusion criterion #11 to indicate that 
CD4+ counts ˂200 cells/µL are not exclusionary; 
• 
Offer clarification that withdrawal assessments will 
be performed for any participant who withdraws 
prematurely from the Maintenance or Extension 
Phase.  Additional guidance for participants 
withdrawing at Week 52 or Week 100 has been 
added;  
• 
Offer guidance to monitor medications that are 
dependent on OAT1 and OAT3 transport upon 
concomitant exposure with CAB; 
• 
Specify that 2-hour post-dose ECG should be 
performed at Day 1 and Week 48 only for 
participants receiving CAB LA + RPV LA as it is not 
required to perform 2-hour post-dose ECG for 
those receiving oral CAB + RPV at Day 1; 


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Revision Chronology: 
• 
Exclude language that previously indicated 
hormonal contraception may be susceptible to 
interaction with the study drugs.  The lack of a 
demonstrated interaction with a representative 
contraceptive supports use of CAB and RPV across 
a broad range of estrogen and progestin or 
progestin only hormonal contraceptives; 
• 
Add minor clarifications and corrections to 
typographical errors/formatting to protocol text. 
2017N326521_03 
21-May-2020 
The primary reason for protocol amendment 03 is to include 
information on Covid-19 specific guidance for clinical trial 
continuity (participant and study management) during the 
pandemic. This information is included within Appendix 10: 
COVID-19 Pandemic and Clinical Trial Continuity. 
2017N326521_04 
05-Aug-2020 
The primary reasons for protocol amendment 04 are to add 
a formal efficacy and safety secondary analysis at Week 
152, allowing participants to continue treatment with 
randomized study medication through at minimum the Week 
152 timepoint. The study endpoints and additional 
assessments in support of the planned secondary analyses 
have been updated for Week 152. Health outcomes 
assessments including the HIV-TSQs, Accept, and PIN 
questionnaires are included at Week 152 to gain further 
insight into participant’s long-term treatment experience with 
Long-acting Cabotegravir Plus Long-acting 
Rilpivirine. The Preference questionnaire will also be 
administered at Week 152 only to participants who received 
oral bridging during the Maintenance and/or Extension 
Phases. Additional minor clarifications to protocol language 
have also been incorporated. 
TMF-11797977 
16-Apr-2021 
The primary purposes of this amendment are: 
• 
To allow participants who become pregnant to 
remain in the study and not be withdrawn due to 
pregnancy. Allowing pregnant participants to 
continue in the study will negate any additional and 
subsequent fetal exposures to new antiretrovirals 
agents that would occur if the pregnant participant 
was withdrawn from the study and placed on an 
oral SOC regimen. An Appendix, “Information and 
Guidance for Managing Pregnant Participants” was 
inserted as Appendix 11, and all subsequent 
appendices were renumbered accordingly. 
• 
Contraceptive methods have been updated to 
permit the use of progestogen-only implantable and 
injectable contraceptives without the requirement of 
a second highly effective method. 
• 
Removal of the optional collection of cord blood 
and/or breast milk after delivery. 


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Revision Chronology: 
• 
Removal of the option for study treatment 
rechallenge following suspected druginduced liver 
injury (DILI) 
• 
Clarification of which participants enter the LTFU 
phase when CAB+RPV LA marketed product is 
locally available. 
• 
Clarification added: The Reason for Oral 
Bridgingand Preference questionnaire will also be 
administered at Withdrawal if it occurred at or 
before Week 152 only to participants who received 
oral bridging during the Maintenance and/or 
Extension Phases. 
• 
Medical Device reporting requirement added 
• 
Co-enrolment (Only applicable for South African 
participants) 
• 
Clinical and safety references updated 
• 
Removal of the reference to “randomized study 
treatment” in Overall design sections for alignment 
with CAB program studies and transition to 
marketed product plan. 
TMF-13901227 
11-Aug-2021 
The primary purposes of this amendment are: 
• 
Included Thigh Injection Sub-study appendix 
• 
Added safety and PK laboratory assessments 
during pregnancy for subjects who become 
pregnant during the study and decide to continue 
receiving IM treatment in the study. 
• 
Medical device deficiencies reporting requirements 
updated to be aligned with GSK reporting 
processes. 
• 
Updated safety information 
• 
Other minor clarifications added 
 
1.1. 
RAP Amendments 
Revision Chronology: 
RAP Section 
Amendment Details 
Reporting and Analysis Plan_Study207966_Final_V1 [17-JAN-2019] 
Reporting and Analysis Plan_Study207966_Amendment_Final_V1 [23-JUN-2020] 
Reporting and Analysis Plan_Study207966_Amendment_2_Final_V1 [28-JUN-2020] 
Reporting and Analysis Plan_Study207966_Amendment_3_Final_V1 
Data Handling and Data 
Displays for Sub-study 
• 
Updated visit/phase slotting algorithms to handle the newly added 
assessments and time points in the protocol. 
• 
Added new analysis populations for sub-study analysis. 


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• 
Defined a separate list of displays for sub-study analysis. 
Safety Analysis 
• 
Added calculation methods for extent of exposure in sub-study. 
• 
Extended lipid LOCF approach to include both Thigh Injection and 
Return to Gluteal Injection phases in sub-study. 
• 
Updated the display shells for summaries of COVID-19 assessments to 
accommodate possible scenarios of multiple COVID-19 case diagnosis 
per participant. 
PK Analysis 
• 
Added analysis methods for PK parameters derived from sub-study 
concentration-time data. 
• 
Extended evaluability criteria to include sub-study PK concentration 
data. 
Study Population Analysis 
• 
Added windows for evaluating concomitant ART/non-ART medications 
in sub-study. 
• 
Added a listing for data collected from the Transition to CAB + RPV LA 
Marketed Product Status eCRF form. 
Health Outcomes Analysis 
• 
Added analysis for the newly added Preference Thigh Injection vs 
Gluteal Injection questionnaire. 
General Updates 
• 
Added sub-study Schedule of Activities per new protocol. 
• 
Added additional minor clarifications and corrections to typographical 
errors/formatting to RAP text. 
 


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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol amendment 6 [(Dated: 11/AUG/2021)]. 
2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• 
To demonstrate the non-inferior 
antiviral activity of CAB LA + RPV LA 
every 8 weeks (every two months) 
compared to CAB LA + RPV LA every 
4 weeks (monthly) over 48 weeks 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 Week 48 
(Intent-to-Treat Exposed [ITT-E] population) 
Secondary Objectives 
Secondary Endpoints 
• 
To demonstrate the antiviral and 
immunologic activity of CAB LA + 
RPV LA every 8 weeks compared to 
CAB LA + RPV LA every 4 weeks 
• 
Proportion of participants with plasma HIV-1 RNA <50 
c/mL (c/mL) at Week 24, Week 48, Week 96 and Week 
152 using the FDA Snapshot algorithm (Intent-to-Treat 
Exposed [ITT-E] population) 
• 
Proportion of participants with protocol-defined confirmed 
virologic failure (CVF) through Week 24, Week 48, Week 
96 and Week 152 
• 
Proportion of participants with HIV-RNA greater than or 
equal to 50 c/mL as per FDA Snapshot algorithm at Week 
24, Week 96 and Week 152 
• 
Absolute values and changes from Baseline in viral load 
and CD4+ cell counts over time including Week 48 and 
Week 96 and Week 152 
• 
To evaluate the safety and tolerability 
of CAB LA + RPV LA every 8 weeks 
compared to CAB LA + RPV LA every 
4 weeks 
• 
Incidence and severity of AEs and laboratory 
abnormalities over time including Week 24, Week 48, 
Week 96 and Week 152 
• 
Proportion of participants who discontinue treatment due 
to AEs over time including Week 24, Week 48, Week 96 
and Week 152 
• 
Change from Baseline in laboratory parameters over time 
including Week 48, Week 96 and Week 152 
• 
To assess viral resistance in 
participants experiencing protocol-
defined confirmed virologic failure 
• 
Incidence of treatment emergent genotypic and 
phenotypic resistance to CAB, RPV through Week 24, 
Week 48, Week 96 and Week 152 
• 
To characterize CAB and RPV 
concentrations and population 
pharmacokinetics and identify 
important determinants of variability 
• 
Plasma PK parameters for CAB LA and RPV LA (when 
evaluable, Ctrough, concentrations post dose [~Cmax], 
and area under the curve [AUC]) 
• 
Demographic parameters including, but not limited to, 
age, sex, race, body weight, body mass index, and 
relevant laboratory parameters will be evaluated as 


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Objectives 
Endpoints 
potential predictors of inter- and intra-participant 
variability for pharmacokinetic parameters 
• 
To assess preference for CAB LA + 
RPV LA every 8 weeks or CAB LA + 
RPV LA every 4 weeks LA compared 
to oral antiretroviral (ARV) 
• 
To assess preference for CAB LA+ 
RPV LA every 8 weeks compared to 
CAB LA + RPV LA every 4 weeks 
• 
Preference for CAB LA + RPV LA every 8 weeks and 
CAB LA + RPV LA every 4 weeks compared to oral ARV 
and preference for CAB LA + RPV LA every 8 weeks 
compared to CAB LA + RPV LA every 4 weeks will be 
assessed using a preference questionnaire at week 48 
(or Withdrawal). 
• 
To assess patient reported health-
related quality of life, treatment 
satisfaction, injection tolerability, and 
treatment acceptance.   
• 
Change from Baseline (Day 1) in HRQoL at Week 24, 
and Week 48 (or Withdrawal) 
• 
Change from baseline (Day 1) in total “treatment 
satisfaction” score, and individual item scores of the HIV 
Treatment Satisfaction Status Questionnaire (HIVTSQs) 
at Week 24, 48 and 152 (or Withdrawal) 
• 
Change in treatment satisfaction over time using the HIV 
Treatment Satisfaction Change Questionnaire HIVTSQc 
at Week 48 (or Withdrawal). 
• 
Change from Week 8 in Dimension scores (“Bother of 
ISRs”, “Leg movement”, “Sleep”, and “Injection 
Acceptance”) and individual item scores assessing pain 
during injection, anxiety before and after injection, 
willingness to be injected in the future and overall 
satisfaction with mode of administration over time will be 
assessed using the Perception of Injection questionnaire 
(PIN) at Weeks 24, 48 and 152 (or Withdrawal)  
• 
Change from Baseline (Day 1) in treatment acceptance at 
Week 24, Week 48 and 152 (or Withdrawal) will be 
assessed using the “General acceptance” dimension of 
the Chronic Treatment Acceptance (ACCEPT) 
questionnaire 
Exploratory Objectives 
Exploratory Endpoints 
• 
To evaluate the antiviral and 
immunologic effects, safety and 
tolerability, and viral resistance of 
CAB LA + RPV LA for all participants 
in the Extension Phase. 
• 
Proportion of participants with plasma HIV-1 RNA <50 
c/mL over time 
• 
Proportion of participants with confirmed virologic failure 
over time 
• 
Incidence of treatment emergent genotypic and 
phenotypic resistance to CAB and RPV over time 
• 
Incidence and severity of AEs and laboratory 
abnormalities over time 
• 
Proportion of participants who discontinue treatment due 
to AEs over time 
• 
Absolute values and changes in laboratory parameters 
over time 
• 
Incidence of disease progression (HIV-associated 
conditions, acquired immunodeficiency syndrome [AIDS] 
and death) 
• 
To explore the effect of patient 
characteristics on virologic and 
immunologic responses to CAB LA+ 
• 
Proportion of participants by patient subgroup(s) (e.g., by 
age, gender, BMI, race, HIV-1 subtype, Baseline CD4+, 
type of oral treatment [NNRTI, PI, or INSTI], duration prior 


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Objectives 
Endpoints 
RPV LA every 8 weeks compared to 
CAB LA + RPV LA every 4 weeks 
CAB LA and RPV LA exposure [0 weeks, 1-24 weeks, > 
24 weeks]) with HIV-RNA greater than or equal to 50 
c/mL, and with protocol-defined confirmed virologic failure 
over time including Week 48, Week 96 and Week 152 
using the Snapshot algorithm for the ITT-E population 
• 
Change from Baseline in CD4+ cell counts by subgroups 
at Week 48, Week 96 and Week 152 
• 
To explore relationship(s) between 
plasma concentrations of CAB and 
RPV and pharmacodynamic 
endpoints. 
• 
Relationship between plasma CAB and RPV 
concentrations and virologic, immunologic responses, 
and/or occurrence of adverse events [AEs] over time. 
• 
To assess reason for switching using 
a single question.  
• 
To assess reason for continuation 
using a single question 
• 
For patients randomized from oral SOC, the reasons for 
willingness to switch ART at baseline (Day 1) will be 
assessed 
• 
For patients randomized from CAB LA + RPV LA every 4 
weeks in ATLAS, the reasons for willingness to continue 
long-acting ART at baseline (Day 1) will be assessed 
• 
To assess preference for CAB LA + 
RPV LA every 8 weeks or every 4 
weeks compared to daily oral for 
participants receiving oral bridging 
during the Maintenance and/or 
Extension phases 
• 
Preference for CAB LA + RPV LA every 8 weeks or every 
4 weeks compared to daily oral for participants receiving 
oral bridging during the Maintenance and/or Extension 
phases will be assessed using a preference questionnaire 
at week 152 
 
2.2.1. 
Thigh PK Sub-study Objectives and Endpoints 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• 
To evaluate the PK of monthly and 
every two months dosing of CAB LA 
and RPV LA injections following 
intramuscular administration in the 
vastus lateralis (thigh) muscle 
(compared to gluteal injections) in 
HIV-1 infected participants currently 
enrolled in the A2M sub-study 
• 
Plasma PK parameters for CAB LA and RPV LA (Ctau, 
concentrations post dose [~Cmax], and area under the 
curve [AUC (0-tau)]) for thigh injections during the thigh 
injection phase compared with similar PK parameters for 
gluteal injections. 
Secondary Objectives 
Secondary Endpoints 
• 
To assess safety and tolerability of 
monthly and every two months 
dosing of CAB LA and RPV LA 
following intramuscular injections in 
the vastus lateral (thigh) muscle in 
HIV-1 infected participants currently 
enrolled in the A2M sub-study. 
• 
Incidence and severity of ISRs and AEs of special interest 
during the thigh injection phase. 
• 
Proportion of participants who discontinue treatment due 
to ISRs and AEs of special interest during the thigh 
injection phase. 
• 
To assess the ability to maintain 
virologic suppression (HIV-RNA < 50 
copies/mL) in subjects who transition 
to thigh administrations of CAB and 
• 
Proportion of participants with plasma HIV-1 RNA <50 
c/mL over time (including at Week 16) during the thigh 
injection phase using the FDA Snapshot algorithm. 
• 
Proportion of participants with plasma HIV-RNA ≥50 c/mL 
over time (including at Week 16) as per Food and Drug 


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Objectives 
Endpoints 
RPV after receiving at least 3 years of 
gluteal injections. 
Administration (FDA) Snapshot algorithm during the thigh 
injection phase. 
• 
Proportion of participants with protocol-defined confirmed 
virologic failure (CVF) during the thigh injection phase. 
• 
To assess viral resistance in 
participants experiencing protocol-
defined confirmed virologic failure. 
• 
Incidence of treatment emergent genotypic and 
phenotypic resistance to CAB, RPV during the thigh 
injection phase. 
• 
To assess patient reported outcomes 
during the thigh injection phase by 
administering the following health 
outcome measurements: Numerical 
Rating Scale (NRS) and HIVTSQ. 
• 
Numerical Rating Scale (NRS): To assess the 
tolerability of injections during both the Thigh and Gluteal 
Injection Phase 
• 
HIVTSQ (both s and c versions): To measure levels of 
satisfaction and detect change in satisfaction when 
switching from gluteal to thigh injections in total 
“treatment satisfaction” score, and individual item scores 
of the HIV Treatment Satisfaction Questionnaire 
(HIVTSQ) during the Thigh Injection Phase as well as the 
change from thigh during the Return to Gluteal Phase. 
• 
To assess participant’s preference of 
thigh injections during the thigh 
injection phase compared to gluteal 
injections. 
• 
 Preference Questionnaire: To assess patient’s 
preference, and reasons for preference, for injections 
received during the Thigh Injection Phase compared with 
prior gluteal injections as well as for injections received 
during the Return to Gluteal phase compared with prior 
thigh injections. 
Exploratory Objectives 
Exploratory Endpoints 
• 
To assess additional safety events 
including other AEs, SAEs, and safety 
labs of monthly and every two months 
dosing of CAB LA and RPV LA 
following intramuscular injections in 
the vastus lateral (thigh) muscle in 
HIV-1 infected participants currently 
enrolled in the A2M sub-study. 
• 
Incidence of other AEs not of special interest, SAEs and 
change in laboratory and change in laboratory 
parameters from the last gluteal injection (prior to the 
Thigh Injection Phase). 
 


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2.3. 
Study Design 
Overview of Study Design and Key Features 
Main Study: 
 
N=1020, randomized 1:1 to each arm and stratified by prior CAB+RPV Exposure 
# SOC Patients not transitioning from the ATLAS study must be on uninterrupted current regimen (either the initial 
or second cART regimen) for at least 6 months prior to Screening. Documented evidence of at least two plasma 
HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and 
one within 6 months prior to Screening.  No history of virologic failure.  No evidence of viral resistance based on the 
presence of any resistance-associated major INI, or NNRTI mutation (except K103N) from prior genotype assay 
results. No current or prior history of etravirine use. 
†Optional Extension Phase to continue randomized CAB LA + RPV LA Q4W or Q8W at Wk 100 
¥Participants who withdraw from IM arm must go into 52 week long term follow up phase if randomized regimen is 
not yet locally approved and commercially available.  
 
Sub-study: 
 
Note: All injection visits during the sub-study should be kept to the same projected visit schedule as in the main 
study. 
 


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Overview of Study Design and Key Features 
Design 
Features 
• 
Study 207966 (Antiretroviral Therapy as Long Acting Suppression every 2 Months-
ATLAS-2M) is a Phase IIIb, randomized, open-label, active-controlled, multicenter, 
parallel-group, non-inferiority study designed to assess the antiviral activity and 
safety of CAB LA + RPV LA administered every 4 weeks compared CAB LA + RPV 
LA administered every 8 weeks in approximately 1020 adult HIV-1 infected patients.   
• 
The ATLAS-2M main study comprises a Screening Phase (up to 35 days), and a 
Maintenance Phase (Day 1 to Week 100), followed by an Extension Phase (post 
Week 96). Additionally, any participant who receives at least a single dose of CAB 
LA and/or RPV LA and discontinues the CAB LA + RPV LA regimen will enter the 
Long-term Follow-up Phase and will initiate highly active antiretroviral therapy 
(HAART) for 52 weeks after the last dose of CAB LA and/or RPV LA, or until the 
assigned CAB LA + RPV LA regimen is locally approved and commercially 
available. 
• 
Two groups of patients who fulfill eligibility requirements will be randomized (1:1) at 
Day 1 in the main study to receive CAB LA + RPV LA Q4W, or CAB LA + RPV LA 
Q8W regimen for at least 100 weeks: 
• 
Group 1: Patients randomized from current ART Standard of Care (SOC) 
therapy 
• 
Group 2: Patients currently receiving CAB LA + RPV LA Q4W 
• 
After a minimum of 152 weeks on the ATLAS-2M main study, approximately 82 (41 
per treatment arm) eligible participants will be enrolled in the sub-study. The 
enrolled sub-study participants will receive the study treatment on the same 
frequency as their randomized treatment, for example, participants randomized to 
the Q8W treatment in the main study will continue receiving the study treatment in 
every 8 weeks in the sub-study.  
• 
The ATLAS-2M sub-study will consist of three phases including a Screening Phase 
(1 injection interval: 4 weeks for Q4W participants and 8 weeks for Q8W 
participants), a Thigh Injection Phase with 16 weeks of thigh injections (4 injection 
intervals for Q4W participants and 2 injection intervals for Q8W participants) and a 
Return to Gluteal Injection Phase with 8 weeks of gluteal injections for both Q4W 
and Q8W participants. At the conclusion of the sub-study, participants will have the 
option to continue on the A2M main study or if commercial access treatment is 
available, the participants can transition off the sub-study and withdraw from 
ATLAS-2M and proceed directly to CAB/RPV LA. 
Dosing 
• 
Group 1: oral therapy with CAB 30 mg + RPV 25 mg once daily at main study Day 1 
for 28 days (3 days) to determine individual safety and tolerability, followed by 
CAB LA + RPV LA Q4W or CAB LA + RPV LA Q8W (as randomized at main study 
Day 1) 
• 
Group 2: CAB LA + RPV LA Q4W or CAB LA + RPV LA Q8W (as randomized at 
main study Day 1) 
Time & 
Events 
• 
Refer to Appendix 2: Schedule of Activities 
Treatment 
Assignment 
• 
Randomized (1:1) at Day 1 to receive CAB LA + RPV LA Q4W or CAB LA + RPV 
LA Q8W 
• 
GSK RandAll NG used to generate randomization schedules 
• 
Stratified Randomization by prior CAB+RPV exposure (0 weeks, 1 to 24 weeks, >24 
weeks) 
Interim 
Analysis 
• 
Futility analysis at (approx.) 50% of subjects completing Week 24  
• 
Continuous time monitoring of confirmed virologic failure (CVF) in the Q8W 
randomized arm until all participants complete Week 24 visit 


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Overview of Study Design and Key Features 
• 
The main analysis will be conducted to evaluate the primary objective of the 
protocol at Week 48.  
• 
Preliminary analyses at Week 24 and analyses at Week 96 and Week 152 
• 
Sub-study analysis 
• 
Further data cuts and analyses may be conducted as necessary in order to support 
regulatory submissions and publications. 
2.4. 
Statistical Hypotheses / Statistical Analyses 
The study is designed to demonstrate that the antiviral effect of Q8W dosing with CAB 
LA + RPV LA is non-inferior to Q4W dosing CAB LA + RPV LA in subjects stably 
suppressed on an oral SOC regimen or Q4W CAB LA + RPV LA regimen prior to 
randomization.  Non-inferiority in the proportion of participants with HIV-1 RNA 50 
c/mL at Week 48 (defined by the US FDA snapshot algorithm) can be concluded if the 
upper bound of a two-sided 95% confidence interval for the difference between the two 
treatment arms (Q8W – Q4W) is less than 4%. 
If fQ8W is the snapshot failure rate for Q8W CAB LA + RPV LA, and fQ4W is the snapshot 
failure rate for Q4W CAB LA + RPV LA then the null (H0) and alternative (Ha) 
hypotheses can be written as follows: 
Ho: fQ8W – fQ4W  4% vs Ha: fQ8W – fQ4W < 4% 


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3. 
PLANNED ANALYSES 
Analyses will be conducted to support Independent Data Monitoring Committee (IDMC) 
review of study data. At least four analyses in main study will be conducted to evaluate 
the objectives of the protocol after all subjects have completed their visits at Week 24, 
Week 48, Week 96 and Week 152, respectively. Prior to Week 48 analysis complete, the 
Week 24 results will be restricted to only those study team members and GSK/ViiV 
Healthcare senior management who need to be involved in the analysis and interpretation 
of the results for reporting to regulatory authorities. Details on protection against 
operation bias for Week 48 analysis are documented in the Blinded Team Operating 
Principles for this study. There is no planned hypothesis testing on the treatment 
difference at Week 24 and no decisions will be made based on the Week 24 results. 
Details of the planned displays for Week 24 analyses are provided in Section 15.15.4. 
Further data cuts and analyses may be conducted as necessary in order to support 
regulatory submissions and publications (first publication at Week 48). The Week 48 
analysis will be primary and no results will be shared publicly until Week 48 analysis is 
complete. Additional analysis will be conducted to evaluate the objectives of the sub-
study after all subjects have completed their visits at Sub-study Week 24. A final End-of-
Study analysis will be conducted when all subjects have completed the study. 
3.1. 
IDMC Analyses 
An IDMC will be instituted to ensure external objective medical and/or statistical review 
of efficacy and safety to protect the ethical interests and well-being of subjects and to 
protect the scientific validity of this study.  
The IDMC will evaluate accumulating efficacy, tolerability, safety and PK of CAB LA + 
RPV LA Q8W during the study.  An interim futility analysis will be performed for the 
IDMC to evaluate the efficacy of CAB LA + RPV LA Q8W prior to the final analyses.   
The interim futility analysis will be performed with the intent of having approximately 
50% of participants reaching Week 24 and providing sufficient lead time to allow the 
IDMC to review the data prior to any participants reaching the Week 48 visit. A futility 
rule based on Bayesian posterior predictive probability approach will be applied to assess 
the probability that the CAB LA + RPV LA Q8W injectable regimen demonstrates non-
inferiority to the CAB LA + RPV LA Q4W regimen at Week 24, given the partial data 
set.  The sponsor will remain blinded to this analysis. 
In addition, the IDMC may also monitor the incidence of participants meeting Confirmed 
Virologic Failure (CVF) criteria before all subjects have completed Week 24 to ensure 
that subjects are not being sub-optimally treated in the CAB LA + RPV LA Q8W arm. 
Full details of the analyses, estimated timing, and the decision criteria that will be used to 
determine regimen performance will be pre-specified in the IDMC Charter. 
A list of outputs required for each IDMC analysis will be provided in the IDMC Charter. 
Data handing methods and derived data definitions will be the same as detailed in this 
RAP, unless otherwise stated. 


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3.2. 
Final Analyses 
The primary analysis will be conducted to evaluate the primary objective of the protocol 
at Week 48. These analyses will be performed after the completion of the following 
sequential steps: 
1. All subjects have completed Week 48 and had a re-test for HIV-1 RNA if necessary.  
2. All required database cleaning activities have been completed and database release 
(DBR) and database freeze (DBF) or database lock (DBL) has been declared by Data 
Management. 
3. All criteria for unblinding the randomization codes have been met. 
4. Randomization codes have been distributed according to Ramos NG procedures. 
Three secondary analyses in main study will be conducted at Week 24, Week 96 and 
Week 152, sub-study analysis, and a final End-of-Study analysis will be conducted when 
all subjects have completed the study as defined in the protocol. 
 
 


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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened  
• 
Comprised of all subjects screened for inclusion in the 
study.  
• 
Subjects may be re-screened once, for which they will 
receive a new subject number.  
• 
For disposition displays, except for the listing of subjects 
who were rescreened, only the latest re-screening data 
will be included. All screening data will be summarized or 
listed for other displays. 
• 
Study Population 
Randomized  
 
• 
All subjects who were randomly assigned to treatment in 
the study. 
• 
In this study, the randomized population includes all 
enrolled participants, i.e. the randomized population is 
equivalent to the enrolled population. 
• 
This population will be based on the treatment the 
participant was randomized to. 
• 
Study Population 
Safety 
• 
All randomized subjects who received at least one dose 
of study treatment. 
• 
Participants will be assessed according to actual 
treatment received. 
• 
Safety 
Intent-to-Treat 
Exposed (ITT-E) 
• 
All randomized subjects who received at least one dose 
of study treatment. 
• 
Subjects will be assessed according to their randomized 
treatment, regardless of the treatment they received.  
• 
Study Population 
• 
Efficacy 
• 
Health Outcomes 
Per-Protocol  
(PP) 
• 
All subjects in the ITT-E population with the exception of 
major protocol violators. 
• 
Protocol deviations that would exclude participants from 
the PP population are defined in Section 4.1 (Protocol 
Deviations) and Appendix 1: Protocol Deviation 
Management and Definitions for Per Protocol 
Population). 
• 
Efficacy 
(Sensitivity 
Analysis) 
Pharmacokinetic 
(PK) 
• 
All subjects who received CAB and / or RPV and 
underwent PK sampling during the study and provide at 
least 1 non-missing CAB and / or RPV plasma 
concentration value (Non-quantifiable [NQ] values will be 
considered as non-missing values). 
• 
PK 
Confirmed 
Virologic Failure 
(CVF) 
• 
All subjects in the ITT-E population who met Confirmed 
Virologic Failure (CVF) criteria. 
• 
Virology 
• 
Efficacy 
Long-term Follow-
up (LTFU) 
• 
All subjects receiving at least one dose of CAB LA and/or 
RPV LA who have discontinued the CAB LA + RPV LA 
regimen and have either at least one Long-term Follow-
up phase clinic visit (i.e. have at least one long-term 
follow-up visit shown in the study database, LTFU month 
1, LTFU month 3, etc) or have filled out the LTFU phase 
conclusion form or have indicated the continuation to 
LTFU phase in the subject continuation form. 
• 
Safety 
• 
Study Population 


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Population 
Definition / Criteria 
Analyses Evaluated 
Week 24 Futility 
• 
All subjects in the ITT-E population who started study 
treatment at least 168 days prior to the IDMC cut-off date 
(in order to account for subjects who withdrew early but 
would have reached Week 24) 
• 
The IDMC cut-off date is the predicted Week 24 visit date 
(Last Subject Last Visit) corresponding to the time at 
which approximately 50% of subjects have completed 
Week 24. 
• 
IDMC Futility 
Analysis (i.e. 
IDMC Week 24 
Analyses) 
Oral Lead-in 
• 
All subjects who received at least one dose of study 
treatment during the oral lead-in period in ATLAS-2M 
study. 
• 
Safety 
• 
Study Population 
• 
Efficacy 
Q4W ATLAS 
• 
All subjects in the ITT-E population who were 
randomized to Q4W arm in ATLAS. 
• 
Health Outcomes 
SOC 
• 
All subjects in the ITT-E population who either were 
randomized to SOC arm in ATLAS or did not participate 
in ATLAS. 
• 
Health Outcomes 
Oral Bridging 
• 
All subjects in the ITT-E population who received the oral 
bridging during the Maintenance and/or Extension 
phases. 
• 
Health Outcomes 
Sub-study 
Screened 
• 
Comprised of all subjects screened for inclusion in the 
sub-study.  
• 
All screened subjects will continue using their subject 
numbers received in the main study.  
• 
Study Population 
Sub-study Safety 
• 
All randomized subjects who received at least one CAB 
and/or RPV thigh injection. 
• 
Subjects will be assessed according to actual treatment 
received. 
• 
Safety 
• 
Virology 
Sub-study ITT-E 
• 
All randomized subjects who received at least one CAB 
and/or RPV thigh injection. 
• 
Subjects will be assessed according to their randomized 
treatment, regardless of the treatment they received. 
• 
Study Population 
• 
Efficacy 
• 
Health Outcomes 
Sub-study PK 
Concentration 
• 
All subjects who received at least one CAB and/or RPV 
thigh injection and provided at least one non-missing 
CAB and/or RPV plasma concentration value (non-
quantifiable values will be considered as non-missing 
values) during the sub-study.  
• 
PK 
Sub-study PK 
Parameter 
• 
All subjects who received at least one CAB and/or RPV 
thigh injection and had at least one evaluable PK 
parameter estimate during the sub-study. 
• 
PK 
Sub-study CVF 
• 
All subjects receiving at least one CAB and/or RPV thigh 
injection who met Confirmed Virologic Failure (CVF) 
criteria in the sub-study. 
• 
Virology 
• 
Efficacy 


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Population 
Definition / Criteria 
Analyses Evaluated 
Sub-study LTFU 
• 
All subjects receiving at least one CAB and/or RPV thigh 
injection who have discontinued the CAB LA + RPV LA 
regimen and have either at least one Long-term Follow-
up phase clinic visit (i.e. have at least one long-term 
follow-up visit shown in the study database, LTFU month 
1, LTFU month 3, etc) or have filled out the LTFU phase 
conclusion form or have indicated the continuation to 
LTFU phase in the subject continuation form. 
• 
Study Population 
Refer to Section 15.15: List of Data Displays which details the population used for each display. 
 
 
4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed. 
Important deviations which result in exclusion from the analysis population will also be 
summarised and listed. (Please refer to Appendix 1: Protocol Deviation Management and 
Definitions for Per Protocol Population). 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan. 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations and deviations which may lead to exclusion from the analysis are 
captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF. 


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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
RandAll NG Randomization System 
Data Displays for Reporting  
Code 
Description 
Description 
Order in TLF  
A 
Q8W  
Q8W 
1 
B 
Q4W  
Q4W 
2 
C/A 
Oral followed by Q8W  
Q8W 
1 
C/B 
Oral followed by Q4W  
Q4W 
2 
Notes: 
• 
Unless stated otherwise, data displays will present two treatment group columns (Q8W and Q4W), where 
treatment sequence C/A is pooled with sequence A and treatment sequence C/B is pooled with sequence B. The 
detailed treatment sequence descriptors (i.e. C/A and C/B) may be used in selected data listings. Treatment C 
refers to oral CAB + oral RPV, used for oral lead-in for subjects entering the study with no prior CAB+RPV 
exposure. 
 
Treatment comparisons will be displayed as follows using the descriptors as specified: 
1. Q8W vs Q4W 
 
5.2. 
Baseline Definitions 
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-treatment (see Table 8) assessment with a non-missing value, including those 
from unscheduled visits. ‘Pre-treatment’ in main study refers to prior to the study 
treatment (i.e. CAB and/or RPV) in this study, and ‘pre-treatment’ in sub-study refers to 
prior to the first CAB and/or RPV thigh injection. 
Electrocardiograms (ECGs) are to be performed in triplicate on main study Day 1 visit. 
The baseline value for an ECG parameter will be the mean of the last pre-treatment set of 
assessments from the same date, so long as at least one of the triplicate assessments is 
available. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
5.3. 
Multicentre Studies 
Data will be summarized for all centres combined. Country will be treated as an 
exploratory subgroup for analyses of the primary efficacy endpoint as described in 
Section 7.1.5.1 and secondary efficacy endpoint (HIV-1 RNA <50 c/mL) as described in 
Section 7.2.5.1. Some countries may be combined for exploratory subgroup analyses with 
consideration due to the number of participants enrolled. 


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5.4. 
Examination of Covariates, Other Strata and Subgroups 
5.4.1. 
Covariates and Other Strata 
The list of covariates and other strata may be used in descriptive summaries and 
statistical analyses, some of which may also be used for subgroup analyses. Additional 
covariates and other strata of clinical interest may also be considered. 
Category 
Details 
Strata 
Randomization Strata: 
 
For the proportion of participants with plasma HIV-1 RNA ≥ 50 c/mL per FDA Snapshot 
algorithm at Week 48 (primary endpoint), a stratified analysis with Cochran-Mantel 
Haenszel weights will be used to adjust the primary treatment comparison for the 
randomization strata corresponding to prior exposure to CAB+RPV (0 weeks, 1-24 
weeks, >24 weeks). A similar approach will be used to adjust the analysis of the 
proportion of participants with HIV-1 RNA <50 c/mL (per the FDA’s Snapshot algorithm) 
at Week 48 (key secondary endpoint) and repeat analyses of these endpoints at Week 
96 and Week 152.   
 
See Section 7.1.5.1 for additional details on the statistical analysis methodology. 
Other 
Subgroups / 
Covariates 
See details in Section 5.4.2 
 
5.4.2. 
Examination of Subgroups 
The following is a list of subgroups that may be used in descriptive summaries and 
statistical analyses. Additional subgroups of clinical interest may also be considered. 
• If the percentage of subjects is small within a particular subgroup, then the 
subgroup categories may be combined prior to un-blinding the trial. 
• If the category cannot be refined further, then descriptive rather than statistical 
comparisons may be performed for the particular subgroup. 
• For subgroup analysis, per European Medicines Agency Guideline on the 
investigation of subgroups in confirmatory clinical trials (EMA, 2014), factors 
defining a subgroup population may be put in three categories: 
EMA Subgroup Category 1: Factors with strong reason to expect a heterogeneous 
response to treatment. In this case separate trials should usually be planned. There are no 
factors falling into this category in this study. 
EMA Subgroup Category 2: Factors with at least some biological plausibility or external 
evidence such that a heterogeneous response might be hypothesized. In this study, 
stratified randomization strata, key demographic factors, Baseline CD4, CDC stage will 
be fall into this category. For these factors, subgroup analyses will be performed but 


CONFIDENTIAL 
 
 
 
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likely underpowered so that a formal proof of efficacy will not be available individually 
in all subgroups. If consistent findings across multiple comparisons were observed then 
these analyses would still be suggestive of a generalizable finding from the overall 
population. 
EMA Subgroup Guideline Category 3: Factor with good argumentation why 
homogeneity of response to treatment is plausible. The impact of factors falling into this 
category will be explored. 
• Additional covariates of clinical interest may also be considered. 
Category 
Covariates and / or Subgroups 
EMA Subgroup Category 2: 
Randomization Strata  
• 
Prior exposure to CAB+RPV (0 weeks, 1-24 weeks, >24 weeks) 
 
For analysis purposes, randomization strata will be rederived using 
eCRF data, even if this differs from the strata captured in RAMOS 
NG. 
 
All statistical analyses will adjust for the above randomization strata, 
unless stated otherwise. Treatment-by-Strata interactions will be 
assessed as specified in the analysis sections. 
Demographic and Baseline 
Characteristic Subgroups 
• 
Age: 
o < 35, 35 - < 50, ≥ 50 
For the statistical modelling, ‘< 35’ and ’35 - < 50’ will be 
consolidated i.e. the following age group will be used: 
o < 50, ≥ 50 
For the summary of demographic characteristics, the 
following age groups will also be presented: 
o ≤ 18, 19 - 64, ≥ 65 (FDAAA requirement) 
o 18 - 64, 65 - 84, ≥ 85 (EMA requirement) 
• 
Race: 
o White, Non-White 
o Black/African American, Non-Black/African American 
For the statistical modelling, only White vs Non-White is 
considered. 
• 
Sex at birth: 
o Female 
o Male 
• 
Country (not used for statistical modelling) 
o Argentina 
o Australia 
o Canada 
o France 
o Germany 
o Italy 
o Korea, Republic of 
o Mexico 


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Category 
Covariates and / or Subgroups 
o Russian Federation 
o South Africa 
o Spain 
o Sweden 
o United States 
• 
Baseline CD4+ cell count (cells/mm3): 
o  <350  
o 350 - < 500 
o ≥ 500 
• 
Baseline HIV-1 RNA (c/mL):  
o <50  
o ≥ 50 
• 
Derived Baseline Centers for Disease Control and Prevention 
(CDC) category: 
o Stage I  
o Stage II  
o Stage III  
• 
Prior Exposure to CAB+RPV: 
o 0 weeks 
o ≥ 1 weeks  
This subgroup will be used in efficacy analysis, in addition to 
the redrived randomization strata (prior exposure to 
CAB+RPV: 0, 1-24, and >24 weeks). It will also be used in 
health outcomes analysis. In other types of analysis, only the 
rederived randomization strata will be used. 
• 
Baseline BMI (kg/m2) 
o <30 
o ≥30 
• 
Baseline Third Agent Class: 
o CAB+RPV (for subjects with prior exposure to 
CAB+RPV in ATLAS, i.e. subjects transitioning from 
ATLAS who received CAB+RPV in ATLAS before 
entering ATLAS-2M) 
o NNRTI 
o INI 
o PI 
• 
Baseline Genotypic Subgroup Variables: 
The Baseline genotypic data became available for most of the 
subjects after the Week 48 analysis data cut, the following 
subgroups will be used in post-Week 48 analyses as appropriate. 
The baseline genotypic data for subjects transitioning from 
ATLAS comes from ATLAS PBMC samples collected at Baseline 
and the baseline genotypic data for new subjects comes from 
ATLAS-2M PBMC samples collected at Baseline. Different types 
of mutation are defined in Section 15.6.7. 
o Baseline HIV-1 Subtype: 
▪ 
A, A1, AG Combined 
▪ 
B 


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Category 
Covariates and / or Subgroups 
▪ 
C 
▪ 
Other 
o Baseline L74I (Non-mixture) INSTI Mutation: 
▪ 
Present 
▪ 
Not Present 
o Baseline Pre-specified INSTI Mutation (Excluding L74I 
Non-mixture): 
▪ 
Present 
▪ 
Not Present 
o Baseline RPV RAM: 
▪ 
Present 
▪ 
Not Present 
o Baseline NNRTI RAM (Excluding RPV RAM): 
▪ 
Present 
▪ 
Not Present 
EMA Subgroup Category 3: 
Additional subgroup/covariates for 
PK/PD efficacy analysis 
PK/PD efficacy analysis will be performed for participants without prior 
exposure to CAB + RPV. 
• 
Week 8 CAB/RPV Trough PK concentration (i.e. pre-dose PK 
concentration at nominal visit of Week 8) 
The above covariate will be dichotomized into two subgroup factors 
as follows:  
o ≤ first Quartile vs > first quartile, 
o ≤ Median vs > Median 
 
The concentration will also be treated as continuous variable in 
logistic regression modelling analysis (i.e. the concentration data will 
be log2 transformed in this analysis so that, for assessing the effect, 
one unit increase of the point estimate of log2 PK concentration is 
equivalent to ‘doubling the concentration’ in the original value). 
 
• 
Length of First CAB/RPV Injection Needle (<2, ≥2 inches) 
Additional subgroup/covariates for 
PK/PD safety analysis 
Last CAB/RPV trough PK concentration  
For the plot of Maximum Change from Baseline (CFB) in ALT/Total 
Bilirubin versus Last Trough CAB/RPV PK Concentrations, Last 
CAB/RPV Trough PK Concentration is the most recent trough PK 
concentration prior or equal to the date of the lab assessment with 
maximum CFB during the maintenance phase. 
For the Plot of Maximum Toxicity Grades of Most Frequently 
Reported Study Drug ISR adverse events (AEs) versus Last Trough 
CAB/RPV PK Concentrations, Last CAB/RPV Trough PK 
Concentration is the most recent trough PK concentration prior or 
equal to the earliest onset date of the most frequently reported Study 
Drug ISR AE with maximum toxicity grade, during the maintenance 
phase. If a participant has no Study Drug ISR AE most commonly 


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Category 
Covariates and / or Subgroups 
reported, then the last trough value during the maintenance phase will 
be used for the plot.  
Additional subgroup for common 
drug-related study drug injection 
site reaction (ISR) with maximum 
toxicity grade 
For each preferred term of the common drug-related study drug ISR 
with maximum toxicity grade (pain, induration, nodules and any other 
study drug ISR with >=5% subjects in either treatment arm) during the 
maintenance phase: 
• 
Needle Length for Last CAB Injection prior to and including the 
onset date of the earliest corresponding drug-related CAB ISR 
with maximum toxicity grade during the maintenance phase: 
≤1.5, >1.5 to <2, ≥2 inches 
• 
Needle Length for Last RPV Injection prior to and including the 
onset date of the earliest corresponding drug-related RPV ISR 
with maximum toxicity grade during the Maintenance Phase: 
≤1.5, >1.5 to <2, ≥2 inches 
 
Note: If there is no ISR of interest reported during the period of 
interest for a subject, the needle length of last injection during that 
period will be used in the summary. 
 
5.5. 
Multiple Comparisons and Multiplicity 
5.5.1. 
Primary Comparison of Interest 
The primary analysis will be based on the ITT-E population. The primary comparison 
will be made at a one-sided 2.5% level of significance. Treatment with Q8W will be 
declared non-inferior to Q4W if the upper end of a two-sided 95% confidence interval for 
the difference between the two groups (Q8W – Q4W) in the proportion of participants 
with HIV-1 RNA ≥50 c/mL at Week 48 (defined by the US FDA snapshot algorithm) lies 
below 4%. 
The primary comparison of interest is the comparison between Q8W (CAB LA + RPV 
LA Q8W) and Q4W (CAB LA + RPV LA Q4W) for the primary endpoint in the ITT-E 
population. This analysis will be adjusted for by the re-derived randomization strata 
based on eCRF data. 
5.5.2. 
Other Comparisons of Interest 
If the primary comparison of interest (Section 5.5.1) using the ITT-E population 
demonstrates non-inferiority of Q8W compared to Q4W then the following key 
secondary comparisons will be tested:  
• Treatment with Q8W will be declared non-inferior to Q4W with respect to the 
proportion of participants with HIV-1 RNA < 50 c/mL at Week 48 (defined by the 
US FDA snapshot algorithm) if the lower end of a two-sided 95% confidence 
interval for the difference between in rates (Q8W – Q4W) lies above -10% using 
the ITT-E population 


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• Superiority of Q8W compared to Q4Wwith respect to change from baseline 
HIVTSQs total score at Week 48 using the ITT-E population and a two-sided 5% 
level of significance. Refer to Section 12.5.1 for details. 
For the primary endpoint treatment comparison at Week 48, no multiple comparison 
adjustment is necessary for testing non-inferiority followed by superiority (conditional on 
achieving a significant test for non-inferiority) since testing follows a pre-specified 
sequence of hypothesis such that if the first hypothesis tested is not significant, all 
subsequent tests will not be performed. This fixed sequence procedure controls the type I 
error rate at the nominal level. The primary endpoint treatment comparison at Week 48 
will also be performed using the PP population and the results will be compared for 
consistency with the results from the ITT-E population. 
In addition to the primary and the key secondary comparisons, the comparisons between 
two treatment arms for ACCEPT (general acceptance score), PIN (Domain scores 
(Bother of ISRs, Leg movement, Sleep, and Acceptance) and Individual Items Scores 
(Anxiety before, Pain, Satisfaction, Anxiety After, Willingness)), HAT-QoL (Life 
satisfaction, HIV medications, disclosure worries) and HIVTSQc (Treatment Satisfaction 
score) at timepoints through Week 48 will also be performed as supportive analyses. 
Lastly, for the IDMC interim analyses, since the statistical stopping guidelines will not 
result in early stopping for positive efficacy findings, these interim treatment 
comparisons will not inflate the Type I error rate for the primary treatment comparison. 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 
Section 
Component 
15.2.3 
Error! Not a valid result for table.: Assessment Windows 
15.4 
Appendix 4: Study Phases and Treatment State 
15.5 
Appendix 5: Data Display Standards & Handling Conventions 
15.6 
Appendix 6: Derived and Transformed Data 
15.7 
Appendix 7: Reporting Standards for Missing Data 
15.8 
Appendix 8: Values of Potential Clinical Importance 
15.9 
Appendix 9: Snapshot Algorithm Details 
15.10 
Appendix 10: Variables Defined for Time to Event Analysis 
15.11 
Appendix 11: Identification of Adverse Events of Special Interest 
15.12 
Appendix 12: Identification of COVID-19 Adverse Events 
15.13 
Appendix 13: IDMC 
 


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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the Intent-to-Treat Exposed population, 
unless otherwise specified. 
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and oral study treatment accountability will be based on GSK Core Data Standards.  
Table 1 provides an overview of the planned study population analyses, with details of 
the planned displays are presented in Appendix 15: List of Data Displays. 
Table 1 
Overview of Planned Study Population Analyses  
Display Type 
Data Displays Generated 
Table 
Listing 
Randomization 
Randomization [1] 
 
Y[2] 
Subject Disposition 
Study Populations [3] 
Y 
 
Study Recruitment [3] 
Y 
 
Reasons for Screening Failures [3] 
Y 
Y 
Rescreened Subjects [3]   
 
Y 
Age Ranges 
Y 
 
Subject Disposition 
Y[4][5] 
 
Reasons for Withdrawal 
Y[4][5] 
Y 
IP Discontinuation 
Y 
Y 
Important Protocol Deviations 
Y 
Y 
Deviations leading to exclusion from PP 
Y 
Y 
Inclusion and Exclusion Criteria Deviations 
Y 
Y  
Demography and Baseline 
Demographics Characteristics [6] 
Y 
Y 
Race & Racial Combinations [7] 
Y 
Y 
Hepatitis Status at Entry 
Y 
 
Baseline CDC Classification of HIV infection (2014) 
Y 
 
Baseline Cardiovascular Risk Assessments 
Y 
 
Distribution of CD4+ Cell Counts at Screening and Baseline 
Y 
 
Prior Exposure to CAB+RPV 
Y 
 
HIV-1 Risk Factors 
Y 
 


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Display Type 
Data Displays Generated 
Table 
Listing 
Medical Conditions, Concomitant Medications & Antiretroviral Therapy 
Medical Conditions (Current/Past) [8] 
Y 
 
Medical Conditions: Sub-conditions (Current/Past) [9, 10] 
Y  
 
Concomitant Medications (non-ART) 
Y[10] 
 
Prior ART Medications 
Y 
Y 
Concomitant ART Medications during Maintenance Phase 
 
Y 
ART Medications Received during LTFU Phase 
 
Y 
Lipid Modifying Agents (Baseline and during Maintenance Phase) 
Y 
 
Substance use at Entry 
Y 
 
Medical History of Seizure 
 
Y 
Other  
Oral Study Treatment Accountability [11] 
 
Y 
Transition to CAB+RPV LA Marketed Product  
 
Y 
NOTES: 
• 
T = Tables, L = Listings, Y = Display Generated, 
1. 
Base on Randomized population. 
2. 
One listing of participants randomized but not treated, and one listing of randomized and actual strata and 
treatment assignment. 
3. 
All Subjects screened population. 
4. 
Participants who have not been recorded as either completing or withdrawing from the study will be categorized 
as “Ongoing at time of the analysis” for summary purposes. 
5. 
Analysis of subject disposition will be performed for each Study Phase separately, as well as for overall study 
conclusion. 
6. 
Age and ethnicity collected at Screening; weight and height collected at Baseline. 
7. 
The five high level FDA race categories and designated Asian subcategories will be summarised along with all 
combinations of high level categories which exist in the data. The nine race categories collected will be 
summarised along with categories for mixed race. A by-subject listing of race will also be produced. 
8. 
Medical conditions will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
9. 
Sub conditions are Cardiac, Gastrointestinal, Metabolism and Nutrition, Psychiatric, Renal and Urinary, and 
Nervous System Conditions. 
10. summarised by, Ingredient combinations.  
11. Dispensation information (dates and number of tablets dispensed and returned). 
6.2. 
Prior and Concomitant Medications 
Non-ART and/or ART Medications will be classified by categories shown in Table 2. 
The same medication may be classified by more than one category. For example, if the 
medication was started after the maintenance treatment start date and was stopped at 
nominal Week 104 visit while subject was still receiving study treatment, this medication 
would be considered both ‘concomitant during maintenance’ and ‘concomitant during 
extension’. 
 
 


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Table 2 
Derived Data for Non-ART Medications/ART Medications 
 
Definition 
Prior 
Medication Taken < Maintenance Treatment Start Date 
Concomitant 
during 
Maintenance 
For subjects continuing into Extension Phase: 
Maintenance Treatment Start Date[a] ≤ Medication Taken < Date of Nominal Week 
100 Visit  
 
For subjects not continuing into Extension Phase: 
For participants continuing into LTFU Phase: 
Maintenance Treatment Start Date[a] ≤ Medication Taken < LTFU ART Start Date[b] 
 
Concomitant 
during Extension 
For subjects continuing into Extension Phase and not entering the sub-study: 
If subjects continued into LTFU Phase after the Extension phase: 
Date of Nominal Week 100 Visit[c] ≤ Medication Taken < LTFU ART Start Date 
If subjects transitioned to marketed product/alternative HAART and did not withdraw 
study due to safety related reason, then 
Date of Nominal Week 100 Visit[c] ≤ Medication Taken < Date of end of study +35 
days (Q4W)  or + 63 days (Q8W) 
For subjects continuing into Extension Phase, entering the sub-study but not 
returning to Extension Phase: 
Date of Nominal Week 100 Visit[c] ≤ Medication Taken < Date of First Sub-study 
Record  
For subjects continuing into Extension Phase, entering the sub-study and 
returning to Extension Phase: 
Before the sub-study: Date of Nominal Week 100 Visit[c] ≤ Medication Taken < Date of 
First Sub-study Record 
After the sub-study:  
For participants continuing into LTFU Phase after return to extension phase: 
End of Sub-study Date[c] < Medication Taken < LTFU ART Start Date[b] 
For participants transitioned to marketed product/alternative HAART and did 
not withdraw study due to safety related reason: 
End of Sub-study Date[c] < Medication Taken < Date of end of study +35 days (Q4W)  
or + 63 days (Q8W) 
Concomitant 
during Sub-study 
Screening 
For subjects entering the sub-study and not receiving any thigh injection: 
If participants continued into LTFU Phase after the sub-study, then  
Date of First sub-study record ≤ Medication Taken < LTFU ART Start Date[b] 
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of First sub-study record ≤ Medication Taken < Date of end of study +35 days 
(Q4W)  or + 63 days (Q8W) 
If participants continued into Extension Phase after the sub-study, then 
Date of First sub-study record ≤ Medication Taken ≤ End of Sub-study Date[c] 
For participants entering the sub-study and receiving thigh injection(s): 
Date of First sub-study record ≤ Medication Taken < Date of First Thigh Injection 


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Concomitant 
during Thigh 
Injection 
For participants continuing into Return to Gluteal Injection Phase: 
Date of First Thigh Injection[d] ≤ Medication Taken < Date of Nominal Sub-study Week 
16 Visit[c] 
For participants not continuing into Return to Gluteal Injection Phase: 
If participants continued into LTFU Phase after the sub-study, then  
Date of First Thigh Injection ≤ Medication Taken < LTFU ART Start Date[b] 
If participants continued into Extension Phase after the sub-study, then 
Date of First Thigh Injection ≤ Medication Taken ≤ End of Sub-study Date[c] 
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of First Thigh Injection ≤ Medication Taken ≤ Date of end of study +35 days 
(Q4W)  or + 63 days (Q8W) 
Concomitant 
during Return to 
Gluteal Injection 
For participants continuing into Extension Phase after the sub-study: 
Date of Nominal Sub-study Week 16 Visit[c] ≤ Medication Taken ≤ End of Sub-study 
Date[c] 
For participants continuing into LTFU Phase after the sub-study: 
Date of Nominal Sub-study Week 16 Visit[c] ≤ Medication Taken < LTFU ART Start 
Date[b] 
For participants transitioned to marketed product/alternative HAART and did 
not withdraw study due to safety related reason: 
Date of Nominal Sub-study Week 16 Visit[c] ≤ Medication Taken ≤ Date of end of 
study +35 days (Q4W)  or + 63 days (Q8W) 
Received during 
Long-term Follow-
up 
For subjects Who received at least one CAB and/or RPV injection and have 
started LTFU ART: 
Medication Taken ≥ LTFU ART Start Date 
NOTES:  
• 
Please refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and 
partial dates for medications. Use the rules in this table if medication date is completely missing. 
• 
[a] The ART medication stopped on start date of Maintenance treatment will be considered a prior 
medication and will not be considered concomitant during the Maintenance phase. If the stop date 
of ART medication is completely missing and this medication is recorded in eCRF as prior (e.g. 
prior ART or prior ATLAS ART forms), it will be considered a prior medication and will not be 
considered concomitant during the Maintenance phase. 
• 
[b] If subjects have missing LFTU ART start date, only the lower bound will be considered in the 
derivation. 
• 
[c] Refer to Section 15.6.1 for the definition. 


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7. 
EFFICACY ANALYSES 
7.1. 
Primary Efficacy Analyses 
7.1.1. 
Endpoint / Variables 
Proportion of participants with plasma HIV-1 RNA ≥50 c/mL as per Food and Drug 
Administration (FDA) Snapshot algorithm at Week 48 (Intent-to-Treat Exposed [ITT-E] 
population); see Section 15.9 for additional details. 
7.1.2. 
Summary Measure 
Difference in the proportion of participants with HIV-1 RNA 50 c/mL at Week 48 
(defined by the US FDA snapshot algorithm) between each treatment group (Q8W – 
Q4W). 
7.1.3. 
Population of Interest  
The primary efficacy analyses will be based on the Intent-to-Treat Exposed population, 
unless otherwise specified. 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
As defined by the Snapshot algorithm, HIV-1 RNA  50 c/mL is determined by the last 
available HIV-1 RNA measurement while the participant is on treatment within the 
analysis visit window of interest.   
Participants without on-treatment HIV-1 RNA data for the visit of interest and who 
discontinue treatment for reasons not related to adverse event while having HIV-1 RNA 
 50 c/mL at time of discontinuation or who change study treatment not permitted per 
protocol before the analysis window are classified as having HIV-1 RNA  50 c/mL. 
7.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 15: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
7.1.5.1. 
Statistical Methodology Specification 
Endpoint 
• Proportion of Participants with plasma HIV-1 RNA  50 c/mL at Week 48 using the Snapshot 
algorithm for the ITT-E population. Subjects with ‘HIV-1 RNA  50 c/mL’ per Snapshot 
algorithm include those who had plasma HIV-1 RNA ≥ 50 c/mL at Week 48, who discontinued 
for lack of efficacy, who discontinued for other reasons while not <50 c/mL, or who changed 
ART.  


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Snapshot Dataset 
• Virologic outcome (‘HIV-1 RNA <50 c/mL’ or ‘HIV-1 RNA  50 c/mL’) per Snapshot algorithm is 
determined by the last available on-treatment HIV-1 RNA measurement within the analysis visit 
window of interest (please refer to analysis window defined in Table 10). In addition, subjects 
who discontinue for reasons not related to adverse event with on-treatment HIV-1 RNA result 
at the time of discontinuation  50 c/mL or who change study treatment not permitted per 
protocol during maintenance phase before the analysis visit are classified as ‘HIV-1 RNA  50 
c/mL’.   
• Full details of the Snapshot algorithm are provided in Section 15.9.  
Model Specification 
• The primary efficacy endpoint will be analysed using a stratified analysis with Cochran-Mantel-
Haenszel (CMH) weights, adjusting for the rederived randomization strata corresponding to 
prior exposure to CAB+RPV (0 weeks, 1-24 weeks, >24 weeks) 
• The CMH estimate of the adjusted treatment difference will be calculated as a weighted 
average of strata-specific estimates of the treatment difference calculated within each stratum 
as follows: 
o If nk is the number of Q8W treated participants, mk is the number of Q4W arm treated 
participants, and Nk = nk + mk is the total number of participants in the kth stratum, then 
the CMH estimate is given by 
 
where 
 
are CMH weights and       are estimates of the differences in proportions between the two 
treatment arms, fQ8W-fQ4W, for the kth stratum. 
 
• The corresponding two-sided 95% CI will be calculated as 
𝑑̂𝑐𝑚ℎ± 1.96 × √𝑣𝑎𝑟
̂ (𝑑̂𝑐𝑚ℎ) 
where the variance estimator [Sato, 1989] is consistent in both sparse data and large strata 
and is given below: 
(
)
(
)
(
)
(
)
(
)2
2
ˆ
ˆ
ˆ
raˆ
v


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

+
=
+
=
k
k
k
cmh
k
k
k
k
k
cmh
cmh
W
Q
P
d
N
m
n
Q
P
d
d
  
where 


=
k
k
k
cmh
W
d
W
d
ˆ
ˆ
k
k
k
k
N
m
n
W
=
k
dˆ


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2
2
2
2
/)
(
k
k
k
k
k
k
k
k
k
k
N
n
m
m
n
x
m
y
n
P
−
+
−
=
 
2
/)
(
/)
(
k
k
k
k
k
k
k
k
k
N
x
n
y
N
y
m
x
Q
−
+
−
=
 
with xk and yk corresponding to the number of participants with Plasma HIV-1 RNA  50 c/mL 
at Week 48 per FDA Snapshot for Q8W and Q4W, respectively, for the kth stratum. 
Model Results Presentation 
• Adjusted CMH estimate of the difference in the proportion of subjects with Plasma HIV-1  50 
c/mL between each treatment group (Q8W – Q4W) and corresponding 95% confidence 
interval.  
• Non-inferiority will be concluded if the upper bound of the two-sided 95% confidence interval 
for the CMH adjusted treatment difference (Q8W – Q4W) is less than 4%. 
• If this analysis shows non-inferiority, then a superiority hypothesis will be tested at the two-
sided 5% level of significance. Superiority favoring Q8W will be declared if the upper bound of 
the confidence interval is below 0% for the ITT-E population analysis. If superiority is declared, 
the p-value for superiority will also be calculated. 
Subgroup Analyses 
1. Treatment Heterogeneity across rederived randomization strata [prior exposure to CAB+RPV 
(0 weeks, 1-24 weeks, >24 weeks)]: 
• The weighted least squares chi-squared statistic [Fleiss, 1981] will be used to test for one-
way homogeneity across the levels of each categorical variable, with each categorical 
variable considered separately.  
• Following Lui and Kelly [Lui, 2000] ½ will be added to each cell in any strata for which the 
stratum-specific rate estimates of either fQ8W or fQ4W are zero or one, and tests will be one-
sided.  
• Any heterogeneity found to be statistically significant will be explored and if necessary 
results will be reported for each level of the categorical variable. Investigation of 
heterogeneity will be confined to the primary endpoint. Tests of homogeneity will be 
assessed at the one-sided 10% level of significance. 
 
2. Stratum-specific analyses for two groups of participants: (Group 1) those currently receiving 
Standard of Care antiretroviral therapy at Baseline (i.e. no prior exposure to CAB+RPV), 
(Group 2) those receiving Q4W CAB LA + RPV LA therapy in the ongoing ATLAS study (i.e. 
have prior exposure to CAB+RPV).  For each stratum (Group 1 and Group 2), the following will 
be presented: 
• Proportion of subjects with plasma HIV-1 RNA ≥ 50 c/mL at Week 48 by treatment group. 
• Unadjusted difference in proportions between treatment groups and corresponding two-
sided 95% CI. 
• Summary of study outcomes (i.e. HIV-1 RNA < 50 c/mL, HIV-1 RNA ≥50 c/mL and reason 
for no data in the window) 
 


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For Group 2, a stratum-adjusted analysis will also be provided, with adjustment for prior CAB+RPV 
exposure (1 to 24 weeks vs. >24 weeks) using Cochran-Mantel Haenszel (CMH) weights, as 
described in the model specification above for the overall primary analysis. 
 
3. Exploration of Subgroups 
• An analysis for subgroups listed in Section 5.4.2 will be performed. This will show the 
proportion of subjects with plasma HIV-1 RNA ≥50 c/mL at the time of analysis (Week 48) 
based on the Snapshot algorithm and will be presented by treatment group. 
• Unadjusted difference in proportions between treatment groups and corresponding two-
sided 95% CI will also be presented by subgroups.  The confidence interval will be 
calculated using an unconditional exact method [Chan, 1999] with two inverted one-sided 
tests based on the score statistic. These results will also be presented graphically.   
• Summary of study outcomes (i.e. HIV-1 RNA < 50 c/mL, HIV-1 RNA ≥50 c/mL or reason 
for no data in the window) by subgroup will be produced. 
 
Note: These subgroup analyses will be exploratory and likely underpowered so that 
interpretation may therefore focus on point estimates as well as the upper bounds of 95% CIs 
for the treatment differences and response rates. Additionally, multiple comparisons are being 
made which inflates the risk of false positive findings. Therefore, if consistent findings across 
the multiple comparisons were observed then these analyses would still be suggestive of a 
generalizable finding of non-inferiority. 
Sensitivity and Supportive Analyses 
1. Per-protocol population analysis: 
• To assess the impact of important protocol deviations, statistical analysis will be repeated 
using the Per-protocol population and compared for consistency with the results from the 
primary ITT-E population analysis. 
7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoints 
The key secondary efficacy endpoint is the proportion of participants with plasma HIV-1 
RNA < 50 c/mL at Week 48 using the FDA Snapshot algorithm (Intent-to-Treat Exposed 
[ITT-E] population). 
Other secondary efficacy endpoints for the study are listed below: 
• Proportion of participants with plasma HIV-1 RNA < 50 c/mL at Week 24, Week 
96 and Week 152 using the FDA Snapshot algorithm (ITT-E population) 
• Proportion of participants with plasma HIV-1 RNA < 50 c/mL over time 
(including at Sub-study Week 16) using the FDA Snapshot algorithm during the 
Sub-study Thigh Injection phase (Sub-study ITT-E population) 
• Proportion of participants with protocol-defined confirmed virologic failure 
(CVF) through Week 24, Week 48, Week 96 and Week 152 
• Proportion of participants with protocol-defined confirmed virologic failure 
(CVF) through the Sub-study Thigh Injection phase 


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• Proportion of participants with HIV-1 RNA ≥50 c/mL as per FDA Snapshot 
algorithm at Week 24, Week 96 and Week 152 
• Proportion of participants with plasma HIV-1 RNA ≥ 50 c/mL over time 
(including at Sub-study Week 16) using the FDA Snapshot algorithm during the 
Sub-study Thigh Injection phase 
• Absolute values and changes from Baseline in viral load and CD4+ cell counts 
over time including Week 48, Week 96 and Week 152 
7.2.2. 
Summary Measure 
Difference in the proportion of participants with HIV-1 RNA < 50 c/mL at Week 24, 
Week 48, Week 96 and Week 152 (defined by the US FDA snapshot algorithm) between 
each treatment group (Q8W – Q4W). 
Difference in the proportion of participants with HIV-1 RNA ≥ 50 c/mL at Week 24,  
Week 96 and Week 152 (defined by the US FDA snapshot algorithm) between each 
treatment group (Q8W – Q4W). 
7.2.3. 
Population of Interest  
The secondary efficacy analyses will be based on the Intent-to-Treat Exposed population, 
unless otherwise specified. 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events 
As defined by the snapshot algorithm, participants with last available HIV-1 RNA 
measurement less than 50 c/mL while the participant is on treatment within the analysis 
visit window of interest are classified as HIV-1 RNA < 50 c/mL.  
Participants without on-treatment HIV-1 RNA data for the visit of interest and who 
discontinue treatment for reasons not related to adverse event while having HIV-1 RNA 
 50 c/mL at time of discontinuation or who change study treatment not permitted per 
protocol before the analysis window are classified as having HIV-1 RNA  50 c/mL. 
7.2.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 15: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
7.2.5.1. 
Statistical Methodology Specification 
Key Secondary Statistical Analysis  
Endpoint 
• Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA 
Snapshot algorithm (Intent-to-Treat Exposed [ITT-E] population) 


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Key Secondary Statistical Analysis  
Snapshot Dataset 
• As Section 7.1.5.1 and Section 15.9 
Model Specification 
• As specified in Section 7.1.5.1 but with ‘HIV-1 RNA <50 c/mL’ replacing HIV-1  50 c/mL 


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Key Secondary Statistical Analysis  
Model Results Presentation 
• Adjusted CMH estimate of the difference in the proportion of participants with HIV-1 RNA < 50 
c/mL at Week 48 between each treatment group (Q8W – Q4W) and corresponding 95% 
confidence interval.  
• Non-inferiority will be concluded if the lower bound of the two-sided 95% confidence interval for 
the CMH adjusted treatment difference (Q8W – Q4W) is greater than -10%.    
Subgroup Analyses 
• As specified in Section 7.1.5.1 but with HIV-1 RNA < 50 c/mL replacing ‘HIV-1 RNA  50 c/mL. 
Sensitivity and Supportive Analyses 
1. Per-protocol population analysis: 
• To assess the impact of important protocol deviations, statistical analysis will be repeated 
using the Per-protocol population and compared for consistency with the results from the 
primary ITT-E population analysis.  
 


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7.3. 
Exploratory Efficacy Analyses 
Table 3 provides an overview of the planned exploratory efficacy analyses. Details of the 
planned displays are provided in Appendix 15: List of Data Displays and will be based on 
GSK data standards and statistical principles. The exploratory efficacy analyses will be 
based on the Intent-to-Treat Exposed population, unless otherwise specified. 
Table 3 
Overview of Exploratory Efficacy Analyses 
Endpoints 
Absolute  
Change from Baseline  
Stats Analysis 
Summary Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Proportion of participants without efficacy-related discontinuation (ERDF) or treatment-related 
discontinuation (TRDF) failure at Week 24/Week 48/Week 96/Week 152 
Kaplan-Meier estimate 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Proportion of participants with plasma HIV-1 RNA ≥50 c/mL over time (Maintenance Phase) - 
Snapshot 
by visit 
 
 
 
Y 
Y[1] 
 
 
 
 
 
 
 
 
 
By visit and subgroup 
 
 
 
Y 
Y[2] 
 
 
 
 
 
 
 
 
 
Proportion of participants with plasma HIV-1 RNA <50 c/mL over time (Maintenance Phase) - 
Snapshot 
by visit 
 
 
 
Y 
Y[3] 
 
 
 
 
 
 
 
 
 
By visit and subgroup 
 
 
 
Y 
Y[2] 
 
 
 
 
 
 
 
 
 
Proportion of participants with plasma HIV-1 RNA ≥200 c/mL over time (Maintenance Phase) - 
Snapshot 
by visit 
 
 
 
Y[4] 
Y[5] 
 
 
 
 
 
 
 
 
 
Proportion of participants with plasma HIV-1 RNA <200 c/mL over time (Maintenance Phase) - 
Snapshot 
by visit 
 
 
 
Y[4] 
Y[5] 
 
 
 
 
 
 
 
 
 
Proportion of participants with plasma HIV-1 RNA ≥50 c/mL at Week 48/Week 96/Week 152 by delay 
in IP injection - Snapshot 
by delay in IP injection 
[6] 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Proportion of participants with plasma HIV-1 RNA <2 c/mL over time (Maintenance Phase) 
by visit 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
Plasma HIV-1 RNA over time  
by visit 
 
 
 
Y[7] 
 
Y[8] 
Y[9] 
 
 
 
 
 
 
Y[9] 
Target Detected vs 
Target Not Detected by 
visit [10] 
 
 
 
Y 
 
 
Y[11] 
 
 
 
 
 
 
 
Confirmed Virologic Failure (CVF) 
CVF overall   
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
CVF by visit 
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 


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Endpoints 
Absolute  
Change from Baseline  
Stats Analysis 
Summary Individual 
Stats Analysis 
Summary Individual 
T 
F 
L 
T 
F 
F 
L 
T 
F 
L 
T 
F 
F 
L 
Plasma HIV-1 RNA at 
time of suspected and 
confirmed virologic 
failure 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
CD4+ & CD8+ Cell Counts Over Time 
CD4+ observed [12] 
 
 
 
Y 
 
 
 
 
 
 
Y 
 
 
 
CD8+ observed [12] 
 
 
 
Y 
 
 
 
 
 
 
Y 
 
 
 
CD4+/CD8+ ratio 
observed [12] 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
HIV-1 Conditions and Disease Progression 
HIV Conditions 
including/excluding 
Recurrences as 
recorded in eCRF  
 
 
 
Y 
 
 
Y 
 
 
 
 
 
 
 
HIV Disease 
Progressions [13] 
 
 
 
Y 
 
 
 
 
 
 
 
 
 
 
NOTES: 
• 
T = Table, F = Figures, L = Listings, Y = Yes display generated 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TF related to any summaries (i.e. descriptive statistics) of data. 
• 
Individual = Represents FL related to any displays of individual participant’s data. 
1. 
Line plots, with 95% confidence intervals (CIs), for the proportion of participants with HIV-1 RNA ≥50 c/mL by 
treatment group at each visit. The 95% CIs will be calculated using Exact (Clopper-Pearson) confidence interval if 
the proportion is 0%; otherwise, they are derived using the normal approximation. 
2. 
Plot of the unadjusted treatment difference and its 95% confidence intervals (Snapshot algorithm) overall and by 
subgroup at Week 48/Week 96/Week 152. 
3. 
Line plots, with 95% confidence intervals, for the proportion of participants with HIV-1 RNA<50 c/mL by treatment 
group at each visit. The 95% CIs will be calculated using Exact (Clopper-Pearson) confidence interval if the 
proportion is 100%; otherwise, they are derived using the normal approximation. 
4. 
Study outcomes (i.e., HIV-1 RNA <200 c/mL, HIV-1 RNA ≥200 c/mL, or reason for no data in the window) based 
on the snapshot algorithm at Week 48 will also be produced. 
5. 
Line plots, with 95% confidence intervals, for the proportion of participants with HIV-1 RNA <200 c/mL and ≥200 
c/mL by treatment group at each visit. The 95% CIs will be calculated using Exact (Clopper-Pearson) confidence 
interval if the proportion is 0% or 100%; otherwise, they are derived using the normal approximation. 
6. 
Delay in IP injection (days) is defined in Section 15.6.3. 
7. 
Using log10 transformed values. 
8. 
Individual plasma HIV-1 RNA only for participants who are in the category of ‘viral load ≥50 c/mL’ at Week 48 per 
Snapshot algorithm or who are CVF participants. The figures will display all HIV-1 RNA values collected. 
9. 
For CVF participants, participants with viral load ≥ 50 c/mL during the Maintenance Phase, and participants with 
viral load ≥ 50 c/mL during the Maintenance oral lead-in period. 
10. See Section 15.6.3 for definition of “Target Detected” and “Target Not Detected”, and for the specification of 
corresponding summary table. 
11. Target Detected” and “Target Not Detected” are included in the listing for plasma HIV-1 RNA by visit. 
12. Using available data without imputation for missing values. 
13. See Section 15.6.3 for HIV disease progressions. 


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8. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety population, unless otherwise specified. 
8.1. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs), 
COVID-19 AEs and other significant AEs will be based on GSK Core Data Standards. 
The details of the planned displays are provided in Section 15.15: List of Data Displays. 
8.1.1. 
Analyses for Injection Site Reaction Adverse Events from Study 
Drug Injection 
Injection Site Reaction (ISR) adverse events of interest are those from study drug 
injections. For the summary of study drug ISR adverse events by visit and maximum 
severity (overall and by common ISRs): ISRs will be assigned based on onset date to the 
most recent planned IM injection visit prior or equal to the AE onset date.  
Maximum grade at each visit will be derived as the maximum grade among ISRs 
assigned to the particular visit, with consideration for whether the summary applies to a 
particular preferred term (vs. across preferred terms), drug-related associated to CAB 
and/or RPV, or stratification by subgroup (such as needle length, refer to Section 5.4.2). 
Drug-related ISRs (based on investigator discretion) from study drug injections will be 
attributed to the causal agent (CAB vs. RPV) when this can be determined specifically 
based on the side of injection administration and the side of the reported ISR (as collected 
in the eCRF). If we are unable to determine the causal agent in those cases where both 
drugs are given on one side and the ISR is reported non-specifically, then the attribution 
to a specific causal agent will remain unknown. 
Common study drug ISR adverse events are defined by MedDRA preferred terms 
including injection site pain, injection site induration, injection site nodules and preferred 
terms of any other ISR with ≥5% participants in either treatment arm, coming from study 
drug injections. The same set of common terms will be applied to ‘overall’ (CAB and/or 
RPV), CAB alone, RPV alone. 
Study drug ISRs will be attributed to the needle length (≤1.5, >1.5 to <2, ≥ 2 inches) 
specifically based on the side of injection administration and the side of the reported ISR 
(as collected in the eCRF). If we are unable to determine the needle length for events 
where both drugs are given on one side and their needle lengths are different, then the 
attribution to a needle length will remain unknown. 
8.2. 
Adverse Events of Special Interest Analyses 
Adverse events of special interest (AESI) are determined for CAB and/or RPV based on 
pre-clinical and clinical experience, along with information for the Integrase Inhibitor 
class of HIV medications and RPV safety profile. Table 4 shows the currently identified 
AESI, drug(s) of Interest and the reasons for inclusion. Changes to the MedDRA 
dictionary may occur between the start of the study and the time of reporting, and/or 


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emerging data from on-going studies may highlight additional adverse events of special 
interest, therefore the list of AESIs may change at the time of reporting.  
A summary by system organ class and preferred term will be provided for each of AESI. 
The characteristics of event occurrences will be summarized in main study for common 
AESI which have at least 20 participants in either treatment arm, and will be summarized 
in sub-study for common AESI which have at least five participants in either treatment 
arm. For Depression, anxiety and suicidal ideation/behaviour AESI, a summary by 
system organ class, maximum DAVIDS toxicity grade and prior history of suicidal 
ideation will be provided. The details of the planned grouping and planned displays are 
provided in Section 15.11 and Appendix 15: List of Data Displays. 
Table 4 
Adverse Events of Special Interest 
Adverse Events of Special Interest 
Drug(s) of 
Interest 
Reason for Inclusion 
Hepatic Safety Profile: Assessment of Risk of 
hepatoxicity 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Hypersensitivity Reactions (HSR) 
CAB 
Class, Regulatory Interest, 
Occurs in HIV population 
Rash 
RPV 
Class, Regulatory Interest, 
Occurs in HIV population 
Prolongation of the Corrected QT Interval of the 
ECG in Supratherapeutic Doses 
RPV 
Non-clinical, Clinical, 
Regulatory Interest 
Suicidal Ideation/Behaviour 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Depression 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Bipolar Disorder 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Psychosis 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 
Mood Disorders 
CAB+RPV 
Clinical, Class, Regulatory 
Interest 
Anxiety 
CAB+RPV 
Clinical, Class, Regulatory 
Interest 
Sleep Disorders 
CAB+RPV 
Clinical, Class, Regulatory 
Interest, More prevalent in 
HIV population 


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Adverse Events of Special Interest 
Drug(s) of 
Interest 
Reason for Inclusion 
Injection Site Reactions (ISR) from Study Drug 
Injections [1] 
CAB+RPV 
Clinical 
Seizures and Seizure-like Events 
CAB 
Clinical, Regulatory Interest 
Weight Gain 
CAB 
Clinical, Class 
Rhabdomyolysis 
CAB 
Clinical, Class 
Pancreatitis 
CAB 
Clinical, Therapeutic Area, 
More prevalent in HIV 
population 
Impact on Creatinine 
CAB+RPV 
Regulatory Interest, 
Therapeutic Area, More 
prevalent in HIV population 
Safety in Pregnancy 
CAB 
Regulatory Interest, Class 
Hyperglycaemia 
CAB 
Class, Regulatory Interest 
NOTE: 
[1] A separate analysis will be performed for ISRs from study drug injections as described in Section 8.1.1. 
 
8.3. 
Clinical Laboratory Analyses 
Laboratory evaluations including the analysis of results of Chemistry laboratory tests, 
Haematology laboratory tests, Urinalysis, and liver function tests will be based on GSK 
Core Data Standards. The details of the planned displays are in Appendix 15: List of Data 
Displays. 
8.4. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. The details of the 
planned displays are presented in Appendix 15: List of Data Displays. 
ECG values of potential clinical importance are defined as a QTc of > 500 msec or 
increase from baseline in QTc ≥ 60 msec. 


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9. 
PHARMACOKINETIC ANALYSES 
The GSK Division of Clinical Pharmacology Modelling and Simulation (CPMS) will be 
responsible for the PK analysis of CAB. The Division of Clinical Pharmacology and 
Pharmacometrics at Janssen Research and Development will be responsible for conduct 
or oversight of the PK analysis for RPV. 
9.1. 
Endpoint / Variables 
9.1.1. 
Drug Concentration Measures 
Refer to Appendix 5 Data Display Standards & Handling Conventions (Section 15.5.3 
Reporting Standards for Pharmacokinetic) 
9.2. 
Overview of Planned Analyses 
Table 5 provides an overview of the planned analyses with full details being presented in 
Appendix 15: List of Data Displays. All PK displays will be based on the PK Population, 
unless otherwise specified. 
Table 5 
Overview of Planned Pharmacokinetic Analyses 
 
Stats Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
Pharmacokinetic [5] 
Plasma CAB concentration by visit 
 
 
 
Y[1][2] 
Y[1][3][4] 
Y[3] 
Y 
Plasma RPV concentration by visit 
 
 
 
Y[1][2] 
Y[1][3][4] 
Y[3] 
Y 
Steady state concentration 
Y 
 
 
 
 
 
 
Plasma CAB parameters by dosing 
interval 
Y 
Y 
 
Y 
 
 
Y 
Plasma RPV parameters by dosing 
interval 
Y 
Y 
 
Y 
 
 
Y 
NOTES: 
• 
T = Table, F = Figure, L = Listings, Y = Display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TF related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data. 
• 
Unless otherwise specified, all displays for evaluable concentrations except for individual displays will be 
presented by both overall and the rederived randomization strata. 
1. 
For both ‘all’ concentration and the ‘evaluable’ concentration. The evaluable concentration is derived from 
samples collected within pre-specified Time window (Section 15.6.5 ) 
2. 
For both ‘untransformed’ and ‘log–transformed’ statistics.  
3. 
The plots will be produced for the untransformed scale (i.e., a linear plot) and the log transformed scale (i.e., 
log-linear plot), separately. 
4. 
Separate plots will be produced for Mean (SD) and Median concentration. 
5. 
Standard summary statistics for concentration data will be calculated (i.e., mean, standard deviation, 
coefficient of variation, median, minimum and maximum).  For Logarithmically transformed data, the summary 
statistics (i.e. geometric mean, between subject coefficient of variation, 95% confidence interval for the 
geometric mean and standard deviation) will also be calculated.  


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9.3. 
Statistical Analyses / Methods 
Planned PK statistical analysis 
Steady State Concentration 
Endpoints 
• loge-transformation of the Trough/Pre-dose evaluable plasma concentrations (CAB/RPV) on 
Week 16-48 (i.e. Weeks 16, 24, 32, 40 and 48) for participants receiving Q8W study 
treatment 
Covariates 
• Study Week 
Data Handling 
• All data remains as is (observed). 
Model Specification 
• A mixed effects ANOVA model will be fitted for each rederived randomization stratum [prior 
exposure to CAB+RPV (0 weeks, 1-24 weeks, >24 weeks)] with Study Week (continuous 
variable) as a fixed effect and subject as a random effect for each analysis separately. The 
Kenward & Roger (KR) degrees of freedom approach will be used. The coefficient for the 
slope of the week effect on the loge-scale will be used to evaluate steady state for each drug 
(CAB/RPV). The 90% confidence intervals for the slope for each treatment will be calculated. 
If it does not appear that steady-state has been demonstrated, early weeks (e.g. Week 16, 
24, etc...) results will be dropped and the analysis repeated. 
Model Checking & Diagnostics 
• The steady state will be claimed (the coefficient for the slope of the week effect on the 
(natural) log scale was close to 0 or the 90% CI for the slope estimate included zero. If 
steady-state is not demonstrated, concentrations from early weeks (e.g. Week 16, 20, 24, 
etc...) dropped in sequence and the analysis repeated until either steady state is shown or 
only two timepoints remain. 
Model Results Presentation 
• The coefficient for the slope of the week effect on the loge-scale, its standard error and 90% 
interval will be presented for each rederived randomization stratum. 
PK Parameters 
Endpoints 
• As data permit, Loge-transformation of the PK parameters (Ctau, Cmax and AUC(0-tau) for 
each sub-study dosing interval (refer to Section 15.6.5 for definition of the dosing interval) for 
participants enrolled in the sub-study 
Model Specification 
• Following Loge-transformation, PK parameters will be separately analyzed by treatment arm 
and analyte using a mixed effects model with dosing interval (gluteal injection, first thigh 
injection and last thigh injection) as fixed effects and subject as random effects. In each 
model, only subjects with evaluable PK parameter estimates in both dosing intervals are 
included. For example, in the model for comparing Cmax estimated from the first CAB thigh 


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injection interval with Cmax estimated from the gluteal injection interval among Q8W 
subjects, only the Q8W subjects with evaluable Cmax estimates from both first CAB thigh 
injection interval and gluteal injection interval are included. 
Model Checking & Diagnostics 
• Model assumptions will be applied, but appropriate adjustments may be made based on the 
data. 
Model Results Presentation 
• The estimated difference and 90% CI obtained on the loge scale will be exponentiated to 
provide an estimate of geometric mean ratio and its associated 90% CI. The estimate of 
within-subject variability (%CVw) will also be provided. 
 


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10. 
POPULATION PHARMACOKINETIC ANALYSES 
The Population PK analyses will be described under a separate Population-PK Reporting 
and Analysis Plans for CAB LA and RPV LA 
11. 
PHARMACOKINETIC / PHARMACODYNAMIC 
ANALYSES 
The primary goal of this analysis is to characterize the pharmacokinetic / 
pharmacodynamic relationship of CAB/RPV administered in participants with HIV-1-
infection who are virologically suppressed. The influence of subject demographics and 
baseline characteristics and additional subgroups/covariates in this population will be 
investigated. 
11.1. 
Overview of Planned Analyses 
Table 6 provides an overview of the planned analyses with full details being presented in 
Appendix 15: List of Data Displays. All PK displays will be based on the PK Population, 
unless otherwise specified. 
Table 6 
Overview of Planned Pharmacokinetic / Pharmacodynamic Analyses 
 
Stats Analysis 
Summary 
Individual 
T 
F 
L 
T 
F 
F 
L 
CAB/RPV Week 8 concentrations by 
snapshot ‘HIV-1 RNA ≥50 c/mL’ (Yes vs. 
No) at Week 48 for participants without 
prior exposure to CAB+RPV 
 
 
 
Y 
Y 
 
 
Analysis of snapshot ‘HIV-1 RNA ≥50 
c/mL’ at Week 48 by Week 8 trough 
concentration, and subgroup [1] – 
univariable analysis /multivariable 
analysis for participants without prior 
exposure to CAB+RPV 
Y 
 
 
 
 
 
 
Individual CAB/RPV concentration-time 
profiles for participants with snapshot 
‘HIV-1 RNA ≥50 c/mL’ at Week 48 or 96 
or 152 
 
 
 
 
Y 
 
 
Maximum change from baseline in 
ALT/Total Bilirubin versus last trough 
CAB/RPV concentrations for Week 48 
and Week 152 analyses[2] 
 
 
 
 
Y 
 
 
Change from baseline in pre-dose QTcF 
versus CAB/RPV concentrations at 
Week 48 or 152 
 
 
 
 
Y 
 
 
Maximum toxicity grades of most 
frequently reported study drug ISR AEs 
[3] versus last trough CAB/RPV PK 
concentrations for Week 48 analysis[2] 
 
 
 
 
Y 
 
 
 


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NOTES: 
• 
T = Table, F = Figure, L = Listings, Y = Display generated. 
• 
Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted. 
• 
Summary = Represents TF related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data. 
1. 
Refer to Section 11.2. 
2. 
Display by rederived randomization strata, i.e. prior exposure to CAB+RPV (0, 1-24, >24 weeks) derived 
based on eCRF. 
3. 
Most frequently reported study drug ISR AEs are those top 5 in incidence in either treatment arm (i.e. Q8W or 
Q4W arm). 
 


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11.2. 
Statistical Analyses / Methods 
PK/PD Efficacy Analysis for Participants without Prior Exposure to CAB+RPV 
Endpoints 
• Snapshot ‘HIV-1 RNA≥50 c/mL’ at Week 48 
Covariates 
• Treatment, demographic and baseline characteristics except for country and Prior Exposure 
to CAB+RPV (0, ≥1 weeks), and additional subgroup/covariates for PK/PD efficacy analysis - 
see derivation details in Section 5.4.2. 
Data Handling 
• All data remains as is (observed). 
Model Specification 
• Logistic regression will be used to exam the correlation between the endpoint (Snapshot 
‘HIV-1 RNA≥50 c/mL’) at Week 48 and the covariates/subgroups. This logistic regression 
analysis will be performed for each covariate or subgroup, separately (univariable analysis), 
and will also be performed with one multivariable analysis using Backward stepwise selection 
approach to identify the covariates/subgroups potentially affecting virologic response. 
Model Checking & Diagnostics 
• For the multivariable analysis, a logistic regression model that best predicts the dependent 
variable (i.e. snapshot ‘HIV-1 RNA≥50 c/mL’) from the independent variables (i.e. 
covariates/factors with P <0.15 from univariable analysis) will be determined using the 
backward stepwise selecting approach. Week 8 trough PK concentration will be 
logarithmically transformed with base of 2 (i.e. one-unit increase of the point estimate of log2 
PK concentration is equivalent to ‘doubling the concentration’ in the original value). The 
analysis will start with all covariates in the model and remove a covariate with the largest p-
value (i.e. the least statistically significant) each time and continue until the stopping rule is 
reached when all remaining covariates have p-value <15%. 
• If problems with model convergence occur due to zero event counts or complete/quasi-
complete separation, then alternative methods such as exact logistic regression may be 
used. 
Model Results Presentation 
• The odds ratio, 95% confidence interval, and p-value will be presented. 
 


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12. 
HEALTH OUTCOMES ANALYSES 
12.1. 
Endpoint / Variables 
12.1.1. 
Main Study 
• Preference between injections of LA HIV treatment and daily oral HIV treatment 
at Week 48 
• Preference between LA injection every 8 weeks and LA injection every 4 weeks 
at Week 48 (Q8W arm only) 
• Change from baseline in total “treatment satisfaction” score, and individual item 
scores of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) at 
Weeks 24, 48 and 152 
• Change from baseline in life satisfaction, HIV medication, and disclosure worries 
using HIV/AIDS Targeted Quality of Life (HAT-QoL) at Weeks 24 and 48 
• Change in treatment satisfaction over time using the HIV Treatment Satisfaction 
Change (HIVTSQc) questionnaire at Week 48 
• Change from Week 8 in Dimension Scores and individual item scores assessing 
pain during injection, anxiety before and after injection, willingness to be injected 
in the future and overall satisfaction with mode of administration over time using 
Perception of Injection (PIN) questionnaire at Weeks 24, 48 and 152 
• Change from baseline in treatment acceptance using ACCEPT at Weeks 24, 48 
and 152 
• Reasons for continuation of receiving injectable HIV treatment at Baseline (Day 
1) visit. This is an exploratory endpoint. 
• Reasons for switching to injectable HIV treatment at Baseline (Day 1) visit. This 
is an exploratory endpoint. 
• Preference for CAB LA + RPV LA injection compared to daily oral for 
participants receiving oral bridging during the Maintenance and/or Extension 
phases at Week 152. This is an exploratory endpoint. 
12.1.2. 
Sub-study 
• Change from gluteal to thigh in total “treatment satisfaction” score, and individual 
item scores of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) 
during the Thigh Injection phase as well as the change from thigh to gluteal 
during the Return to Gluteal Injection phase 
• Change from gluteal to thigh using the HIV Treatment Satisfaction Change 
(HIVTSQc) questionnaire at Sub-study Week 16 
• Changes in the tolerability of injections (NRS) over time during the sub-study 
• Preference for thigh injections compared with prior gluteal injections and the 
injections received during the Return to Gluteal Injection phase respectively.   


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12.2. 
Summary Measure 
For main study, mean treatment difference (Q8W – Q4W) at visits of interest, except for 
Preference between LA injection every 8 weeks and LA injection every 4 weeks at Week 
48. 
For sub-study, mean difference between thigh injections and gluteal injections from visits 
of interest, except for the Preference between thigh injections and gluteal injections.  
12.3. 
Population of Interest  
The health outcomes analyses will mainly be based on the Intent-to-Treat Exposed 
population, unless otherwise specified. 
Analysis of Reason for continuation will be based on a subset of the Intent-to-Treat 
Exposed population who were randomized to Q4W arm in ATLAS (i.e. ATLAS Q4W 
population). 
12.4. 
Analysis of Reason for switch will be based on a subset of 
Intent-to-Treat Exposed population who either were 
randomized to SOC arm in ATLAS or did not participate in 
ATLAS study (i.e. SOC population).Strategy for Intercurrent 
(Post-Randomization) Events 
If a participant discontinues treatment prior to the timepoint of interest such that there is 
no evaluable assessment for the timepoint of interest, the data will be computed or 
imputed (see Section 15.6.6). 
12.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 15: List of Data Displays and 
will be based on GSK Data Standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 12.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
12.5.1. 
Statistical Methodology Specification 
Statistical Analyses 
Endpoints 
• Change from Baseline in 
o 
HIVTSQs total treatment satisfaction score at Weeks 24,48 and 152 
o 
ACCEPT general acceptance score at Weeks 24, 48 and 152 
o 
HAT-QoL (Life satisfaction, HIV medications, disclosure worries) at Weeks 24 and 48 
• Change from Week 8 in PIN Domain Scores (Bother of ISRs, Leg movement, Sleep, and 
Acceptance) and Individual Items Scores (Anxiety before, Pain, Satisfaction, Anxiety After, 
Willingness) at Weeks 24, 48 and 152 


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Statistical Analyses 
Model Specification 
• The analysis for HIVTSQs, ACCEPT and HAT-QoL will be performed for subjects with and 
without prior exposure to CAB+RPV separately. 
o  For subjects without prior exposure to CAB+RPV, an analysis of covariance 
(ANCOVA) model will be used at each visit during the maintenance phase with 
covariates: treatment, age (<50,  50 years old), sex at birth, race (i.e. white, non-
white) and baseline score value for other endpoints (as a continuous variable). 
o For subjects with prior exposure to CAB+RPV, an analysis of covariance (ANCOVA) 
model will be used at each visit during the maintenance phase with covariates: 
treatment, age (<50,  50 years old), prior exposure to CAB+RPV (i.e. 1 to 24 weeks, 
>24 weeks), sex at birth, race (i.e. white, non-white) and baseline score value (as a 
continuous variable). 
• For PIN, an analysis of covariance (ANCOVA) model will be used at each visit during the 
maintenance phase with covariates: treatment, age (<50,  50 years old), prior exposure to 
CAB+RPV (i.e. 0 weeks, 1 to 24 weeks, >24 weeks), sex at birth, race (i.e. white, non-white), 
and Week 8 score value (as a continuous variable). 
• Adjusted point estimates will be derived as LSMEANS using the observed margins (OM) 
option within PROC MIXED in SAS. 
• The superiority testing of Q8W compared to Q4W with respect to change from baseline in 
HIVTSQs total score at Week 48 will be performed using the fixed sequence procedure to 
control for the type I error rate at the nominal level of 5%. If the superiority testing within 
subjects without prior exposure to CAB+RPV demonstrates Q8W is superior to Q4W in 
change from baseline in HIVTSQs total score at Week 48 at two-sided 5% level of 
significance, the superiority testing at the same level of significance (i.e. two-sided 5%) within 
subjects with prior exposure to CAB+RPV will be followed. No adjustment for multiplicity will 
be applied for other tests as they will be considered supportive. 
• Interactions between treatment and each of the covariates will not be assessed unless the 
exploratory subgroup analyses on the primary endpoint highlights significant interactions. In 
this situation, the interaction(s) of interest will be assessed and, if necessary, results will be 
reported in the clinical study report. Interactions between treatment and the baseline score will 
be investigated but not included in the model. If interactions are found to be significant 
(p<0.10), results may be presented separately by subgroup. 
Dataset 
• LOCF dataset will be used. 
Model Results Presentation 
• Adjusted treatment difference (Q8W – Q4W), its 95% CI and the associated p-value. The 
interaction between treatment and the baseline score will be included in a footnote. 
• Plots of adjusted mean change from baseline (95% CI) for each treatment group, and the 
adjusted mean difference (95%CI) between the two treatment arms from the model will be 
generated across visit.  
 
Statistical Analyses 
HIVTSQc 
• Total Treatment Satisfaction Score (Change) at Week 48 


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Model Specification 
• An analysis of variance (ANOVA) model will be used with covariates: treatment, age (<50,  50 
years old), prior exposure to CAB+RPV (i.e. 0 weeks, 1 to 24 weeks, >24 weeks), sex at birth 
and race (i.e. white, non-white). 
• Adjusted point estimates will be derived as LSMEANS using the observed margins (OM) option 
within PROC MIXED in SAS. 
• Interactions between treatment and each of the covariates will not be assessed unless the 
exploratory subgroup analyses on the primary endpoint highlights significant interactions. In this 
situation, the interaction(s) of interest will be assessed and, if necessary, results will be 
reported in the clinical study report. If interactions are found to be significant (p<0.10), results 
may be presented separately by subgroup. 
• No adjustment for multiplicity will be applied as these analyses will be considered supportive. 
Dataset 
The observed case (OC) dataset uses only the data that is available at Week 48, with no imputation 
for missing values. 
Model Results Presentation 
Adjusted means, 95% CI, and associated p-value will be presented for the treatment difference 
(Q8W – Q4W).  
 
Statistical Analyses 
PIN/HIVTSQs 
• Change from Week 8 in the PIN acceptance score at Week 24, Week 48 and Week 152 
• Change from Sub-study Baseline in the HIVTSQs total treatment satisfaction score at Sub-
study Week 16, Sub-study Week 24 (for Q8W arm) or Sub-study Week 20 (for Q4W arm).  
Statistical Test 
• The Wilcoxon Signed-Rank Test will be used to evaluate: 
For PIN, whether the change from Week 8 to each post Week 8 main study visit, is statistically 
different from zero based on a two-sided p<0.05. 
For HIVTSQs, whether the change from Sub-study Baseline to each post-baseline sub-study 
visit is statistically different from zero based on a two-sided p<0.05. 
Dataset 
• For PIN, LOCF dataset will be used. 
• For HIVTSQs, observed dataset will be used. 
Results Presentation 
• For PIN, summary statistics at each timepoint (Week 8, Week 24, Week 48 and Week 152) 
and p-value for each comparison between scores at Week 24/48/152 with scores at Week 8. 
• For HIVTSQs, summary statistics at Sub-study Baseline, Sub-study Week 16, Sub-study 
Week 24 (for Q8W arm) or Sub-study Week 20 (for Q4W arm), and p-value for the comparison 
between scores at each post-baseline sub-study visit with scores at Sub-study Baseline. 
 


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13. 
VIROLOGY 
The virology analyses will mainly use genotype and phenotype data based on plasma 
sample for CVF population, unless otherwise specified. Additional analyses for HIV-1 
resistance may be carried out on peripheral blood mononuclear (PBMC) samples 
collected at Day 1, Week 48, Week 96, Week 152 or Withdrawal if prior to Week 152, 
Sub-study Day 1. 
If pre-treatment genotypic/phenotypic results are available from both the central 
laboratory and Monogram Biosciences, then Baseline genotype/phenotype will be 
determined based only upon the data provided by Monogram assays.   
Table 7 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 15: List of Data Displays. 
 
Table 7 
Overview of Planned Virology Analyses 
Endpoint  
Absolute 
Summary 
Individual 
T 
F 
F 
L 
Genotypic resistance at time of CVF[1] 
Prevalence of Resistance Mutations 
Y [2] 
 
 
Y 
Prevalence of Genotypic Susceptibility 
Y 
 
 
 
Phenotypic resistance at time of CVF[1] 
Prevalence of Phenotype   
Y [3] 
 
 
Y 
Fold Change to CAB and RPV 
Y 
 
 
Y[4] 
IN, PR/RT Replication Capacity  
 
 
 
Y 
Other 
Viral load, Genotypic and Phenotypic data for 
Participants with genotype and/or phenotype 
data for CVF and non-CVF participants  
 
 
 
Y[4] 
Net Assessment 
Y 
 
 
 
NOTES: 
• 
T = Table, F = Figure, L = Listing, Y = Yes display generated. 
• 
Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data. 
• 
Individual = Represents FL related to any displays of individual participant observed raw data.    
1. 
For the CVF as indicated by two consecutive plasma HIV-1 RNA levels 200 c/mL after prior suppression to 
<200 c/mL, the first visit of these two consecutive visits is defined as ‘the suspected visit’, and the 2nd one is the 
confirmed visit. Sample used for resistance testing is taken at the suspected visit, and only tested once a 
participant confirms virological failure at a subsequent visit.  If the test fails with the sample at the suspected 
visit, we will just report it as ‘no data’. The sample from the confirmed visit may be used for exploratory analyses. 
2. 
No. and percentage of participants with IN resistance mutations or major mutations in the classes of NNRTI, 
NRTI, PI, respectively, as defined in Section 15.6.7. 
3. 
Separate outputs by phenotypic susceptibility and by number of drugs to which participants are phenotypic 
resistant or partial sensitive or sensitive. 


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Endpoint  
Absolute 
Summary 
Individual 
T 
F 
F 
L 
4. 
Fold change to CAB and RPV will be included in the listing for viral load, genotypic and phenotypic data for 
participants with genotype and/or phenotype data for CVF and non-CVF participants. 


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14. 
REFERENCES 
Chan, I. S. F. and Zhang, Z. (1999), “Test-Based Exact Confidence Intervals for the 
Difference of Two Binomial Proportions,” Biometrics, 55, 1202–1209. 
Chevat C, Viala-Danten M, Dias-Barbosa C, Nguyen VH. Development and 
psychometric validation of a self-administered questionnaire assessing the acceptance of 
influenza vaccination: the Vaccinees’ Perception of Injection questionnaire. Health Qual 
Life Outcomes. 2008 mar 4; 7:21 
D’Agostino RB, Vasan RS, Pencina MJ, et al. General Cardiovascular Risk Profile for 
Use in Primary Care (The Framingham Heart Study). Circulation 2008; 117: 743-753. 
EMA/CHMP/539146/2013, Guideline on the investigation of subgroups in 4 
confirmatory clinical trials, 23 January 2014 
Fleiss J.L. Statistical Methods for Rates and Proportions. 2nd ed. New York: John Wiley; 
1981. 
Gilet H, Arnould B.  Acceptance by the patients of their treatment (ACCEPT) 
Questionnaire, 2014.  
Grundy S.M., et al. Executive summary of the third report of the National Cholesterol 
Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of 
High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285 (19): 
2486-2497.  
HIVTSQ user guidelines, Health Psychology Research Unit, Royal Holloway, University 
of London, 2016 
Holmes WC, HIV/AIDS-Targeted Quality of Life Instrument 1999.  
Kalbfleisch J.D., Prentice R.L. The Statistical Analysis of Failure Time Data. 1st ed. New 
York: John Wiley & Sons; 1980.  
Levey AI, Christopher HS, Hocine T, John HE, Harold IF, Tom G, et al. Esitmating 
Glomerular Filtration Rate from Serum Creatinine and Cystatin C. N Engl J Med 2012, 
367: 20-29. 
Lui K.J., Kelly C. A Revisit on Tests for Homogeneity of the Risk Difference, 
Biometrics, 2000; 56:309-315. 
Nilsson ME, Suryawanshi S, Gassmann-Mayer C et al, Columbia–Suicide Severity 
Rating Scale, Scoring and Data Analysis Guide, 2013. 
Sato T. On the variance estimator for the Mantel-Haenszel risk difference. Biometrics. 
1989; 42:311-323.  
Wensing AM et al. Update of the Drug Resistance Mutations in HIV-1 Volume 27 Issue 
3 July/August 2019 


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15. 
APPENDICES 
15.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population 
15.1.1. 
Exclusions from Per Protocol Population 
Important protocol deviations leading to exclusion from the Per Protocol population are 
those deviations which may 
• directly impact the efficacy endpoint of HIV-1 RNA; or 
• lead to permanent discontinuation of IP/withdrawal and hence indirectly impact 
the efficacy endpoint by causing data to be missing. 
The following criteria define the important protocol deviations which, if they occur prior 
to an analysis timepoint of interest (e.g. Week 48/96/152), will lead to exclusion of a 
participant from the Per-Protocol population for that analysis. Potential protocol 
deviations leading to exclusion from PP population will be reviewed by the study team to 
confirm that they meet these criteria. A final review will occur before the clinical 
database has been frozen for analysis. 
A participant meeting any of the following criteria will be excluded from the Per Protocol 
population based on case-by-case clinical determination: 
Number Exclusion Description 
01 
Participant deviates from any inclusion or exclusion criteria that may significantly affect 
exposure, response to therapy or participant safety or that are fundamentally inconsistent with 
the intended study population, as recorded in the Protocol Deviation form in the eCRF based 
on study team review (where indicated in the PDMP as case-by-case determination). 
02 
Participant has maintenance phase non-compliance (including IM dosing errors) with 
investigational product up to an analysis timepoint of interest, meeting one of the following 3 
conditions. For Week 48 analysis, the analysis timepoint of interest is the date of last on-
treatment viral load up to Study Day 378 during maintenance phase, where Study Day 378 is 
the upper bound of snapshot window for Week 48 visit. For Week 96 analysis, the analysis 
timepoint of interest is the date of last on-treatment viral load up to Study Day 714 during the 
maintenance phase, where Study Day 714 is the upper bound of snapshot window for Week 
96 visit. For Week 152 analysis, the analysis timepoint of interest is the date of last on-
treatment viral load up to Study Day 1106 during the maintenance and extension phase, 
where Study Day 1106 is the upper bound of snapshot window for Week 152 visit.  
 
1. Week 48 analysis only: 
• 
Two or more injection intervals affected by over dosage deviations, for example 
o Extra injection or excessive volume administered.  
o For Q8W participants requiring oral lead-in: length of time between 
Week 4B injection and Week 8 injection less than 3 weeks, or between 
injections post Week 8 less than 7 weeks, excluding split doses. 
o For Q8W participants not requiring oral lead-in: length of time between 
injections less than 7 weeks, excluding split doses. 


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Number Exclusion Description 
o For Q8W participants requiring reloading injections: length of time 
between the reloading injection and the injection after reloading less 
than 3 weeks, excluding split doses.  
o For Q4W participants: length of time between injections less than 3 
weeks, excluding split doses.  
2. Week 96 analysis only: 
• 
For participants who permanently discontinued study treatment on/before the 
analysis timepoint of interest for Week 48 analysis (i.e. the date of last on-
treatment viral load up to Study Day 378): two or more injection intervals 
affected by over dosage deviations.  
• 
For participants who received injections beyond the analysis timepoint of interest 
for Week 48 analysis (i.e. the date of last on-treatment viral load up to Study 
Day 378): three or more injection intervals affected by over dosage deviations. 
3. Week 152 analysis only: 
• 
For participants who permanently discontinued study treatment on/before the 
analysis timepoint of interest for Week 48 analysis (i.e. the date of last on-
treatment viral load up to Study Day 378): two or more injection intervals 
affected by over dosage deviations.  
• 
For participants who received injections beyond the analysis timepoint of interest 
for Week 48 analysis (i.e. the date of last on-treatment viral load up to Study 
Day 378): five or more injection intervals affected by over dosage deviations. 
 
4. ≥ 10% of total time on-treatment with under dosing deviations. The percentage of total 
time on-treatment with under dosing deviations will be calculated by (the total number of 
non-compliant dosing days / the total number of intended exposure days) * 100%. 
 
Number of Intended Exposure Days = Date of Last Viral Load – Start Date of Study 
Treatment + 1, 
where the last viral load refers to the last on-treatment viral load up to Study Day 378 
during maintenance phase for Week 48 analysis, the last on-treatment viral load up to 
Study Day 714 during maintenance phase for Week 96 analysis, the last on-treatment 
viral load up to Study Day 1106 during maintenance and extension phase for Week 152 
analysis . 
 
The total number of non-compliant dosing days up to the analysis timepoint visit (or date 
of IP discontinuation/ withdrawal, whichever is earlier), is derived as follows (summing 
across all instances): 
• 
For Q4W arm participants requiring oral lead-in: 
o Length of time (in days) until next injection from date of dosage 
deviation (e.g. 2 mL administered instead of 3mL for Week 4B injection, 
1ml administered instead of 2 mL for post Week 4B injections). 
o Length of time (in days) in excess beyond 35 days between injections 
post Week 12 and in excess beyond 28 days for Week 8 and Week 12 
(e.g. missed or late injection visit). 
o Length of time (in days) in excess beyond 35 days from last injection 
until start of oral bridging post Week 12 and in excess beyond 28 days 
for Week 8 and Week 12. 
• 
For Q4W arm participants not requiring oral lead-in: 


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Number Exclusion Description 
o Length of time (in days) until next injection from date of dosage 
deviation (e.g. 1 mL administered instead of 2 mL). 
o Length of time (in days) in excess beyond 35 days between injections. 
o Length of time (in days) in excess beyond 35 days from last injection 
until start of oral bridging. 
• 
For Q8W arm participants requiring oral lead-in: 
o Length of time (in days) until next injection from date of dosage 
deviation (e.g. 2 mL administered instead of 3mL). 
o Length of time (in days) in excess beyond 63 days between injections 
post Week 16 and in excess beyond 28 days for Week 8 and 56 days 
for Week 16 (e.g. missed or late injection visit). The similar calculation 
of the length of time in excess will be used for the period after the 
reloading dose injection visit.  
o Length of time (in days) in excess beyond 63 days from last injection 
until start of oral bridging post Week 16 and in excess beyond 28 days 
for Week 8 and 56 days for Week 16. 
• 
For Q8W arm participants not requiring oral lead-in: 
o Length of time (in days) until next injection from date of dosage 
deviation (e.g. 2 mL administered instead of 3 mL). 
o Length of time (in days) in excess beyond 63 days between injections. 
o Length of time (in days) in excess beyond 63 days from last injection 
until start of oral bridging. 
• 
For subjects requiring reloading injections, the number of non-compliant days for 
the first and second injection visits after the reloading will be calculated similarly 
to that for Week 8 and Week 12 for subjects on the same treatment arm 
requiring oral lead-in. 
• 
Interrupted days in oral study treatment (oral lead-in or oral bridging) if the oral 
dose has been interrupted for 3 or more consecutive days and the primary 
interruption reason is not adverse event or laboratory abnormality (based on the 
eCRF Exposure forms). 3 days will be assumed if such interrupted days are not 
available in the database.  
03 
Prohibited medications: receiving ART medication other than that prescribed/allowed by the 
study (excluding permanent changes in ART regimen; such cases will be retained as ‘HIV1-
RNA ≥50 c/mL’ in the per protocol snapshot analysis) or receiving prohibited concomitant 
medication that would impact exposure or response to therapy with duration and route of 
administration taken into consideration, as recorded in the Protocol Deviation form in the 
eCRF based on study team review (where indicated in the PDMP as case-by-case 
determination). 
04 
Permanent discontinuation of IP/withdrawal due to a reason of “Protocol Deviation” (as 
recorded in the eCRF). 
05 
Other important protocol deviations that exclude Participant from per protocol population as 
recorded in the Protocol Deviation form in the eCRF based on study team review (where 
indicated in the PDMP as case-by-case determination). The participants who has taken SOC 
oral bridging at/prior to the analysis timepoint due to COVID-19 may be excluded from per 
protocol population for the analysis and will be evaluated based on case-by-case clinical 
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15.2. 
Appendix 2: Schedule of Activities 
While some assessments included in the Time and Events Table are conducted less 
frequently following the primary endpoint (Week 48), IM injections for participants 
during the Extension Phase will continue to be administered Q4W or Q8W based on 
original study randomization assignment. 
All patients will be randomized at Day 1 to initiate either Q4 weekly or Q8 weekly 
administration of IM CAB LA + RPV LA. Only participants randomized from oral SOC 
treatment will participate in the Day 1 to Week 4 Oral CAB + Oral RPV lead-in 
treatment. 
 


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15.2.1. 
Protocol Defined Schedule of Events for Q4W Arm in Main Study 
 


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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.   Participants transitioning from the 201585 (ATLAS) study must reach 
ATLAS Week 48 (at minimum) prior to initiating Screening procedures for ATLAS-2M and must reach ATLAS Week 52 (at minimum) prior to 
randomization in ATLAS-2M.  
b. 
Visits Week 4a is part of the CAB + RPV Oral Lead-in period and is required only for participants transitioning from current SOC to CAB LA + RPV LA. 
c. 
Confirmation of eligibility to continue the Maintenance Phase and eligibility to enter the Extension Phase.  
d. 
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. 
e. 
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.   
f. 
Height collected at Baseline Day 1 only. 
g. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
h. 
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. For participants 
transitioning from ATLAS, the pre-dose Week 48 ECG can also serve as the ATLAS-2M Screening ECG.  ECG pre-dose will be performed in triplicate at 


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Day 1.  A 2-hour post-dose ECG will also be performed at Days 1 and Week 48 for participants receiving CAB LA + RPV LA with an allowable window of 
30 minutes. 
i. 
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. 
j. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  The eC-SSRS will preferably 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. 
k. 
Women of childbearing potential only.  SR=serum, UR=urine.  Pregnancy events will be captured starting at Day 1 following initial exposure to study drug.  
Urine pregnancy test performed at Day 1 prior to administration of study drug, at Week 4B, and at study visits when other blood draws are not required in 
order to limit needle sticks.  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. 
l. 
Week 48, Week 96 and Week 152 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. 
m. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; and urine phosphate. Urine phosphate 
results from visit 4a are not required by protocol to inform the safety review at visit 4b prior to receipt of initial CAB LA + RPV LA injections. 
n. 
An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
o. 
Only collect if the Withdrawal visit occurs at Week 48, Week 96 or Week 152. 
p. 
Whole blood/PBMC collection samples may be used for virologic analyses.  PBMCs will be collected at baseline Day 1, Week 48, Week 96, Week 152 or 
Withdrawal if prior to Week 152. 
q. 
Genetics sample should be collected only for patients who did not participate in the 201585(ATLAS) study (sample was previously collected and stored). 
Informed consent for genetic research must be obtained before sample collection.  Sample may be collected at any visit after signing informed consent, but 
preferably at the Day 1 visit.  
r. 
One blood sample for CAB and RPV each to be collected at each PK timepoint.  At Day 1, for participants from the ATLAS Q4W arm, PK samples are to be 
collected pre-dose relative to IM administration.  At Week 4B, for participants randomized from SOC, Pre dose PK samples are to be collected: AFTER 
review of the PK diary to ensure that the samples are taken 20/28 hours after previous oral dose (diaries to be given at Day 1 or W4a); PRIOR to the final oral 
dose of CAB + RPV; PRIOR to the first IM injection.  
s. 
Only for Participants entering CAB + RPV Oral Treatment 
t. 
Participants switching to CAB LA + RPV LA will take final dose of oral lead-in regimen in the clinic at the Week 4B visit and begin injections.  If possible, 
injections should be spaced approximately 2 cm from one another and from the site of any previous injection and or any injection site reaction.  Bring RPV LA 
to approximately room temperature prior to injecting.  Time and location of injection (right or left) as well as needle length used will be collected in the eCRF. 
The first injection can be performed as soon as central lab results become available and safety parameters are reviewed.   


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u. 
All Patient Report Questionnaires/Surveys will be administered via paper instrument at the beginning of the visit before any other assessments are conducted 
and prior to administration of the eC-CSSRS.  Conduct questionnaires/surveys at Withdrawal only if occurring at or prior to Week 152. 
v. 
The HIV-TSQc is to be administered to all participants transitioning from ATLAS and new participants transitioning from oral SOC.  For participants 
transitioning from ATLAS, the version of the HIV-TSQc instrument to be administered will be based on the initial randomization arm at ATLAS Day 1.  
w. 
For patients randomized to oral SOC at Day 1 in ATLAS or new patients on SOC, the reasons for willingness to switch ART will be assessed at Day 1.  For 
patients randomized to CAB LA + RPV LA Q4W in ATLAS, the reasons for willingness to continue long-acting ART in ATLAS-2M will be assessed at Day 
1. 
x. 
Preference Questionnaire will be administered to all participants. 
y. 
Refer to Section 5.5 of the protocol for additional information on performing withdrawal assessments.  HIV-1 RNA will be collected as Storage sample only if 
withdrawal assessments coincide with Week 52 or Week 100 or Week 156 (as per Section 5.5)  
z. 
Participants receiving one or more injections with CAB LA and/or RPV LA will be assessed with clinic visits at months 3, 6, 9 and 12 during the Long-Term 
Follow-Up Phase 
aa. 
Preference at Week 152 will be administered only to participants who received oral bridging during the Maintenance and/or Extension Phases 
 
Note: BP – Blood pressure, HR – Heart Rate, HDL – High Density Lipoprotein, LDL – Low Density Lipoprotein, PT Prothrombin Time, PTT Partial Thromboplastin 
Time, INR International normalized ratio 
 


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15.2.2. 
Protocol Defined Schedule of Events for Q8W Arm in Main Study 
 


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a. 
Participants may be rescreened once and will be assigned a new participant number.  Participants transitioning from the 201585 (ATLAS) study must reach 
ATLAS Week 48 (at minimum) prior to initiating Screening procedures for ATLAS-2M and must reach ATLAS Week 52 (at minimum) prior to 
randomization in ATLAS-2M.  
b. 
Visits Weeks 4A and 4B are part of the CAB + RPV Oral Lead-in period and are required only for participants transitioning from current SOC to CAB LA + 
RPV LA. 
c. 
Confirmation of eligibility to continue the Maintenance Phase, and eligibility to enter the Extension Phase.  


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d. 
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. 
e. 
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.   
f. 
Height collected at Baseline Day 1 only. 
g. 
Measure vital signs after about 5 minutes of rest in a semi-supine position. 
h. 
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. For participants 
transitioning from ATLAS, the pre-dose Week 48 ECG can also serve as the ATLAS-2M Screening ECG.  ECG pre-dose will be performed in triplicate at 
Day 1.  A 2-hour post-dose ECG will also be performed at Days 1 and Week 48 for participants receiving CAB LA + RPV LA with an allowable window of 
 30 minutes. 
i. 
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. 
j. 
On Day 1, the eC-SSRS is to be administered prior to randomization.  The eC-SSRS will preferably 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. 
k. 
Women of childbearing potential only.  SR=serum, UR=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. 
l. 
Week 48, Week 96 and Week 152 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. 
m. 
A morning specimen is preferred.  To assess biomarkers: urine albumin/creatinine ratio; urine protein/creatinine ratio; and urine phosphate.  Urine phosphate 
results from visit 4a are not required by protocol to inform the safety review at visit 4b prior to receipt of initial CAB LA + RPV LA injections. 
n. 
An overnight fast is preferred; however, a minimum of a 6-hour fast is acceptable. 
o. 
Only collect if the Withdrawal visit occurs at Week 48, Week 96 or Week 152. 
p. 
Whole blood/PBMC collection samples may be used for virologic analyses.  PBMCs will be collected at baseline Day 1, Week 48, Week 96, Week 152 or 
Withdrawal if prior to Week 152. 
q. 
Genetics sample should be collected only for patients who did not participate in the 201585(ATLAS) study (sample was previously collected and stored). 
Informed consent for genetic research must be obtained before sample collection.  Sample may be collected at any visit after signing informed consent, but 
preferably at the Day 1 visit. 
r. 
One blood sample for CAB and RPV each to be collected at each PK timepoint.  At Day 1, for participant from the ATLAS Q4W arm, PK samples are to be 
collected pre-dose relative to IM administration. injection. At Week 4B, for participants randomized from SOC, Pre dose PK samples are to be collected: 
AFTER review of the PK diary to ensure that the samples are taken 20/28 hours after previous oral dose (diaries to be given at Day 1 or W4a); PRIOR to the 
final oral dose of CAB + RPV; and PRIOR to the first IM injection.  At Week 9 and 41, the PK samples should be collected 3 to 10 days after the Week 8 
and Week 40 visits, respectively.  
s. 
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t. 
Participants switching to CAB LA + RPV LA will take final dose of oral lead-in regimen in the clinic at the Week 4B visit and begin injections.  If possible, 
injections should be spaced approximately 2 cm from one another and from the site of any previous injection and or any injection site reaction.  Bring RPV 
LA to approximately room temperature prior to injecting.  Time and location of injection (right or left) as well as needle length used will be collected in the 
eCRF.  The first injection can be performed as soon as central lab results become available and safety parameters are reviewed.   
u. 
All Patient Report Questionnaires/Surveys will be administered via paper instrument at the beginning of the visit before any other assessments are conducted 
and prior to administration of the eC-CSSRS. Conduct questionnaires/surveys upon Withdrawal only if occurring at or prior to Week 48 
v. 
The HIVTSQc is to be administered to all participants transitioning from ATLAS and new participants transitioning from oral SOC. For participants 
transitioning from ATLAS, the version of the HIV-TSQc instrument to be administered will be based on the initial randomization arm at ATLAS Day 1 
w. 
For patients randomized to oral SOC at Day 1 in ATLAS or new patients on SOC, the reasons for willingness to switch ART will be assessed at Day 1.  For 
patients randomized to CAB LA + RPV LA Q4W in ATLAS, the reasons for willingness to continue long-acting ART in ATLAS-2M will be assessed at 
Day 1. 
x. 
Preference Questionnaire will be administered to all participants 
y. 
Refer to Section 5.5 of the protocol for additional information on performing withdrawal assessments.  HIV-1 RNA will be collected as Storage sample only 
if withdrawal assessments coincide with Week 52 or Week 100 (as per Section 5.5) 
z. 
Participants receiving one or more injections with CAB LA and/or RPV LA will be assessed with clinic visits at months 3, 6, 9 and 12 during the Long-Term 
Follow-Up Phase 
aa. 
Preference at Week 152 will be administered only to participants who received oral bridging during the Maintenance and/or Extension Phases 
Note: BP – Blood pressure, HR – Heart Rate, HDL – High Density Lipoprotein, LDL – Low Density Lipoprotein, PT Prothrombin Time, 
PTT Partial Thromboplastin Time, INR International normalized ratio


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15.2.3. 
Protocol Defined Schedule of Events for Q4W Arm in Sub-study 
 
 
 


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15.2.4. 
Protocol Defined Schedule of Events for Q8W Arm in Sub-study 
 


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15.3. 
Appendix 3: Assessment Windows 
15.3.1. 
Definitions of Assessment Windows for Analyses 
Laboratory data, vital signs, ECGs, health outcomes assessments, and 
genotypic/phenotypic data will be assigned to assessment windows according to actual 
dates rather than the nominal visit labels as recorded on the eCRF or in the laboratory 
database. 
In most cases the window around an assessment will include all dates from the midpoints 
between the target day and that of the previous and the proceeding visits. In general, the 
nominal target study day for week w is (7*w)+1.   
For parameters which are not scheduled to be assessed at particular visits, the all-
inclusive assessment windows will still be used; however, data summaries will only 
report scheduled visits. Assessments at unscheduled visits will be included for ‘any time 
On-treatment’ time points and in data listings, as well any algorithms that make use of 
additional data (e.g., Snapshot). 
Prior to visit slotting, assessments are first assigned to a study phase (screening, 
maintenance, extension, sub-study screening, thigh injection, return to gluteal injection or 
long-term follow-up) based on the Tables in Section 15.4.1 and treatment state based on 
Section 15.4.2. 
Maintenance phase assessments other than health outcome and PK are assigned based on 
the Study Day as shown in Table 8. Table 8 also includes visiting slotting for screening 
assessments. The analysis visits from Week 4 to Week 100 should be only applied to the 
assessments that are already assigned to Maintenance phase (on-treatment). Extension 
phase assessments other than health outcome and PK are assigned based on the Study 
Day as shown in Table 9. The analysis visits from Week 104 (except for Follow-up) in 
the Extension phase should be only applied to the assessments that are already assigned 
to Extension phase (on-treatment). The snapshot visits up to Week 152 during the 
Maintenance or Extension phase are assigned based on Study Day as shown in Table 10. 
The sub-study assessments other than health outcome, PK and HIV-1 RNA are assigned 
analysis visits based on Study Day as shown in Table 11. The assessment visit windows 
for HIV-1 RNA data are defined in Table 12, and the snapshot windows for visits up to 
Sub-study Week 16 are defined in Table 13. 
Long-term Follow-up phase assessments are assigned based on the LTFU study day as 
shown in Error! Reference source not found. The analysis visits in LTFU should be 
only applied to the assessments that are already assigned to LTFU phase regardless of 
treatment state. See Section 15.6.1, for derivation of Study Day and LTFU Study Day. 


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15.3.2. 
Definitions of Assessment Windows for Analyses other than 
Health Outcome and PK 
Table 8 
Assessment Windows for Screening and Maintenance Phase Data 
All Parameters 
except for where 
noted[c] 
Target Study Day 
Analysis Window 
Analysis 
Timepoint 
 
The study day of 
first record 
Study Day ≤ 1 
Screening 
 
1 
Last available recorded value up to 
and including the Maintenance 
treatment start date, excluding 
post-dose ECG taken on the 
Maintenance treatment start date 
Baseline 
ECG 
1 
Value taken post-dose on the 
Maintenance treatment start date 
Day 1 (Post Dose) 
Urinalysis[a] 
29 
2  Study Day  70 
Week 4 
 
2  Study Day  42 
 
57 
43  Study Day  84 
Week 8 
 
113 
85  Study Day  140 
Week 16 
Urinalysis[a], CD8, 
CD4/CD8 ratio 
169 
141  Study Day  210 
Week 24 
 
141  Study Day  196 
 
225 
197  Study Day  252 
Week 32 
 
281 
253  Study Day  308 
Week 40 
Urinalysis[a], fasting 
glucose, lipids[b], CD8, 
CD4/CD8 ratio, weight, 
vital signs, ECG 
337 
309  Study Day  378 
Week 48 
  
309  Study Day  364 
 
393 
365  Study Day  420 
Week 56 
 
449 
421  Study Day  476 
Week 64 
 
505 
477  Study Day  532 
Week 72 
 
561 
533  Study Day  588 
Week 80 
 
617 
589  Study Day  644 
Week 88 
Urinalysis[a], fasting 
glucose, lipids[b], CD8, 
CD4/CD8 ratio, weight, 
vital signs, ECG 
673 
645  Study Day  714 
Week 96 
 
645  Study Day  min (Study Day 
of Nominal Week100 Visit -1, 700) 


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All Parameters 
except for where 
noted[c] 
Target Study Day 
Analysis Window 
Analysis 
Timepoint 
 
701 
min (Study Day of Nominal Week 
100 Visit, 701)  Study Day  
(Study Day of Nominal Week 100 
Visit)  
Week 100 
If a participant permanently discontinued study treatment: 
 
 
For Participants on Q8W Arm: 
Date > max (Date of Last Dose of 
Oral Study Treatment (CAB+RPV 
or SOC Bridging) + 1, Date of Last 
Injection + 63) 
Follow-up 
For Participants on Q4W Arm: 
Date > max (Date of Last Dose of 
Oral Study Treatment (CAB+RPV 
or SOC Bridging) + 1, Date of Last 
Injection + 35) 
NOTES: 
• 
The nominal Week 100 visit refers to the Week 100 visit per eCRF. 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
[a] Urinalysis: All parameters provided by the central laboratory under the category of urinalysis, including Urine 
Albumin/Creatinine, Urine Creatinine, Urine pH, Urine Protein/Creatinine, Urine Erythrocytes, Urine Specific Gravity, 
Urine Leukocytes, Urine Retinol Binding Protein, Urine Phosphate, Urine Creatinine. 
[b] Lipids: Cholesterol, HDL Cholesterol Direct, LDL Cholesterol Calculation, LDL Cholesterol Direct, Total 
Cholesterol/HDL Cholesterol Ratio, Triglycerides 
[c] Analysis windows for parameters with sparse collection are noted.   
 
Table 9 
Assessment Windows for Extension Phase Data 
All Parameters 
except for 
where noted[d] 
Target 
Study Day 
Analysis Window 
Analysis Timepoint 
 
729 
(Study Day of Nominal Week 100 Visit + 
1)  Study Day  756 
Week 104[a] 
 
785 
757  Study Day  812 
Week 112 
 
841 
813  Study Day  868 
Week 120 
 
897 
869  Study Day  924 
Week 128 
 
953 
925  Study Day  980 
Week 136 
 
1009 
981  Study Day  1036 
Week 144 
Urinalysis[b], 
fasting glucose, 
lipids[c], CD8, 
CD4/CD8 ratio, 
weight, vital 
signs, ECG 
1065 
1037  Study Day  1106 
Week 152 
 
1037  Study Day  1092 


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All Parameters 
except for 
where noted[d] 
Target 
Study Day 
Analysis Window 
Analysis Timepoint 
 
7*w + 1 
(7*w - 27) 
 Study Day  (7*w + 28) 
Week w 
w = 160, 168, 
If a participant permanently discontinued study treatment: 
 
For participants on Q8W Arm: 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 
63) 
Follow-up 
For participants on Q4W Arm: 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 
35) 
NOTES: 
• 
The nominal Week 100 visit refers to the Week 100 visit per eCRF. 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
[a] Assessments taken after Week 100 injection at the nominal Week 100 visit will be assigned to Week 104. 
Adverse events started on the same day as nominal Week 100 visit date will also be assigned to Week 104. 
[b] Urinalysis: All parameters provided by the central laboratory under the category of urinalysis, including Urine 
Albumin/Creatinine, Urine Creatinine, Urine pH, Urine Protein/Creatinine, Urine Erythrocytes, Urine Specific 
Gravity, Urine Leukocytes, Urine Retinol Binding Protein, Urine Phosphate, Urine Creatinine. 
[c] Lipids: Cholesterol, HDL Cholesterol Direct, LDL Cholesterol Calculation, LDL Cholesterol Direct, Total 
Cholesterol/HDL Cholesterol Ratio, Triglycerides 
[d] Analysis windows for parameters with sparse collection are noted.   
 


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Table 10 
Assessment Windows for Summary of Snapshot Data Up to Week 
152— Data Assigned to Maintenance or Extension Phase 
Snapshot Analysis Windows 
(If no on-treatment viral load data in default window, use expanded window) 
Analysis 
Timepoint 
Default 
Expanded +6 Week Upper Windowa 
Last available recorded value up to and 
including the date of first Maintenance Phase 
dose of IP 
Last available recorded value up to and 
including the date of first Maintenance Phase 
dose of IP 
Baseline 
2  Study Day  42 
2  Study Day  70 
Week 4 
43  Study Day  84 
43  Study Day  98 
Week 8 
85  Study Day  140 
85  Study Day  154 
Week 16 
141  Study Day  196 
141  Study Day  210 
Week 24 
197  Study Day  252 
197  Study Day  266 
Week 32 
253  Study Day  308 
253  Study Day  322 
Week 40 
295  Study Day  378 
295  Study Day  378 
Week 48 
365  Study Day  420 
365  Study Day  434 
Week 56 
421  Study Day  476 
421  Study Day  490 
Week 64 
477  Study Day  532 
477  Study Day  546 
Week 72 
533  Study Day  588 
533  Study Day  602 
Week 80 
589  Study Day  644 
589  Study Day  658 
Week 88 
631  Study Day  714 
631  Study Day  714 
Week 96 
(Study Day of Nominal Week 100 Visit + 1)  
Study Day  756 
(Study Day of Nominal Week 100 Visit + 1)  
Study Day  770 
Week 104 
757  Study Day  812 
757  Study Day  826 
Week 112 
813  Study Day  868 
813  Study Day  882 
Week 120 
869  Study Day  924 
869  Study Day  938 
Week 128 
925  Study Day  980 
925  Study Day  994 
Week 136 
981  Study Day  1036 
981  Study Day  1050 
Week 144 
1023  Study Day  1106 
1023  Study Day  1106 
Week 152 
NOTES: 
• For post-baseline visits (i.e. Week 4 and afterwards), apply Snapshot analysis windows only to viral load data 
that is on-treatment (per Table 20) within the Maintenance Phase (per Table 18). 
• An on-treatment viral load assessment may be assigned to more than one snapshot analysis window, e.g. on-
treatment assessment taken on Study Day 300 will be in both Week 40 and Week 48. 
a. 
 6 Week window is always used at key analysis timepoints (Week 48, Week 96 and Week 152). For analysis 
timepoint of Week 24, if no viral load data in default window, expand to  6 Week window, i.e. (127  Study 
Day  210) in Week 24 IDMC and Week 24 Analyses, and expand upper bound to +6 weeks in all other 
analyses. 
 
Table 11 Assessment Windows for Sub-study Baseline, Thigh Injection Phase and 
Return to Gluteal Injection Phase Data (Excluding HIV-1 RNA Data) 
All Parameters 
except for where 
noted[c] 
Target Study 
Day 
Analysis Window 
Analysis Timepoint 
 
7*w + 1 
Last available recorded value up to 
and including the date of first thigh 
injection, excluding post-dose ECG 
taken on the date of first thigh injection 
Sub-study 
Baseline[d] 


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All Parameters 
except for where 
noted[c] 
Target Study 
Day 
Analysis Window 
Analysis Timepoint 
ECG 
7*w + 1 
Value taken post-dose on the date of 
first thigh injection 
Sub-study Day 1 
(Post Dose) 
Injection Site Reaction 
7*w + 1 
First thigh injection dateStudy Day 
max (7*w + 1, First thigh injection date 
+1) 
Sub-study Day 1 
 
7*(w+8) + 1 
Min (7*w + 2, first thigh injection 
date+1)  Study Day  7*(w+12) 
Sub-study Week 8 
Urinalysis[a], fasting 
glucose, lipids[b], CD8, 
CD4/CD8 ratio, weight, 
vital signs, ECG 
7*(w+16) + 1 
7*(w+12) + 1  Study Day  7*(w+22) 
Sub-study Week 16 
  
7*(w+12) + 1   Study Day  7*(w+20) 
 
7*(w+24) + 1 
7*(w+20) + 1   Study Day  7*(w+28) 
Sub-study Week 24 
If a participant permanently discontinued study treatment: 
 
 
For Participants on Q8W Arm: 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 
63) 
Follow-up 
For Participants on Q4W Arm: 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 
35) 
NOTES: 
• 
The “w” in the target study day calculation refers to the corresponding week number in Extension for the 
planned Sub-study Day 1 visit. For example, if a participant’s last planned Extension phase visit before 
entering the Sub-study is Week 192, the “w” would be 200 if the participant is on Q4W arm and would be 208 if 
the participant is on Q8W arm. 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
• 
Sub-study Day 1 (Post Dose), Sub-study Week 8 and Sub-study Week 16 visits are Thigh Injection phase 
visits, Sub-study Week 24 is Return to Gluteal Injection phase visit. 
[a] Urinalysis: All parameters provided by the central laboratory under the category of urinalysis, including Urine 
Albumin/Creatinine, Urine Creatinine, Urine pH, Urine Protein/Creatinine, Urine Erythrocytes, Urine Specific Gravity, 
Urine Leukocytes, Urine Retinol Binding Protein, Urine Phosphate, Urine Creatinine. 
[b] Lipids: Cholesterol, HDL Cholesterol Direct, LDL Cholesterol Calculation, LDL Cholesterol Direct, Total 
Cholesterol/HDL Cholesterol Ratio, Triglycerides 
[c] Analysis windows for parameters with sparse collection are noted.  
[d] The values considered for deriving Sub-study Baseline value include both Extension phase and sub-study data. 
 
Table 12 Assessment Windows for Sub-study Baseline, Thigh Injection Phase and 
Return to Gluteal Injection Phase HIV-1 RNA Data 


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Phase 
Target Study 
Day 
Analysis Window 
Analysis Timepoint 
Sub-study Screening 
7*w + 1 
Last available recorded value up to 
and including the date of first thigh 
injection 
Sub-study 
Baseline[a] 
Thigh Injection 
7*(w+4) + 1 
Min (7*w + 2, first thigh injection date 
+1)  Study Day  7*(w+6) 
Sub-study Week 4 
7*(w+8) + 1 
7*(w+6) + 1  Study Day  7*(w+10) 
Sub-study Week 8 
7*(w+12) + 1 
7*(w+10) + 1  Study Day  7*(w+14) 
Sub-study Week 12 
7*(w+16) + 1 
7*(w+14) + 1  Study Day  7*(w+20) 
Sub-study Week 16 
Return to Gluteal 
Injection 
7*(w+24) + 1 
7*(w+20) + 1  Study Day  7*(w+28) 
Sub-study Week 24 
If a participant permanently discontinued study treatment: 
 
 
For Participants on Q8W Arm: 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 
63) 
Follow-up 
For Participants on Q4W Arm: 
Date > max (Date of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC 
Bridging) + 1, Date of Last Injection + 
35) 
NOTES: 
• 
The “w” in the target study day calculation refers to the corresponding week number in Extension for the 
planned Sub-study Day 1 visit. For example, if a participant’s last planned Extension phase visit before 
entering the Sub-study is Week 192, the “w” would be 200 if the participant is on Q4W arm and would be 208 if 
the participant is on Q8W arm. 
• 
Follow-up will be derived only for participants who permanently discontinued study treatment. 
[a] The values considered for deriving Sub-study Baseline value include both Extension phase and sub-study data. 
 
Table 13 
Assessment Windows for Summary of Snapshot Data Up to Week 16 
in Sub-study— Data Assigned to Thigh Injection Phase 
Snapshot Analysis Windows 
(If no on-treatment viral load data in default window, use expanded 
window) 
Analysis Timepoint 
Default 
Expanded +6 Week Upper Windowa 
Last available recorded value up to 
and including the date of first thigh 
injection 
Last available recorded value up to and 
including the date of first thigh injection 
Sub-study Baseline[a] 
Min(7*w + 2, first thigh injection 
date+1)  Study Day  7*(w+6) 
Min (7*w + 2, first thigh injection date+1)   
Study Day  7*(w+10) 
Sub-study Week 4 
7*(w+6) + 1  Study Day  7*(w+10) 
7*(w+6) + 1  Study Day  7*(w+14) 
Sub-study Week 8 
7*(w+10) + 1  Study Day  7*(w+14) 
7*(w+10) + 1  Study Day  7*(w+16) 
Sub-study Week 12 
7*(w+10) + 1  Study Day  7*(w+22) 
7*(w+10) + 1  Study Day  7*(w+22) 
Sub-study Week 16 
NOTES: 
• 
The “w” in the target study day calculation refers to the corresponding week number in Extension for the 
planned Sub-study Day 1 visit. For example, if a participant’s last planned Extension phase visit before entering 


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the Sub-study is Week 192, the “w” would be 200 if the participant is on Q4W arm and would be 208 if the 
participant is on Q8W arm. 
• For post-baseline visits (i.e. Week 4 and afterwards), apply Snapshot analysis windows only to viral load data 
that is on-treatment (per Table 20) within the Thigh Injection Phase (per Table 18). 
• An on-treatment viral load assessment may be assigned to more than one snapshot analysis window, e.g. on-
treatment assessment taken on 7*(w+14) will be in both Sub-study Week 12 and Sub-study Week 16 visits. 
•  6 Week window is always used at the key analysis timepoint, Sub-study Week 16 visit. 
[a] The values considered for deriving Sub-study Baseline value include both Extension phase and sub-study data. 
 
Table 14 
Assessment Windows for Summaries of Long-Term Follow Up 
Phase Data for Participants Who Received At Least One Injection of 
CAB+RPV and Permanently Discontinued Study Treatment 
Analysis Window 
Analysis Timepoint 
Target Study 
Day of Window 
1  LTFU Study Day  63 
LTFU Month 1/WD[a] 
30 
64  LTFU Study Day  135 
LTFU Month 3 
90 
136  LTFU Study Day  225 
LTFU Month 6 
180 
226  LTFU Study Day  315 
LTFU Month 9 
270 
316  LTFU Study Day  405 
LTFU Month 12 
360 
(30*m - 44)  LTFU Study Day   (30*m + 45) LTFU Month m 
m = 15, 18,21, 
30*m  
NOTES: 
• 
An assessment may be assigned to both LTFU and maintenance/extension phases. 
a. For participants who receives at least one injection of CAB+RPV and permanently discontinues study 
treatment, they will not complete withdrawal visit, will instead move directly into the LTFU and have LTFU 
Month 1 visit as the first planned LTFU visit per protocol amendment 1;  however, per protocol amendment 2, 
they will complete withdrawal visit and then have LTFU Month 3 visit as the first planned LTFU visit. Data have 
been collected either per protocol amendment 1 or per protocol amendment 2 and are included in the 
database. The analysis timepoint of LTFU Month 1/WD is intended for slotting data mainly collected from either 
LTFU Month 1 visit per protocol amendment 1 or withdrawal visit per protocol amendment 2 if the date of 
assessments or onset date of event falls within the specified analysis window. 
15.3.3. 
Assessment Window for Phase Conclusion 
The ‘Phase Conclusion’ records in disposition data will be slotted based on Table 8 (for 
Maintenance Phase conclusion records), Table 9 (for Extension Phase conclusion 
records), and Table 12 (for Thigh Injection Phase and Return to Gluteal Injection Phase 
conclusion records). However, if the discontinuation date is post-treatment per Table 20, 
the record will be slotted to the last on-treatment visit within the same phase rather than 
follow up. 
15.3.4. 
Assessment Window for Health Outcome Data 
15.3.4.1. 
PIN / HAT-QoL / HIVTSQs / HIVTSQc / ACCEPT / Preference in Main 
Study 
PIN, HAT-QoL, HIVTSQs, HIVTSQc, ACCEPT, Preference, reasons for oral bridging 
and preference questionnaire assessments will be assigned to analysis visits as follows: 


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1. Baseline will be defined as last available recorded value up to and including the 
Maintenance treatment start date (expected to be collected at Day 1). Baseline is 
not applicable for PIN, HIVTSQc and Preference assessments. 
2. For post-baseline visits, if the nominal visit identifier as captured in the source 
dataset corresponds to a scheduled collection per the Time and Events Schedule 
(see Section 15.2 and Table 15) and the assessment is collected in the 
Maintenance or Extension Phase (per Table 18), then the nominal visit identifier 
will be kept as the analysis visit. 
3. For post-baseline visits, if the nominal visit identifier is unscheduled or 
withdrawal, then the following procedure will be used: 
a) Assign the assessment to a study phase according to Table 18. Proceed to 
step b if the assessment is assigned to the Maintenance or Extension 
Phase. 
b) Identify the ‘last nominal visit’ with the HO assessment performed prior to 
the unscheduled/withdrawal visit to be slotted in the same phase.  
c) The unscheduled/withdrawal visit will be slotted to the planned nominal 
visit subsequent to the ‘last nominal visit’ in the same phase. If the ‘last 
nominal visits’ does not exist (e.g. no records originate from a planned 
nominal visit), then the unscheduled/withdrawal visit will be slotted to the 
first planned nominal visit after Day 1 in the same phase. If the planned 
nominal visit subsequent to the ‘last nominal visit’ is not available, then 
the unscheduled/withdrawal visit will be slotted to the last planned 
nominal visit after Day 1 in the same phase. 
Example 1, for HATQoL, the planned nominal visits are Day 1, Week 24, and 48. If a 
participant has the ‘last nominal visit’ (with HATQoL assessment) at Week 24 prior to 
withdrawal at Week 36, the withdrawal assessment will be slotted to the subsequent 
planned nominal visit of Week 48.  
Example 2, for HATQoL, if there is unscheduled visit between Week 24 and Week 48. 
This unscheduled visit will be slotted to Week 48 per the rule.  In this case, there are two 
assessments with analysis visit equal to Week 48 (i.e. the slotted value and the value at 
original nominal week 48 visit). The original nominal value will be selected for summary 
per the rule below for multiple records—see Section 15.3.5.1. 
Table 15 
Planned Nominal Visit of Health Outcome Data in Main Study 
Questionnaire 
Day 1 
Week 8 
Week 24 
Week 48 Week 152 
PIN 
 
x 
x 
x 
x 
HAT-QoL 
x 
 
x 
x 
 
HIVTSQs 
x 
 
x 
x 
x 
HIVTSQc 
 
 
 
x 
 
ACCEPT 
x 
x 
x 
x 
Preference 
 
 
 
x 
 
Reasons for Oral Bridging and 
Preference 
 
 
 
 
x 
NOTES: 
Day 1 visits are recorded as “Baseline” visits in the database. 


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15.3.4.2. 
Reasons for Continuation/Switch in Main Study 
Reasons for Continuation/Switch assessments are planned to be taken at nominal 
Baseline (Day 1) visit only. The assessments taken within ± 2 weeks window from 
maintenance phase treatment start date will be regarded as evaluable. The assessments 
taken outside this window will be excluded from the summary. 
15.3.4.3. 
HIVTSQs/HIVTSQc/Preference in Sub-study 
HIVTSQs, HIVTSQc, Preference Thigh Injection vs Gluteal Injection questionnaire 
assessments will be assigned to analysis visits as follows: 
1. Sub-study Baseline will be defined as last available recorded value up to and 
including the date of first thigh injection. Baseline is not applicable for HIVTSQc 
and Preference Thigh Injection vs Gluteal Injection assessments as they are not 
planned to be collected during the Sub-study Baseline. In Sub-study Baseline 
value derivation for HIVTSQs, the assessments conducted in the main study will 
also be considered.  
2. For post-baseline visits, if the nominal visit identifier as captured in the source 
dataset corresponds to a scheduled collection per the Time and Events Schedule 
(see Section 15.2) and the assessment is collected in the planned phase (per Table 
18, visits at/before Sub-study Week 16 belong to Thigh Injection phase, and visits 
after Sub-study Week 16 belong to Return to Gluteal Injection phase), then the 
nominal visit identifier will be kept as the analysis visit. 
3. For post-baseline visits, if the nominal visit identifier is unscheduled or it is 
scheduled however not conducted in the planned phase (e.g. the sub-study Week 
16 HIVTSQs assessment is conducted after the Week 16 gluteal injection and 
therefore belong to Return to Gluteal Injection phase), then this visit will be 
assigned to the planned visit in the same phase. 
15.3.4.4. 
Tolerability of Injections (NRS) in Sub-study 
After assigning the phases per Table 18, the NRS assessments will be slotted to analysis 
visits per Table 16. 
Table 16 Assessment Window for NRS Data 
Phase 
Assessment Window 
Visit 
Sub-study 
Screening 
Q8W: post-dose and on the Week -8 injection date 
Q4W: post-dose and on the Week -4 injection date 
Q8W: Sub-study Week -8 
Q4W: Sub-study Week -4 
Q8W: (Week -8 injection date+1, Week -8 injection 
date+14), inclusive  
Q4W: (Week -4 injection date+1, Week -4 injection 
date+14), inclusive 
Q8W: Sub-study Week -7 
Q4W: Sub-study Week -3 
 
Thigh 
Injection 
Post-dose and on the Day 1 injection date 
Sub-study Day 1 
(Day 1 injection date+1, Day 1 injection date+14), 
inclusive 
Sub-study Week 1 
Q8W: post-dose and on the Week 8 injection date 
Q4W: post-dose and on the Week 12 injection date 
Q8W: Sub-study Week 8 


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Q4W: Sub-study Week 
12 
Q8W: (Week 8 injection date+1, Week 8 injection 
date+14), inclusive  
Q4W: (Week 12 injection date+1, Week 12 injection 
date+14), inclusive 
Q8W: Sub-study Week 9 
Q4W: Sub-study Week 
13 
Return to 
Gluteal 
Post-dose and on the Week 16 injection date 
Sub-study Week 16 
(Week 16 injection date+1, Week 16 injection 
date+14), inclusive 
Sub-study Week 17 
 
15.3.5. 
Assessment Window for PK Concentration Data 
15.3.5.1. 
Maintenance and Extension Phase Assessments 
For PK concentration data at the withdrawal/unscheduled/LTFU Month 1visits during the 
maintenance and extension phase (after assignment to study phase per Table 18), the visit 
will be slotted to the analysis visit per the following steps: 
• 
Identify the ‘last nominal visit’ with the planned PK pre-dose assessment 
prior to the visit to be slotted during the same study phase 
• 
Identify the nominal visit corresponding to the next planned pre-dose PK 
assessment visit (excluding visits with storage PK collection), that is 
subsequent to the ‘last nominal visit’ with PK pre-dose assessment during 
the same study phase. If the ‘last nominal visit’ during the maintenance 
phase does not exist, the first planned pre-dose PK assessment visit for the 
participant during the maintenance phase will be considered the nominal 
visit corresponding to the next planned pre-dose PK assessment. If the 
‘last nominal visit’ during the extension phase does not exist, slot the PK 
assessment to the nominal visit of the next planned injection occurring on 
or after the date of the PK assessment during the extension phase. 
• 
If the nominal visit corresponding to next planned pre-dose PK assessment 
visit is prior to/at Week 48 visit, the PK assessment at the 
unscheduled/withdrawal/LTFU Month 1 visit will be slotted to this 
nominal visit corresponding to next planned pre-dose PK assessment visit.  
• 
Otherwise, the PK assessment at the unscheduled/withdrawal/LTFU 
Month1 visit will be slotted to the earliest nominal visit from the 
following: 
o Nominal visit corresponding to the next planned pre-dose PK 
assessment visit  
o The nominal visit of the next planned injection occurring on or 
after the date of the PK assessment during the same study phase 
If both the next planned pre-dose PK assessment visit and the next planned 
injection visit during the same study phase are not available, for example, 
withdrawal PK assessment taken after Week 96 for participants on Q8W 
arm, the PK assessment will be slotted to Week 100 visit. 


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During the maintenance and extension phase, the planned nominal visits for PK Pre-dose 
are Week 4B, 8, 16, 24, 32, 40, 48, 96, 152 for Q4W arm; and are Day 1, Week 4B, 8, 16, 
24, 32, 40, 48, 96, 152 for Q8W arm while Day 1 is required only for those transitioning 
from ATLAS on Q4W injections and Week 4B is required only for participants 
transitioning from oral SOC and requiring oral CAB+RPV lead-in. In addition, the 
participants on Q8W arm have planned nominal visits at Week 9 and 41 for 1-week post-
dose.   
For participants requiring oral CAB+RPV lead-in, the planned injection visits are Week 
4B, Week 8, continuing every 4 weeks for Q4W arm and continuing every 8 weeks for 
Q8W arm. For participants not requiring oral CAB+RPV lead-in, the planned injection 
visits are every 4 weeks starting from Day 1 for Q4W arm and every 8 weeks starting 
from Day 1 for Q8W arm.  
Example 1: If a participant on Q8W arm has the ‘last nominal visit’ (with PK pre-dose 
assessment) at Week 24 and then withdraws around Week 28, with the last injection at 
Week 24 and a Maintenance Phase PK assessment labelled at ‘LTFU Month 1’., This PK 
assessment labelled as ‘LTFU Month 1’ will be slotted to the subsequent planned 
nominal visit of Week 32.  
Example 2: If a participant on Q4W arm has the ‘last nominal visit’ (with PK pre-dose 
assessment) at Week 48 and then have an unscheduled Maintenance Phase PK 
assessment around Week 74. This assessment will be slotted to the next planned injection 
visit, Week 76.  
There will be no slotting for planned nominal visits (i.e. analysis visit =visit). 
15.3.5.2. 
Long-term Follow-up Phase Assessments 
PK concentration data at nominal visits other than withdrawal/LTFU Month 1/LTFU 
Month 3/LTFU Month 6/LTFU Month 9/LTFU Month 12/Liver Event which have been 
assigned to the LTFU phase (according to according to Table 18) will be slotting to 
analysis visits per the following steps: 
• 
Identify the ‘last nominal PK visit’ with the PK assessment performed 
prior to the visit to be slotted during the LTFU phase 
• 
The PK assessments will be slotted to the nominal visit corresponding to 
the next planned LTFU PK assessment visit that is subsequent to the ‘last 
nominal PK visit’ during the LTFU phase. If the ‘last nominal visit’ does 
not exist, the PK assessment will be slotted per Error! Reference source 
not found.. 
There will be no slotting for planned PK nominal visits (i.e. analysis visit =visit): LTFU 
Month 1 or withdrawal, LTFU Month 3, LTFU Month 6, LTFU Month 9 and LTFU 
Month 12.  


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15.3.5.3. 
Sub-study Assessments 
Unscheduled sub-study assessments will not be slotted to any analysis visit. There will be 
no slotting for planned nominal visits (i.e. analysis visit=visit). 
15.3.6. 
Multiple Assessments within an Assessment Window 
If after window assignment there are multiple valid assessments of a parameter within the 
same window, then the following hierarchy will be used to determine the value to be used 
for summary statistics of observed values: 
For data other than health outcome/PK concentration:  
1. the assessment closest to the window target Study Day; 
2. if there are multiple assessments equidistant from the target Study Day, then the 
mean of these values will be used. For HIV-1 RNA, the geometric mean of the 
number of copies will be used as opposed to the arithmetic mean. For post-dose ECG, the 
assessment closest to the two-hour post injection will be used. 
For Health outcome and PK concentration data, the following hierarchy will be used to 
determine the value to be used for summary statistics of observed values:  
1. If there are multiple on-treatment assessments assigned to the same analysis visit, 
the assessment from the planned nominal visit will be used for summary 
statistics. 
2. If there are multiple on-treatment assessments assigned to the same analysis visit 
and none originates from a planned nominal visit (e.g. two 
unscheduled/withdrawal nominal visits), then 
a. the assessment closest to the window target Study Day will be used; 
b. if there are multiple assessments equidistant from the target Study Day, 
then the earliest assessment will be used. 
 
Assessments not chosen for use in summary statistics by this algorithm will still appear in 
the associated listings. Also, all applicable valid assessments, irrespective of proximity to 
the target study day, will be used when categorizing values across visits, such as 
‘maximum grade’ or ‘at any time’, and for any algorithm that has specific rules for which 
observation to use (e.g. snapshot algorithm, LOCF or CVF identification). 


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15.4. 
Appendix 4: Study Phases and Treatment State 
15.4.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
the Treatment Start Date defined in Section 15.6.1. 
AEs will be assigned to study phases as defined in Table 17.  For example, adverse 
events on/after start of maintenance phase IP and prior to start of Extension phase 
IP/LTFU ART will be assigned to the Maintenance Phase. 
Laboratory data (efficacy, safety, PK and virology), HIV associated Conditions, health 
outcomes assessments, vital signs, and ECGs will be assigned to study phases as defined 
as in Table 18. For example, assessments/events occurring after start of maintenance 
phase IP and up to and including start of extension phase IP/LTFU ART will be assigned 
to the Maintenance Phase. 
Assessments/events are assigned to study phases sequentially, starting from the top of 
each table, except for the assessments/events occurring after returning to Extension phase 
from the sub-study participation. No study phases will be assigned to medications. 
Table 17 
Assignment of Study Phases for AEs 
Study Phase 
Definition 
Screening 
Date < Maintenance Treatment Start Date 
Maintenance 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date ≤ Date < Date of Nominal Week 100 Visit  
 
For participants not continuing into Extension Phase: 
For participants continuing into LTFU Phase: 
Maintenance Treatment Start Date ≤ Date < LTFU ART Start Date[a] 
 


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Extension 
For participants continuing into Extension Phase and not entering the sub-
study: 
If participants continued into LTFU Phase after the Extension phase:Date of Nominal 
Week 100 Visit ≤ Date < LTFU ART Start Date[a] 
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of Nominal Week 100 Visit[a] ≤ Date < Date of end of study +35 days (Q4W)  or + 
63 days (Q8W) 
For participants continuing into Extension Phase, entering the sub-study but 
not returning to Extension Phase: 
Date of Nominal Week 100 Visit ≤ Date < Date of First Sub-study Record  
For participants continuing into Extension Phase, entering the sub-study and 
returning to Extension Phase: 
Before the sub-study: Date of Nominal Week 100 Visit ≤ Date < Date of First Sub-
study Record 
After the sub-study:  
For participants continuing into LTFU Phase after return to extension phase: 
End of Sub-study Date[b] < Date < LTFU ART Start Date[a] 
For participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason: 
End of Sub-study Date[b] < Date < Date of end of study +35 days (Q4W)  or + 63 days 
(Q8W) 
Sub-study 
Screening 
For participants entering the sub-study and not receiving any thigh injection: 
If participants continued into LTFU Phase after the sub-study, then  
Date of First sub-study record ≤ Date < LTFU ART Start Date[a] 
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of First sub-study record ≤ Date < Date of end of study +35 days (Q4W)  or + 63 
days (Q8W) 
If participants continued into Extension Phase after the sub-study, then 
Date of First sub-study record ≤ Date ≤ End of Sub-study Date[b] 
For participants entering the sub-study and receiving thigh injection(s): 
Date of First sub-study record ≤ Date < Date of First Thigh Injection 
 
Thigh Injection 
For participants continuing into Return to Gluteal Injection Phase: 
Date of First Thigh Injection ≤ Date < Date of Nominal Sub-study Week 16 Visit[c] 
For participants not continuing into Return to Gluteal Injection Phase: 
If participants continued into LTFU Phase after the sub-study, then  
Date of First Thigh Injection ≤ Date < LTFU ART Start Date[a] 
If participants continued into Extension Phase after the sub-study, then 
Date of First Thigh Injection ≤ Date ≤ End of Sub-study Date[b]  
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of First Thigh Injection ≤ Date < Date of end of study +35 days (Q4W)  or + 63 
days (Q8W) 


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Return to Gluteal 
Injection 
For participants continuing into Extension Phase after the sub-study: 
Date of Nominal Sub-study Week 16 Visit[c] ≤ Date ≤ End of Sub-study Date[b] 
For participants continuing into LTFU Phase after the sub-study: 
Date of Nominal Sub-study Week 16 Visit[c] ≤ Date < LTFU ART Start Date[a] 
For participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason: 
Date of Nominal Sub-study Week 16 Visit[c] ≤ Date < Date of end of study +35 days 
(Q4W)  or + 63 days (Q8W) 
NOTES: 
• 
Date = AE Start date 
• 
For AEs started on the End of Sub-study Date, if participants received injection belonging to the 
Extension Phase on End of Sub-study Date, Extension Phase will be assigned to these AEs. 
• 
[a] If participants have missing LFTU ART start date, only the lower bound will be considered in the 
derivation. For AEs leading to withdrawal and started on the same date as LTFU ART Start Date, 
appropriate study treatment associated phase (e.g. Maintenance, Extension, Sub-study Screening, 
Thigh Injection, Return to Gluteal Injection), instead of Long-term Follow-up phase, will be assigned. 
• 
[b] End of Sub-study Date is defined in Section 15.6.1.  
• 
[c] Nominal Sub-study Week 16 Visit Date is defined in Section 15.6.1. 


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Table 18 
Assignment of Study Phases for Lab Assessments (including PK 
and Virology), ECG, Protocol Deviations, Vital Sign, Health 
Outcomes, HIV Associated Conditions 
Study Phase 
Definition 
Screening 
Date ≤ Maintenance Treatment Start Date 
Note: 2-hour post-dose ECG taken on the Maintenance Treatment Start Date will be 
excluded. 
Maintenance 
For participants continuing into Extension Phase: 
Maintenance Treatment Start Date < Date ≤Date of Nominal Week 100 Visit[a] 
Note: 2-hour post-dose ECG taken on the Maintenance Treatment Start Date will be 
included. 
 
For participants not continuing into Extension Phase: 
For participants continuing into LTFU Phase: 
Maintenance Treatment Start Date < Date ≤ LTFU ART Start Date[b] 
For participants transitioned to marketed product/alternative HAART 
and did not withdraw study due to safety related reason: 
Maintenance Treatment Start Date < Date ≤ Date of end of study +35 days 
(Q4W)  or + 63 days (Q8W) 
Note: 2-hour post-dose ECG taken on the Maintenance Treatment Start Date will be 
included. 
Extension 
For participants continuing into Extension Phase and not entering the 
sub-study: 
If participants continued into LTFU Phase after the Extension phase: 
Date of Nominal Week 100 Visit[a] < Date ≤ LTFU ART Start Date[b] 
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of Nominal Week 100 Visit[a] < Date ≤ Date of end of study +35 days 
(Q4W)  or + 63 days (Q8W)For participants continuing into Extension 
Phase, entering the sub-study but not returning to Extension Phase: 
Date of Nominal Week 100 Visit[a] < Date < Date of First Sub-study Record  
For participants continuing into Extension Phase, entering the sub-
study and returning to Extension Phase: 
Before the sub-study: Date of Nominal Week 100 Visit[a] < Date < Date of First 
Sub-study Record 
After the sub-study:  
For participants continuing into LTFU Phase after return to extension 
phase: 
End of Sub-study Date[b] < Date ≤ LTFU ART Start Date[a] 
For participants transitioned to marketed product/alternative HAART 
and did not withdraw study due to safety related reason: 
End of Sub-study Date[b] < Date ≤ Date of end of study +35 days (Q4W)  or + 
63 days (Q8W) 


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Sub-study 
Screening 
For participants entering the sub-study and not receiving any thigh 
injection: 
If participants continued into LTFU Phase after the sub-study, then  
Date of First sub-study record ≤ Date < LTFU ART Start Date[b] 
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of First sub-study record ≤ Date < Date of end of study +35 days (Q4W)  
or + 63 days (Q8W) 
If participants continued into Extension Phase after the sub-study, then 
Date of First sub-study record ≤ Date ≤ End of Sub-study Date[c] 
For participants entering the sub-study and receiving thigh injection(s): 
Date of First sub-study record ≤ Date ≤ Date of First Thigh Injection[d] 
Thigh Injection 
For participants continuing into Return to Gluteal Injection Phase: 
Date of First Thigh Injection[d] < Date ≤ Date of Nominal Sub-study Week 16 
Visit[e] 
For participants not continuing into Return to Gluteal Injection Phase: 
If participants continued into LTFU Phase after the sub-study, then  
Date of First Thigh Injection[d] < Date ≤ LTFU ART Start Date[b] 
If participants continued into Extension Phase after the sub-study, then 
Date of First Thigh Injection[d] < Date ≤ End of Sub-study Date[c] 
If participants transitioned to marketed product/alternative HAART and did not 
withdraw study due to safety related reason, then 
Date of First Thigh Injection ≤ Date ≤ Date of end of study +35 days (Q4W)  
or + 63 days (Q8W) 
Return to 
Gluteal 
Injection 
For participants continuing into Return to Extension Phase after the 
sub-study: 
Date of Nominal Sub-study Week 16 Visit[e] < Date ≤ End of Sub-study Date[c] 
For participants continuing into LTFU Phase after the sub-study: 
Date of Nominal Sub-study Week 16 Visit[e] < Date ≤ LTFU ART Start Date[b] 
For participants transitioned to marketed product/alternative HAART 
and did not withdraw study due to safety related reason: 
Date of Nominal Sub-study Week 16 Visit[c] < Date ≤ Date of end of study +35 
days (Q4W)  or + 63 days (Q8W) 
• 
Date = start or assessment date 
• 
[a] If the collected time of the assessment is available, the assessment taken on the same day as 
nominal Week 100 visit date but after the Week 100 injection will be assigned to Extension Phase. 
• 
[b] If participants have missing LFTU ART start date (i.e. the participants have not started ART in 
LFTU yet), only the lower bound of the window will be considered in the derivation. 
• 
[c] End of Sub-study Date is defined in Section 15.6.1.  
• 
[d] The post-dose assessments (e.g. 2-hour post-dose ECG, 2-hour post-dose PK and NRS) taken on 
the date of first thigh injection will be assigned Thigh Injection Phase, instead of Sub-study Screening 
Phase.  
• 
[e] The Date of Nominal Sub-study Week 16 is defined in Section 15.6.1. The post-dose assessment 
(e.g. NRS) taken on the date of Sub-study Week 16 injection will be assigned Return to Gluteal 
Injection Phase, instead of Thigh Injection Phase. 
 
Table 19 
Assignment to Long-term Follow-up Phase  
Study Phase 
Definition 


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Long-term 
Follow-up 
Date > max (Last IM Injection Date, Last Oral Bridging End Date) 
• 
Date = Assessment/Start Date 
• 
For AEs leading to withdrawal and started on the same date as LTFU ART Start Date, appropriate 
study treatment associated phase, instead of long-term follow-up phase, will be assigned. Refer to 
Table 17 for details. 
Only participants who received at least one CAB and/or RPV injection will enter the 
long-term follow-up. Participants transitioning to CAB+RPV LA marketed product or 
alternative HAART (except due to safety-related reasons) do not need to enter the LTFU 
Phase. Note that the long-term follow-up phase and maintenance/extension/sub-study 
screening/thigh injection/return to gluteal injection phases are not necessarily mutually 
exclusive and are to be defined with separate phase variables in the datasets.  For 
example, an Q4W IM participant who has Week 44 injection and withdrawal at Week 48 
without receiving Week 48 injection, the “Week 48 withdrawal visit” belongs to both the 
maintenance phase and long-term follow-up phase.   
15.4.2. 
Treatment State 
Within each treatment study phase (i.e. Maintenance and Extension—based on 
assignment of study phase described in Section 15.4.1), only those assessments which 
occur within the ranges shown in Table 20 will be considered ‘on-treatment’ for the given 
phase. No treatment states will be assigned to medications. 
Table 20 
Treatment State within Study Phasesb 
Study Phasea 
Treatment State 
Date Range 
Screening 
Pre-treatment 
All assessments/events within the phase 
Maintenance 
On-treatment 
Q8W arm:  
Date  max (Date of Last Injection + 63, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
Q4W arm:  
Date  max (Date of Last Injection + 35, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
Post-treatment 
Q8W arm:  
Date > max (Date of Last Injection + 63, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
Q4W arm:  
Date > max (Date of Last Injection + 35, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
Extension 
On-treatment 
Q8W arm:  
Date  max (Date of Last Injection + 63, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
 
Q4W arm:  


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Date  max (Date of Last Injection + 35, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
Post-treatment 
Q8W arm: 
Date > max (Date of Last Injection + 63, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
 
Q4W arm: 
Date > max (Date of Last Injection + 35, Date of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1) 
Long-term Follow-
up 
On-treatment 
Q8W arm: 
Date  min (LTFU ART start date, max (Date of Last 
Injection + 63, Date of Last Dose of Oral Study Treatment 
(CAB+RPV or SOC Bridging) + 1)) 
 
Q4W arm: 
Date  min (LTFU ART start date, max (Date of Last 
Injection + 35, Date of Last Dose of Oral Study Treatment 
(CAB+RPV or SOC Bridging) + 1)) 
Post-treatment 
Q8W arm: 
Date > min (LTFU ART start date, max (Date of Last 
Injection + 63, Date of Last Dose of Oral Study Treatment 
(CAB+RPV or SOC Bridging) + 1)) 
 
Q4W: 
Date > min (LTFU ART start date, max (Date of Last 
Injection + 35, Date of Last Dose of Oral Study Treatment 
(CAB+RPV or SOC Bridging) + 1)) 
NOTE: 
• 
Date = Assessment/Start Date. 
• 
For Sub-study Screening, Thigh Injection and Return to Gluteal Injection phases, the same on-treatment and 
post-treatment algorithms as those in Extension Phase will be applied. 
a. 
Treatment State is determined after data has been assigned to the study phases as defined in Section 15.4.1. 
b. 
Last injection and/or last dose of oral study treatment (CAB+RPV or SOC bridging) are only applied to 
participants who permanently discontinued the study treatment. The assessments for participants who did not 
permanently discontinue the study treatment will be considered ‘On-treatment’. For participants continuing into 
extension phase, all data assigned to maintenance phase per Section 15.4.1 will be considered ‘On-treatment’. 
 
15.4.2.1. 
Treatment States for AE Data 
For adverse events, partial AE start date will use imputation as described in Section 
15.7.2.1. In the case of a completely missing start date, the event will be considered to 
have started On-treatment in the Maintenance phase unless an end date for the AE is 
provided which is before start of study treatment at Maintenance phase; in such a case the 
AE is assigned as Pre-treatment.  
Additional variables will be derived as shown in Table 21. 


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Table 21 
Days since First Dose of Each Study Phase, Days since Phase Start, 
AE Duration and Relation to Study Treatment 
 
Definition 
Days since 
First Dose 
(Days)a 
AE Start Date – Maintenance Treatment Start Date + 1 
Days since 
Last Dose 
(Days)a 
AE Start Date – Date of Last Dose of Study Treatment prior to/on the 
Start Date of AE + 1 
Days since 
Phase Start 
For AEs in Maintenance Phase: 
AE Start Date - Maintenance Treatment Start Date + 1 
For AEs in Extension Phase before Sub-study: 
AE Start Date – Date of Nominal Week 100 Visit + 1 
For AEs in Extension Phase after Sub-study: 
AE Start Date – End of Sub-study Datec + 1 
For AEs in Long-term Follow-up Phase: 
AE Start Date – Date of Last Dose of Study Treatmentb 
For AEs in Sub-study Screening Phase: 
AE Start Date – Date of First Sub-study Record + 1 
For AEs in Sub-study Thigh Injection Phase: 
AE Start Date - Date of First Thigh Injection + 1 
For AEs in Return to Gluteal Injection Phase: 
AE Start Date - Date of Nominal Sub-study Week 16 Visit + 1 
Duration 
(Days)  
AE Resolution Date – AE Start Date + 1 
Drug-related 
If relationship is marked ‘YES’ on Inform/eCRF or value is missing. 
NOTES: 
a. Days since First/Last Dose will only be derived for AEs assigned to maintenance phase, 
extension phase and long-term follow-up phase. 
b. Date of Last Dose of Study Treatment = max (Last IM Injection Date, Last Oral Bridging End 
Date), only applicable to participants who permanently discontinued study treatment. 
c.  End of Sub-study Date is defined in Section 15.6.1. 
 
15.4.3. 
Study Period 
Certain displays will be produced for data collected during the oral lead-in. The study 
period variable is defined in Table 22 and Table 23. Study period is assigned after the 
study phase is assigned (screening, maintenance, extension, or long-term follow-up) 
based on the Tables in Section 15.4.1. 
Table 22 
Assignment of Study Period for AE Data 
Study Period 
Date range 


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Oral Lead-in 
For participants receiving at least one Injection: 
Maintenance Treatment Start Date ≤ Date < Date of First IM Injection  
 
For participants withdrawing prior to first Injection: 
Date  Maintenance Treatment Start Date 
Note that the oral lead-in period is only applicable to the participants who 
received at least one dose of study treatment during the oral lead-in period in 
the study. Oral lead-in period is within the maintenance phase. 
NOTES: 
• 
Date = AE Start date. 
 
Table 23 
Assignment of Study Period for Lab Assessments: 
Period 
Date range 
Oral Lead-in 
For participants receiving at least one Injection: 
Maintenance Treatment Start Date < Date ≤ Date of First IM 
Injection  
 
For participants withdrawing prior to first Injection: 
Date > Maintenance Treatment Start Date 
 
Note that the oral lead-in period is only applicable to the 
participants who received at least one dose of study treatment 
during the oral lead-in period in the study. Oral lead-in period is 
within the maintenance phase. 
NOTES: 
• 
Date = Date of assessment. 
 


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15.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
15.5.1. 
Reporting Process 
Software 
• The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: us1salx00259 
HARP Compound 
: \ARPROD\GSK1265744\mid207966 
Analysis Datasets  
• Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 
& ADaM IG Version 1.1). 
• For creation of ADaM datasets (ADCM/ADAE), the same version of dictionary datasets 
will be implemented for conversion from SI to SDTM. 
Generation of RTF Files 
• RTF files will be generated for every reporting effort described in the RAP. 
15.5.2. 
Reporting Standards 
General 
• The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, 
unless otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 4.03 to 4.23: General Principles 
• 5.01 to 5.08: Principles Related to Data Listings 
• 6.01 to 6.11: Principles Related to Summary Tables 
• 7.01 to 7.13: Principles Related to Graphics 
Formats 
• GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted 
for reporting of data based on the raw data collected, unless otherwise stated. 
• Numeric data will be reported at the precision collected on the eCRF. 
• The reported precision from non eCRF sources will follow the IDSL statistical principles 
but may be adjusted to a clinically interpretable number of DP’s. 
Planned and Actual Time 
• Reporting for tables, figures and formal statistical analyses: 
o Actual time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
o The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as 
appropriate. 
• Reporting for Data Listings:  
o If space allows, planned and actual time relative to study drug dosing will be shown in 
listings (Refer to IDSL Statistical Principle 5.05.1). 


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o Unscheduled or unplanned readings will be presented within the participant’s listings. 
o When data falls within both maintenance / extension and long-term follow-up phases, it 
will be presented in maintenance / extension phase, unless otherwise specified. 
o Unless otherwise specified, when data falls within both screening and baseline visits per 
analysis visit windows, it will be presented at baseline visit. 
Unscheduled Visits 
• Unscheduled visits will be assigned to a study visit using the all-inclusive windows defined in 
Section 15.2.3. 
• However, data summaries will only report visits that are planned assessment time points for 
each parameter (according to the Time and Events table). 
• Assessments at unscheduled visits will be included for ‘any time On-treatment’ time points 
and in data listings, as well any algorithms that make use of additional data (e.g., Snapshot). 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1. First and third quartiles will also 
be included in the summary. 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• Refer to IDSL Statistical Principals 7.01 to 7.13. 
15.5.3. 
Reporting Standards for Pharmacokinetic 
Reporting of Pharmacokinetic Concentration Data 
Descriptive 
Summary Statistics, 
Graphical Displays 
and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical Principle 6.06.1 
Assign the low limit of quantification (CAB 0.025 ug/mL, RPV 1 ng/mL) to 
NQ values.  
Reporting of Pharmacokinetic Parameters 
Descriptive 
Summary Statistics 
(Loge Transformed) 
N, n, geometric mean, 95% CI of geometric mean, standard deviation 
(SD) of loge transformed data and between participant coefficient of 
variation (CVb (%)) will be reported. 
o 𝐶𝑉𝑏(%) = √exp(𝑆𝐷2) −1 × 100 
             (SD = SD of loge transformed data) 
 


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15.6. 
Appendix 6: Derived and Transformed Data 
15.6.1. 
General 
Multiple Measurements at One Time Point 
• If after window assignment there are multiple valid assessments of a parameter within 
the same window, refer to Section 15.3.5.1 for determination of the value to be used for 
summary statistics of observed values. Assessments not chosen for use in summary 
statistics will still appear in the associated listings. Assessments not chosen for use in 
summary statistics by this algorithm will still appear in the associated listings. Also, all 
applicable valid assessments, irrespective of proximity to the target study day, will be 
used when categorizing values across visits, such as ‘maximum grade’ or ‘at any time’, 
and for any algorithm that has specific rules for which observation to use (e.g. snapshot 
algorithm, LOCF or CVF identification). 
Nominal Week 100 Visit Date 
• For participants who received Week 100 injection, nominal Week 100 visit date is 
defined by the Week 100 injection date. 
• Otherwise, nominal Week 100 visit date is defined by the date of latest Week 100 
assessment. 
• For participants who continued into Extension Phase however missed Week 100 visit, 
nominal Week 100 visit date is defined by the end of Maintenance Phase date (i.e. date 
for the Maintenance Phase conclusion record in the SDTM DS domain) for the analysis 
purpose. 
Nominal Sub-study Week 16 Visit Date 
• For participants who received Sub-study Week 16 injection, nominal Sub-study Week 
16 visit date is defined by the Sub-study Week 16 injection date. 
• Otherwise, nominal Sub-study Week 16 visit date is defined by the date of latest Sub-
study Week 16 assessment. 
• For participants who continued into Return to Gluteal Injection Phase however missed 
Sub-study Week 16 visit, nominal Sub-study Week 16 visit date is defined by the end of 
Thigh Injection Phase date (i.e. date for the Thigh Injection Phase conclusion record in 
the SDTM DS domain) for the analysis purpose. 
End of Sub-study Date 
• For sub-study screen failures, the end of sub-study date is defined by the date they 
failed to meet the inclusion/exclusion criteria in the sub-study. 
• For other sub-study participants, the end of sub-study date is defined by the date of 
completion or withdrawal available in the sub-study conclusion eCRF form. 


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Study Day 
The Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of AE or HIV 
associated condition) will be derived as the number of days between the date of the event and 
the start date of study treatment during the Maintenance Phase as follows: 
 
if date of event  start date of study treatment, then 
• Study Day=date of event - start date of Maintenance Phase treatment +1  
 
if date of event < start date of study treatment, then 
• Study Day=date of event - start date of Maintenance Phase treatment 
 
Note that the start date of study treatment during maintenance phase is considered to be on 
Study Day 1 and the day before this is Study Day -1; i.e., there is no Study Day 0. 
Extension Phase Study Day 
The Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of AE or HIV 
associated condition) will be derived as the number of days between the date of the event and 
the date of nominal Week 100 visit as follows: 
if date of event  date of nominal Week 100 visit, then 
• Study Day=date of event - date of nominal Week 100 visit + 1 
 
if date of event < date of nominal Week 100 visit, then 
• Study Day=date of event - date of nominal Week 100 visit 
 
Note that the date of nominal Week 100 visit is considered to be on Extension Phase Study Day 
1 and the day before this is Extension Phase Study Day -1; i.e., there is no Extension Phase 
Study Day 0. 
Sub-study Phase Study Day 
Each phase Study Day of an event (e.g., lab assessment, vital sign, ECG, start date of AE or 
HIV associated condition) will be derived as the number of days between the date of the event 
and the reference date for each phase of the sub-study as follows: 
if date of event  reference date, then 
• 
 Study Day=date of event - reference date + 1 
 
if date of event < reference date, then 
• Study Day=date of event - reference date 
 
The reference date for the Screening Phase is the date of first screening visit in the sub-study, 
for the Thigh Injection Phase is the date of first thigh injection, and for the Return to Gluteal 
Injection Phase is the nominal sub-study Week 16 visit date as specified in this section. 
Long-term Follow-up Study Day 


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The Long-Term Follow Up (LTFU) Study Day of an event (e.g., lab assessment, start date of AE 
or HIV associated condition) will be derived as the number of days between the date of the 
event and the end of study treatment [i.e. max(Last IM Injection Date, Last Oral Bridging End 
Date)] 
as follows: 
If the date of event falls in Long-term Follow up phase, then 
• LTFU Study Day = Date of Event - End Date of IP 
Change from Baseline 
• Post-Dose Visit Value – Baseline 
o Unless otherwise specified, the baseline definitions specified in Section 5.2 will 
be used for derivations for endpoints / parameters. 
 
15.6.2. 
Study Population 
Demographics and Baseline Characteristics 
Age 
• Age, in whole years, will be calculated with respect to the participant’s Screening visit.  For sub-
study, age will be calculated with respect to the participant’s first sub-study screening visit. 
• GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed 
as follows: 
o Any participant with a missing date and month will have this imputed as ‘30th June’. 
• Birth date will be presented in listings as ‘YYYY’. 
• Completely missing dates of birth will remain as missing, with no imputation applied. 
Consequently, the age of the participant will not be calculated and will remain missing. 
Body Mass Index (BMI) 
• Calculated as Weight (kg) / Height (m)2 
Hepatitis Status 
• Hepatitis C status will be determined using antibody and/or hepatitis C virus (HCV) RNA 
assessments performed during screening or during the conduct of the study.  
• If both antibody and virus RNA assessments are available, then the latter will take precedence 
and positive/negative status will be based on whether HCV RNA is detectable (i.e., ≥ limit of 
quantification) or not. 
• A participant will be considered positive for hepatitis B virus (HBV) if they have a positive 
surface antigen or detectable HBV DNA result. “HBV DNA DETECTED” in the lab comment 
takes precedence over HBV DNA test result for positive hepatitis B status, for example, if a 
participant has HBV test result below level of detection, however, the lab comment shows that 
HBV DNA detected, this participant will be considered positive for hepatitis B. If HBV DNA result 
is available, it will be used to qualify hepatitis B status as positive or negative (positive if ≥ limit 
of quantification); otherwise Hepatitis B status will be determined using the surface antigen 
result. 
• Hepatitis status at entry will be based on the assessments prior to/on the start of the study 
treatment. 
Framingham Risk Equation 


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Demographics and Baseline Characteristics 
• The predicted probability, 𝑝̂ , of having a cardiovascular disease (CVD) within the next 10-years 
according to the Framingham formula [D’Agostino, 2008] is 
For females: 
𝑝̂𝐹= 1 −𝑆0(𝑡)
𝑒𝑥𝑝{2.32888×log(𝑎𝑔𝑒)+1.20904×log(𝑇𝐶)−0.70833×log(𝐻𝐷𝐿)+2.76157×log(𝑆𝐵𝑃𝑢) +
2.82263×log(𝑆𝐵𝑃𝑡)+0.52873×𝐼𝑠+0.69154×𝐼𝑑−26.1931
} 
      For males: 
𝑝̂𝑀= 1 −𝑆0(𝑡)
𝑒𝑥𝑝{3.06117×log(𝑎𝑔𝑒)+1.12370×log(𝑇𝐶)−0.93263×log(𝐻𝐷𝐿)+1.93303×log(𝑆𝐵𝑃𝑢) +
1.99881×log(𝑆𝐵𝑃𝑡)+0.65451×𝐼𝑠+0.57367×𝐼𝑑−23.9802
} 
     where 
𝑆0(𝑡) = {0.95012, females
0.88936, 𝑚𝑎𝑙𝑒𝑠 
 
𝐼𝑠= {1, current smoker
0,          𝑜𝑡ℎ𝑒𝑟𝑤𝑖𝑠𝑒 
𝐼𝑑= {1,       diabetic
0,   𝑜𝑡ℎ𝑒𝑟𝑤𝑖𝑠𝑒 
 
    TC = total serum cholesterol (mg/dL), 
    HDL = serum HDL cholesterol (mg/dL), 
    SBPu = systolic blood pressure (mmHg) if participant is not treated for high blood pressure  
    (note that if a participant is treated for high blood pressure then log(SBPu) = 0) 
    SBPt = systolic blood pressure (mmHg) if participant is treated for high blood pressure 
    (note that if a participant is not treated for high blood pressure then log(SBPt) = 0) 
 
•  A participant will be considered as treated for high blood pressure if during screening it has 
specified that is suffering from hypertension. 
• A participant is classified as diabetic if current or past is indicated in the medical conditions 
eCRF for Type 1 or Type 2 diabetes mellitus, or if baseline fasting glucose ≥7.00 mmol/L (126 
mg/dL).  
• Smoking status is collected in the eCRF at Day 1. A current smoker is defined as currently 
smoking/using tobacco or has smoked/used tobacco within the previous 6 months; a former 
smoker is defined as previously smoked/used tobacco products and has not smoked/used 
tobacco products within the previous 6 months. 
• This calculation will not be performed for participants who have indicated current or past 
myocardial infarction conditions on the eCRF. These participants will not be included in 
summary statistics of risk, but they will be counted in the highest category of risk in the 
summary by category. 
Prior Exposure to CAB+RPV 
• 
For participants transitioning from ATLAS study and having prior exposure to CAB+RPV in 
ATLAS study: Duration of Prior Exposure to CAB+RPV = Randomization Date – Prior Oral CAB 
Start Date in ATLAS Study + 1. 


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Demographics and Baseline Characteristics 
• For participants transitioning from ATLAS study and not having prior exposure to CAB+RPV in 
ATLAS study, or for participants randomized from current SOC, Duration of Prior Exposure to 
CAB+RPV = 0. 
• Duration of Prior Exposure to CAB+RPV will be categorized to 0 weeks, 1-24 weeks and >24 
weeks.  
Lipid-modifying Agents 
• 
The following ATC codes correspond to lipid-modifying agents: 
o ATC Level 2: C10 
o ATC Level 3: C10A, C10B (if Level 2 is not available) 
o ATC Level 4: C10AA, C10AB, C10AC, C10AD, C10AX, C10BA, C10BX (if level 2, 3 are not 
available) 
• 
Participants are considered to have used a lipid-modifying agent at baseline if they are taking 
the medication at the time of their baseline fasting lipid testing date. 
• 
Participants are also considered to have used a lipid-modifying agent at baseline if they 
stopped their lipid modifying medication within 12 weeks prior to their baseline fasting lipid 
testing date. 
 


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15.6.3. 
Efficacy 
Snapshot 
• The Snapshot algorithm is intended to be primarily a virologic assessment of the endpoint, and 
as such follows a “virology first” hierarchy. 
• ‘HIV-1 RNA < 50 c/mL’ or ‘HIV-1 RNA ≥ 50 c/mL’ within an analysis window (see Table 10 and 
Table 13) is typically determined by the last available HIV-1 RNA measurement in that window 
while the participant is On-treatment in the Maintenance Phase (as assigned based on Section 
15.4). 
• When no HIV-1 RNA data is available within a window, a participant cannot be assigned to the 
category of ‘HIV-1 RNA < 50 c/mL’.  Depending on the reason for lack of data, the participant 
will be classified as ‘HIV-1 RNA < 50 c/mL’ or reported as ‘No Virologic Data at Week X’; in the 
latter case, the algorithm further classifies the nature of the missing data. Typically, a participant 
withdrawn (i) due to AE or, (ii) for another reason yet was suppressed at the time, will be 
counted as ‘No Virologic Data at Week X’.  Should a participant withdraw for reasons other than 
AE and was not suppressed at the time, they will be categorized as ‘HIV-1 RNA ≥ 50 c/mL’. 
• Full details of the algorithm, including the handling of special cases, are included in Section 
15.9 
Plasma HIV-1 RNA 
• For summaries and analyses which use HIV-1 RNA level as a continuous measure, the 
logarithm to base 10 of the value will be used. 
• HIV-1 RNA results may be provided as censored values, such as <40 or >9,999,999 c/mL. For 
the purposes of summary statistics, such values will be replaced by the next value beyond the 
limit of detection, e.g., 39 or 10,000,000 c/mL, respectively, for the given examples. Data 
listings will show the censored values as provided. 
Target Detected / Target Not Detected / Super Low Viral Load Testing 
• When a measurement of plasma HIV-1 RNA is below the limit of quantification (i.e. 40 c/mL) 
and is qualitatively observable that will be denoted as a “Target Detected” measure, while HIV-1 
RNA below the limit of quantification that is not qualitatively observable that will be denoted as 
“Target Not Detected”. Any measurements <40 c/mL characterised as “Target Not Detected” or 
“Target Detected” will be captured in the database. 
• Super low viral load will also be tested by BioMONTR Labs for viral loads below the limit of 
quantification at some visits (e.g. Week 48). 
Confirmed Virologic Failure (CVF) 
• The definition of CVF is provided in the Protocol, Section 5.5.4 – Definition of Confirmed 
Virologic Failure. 
• In case there are multiple plasma HIV-1 RNA results on the same day, the worst result (i.e. the 
largest value) will be used in determination of CVF. 
Treatment (TRDF) and Efficacy Related (ERDF) Discontinuation = Failure 
• The analysis of time to confirmed virologic failure (CVF) or discontinuation due to treatment 
related reasons (i.e., drug-related AE, intolerability of injections, protocol defined safety 
stopping criteria, or lack of efficacy) will censor participants who have not met CVF criteria and 
are ongoing in the study, or who have discontinued for reasons other than those related to 
treatment. This will be the Treatment Related Discontinuation = Failure (TRDF) data. 


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• Participants who have not met CVF criteria and are ongoing in the study, or who have 
discontinued for reasons other than lack of efficacy, will be censored in the analysis of the 
Efficacy Related Discontinuation = Failure (ERDF) data. 
• Proportion of Participants without virologic (ERDF) or tolerability (TRDF) failure will be 
estimated using the Kaplan-Meier nonparametric method based on the time to ERDF or TRDF. 
The estimated proportion at time point of interest will be presented by treatment group, along 
with estimated difference in proportions between treatment groups and its associated two-sided 
95% CI. The estimate of the standard error used to derive confidence intervals will be based on 
Greenwood’s formula [Kalbfleisch,1980]. 
• See Appendix 10: Variables Defined for Time to Event Analysis for additional details. 
Summary for Participants per Viral Load Category by Visit 
• Summary will be based on observed available data, with no imputation for missing values. The 
proportion of participants in each viral load category will be calculated using the denominator 
and numerator specified below: 
o 
Denominator: Number of participants with on-treatment viral load within the snapshot visit 
window. 
o 
Numerator: Number of participants with plasma HIV-1 RNA in the specified category based 
on the last on-treatment viral load assessment collected within the snapshot visit window. 
HIV-1 Disease progression Stage 
• Categories: 
o CDC Stage 1 at Baseline to CDC Stage II; 
o CDC Stage I at Baseline to CDC Stage III;  
o CDC Stage II at Baseline to CDC Stage III;  
o CDC Stage III at Baseline to new CDC Stage III event; 
o CDC Stage I, II, III at Baseline to Death.  
 
Please refer to Protocol (Appendix 4: CDC Classification for HIV-1 Infection) for defining Stage. 
• For the purpose of analysis, the CDC at Baseline and at post-baseline during Maintenance 
Phase will be derived as below: 
o At Baseline, the ‘Baseline CDC stage’ for each participant was assessed by investigator 
and recorded in the eCRF. However, for the analysis, Baseline CDC stage will be rederived 
based Baseline CD4+ values as well as whether any HIV-associated/AIDS-defining 
conditions present at baseline per the Criteria’s thresholds (Appendix 4 in Protocol).  
o To analyse disease progression, the most advanced post-baseline CDC stage within the 
period of interest (e.g. Maintenance Phase) will be derived based on the occurrences of 
new AIDs-defining conditions (please refer to Appendix 4 in Protocol for the list of AIDs-
defining Conditions) as well as the nadir value of post-baseline CD4+.  
➢ For example, if a participant with CDC ‘Stage I’ at Baseline had the lowest Maintenance 
Phase CD4+ =120 cell/mm3 without new AIDs-defining conditions, then HIV disease 
progression for this participant during the Maintenance Phase would be considered as 
‘CDC stage I at Baseline to CDC stage III’. 
➢ If a participant with CDC ‘Stage II’ at Baseline had the lowest Maintenance Phase 
CD4+ =220 cell/mm3 AND had at least one new AIDs-defining condition, then HIV 


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disease progression for this participant during the Maintenance Phase would be 
considered as ‘CDC stage II at Baseline to CDC stage III’. 
Delay in IP Injection 
• For participants on the Q4W arm, IM dosing is expected to occur every 4 weeks from Week 4B 
onwards for those transitioning from SOC (i.e. those requiring oral lead-in) and from Day 1 
onwards for those transitioning from CAB+RPV Q4W in ATLAS (i.e. those not requiring oral 
lead-in). The Delay in IP injection (days) will be calculated as: 
Delay in IP Injection (days) =   Injection date - date of preceding injection - 28 days  
• For participants on the Q8W arm, IM dosing is expected to occur at Week 4B and then every 8 
weeks from Week 8 onwards for those transitioning from SOC (i.e. those requiring oral lead-in) 
and every 8 weeks from Day 1 for those transitioning from CAB+RPV Q4W (i.e. those not 
requiring oral lead-in) in ATLAS. If participants receive reloading dose injection after oral 
bridging, the next IM dosing is expected to be 4 weeks from the reloading injection and then 
every 8 weeks onwards. 
o For participants transitioning from SOC on the Q8W arm, if the preceding injection occurs at 
Week 4B, the Delay in IP injection (days) will be calculated as: 
      Delay in IP Injection (days) = Date of Week 8 injection - date of Week 4B injection - 28 days  
o For participants receiving oral bridging medication and then returning to LA injections, if the 
preceding injection occurs at a reloading dose visit, the Delay in IP injection (days) will be 
calculated as: 
Delay in IP Injection (days) = Injection date - date of preceding injection - 28 days 
o For participants transitioning from SOC on the Q8W arm, if the preceding injection occurs at 
a visit later than Week 4B or at non-reloading visit, the Delay in IP injection (days) will be 
calculated as: 
Delay in IP Injection (days) = Injection date - date of preceding injection - 56 days 
o For participants transitioning from CAB+RPV Q4W in ATLAS on the Q8W arm, if the 
preceding injection occurs at non-reloading visit, the Delay in IP injection (days) will be 
calculated as: 
Delay in IP Injection (days) = Injection date - date of preceding injection - 56 days 
• If the preceding study treatment is oral (e.g. CAB+RPV or SOC oral bridging), the Delay in IP 
injection (days) will be calculated as: 
o Delay in IP Injection (days) = Injection date – date of last oral dose on/prior to the injection 
date 
• Delay in IP injection will be grouped into: ≤1, 2-3, 4-7, >7 days.  
• The proportion of participants with HIV-1 RNA ≥50 c/mL at Week 48 (Snapshot) will be 
summarized by last delay in IP Injection. The last delay in IP injection will be the delay in IP 
injection at Week 48, or the delay in last IP injection prior to Week 48 if a participant did not 
receive Week 48 injection (i.e. missing visit or withdrawal). The similar analysis will be done for 
Week 96 and Week 152 timepoints where the proportion of participants with HIV-1 RNA ≥50 
c/mL at Weeks 96 and 152 (Snapshot) and the delay in IP injection at Weeks 96 and 152 are 
considered respectively. 
 


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15.6.4. 
Safety 
Adverse Events 
DAIDS Grading 
• Clinical adverse events will be graded based on the Division of AIDS Table for Grading the 
Severity of Adult and Pediatric Adverse Events Version 2.1, March 2017, as specified in the 
protocol Appendix 11.2. 
Potential QTc Interval Prolonging Events of Interest 
Potential QTc Interval Prolonging Events of Interest will be identified based on Standardised 
MedDRA Query (SMQ) for Torsade de pointes/QT prolongation, broad (MedDRA). The terms per 
this reference are listed below.  
 
AE preferred term 
Electrocardiogram QT interval abnormal 
Electrocardiogram QT prolonged 
Long QT syndrome 
Long QT syndrome congenital 
Torsade de pointes 
Ventricular tachycardia 
Cardiac arrest 
Cardiac death 
Cardiac fibrillation 
Cardio-respiratory arrest 
Electrocardiogram repolarisation abnormality 
Electrocardiogram U wave inversion 
Electrocardiogram U wave present 
Electrocardiogram U-wave abnormality 
Loss of consciousness 
Sudden cardiac death 
Sudden death 
Syncope 
Ventricular arrhythmia 
Ventricular fibrillation 
Ventricular flutter 
Ventricular tachyarrhythmia 
 
Laboratory Parameters 
• If a laboratory value which is expected to have a numeric value for summary purposes, has a 
non-detectable level reported in the database, where the numeric value is missing, but typically 
a character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the 
comment field) is present, the number of significant digits in the observed values will be used to 


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Laboratory Parameters 
determine how much to add or subtract in order to impute the corresponding numeric value. If a 
character value starting with “<=x”, then the numeric value will be x. 
o Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01 
o Example 2: 1 Significant Digit   =  ‘> x’ or ‘>=x’ becomes x + 0.1 
o Example 3: 0 Significant Digits = ‘< x’ becomes x – 1     
Estimate of Glomerular Filtration Rate (GFR) (Levey, 2012) 
• Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [Levey, 2012] will be 
used by the central laboratory to provide an estimate of GFR, in mL/min per 1.73 m2, as follows: 
 
where age (in years) is at time of assessment, κ = 0.7 if female or 0.9 if male, α = -0.329 if female 
and -0.411 if male, min() indicates the minimum of CRT/κ or 1, max() indicates the maximum of 
CRT/κ or 1, and CRTmg/dL is serum creatinine concentration in mg/dL. The serum creatinine 
concentration in mg/dL is obtained from GSK standard units of mol/L as CRTmg/dL =0.0113x 
CRTmol/L.  
• The CKD-EPI GFR will also be calculated using Cystatin C, as follows 
 
133 X min(Scys/0.8, 1) -0.499 X max (Scys/0.8, 1)-1.328 X 0.996 Age X[0.932 if female] 
Where Scys is serum cystatin C mg/Liter, min indicates the minimum of Scr/0.8 or 1, and max 
indicates the maximum of Scys/0.8 or 1. 
Lab Toxicities – DAIDS Grading based on Version 2.1, March 2017, as specified in the protocol 
of Appendix 11.2.  
• Toxicities will be based on the Division of AIDS (DAIDS) grading system, Version 2.1, March 
2.17, as specified in the protocol of Appendix 11.2  
• Toxicity grades provided by the central laboratory do not distinguish between abnormally high 
or low criteria, when both are relevant for a parameter. 
• When summarising toxicity grades for such parameters, they will be categorised as to whether 
they are above or below the midpoint of normal range. 
 
Parameter 
Below Midpoint for 
those ≥Grade 1 
Above Midpoint for 
those ≥Grade 1 
Fasted glucose 
Hypoglycemia 
Hyperglycemia 
Sodium 
Hyponatremia 
Hypernatremia 
Potassium 
Hypokalemia 
Hyperkalemia 
National Cholesterol Education Program (NCEP) Lipid Categories 
• In addition to DAIDS toxicity grades (see protocol), lipid values will be categorized according to 
the 2001 NCEP Adult Lipid Guidelines [Grundy, 2001] 
 


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Laboratory Parameters 
Parameter 
Value Range (mmol/L) 
Value Range (mg/dL) Category 
Triglycerides 
<1.70 
<150 
Normal 
1.70 to <2.26 
150 to <200 
Borderline High 
2.26 to <5.65 
200 to <500 
High 
5.65 
500 
Very High 
Total Cholesterol 
<5.18 
<200 
Desirable 
5.18 to <6.21 
200 to <240 
Borderline High 
6.21 
240 
High 
HDL Cholesterol 
<1.04 
<40 
Low 
1.04 to <1.56 
40 to <60 
Normal 
1.56 
60 
High 
LDL Cholesterol 
<2.59 
<100 
Optimal 
2.59 to <3.37 
100 to <130 
Near/Above Optimal 
3.37 to <4.14 
130 to <160 
Borderline High 
4.14 to <4.92 
160 to <190 
High 
4.92 
190 
Very High 
Percentage change for lipids 
The percentage change from baseline is calculated as: 
% change from baseline = 
 value at Week 48 or 96−baseline value
baseline value
× 100% 
 Total Cholesterol / HDL Cholesterol Ratio 
• When both total cholesterol and HDL cholesterol results are available from the same date for a 
participant, then the ratio will be calculated by dividing the total cholesterol result by the HDL 
cholesterol result. The ratio can be classified as follows: 
Parameter 
Value Range 
Total Cholesterol 
/ HDL Ratio 
< 3.5 
3.5 to < 4.4 
4.4 to < 5 
 5 
 
Other Safety Endpoints 
Corrected QT (QTc) 
When not entered directly in the eCRF, corrected QT intervals by Bazett’s (QTcB) and Fridericia’s 
(QTcF) formulas will be calculated, in msec, depending on the availability of other measurements. 
If RR interval (in msec) is provided then missing QTcB and/or QTcF will be derived as 
1000
RR
QT
QTcB =
  
3
1000
RR
QT
QTcF =
 
where uncorrected QT interval is also measured in msec. 


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Other Safety Endpoints 
If RR interval is not provided directly and one of QTcB or QTcF has been entered, then RR interval 
can be obtained from the above formulas and used to calculate the other correction method value; 
i.e., 
QT
QTcF
QTcB
3
=
 
 
3
2
QTcB
QT
QTcF

=
 
Extent of Exposure 
• Exposure to CAB+RPV (oral lead-in or oral bridging) and CAB LA+RPV LA will be 
calculated from the IP eCRF pages. 
• For Maintenance Phase: 
o Exposure to oral CAB+RPV (oral lead-in) = IP (oral lead-in) stop date - IP (oral 
lead-in) start date +1 
o Exposure to CAB LA + RPV LA = Number of IP injection visits received during 
maintenance phase (up to but not including injections administered at Week 100) 
o Exposure to SOC oral bridging: Duration of the SOC ART medication taken as oral 
bridging during the Maintenance Phase. If the SOC oral bridging is taken in 
different periods during the Maintenance Phase, the duration will be calculated by 
the sum of the non-overlapped periods.  
o Exposure to CAB+RPV oral bridging: Duration of the CAB+RPV taken as oral 
bridging during the Maintenance Phase. If the CAB+RPV oral bridging is taken in 
different periods during the Maintenance Phase, the duration will be calculated by 
the sum of the non-overlapped periods. 
o Overall exposure to study treatment:  
For participants on Q4W arm: min [Date of Latest Maintenance Phase Visit up to 
and including Week 100, max (Date of Last Injection + 35, Date of Last Dose of 
Oral CAB+RPV, Date of Last Dose of SOC Oral Bridging)] – min (Start Date for 
Oral lead-in CAB+RPV, Date of First Study Injection) + 1 
For participants on Q8W arm: min [Date of Latest Maintenance Phase Visit up to 
and including Week 100, max (Date of Last Injection + 63, Date of Last Dose of 
Oral CAB+RPV, Date of Last Dose of SOC Oral Bridging)] – min (Start Date for 
Oral lead-in CAB+RPV, Date of First Study Injection) + 1 
o Overall exposure to IP = Overall exposure to Study Treatment – Exposure to SOC 
Oral Bridging 
 
• For Maintenance + Extension Phase 
o Exposure to CAB LA + RPV LA = Number of IP injection visits received during 
Maintenance Phase and Extension Phase 
o Exposure to SOC or CAB+RPV oral bridging during the Maintenance and 
Extension Phase will be calculated similarly to that during the Maintenance Phase 
except that the exposure includes both Maintenance and Extension Phase.  
o Overall exposure to study treatment:  


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Other Safety Endpoints 
For participants on Q4W arm: min [Date of Latest Maintenance/Extension Phase 
Visit, max (Date of Last Injection + 35, Date of Last Dose of Oral CAB+RPV, Date 
of Last Dose of SOC Oral Bridging)] – min (Start Date for Oral lead-in CAB+RPV, 
Date of First Study Injection) + 1 
For participants on Q8W arm: min [Date of Latest Maintenance/Extension Phase 
Visit, max (Date of Last Injection + 63, Date of Last Dose of Oral CAB+RPV, Date 
of Last Dose of SOC Oral Bridging)] – min (Start Date for Oral lead-in CAB+RPV, 
Date of First Study Injection) + 1 
o Overall exposure to IP = Overall exposure to Study Treatment – Exposure to SOC 
Oral Bridging 
• For Thigh Injection Phase 
o Exposure to CAB LA + RPV LA = Number of IP injection visits received during 
Thigh Injection Phase. Note that the planned Sub-study Week 16 injections belong 
to Return to Gluteal Injection Phase. 
o The SOC or CAB+RPV oral bridging are not allowed in this phase.  
o Overall exposure to IP:  
For participants on Q4W arm: min [Date of Latest Thigh Injection Phase Visit up to 
the Nominal Sub-study Week 16 Visit Date, max (Date of Last Injection + 35, Date 
of Last Dose of Oral CAB+RPV, Date of Last Dose of SOC Oral Bridging)] – Date 
of First Thigh Injection) + 1 
For participants on Q8W arm: min [Date of Latest Thigh Injection Phase Visit up to 
the Nominal Sub-study Week 16 Visit Date, max (Date of Last Injection + 63, Date 
of Last Dose of Oral CAB+RPV, Date of Last Dose of SOC Oral Bridging)] – Date 
of First Thigh Injection + 1 
Note that the Nominal Sub-study Week 16 visit date is defined in Section 15.6.1. 
o Overall exposure to IP = Overall exposure to Study Treatment. 
• For Thigh Injection + Return to Gluteal Injection Phase 
o Exposure to CAB LA + RPV LA = Number of IP injection visits received during 
Thigh Injection or Return to Gluteal Injection Phase. Note that the injections 
received on the date of Sub-study Week 24 visit belong to the Extension Phase in 
main study. 
o The SOC or CAB+RPV oral bridging are not allowed in these two phases.  
o Overall exposure to IP:  
For participants on Q4W arm: min [End of Sub-study Date, max (Date of Last 
Injection + 35, Date of Last Dose of Oral CAB+RPV, Date of Last Dose of SOC 
Oral Bridging)] – Date of First Thigh Injection) + 1 
For participants on Q8W arm: min [End of Sub-study Date, max (Date of Last 
Injection + 63, Date of Last Dose of Oral CAB+RPV, Date of Last Dose of SOC 
Oral Bridging)] – Date of First Thigh Injection + 1 
Note that the End of Sub-study Date is defined in Section 15.6.1. 
o Overall exposure to IP = Overall exposure to Study Treatment. 
 
• Last Injection and/or Last Dose of Oral CAB+RPV and/or Last Dose of SOC Oral Bridging 
are only applicable to those who permanently discontinued study treatment. 


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Other Safety Endpoints 
• Duration of dosing in participant years will be calculated as the sum of participant duration 
of dosing in days (across all participants)/365.25 
• Participants who were randomized but did not report an IP start date will be categorised as 
having zero days of exposure.  
Adherence to CAB/RPV Injection Schedule 
Timeliness of Injections relative to Date of Projected Dosing Visits are assessed by using "actual 
injection visit date - projected visit date from first injection". The injections of interest in adherence 
analysis are those after first injection. For participants requiring the oral CAB+RPV lead-in, the first 
injection is planned to be taken at Week 4B. For participants not requiring the oral CAB+RPV lead-
in, the first injection is planned to be taken at Baseline/Day 1. For participants receiving the oral 
bridging and then returning to injections, if the first injection upon return is a reloading dose 
injection, the immediate next injection visit is planned to be four weeks after the reloading injection 
visit. If a participant has multiple oral bridging episodes, he or she may have more than one 
reloading dose injection visits during the study. Each injection visit is counted only once. Individual 
CAB and RPV injections administered at the same visit are not counted twice. "Extra" unscheduled 
injections are excluded from all derivations. For example, if during a scheduled visit a participant 
receives 1 ml of injection instead of 2 ml due to a dosing error, but this participant returns one week 
later for the remaining 1 ml injection, then the additional visit is excluded. If a participant receives an 
extra injection at an unscheduled visit by mistake, this visit will also be excluded.  
 
The categories of Timeliness of Injections relative to Date of Projected Dosing Visits for summary 
are listed below: 
 
< -14 days 
-14 to   - 8 days 
-7   to   - 4 days  
-3   to   -2 days  
-1 day 
 0 day  
1 day 
2 to 3 days  
4 to 7 days  
8 to 14 days 
>14 days 
Missed Reloading Injection (Non-COVID-19) 
Missed Reloading Injection (COVID-19) 
Missed Injection w/o OB (Non-COVID-19) 
Missed Injection w/o OB (COVID-19) 
Missed Injection with CAB+RPV OB (Non-COVID-19) 
Missed Injection with CAB+RPV OB (COVID-19) 


CONFIDENTIAL 
 
 
 
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Other Safety Endpoints 
Missed Injection with SOC OB (COVID-19) 
Columbia Suicide Severity Rating Scale (C-SSRS) 
• Missing data will not have any imputation performed (Nilsson, 2013). 
 


CONFIDENTIAL 
 
 
 
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127 
 
15.6.5. 
Pharmacokinetic 
This document is intended for planning analysis of PK concentration data and PK 
parameters only. Population pharmacokinetics and identification of important 
determinants of variability will be described in a separate document. 
Pharmacokinetic Analyses 
Plasma CAB and RPV Concentration-time Data 
Plasma samples for determination of CAB and RPV concentration will be collected 
throughout the Maintenance Phase, at Week 152 and at the withdrawal visit in the main 
study, and up to Week 17 in the sub-study. Additional samples will be collected for 
storage during the Long-Term Follow-Up Phase and for female participants who 
become pregnant during the study. 
In rare occasions, PK samples are collected post-dose on the same day as the study 
treatment administration during the main study. The data from these PK samples will be 
excluded from the pre-dose and/or 1-week post-dose summaries in the main study. If 
time was not collected for the oral study treatment, the PK sample collected on the same 
day as the oral study treatment is assumed to be taken prior to the oral dose unless 
medical monitor or data querying informs otherwise. 
PK data collected for liver event will be listed but will not be included in the summaries 
or figures.    
Plasma CAB and RPV PK Parameters 
The following PK parameters will be determined from the sub-study concentration-time 
data for each treatment, analyte and dosing interval, as data permit: maximum 
concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time 
curve through the end of the dosing interval (AUC(0-tau)). These PK parameters will be 
calculated by standard non-compartmental analysis according to current working 
practices and using Phoenix WinNonlin 8.3. All calculations of non-compartmental 
parameters will be based on actual sampling times. Derivation of PK parameters will be 
performed by, or under the direct auspices of, Clinical Pharmacology Modelling and 
Simulation (CPMS), GlaxoSmithKline. 
In addition, the concentration at the end of a dosing interval (Ctau) will be obtained 
from the evaluable pre-dose (trough) concentration collected at start of the subsequent 
interval. For example, the Ctau for last thigh injection interval will be obtained from the 
evaluable pre-dose PK concentration collected at the Sub-study Week 16 visit. 
Treatment Arm 
Dosing Interval in Sub-study 
Gluteal Injection 
First Thigh Injection Last Thigh Injection 
Q8W 
Week -8 to Day 1 
Day 1 to Week 8 
Week 8 to Week 16 
Q4W 
Week -4 to Day 1 
Day 1 to Week 4 
Week 12 to Week 16 
Evaluable Concentration 


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Pharmacokinetic Analyses 
PK concentration will be summarized in two ways: ‘all data’ without regard to timing relative to 
scheduled time and ‘evaluable data’. 
The ‘evaluable data’ are from the samples that met sample collection window criteria. Sampling 
windows are set relative to the previous dose as follows:  
• 20-28 hrs after last oral dose taken and properly administered last 3 oral doses for 
pre-dose sample at Week 4B for participants requiring oral lead-in 
• ± 4 days for pre-dose sample at visits other than Week 4B, and for pre-dose 
samples at Week 4B for participants not requiring oral lead-in (e.g. participants 
transitioning from ATLAS Q4W and remain on Q4W arm in this study) 
• 3-10 days post last injection for 1-week post injection visits  
• 21-35 days post last injection for 4-week post-dose samples (e.g. collected at sub-
study Week -4, Week 4 and Week 12 visits). Note that 4-week post-dose samples 
will be collected from subjects on Q8W arm only. 
• 1-3 hours post last injection for 2-hour post-dose samples  
• Samples impacted by dosing errors (wrong dose) or oral bridging will also be 
excluded 
 
Timepoint 
Evaluable 
Window 
For Programming: 
Pre-dose: WK4B 
for participants 
requiring oral 
lead-in 
20-28 hrs after 
last oral dose 
taken and the 
last 3 oral 
doses 
administered 
properly 
20 hrs ≤ Time since Last Oral Dose ≤ 28 hrs and the 
last 3 oral doses administered on the three consecutive 
days prior to WK4B. 
Pre-dose at other 
visits, Pre-dose 
WK4B for 
participants not 
requiring oral 
lead-in 
± 4 days 
For Q4W arm, Day 1 pre-dose, Week 8 for those 
transitioning from SOC (i.e. requiring oral lead-in), and 
the immediate next visit after reloading on Q8W arm: 
24 days ≤ Days Since Last Injection ≤ 32 days 
For visits other than above on Q8W arm: 52 days ≤ 
Days Since Last Injection ≤ 60 days 
1-WK-Post:  
3-10 days post 
last injection 
3 days ≤ Days Since Last Injection ≤ 10 days 
4-WK-Post: 
21-35 days 
post last 
injection 
21 days ≤ Days Since Last Injection ≤ 35 days 
2-HR-Post: 
1-3 hours post 
last injection 
1 hr ≤ Time since Last Oral Dose ≤ 3 hrs 
 
Relative Time is calculated relative to the date and time of last dose. For example, if the time of 
the last dose (e.g. oral lead-in/oral bridging) is missing, then the relative time for PK sample will 
be set to missing and the sample will not be considered ‘evaluable’.  


CONFIDENTIAL 
 
 
 
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129 
 
Pharmacokinetic Analyses 
If a pre-dose sample is collected on the same day as the first dose of oral bridging, the time of the 
first dose (not recorded in eCRF) is assumed to be ‘after’ the collection of pre-dose sample, 
unless medical monitor or Data querying informs otherwise. 
The time-deviation (hours) from the targeted timepoint will be calculated for the post-dose 
samples using the following formula: 
Time_deviation (hrs) for ‘2-Hour POST’ = Sample date.time - last injection date.time - 2 hours 
Time_deviation (hrs) for ‘1-Week POST’ = Sample date.time - last injection date.time - 7*24 hours 
Time_deviation (hrs) for ‘4-Week POST’ = Sample date.time - last injection date.time - 28*24 
hours 
The following windows are for defining ‘evaluable’ Long-term Follow-up phase PK concentrations.  
Timepoint 
Evaluable Window 
For Programming: 
LTFU MONTH 
1/WD 
± 4 days 
24 days ≤ Days Since Last Injection ≤ 32 days 
LTFU MONTH 3 
± 1 Weeks 
77 days ≤ Days Since Last Injection ≤ 91 days 
LTFU MONTH 6 
± 2 Weeks 
154 days ≤ Days Since Last Injection ≤ 182 days 
LTFU MONTH 9 
± 2 Weeks 
238 days ≤ Days Since Last Injection ≤ 266 days 
LTFU MONTH 12 ± 2 Weeks 
322 days ≤ Days Since Last Injection ≤ 350 days 
 
 
 


C O N FI D E N TI A L  
 
 
 
2 0 7 9 6 6  
1 3 0  
 
1 5. 6. 6.  
H e a lt h O ut c o m e s 
HI V T S Q s  
Q u e sti o n n aire ( Q u e sti o n s 1 -1 2 ar e s c ore d 0 -6) 
T ot al Tr e at m e nt Sati sf acti o n S c or e  
•  T ot al Tr e at me nt S atisfacti on Sc or e is c o m p ut e d wit h ite ms 1 -1 1. It e ms 1 -1 1 ar e su m m e d t o 
pr o d uce a scor e wit h a p ossi bl e r a n ge of 0 t o 6 6.  
•  It e m 1 2 will n ot b e i ncl ud ed i n T ot al Tr eat m e nt S atisf actio n Scor e. Inst e a d, it will b e tr e at e d as a 
st a n d-alo n e it e m o nly.  
•  Hi g h er sc or es r epr es e nt great er tr eat m e nt s atisfacti o n as c o m p ar e d t o t h e p ast f e w w e eks.  
•  A m axi m u m of 5 it e ms c a n b e missi n g, whic h c an b e i m p ut e d t o refl ect th e me a n of t h e 
c o m pl et ed it e m sc or es. If 6 or m or e it e ms ar e missi n g, th e n t h e tr e at m ent  satisf actio n sc ale 
sc or e s h oul d n ot b e co m p ute d a n d inst e ad b e i m p ute d usi n g L O C F.  
I n di vi d u al It e m Sc or e s 
•  It e ms ar e r at e d as 6
 to 0 
 
  
•  Hi g h er sc or es r epr es e nt great er s atisfacti on wit h e ac h as p ect of tr eat m e nt 
•  F or i n divi d u al ite m sc or es out p uts, missi n g sc ores will not be c o m put e d ( acc or di ng to P ag e 
7 of t h e [ HI V T S Q  Us er G ui deli n es, 2 0 16 ]) an d i nste ad b e i m p ut e d usin g L O C F. 
HI V T S Q c  
Q u e sti o n n aire ( Q u e sti o n s 1 -1 2 ar e s c ore d -3 t o 3) 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI


C O N FI D E N TI A L  
 
 
 
2 0 7 9 6 6  
1 3 1  
 
T ot al Tr e at m e nt Sati sf acti o n S c or e ( c ha n g e)  
•  T ot al Tr e at me nt S atisfacti on Sc or e is c o m p ut e d wit h ite ms 1 -1 1. It e ms 1 -1 1 ar e su m m e d t o 
pr o d uce a scor e wit h a p ossi bl e r a n ge of -3 3 t o 3 3  
•  It e m 1 2 will b e c o m put e d as a n i ndivi d u al ite m o nly. 
•  T h e hi gh er th e scor e, th e gr e at er th e im pr ove m e nt i n s atisf acti o n with tr eat m e nt; t h e l o w er t h e 
sc or e, t he gr eat er t h e d et eri or ati o n in s atisfacti o n wit h tre at m e nt.  A sc or e of 
 
  
•  A m axi m u m of 5 it e ms c a n b e missi n g, t h e missi n g sc or es will b e i m p ut e d wit h t h e m e a n of t h e 
c o m pl et ed it e m sc or es. If 6 or m or e it e ms ar e missi n g, th e n t h e ov er all tr eat m ent s atisf acti o n 
sc al e sc or e sh oul d not be co m p ut e d a n d will r e m ai n missi n g.  
I n di vi d u al Tre at m e nt Sati sf a cti o n C h a n g e It e m S c ore s  
•  It e ms ar e r at e d as +3 
 
 t o -3 
  
•  T h e hi gh er th e scor e, th e gr e at er th e i m pr ove m e nt i n s atisf acti o n with e ac h as p ect of tr e at m e nt 
a n d t h e l o w er t he sc or e, t h e gr e ater t he d et erior ati on i n s atisf acti on wit h e ac h as pect of 
tr e at m e nt. 
Q u e sti o n n aire V er si o n  
•  I n m ai n stu dy, thr ee v ersi o ns of th e HI V T S Qc qu estio n naire ar e av ail a bl e wit h th e qu esti ons t he 
s a m e a nd only  t h e over h e ad t ext is diff ere nt.  
o  
Q 4 W A T L A S t o Q 4 W A TL A S -2 M: f or particip a nts w h o r a n do miz e d to Q 4 W ar m i n A T L A S 
a n d t h en r a nd o miz e d t o Q 4 W ar m i n A T L A S -2 M 
o  
Q 4 W A T L A S t o Q 8 W A TL A S -2 M: f or particip a nts w h o r a n do miz e d to Q 4 W ar m i n A T L A S 
a n d t h en r a n d o miz e d t o Q 8 W ar m i n A T L A S-2 M 
o  
S O C t o Q4 W or Q 8 W A T L A S -2 M: f or particip a nts w h o eit h er w er e r an d o miz ed t o S O C 
ar m i n A T L A S or did n ot particip at e i n A T L A S  
•  If a p artici p ant tak es a wr o n g v ersio n of th e q uesti o nn air e  i n m ai n stu dy, t h e d at a coll ect e d fr o m 
t h e wr o n g v ersi on will b e consi d er e d i nv ali d a n d will n ot b e i nclu d ed i n th e su m m ary. 
•  I n s u b-st u dy, all p artici p a nts will t ak e t he s a m e v ersio n of t h e q u esti on naire.  
PI N  
Q u e sti o n n aire ( E a c h q u e sti o n i s s c ore d 1 -5) 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI


C O N FI D E N TI A L  
 
 
 
2 0 7 9 6 6  
1 3 2  
 
Di m e n si o n  Sc or e ( C h e v a t, 2 0 08) 
•  D o m ai ns a nd Cl usters  
o  
 
o  
 
o  
 
o  
 
•  5 it e ms n ot i ncl ud e d i n a ny of t h es e d o m ai ns a nd m ai ntai n e d as i ndivi d u al ite ms (it e ms  
 
 
•  N o ov er all sc or e is c alc ul at e d p er th e g ui da nce   
•  T h e sc or e of a d o m ai n is c alc ul at e d as th e m ea n of all ite ms wit h t he d o m ai n. Hi gh er sc or es 
r e pr es e nt w ors e p erc e pti o n of i nj ecti on. 
•  A m axi m u m of <5 0 % it e ms c a n b e missi n g wit hi n a d o m ai n, w hic h ca n b e i m p ut e d t o r efl ect t h e 
m e a n of t h e c o m plet e d it e m sc or es wit hi n t h e d o m ain. Th us, if t h e n u m ber of missi ng it e ms is 
≥3 
), ≥2 
), ≥1 
, t h e n t he 
t ot al scor e f or th e d o m ai n sh o ul d n ot b e c o m put e d a nd i nst e ad b e i m p ute d usi n g L O C F 
( S ecti o n 1 5.7. 2.2 ) 
I n di vi d u al It e m Sc or e s 
•  It e ms ar e r at e d o n a 5-p oi nt sc al e, r an gi ng fr o m 1(
, etc.) t o 5 ( 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


C O N FI D E N TI A L  
 
 
 
2 0 7 9 6 6  
1 3 3  
 
 etc.).  
•  L o w er sc or es r e pr es e nt w ors e p erc epti on of i nj ecti on  
•  F or i n divi d u al ite m sc or es out p uts, missi n g sc ores will not be c o m put e d a n d i nste ad b e i m p ut e d 
usi n g L O C F ( S ecti on  15. 7. 2. 2 ). 
H A T -Q o L  (H ol m es , 1 9 9 9) 
Q u e sti o n n aire ( Q u e sti o n s 1 -1 4 ar e s c ore d 1 t o 5)  
Lif e s ati sfa cti o n, HI V m e dic ati o n s, dis cl os ur e w orri es  
•  T h e r ati ngs f or It e ms ( a, b, c, d, e) will b e r ec od e d as bel o w f or an alysis:  
R es p o nse o pti o n               Lif e S atisf acti on                  Me dic ati on/ discl osur e w orri es  
•  A m axi m u m of 50 % q u esti on it e ms c a n b e missi n g wit hin a d o m ai n, w hic h ca n b e co m p ut e d 
a n d r epl ac e d wit h t h e m e a n of th e co m pl et ed it e m scor es wit hi n th e d o m ai n. T h us, if t h er e ar e 
m or e t h an 1 it e m missi n g for Lif e Satisf acti on, a n d m or e t h an 2 ite ms missi n g f or 
C CI
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h 
ar e pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


C O N FI D E N TI A L  
 
 
 
2 0 7 9 6 6  
1 3 4  
 
M e dic ati o n/ discl os ur e w orri es, t he n t h e t otal sc or e for th e d o m ai n sh o uld n ot be c o m p ut e d a nd 
i nst e ad b e i m p ute d usi n g L O C F ( S ecti o n 1 5.7. 2. 2 ). A co m p ut e d sc or e f or missi n g v al u e will b e 
a d de d to c alc ulat e a t ot al scor e f or th e d o m ai n. T otal scor e f or e ac h of th e t hr ee d o m ai ns will b e 
c alc ul at e d a n d will b e d en ote d as ‘ LI S A T’ f or lif e satisf acti o n, ‘ M E D W O’ f or m e dicati o n w orri es, 
a n d ‘ DI S W O’ for discl os ur e w orri es.  
•  Tr a nsf or m e ach di m ensi o n’s t ot al i mput e d v al ue  sc or e to t he 0-10 0 scal e usi ng th e f oll o wi n g 
f or mul a e: 
       Lif e satisf actio n:   LI S A T 1 0 0 =( 10 0/( 20 -4))*( LI S A T -4)  
       M edic ati on w orri es:  M E D W O 1 0 0 =( 10 0/( 25 -5))*( M E D W O -5)  
       Discl os ure w orri es:  DI S W O 1 0 0 =( 10 0/(2 5 -5))*( DI S W O -5)  
       Th e hi g h er t h e sc or e, th e gr eat er satisf actio n to life a nd th e l ess worry.  T h e tr a nsf or med  
di m e nsi o n scor e for e ach d o m ai n will b e su m m ariz e d a n d a n alys ed.  
I n di vi d u al It e m Sc or e s 
•  F or i n divi d u al ite m sc or es out p uts, missi n g sc ores will not be c o m put e d a n d i nste ad b e  i mp ut e d 
usi n g L O C F ( S ecti on 15. 7. 2. 2 ). 
A C C E P T ( A c c e pt a n ce/ G e n er al Di me n si o n) ( Gilet , 20 1 4) 
Q u e sti o n n aire ( Q u e sti o n s 1 -3 c o n stit ute t o A cc e pt a n c e/ G e ner al Di m e n si o n)  
•  Pr o p orti on of p artici pa nts wit h i n divi du al it e m scor es will b e calc ul at e d.  
I n di vi d u al It e m Sc or e s 
•  It e ms ar e r at e d as 1 
) t o 4 ( 
 
. a n d ‘5’ wit h ‘ 
  
•  Acc e pta nc e/ G en er al di m ensi o n sc or e is calc ul ate d o nly if at l east 2 it e ms i n th e di me nsi o n ar e 
c o m pl et ed 
•  It e ms will b e r ec od ed t o sc or e as f oll o ws: 
                                       R ati n g                                                                     R ec od e             
1. T otally dis a gr ee/ N ot at all acc e pt a bl e/ N ot at all c o nvinc e d:                          1  
2. S o me w h at dis a gre e/ N ot v ery acc e pt a ble/ N ot r e ally c o nvi nc e d:                    1  
3. S o me w h at a gr ee/ S o m e w h at acce pta bl e/ S o m e wh at c o nvi nce d:                  2  
4. T otally a gr ee/ T ot ally acce pt a bl e/ Tot ally c o nvi nc ed:                                      3  
5. I d o n’t k n o w:                                                                                                    1  
 
•  T h e t ot al sc or e of t h e di m e nsi o n is c alc ul at e d as th e m ea n of t h e r ec od ed it e ms of th e 
di m e n si o n a nd t he n li ne arly tr a nsf or me d t o b e o n a sc ale fr o m 0 t o 1 0 0: sc or e, as b el o w:  
                 Tot al Scor e = ( me a n of th e r eco de d ite ms i n t h e di me nsi o n - 1)/ 2 *1 00  
•  F or i n divi d u al ite m sc or es out p uts, missi n g sc ores will not be c o m put e d a n d i nste ad b e i m p ut e d 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI
C CI


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using LOCF (Section 15.7.2.2). 
Preference 
Questionnaire 
1. Based on your experience which HIV treatment do you prefer? 
□ Injectable Long-Acting HIV Treatment every 4 weeks 
□ Injectable Long-Acting HIV Treatment every 8 weeks (only select this answer if you received the 
8-week injectable regimen of CAB LA + RPV LA during study) 
□ Oral daily HIV Treatment 
□ No preference 
 
If you selected no preference, skip questions 2 and 3.  
If you selected any other response, please continue and complete all questions. 
2. What is the main practical attribute of this HIV therapy supporting your preference?  
□ Mode of administration  
□ Frequency of administration 
□ Time required for administration 
□ Scheduling visits 
□ Storing medications 
□ Impact of side effects 
□ Other, please specify 
3. What is the main benefit related to this HIV therapy supporting your preference? 
□ More convenient, easier to integrate into one’s daily life  
□ Less stressful  
□ Less stigma  
□ Easier to take the drug exactly as prescribed  
□ More efficacious 
□ Other, please specify 
Questionnaire Version 
• Two versions of questionnaire are available. The questions in each version of the questionnaire 
are the same and only the overhead text is different. 
o 
ATLAS (from Q4W ATLAS): for participants randomized to Q4W arm in ATLAS.  
o 
ATLAS-2M (from SOC ATLAS or out): for participants who either were randomized to 
SOC arm in ATLAS or did not participate in ATLAS.  
Data Handling 
• Any missing values will remain missing (i.e. no imputation). 
Reasons for Oral Bridging and Preference 
Questionnaire 
This questionnaire will be administered to participants receiving oral bridging during the 
Maintenance and/or Extension phase. It includes three questions regarding contact mode, main 
reasons for switch back to daily oral HIV medication and the HIV treatment preference. For the 
preference question, it asks participants to provide the statements supporting their preference. The 
details can be found in the eCRF. 
Data Handling 


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• Any missing values will remain missing (i.e. no imputation). 
Preference Thigh Injection vs Gluteal Injection 
Questionnaire 
This questionnaire will be administered to sub-study participants. It includes two questions 
regarding injection site preference and contact mode. For the preference question, it asks 
participants to provide the statements supporting their preference. The details can be found in the 
eCRF. 
Data Handling 
• Any missing values will remain missing (i.e. no imputation). 
Tolerability of Injection (NRS) 
Questionnaire 
• This questionnaire will be administered to sub-study participants. It includes two questions 
regarding the maximum level of pain experienced with the most recent injections and contact 
mode. The score for the maximum level of pain ranges from no pain (0) to extreme pain (10). 
Data Handling 
• Any missing values will remain missing (i.e. no imputation). 
Reasons for Continuation/Switch 
Questionnaires  
• Reasons for Continuation questionnaire is collected for participants who were randomized to 
Q4W arm in ATLAS. 
• Reason for Switch questionnaire is collected for participants who either were randomized to 
SOC arm in ATLAS or did not participate in ATLAS.  
Data Handling 
• If a participant takes a wrong questionnaire, for example, the participant randomized to SOC 
arm in ATLAS took Reasons for Continuation questionnaire, the data collected from this wrong 
version will be considered invalid and will not be included in the summary. 
• If the questionnaire is taken beyond ± 2 weeks window from maintenance phase treatment start 
date (i.e. Study Day < -14 or Study Day > 14) will be consider not evaluable and will not be 
included in the summary. 
• Any missing values will remain missing (i.e. no imputation). 
 
15.6.7. 
Virology 
Genotype 
Amino Acid Changes 
• A mutation is considered present whenever the encoded amino acid residue differs from the 
amino acid that would have been encoded by the wild-type (e.g., HXB2, NL43) comparator 
gene; e.g., Q148K.  
• If the encoded amino acid is seen as a mixture of wild-type and mutant amino acid, e.g., 
Q148Q/K, the mutated amino acid is considered present at the codon of interest.  
• If the encoded amino acid is seen as a mixture of two or more amino acids, which may or may 
not include wild type, e.g., Q184K/H or Q184K/H/Q, etc., for the purposes of calculating the 
number of mutated amino acids, only one mutation is considered to be present at the codon of 


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interest. 
Representation of Amino Acid Changes 
 
 
Mutations 
Amino acid change 
T69S 
Single mutation from amino acid 'T' (vendor reference) to 'S' (sample) at codon '69'  
Q148H/K/R Mixture of amino acid mutations ‘H’, ‘K’ and ‘R’ (sample) from amino acid ‘Q’ 
(vendor reference) at codon ‘148’ 
_69_1T 
First insertion of amino acid 'T' (sample) at codon '69' 
_69_2S 
Second insertion of amino acid 'S' (sample) at codon '69' 
_69_3S/A 
Third insertion of a mixture of amino acids 'S' and 'A' (sample) at codon '69' 
L74L/- 
Mixture of amino acid 'L' (sample) and a deletion at codon '74' 
V75- 
Single deletion of amino acid (sample) at codon '75' 
Resistance Associated Mutations 
• Known INI mutations associated with the development of resistance to CAB, BIC, RAL, EVG or 
DTG: 
 
Amino Acids in 
HIV Integrase for 
Analysis 
H51Y, T66A/I/K, E92Q/V/G, Q95K, T97A, G118R, F121C/Y, E138A/K/T, 
G140A/C/R/S**, Y143C/H/R/K/S/G/A, P145S, Q146P, S147G, Q148H/K/R/N, 
V151A/L, S153F/Y, N155H/S/T, E157Q, G163R/K, S230R, R263K,  
L68V/I*, L74I/M*, E138D*, V151I*, G193E* 
NOTES: 
• 
Draft listing; may be modified in case of additional substantive data availability. 
• 
INI mutations listed taken from Stanford HIV Resistance Database (http://hivdb.stanford.edu/DR/cgi-
bin/rules_scores_hivdb.cgi?class=INI cited 22Feb2021) and accessed on 28Mar2022. 
• 
INI substitutions listed above in bold had a score of =60. 
* Denotes additional INI mutations added as they were identified during in vitro passage of DTG or seen in a 
previous DTG study in INI-experienced participants (ING112574).  
**G140R is potentially associated with CAB based on in-stream data monitoring of CVF participants. 
• Major resistance mutations to other classes (i.e., NRTI, NNRTI, PI) as defined by the 
International Antiviral Society-USA (IAS-USA). The most up to date IAS-USA guidelines 
available at the time of DBL will be used in the analysis [Wensing, 2019]. 
Class 
Major Mutations 
NRTIs 
M41L, A62V, K65R/E/N, D67N, 69 insert, K70E/R, L74V, V75I, F77L, Y115F, F116Y, 
Q151M, M184V/I, L210W, T215Y/F, K219Q/E 
NNRTIs 
L100I, K101E/P, K103N/S, V106A/M, V108I, E138/A/G/K/Q/R, V179L, 
Y181C/I/V, Y188C/L/H, G190S/A, H221Y, P225H, F227C, M230I/L 
PIs 
D30N, V32I, M46I/L, I47A/V, G48V, I50V/L, I54M/L/V, Q58E, T74P, L76V, 
V82A/T/F/L/S, N83D, I84V, N88S, L90M 
Note: List generated from IAS_USA Guideline, [Wensing, 2019] 
• The pre-specified INSTI Mutations are identified as below: 
o Per the IAS-USA list of mutations associated with resistance to Bictegravir, 
Cabotegravir, Dolutegravir, Elvitegravir, or Raltegravir (IAS-USA 2019 resistance 
mutations update volume 27 issue 3, 2019): T66A/I/K, L74M, E92Q/G, T97A, G118R, 
F121Y, E138A/K/T, G140A/C/R/S, Y143C/H/R, S147G, Q148H/K/R, S153F/Y, N155H, 
R263K  


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o Observed mutations during in vitro passage of DTG or seen in a previous DTG study in 
INI-experienced subjects (study ING112574): H51Y, L74I, L68V/I, E92V, Q95K, E138D, 
Y143K/S/G/A, P145S, Q146P, V151I/L/A, N155S/T, E157Q, G163R/K, G193E, S230R 
o Mutations per FDA request for Study 201584: Q146L, T124A 
• The NNRTI resistance associated mutations (RAMs) are identified per IAS-USA NNRTI 
mutations (IAS-USA  2019 resistance mutations update volume 27 issue 3, 2019): 
o V90I, A98G, L100I, K101E/H/P, K103N/S, V106A/I/M/T, V108I, E138A/G/K/Q/R, 
V179D/F/L/T, Y181C/I/V, Y188C/H/L, G190A/E/S, H221Y, P225H, F227C/L/R, 
M230I/L, L234I 
• The RPV RAMs are identified per IAS-USA NNRTI mutations (IAS-USA 2019 resistance 
mutations update volume 27 issue 3, 2019): 
o L100I, K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, M230I/L 
Phenotype 
Phenotypic Susceptibility  
Phenotypic susceptibility to all licensed antiretroviral drugs and CAB will be determined using 
PhenoSense HIV assays from Monogram Inc. and will be reported as fold change (FC) in IC50 
relative to wild-type control virus NL4-3, i.e., FC of sample virus = IC50 of sample virus/IC50 of 
control virus.   
Phenotypic susceptibilities will be categorised according to FC as shown in tables below (based on 
Monogram PhenoSense assay). Clinical cutoffs (where available) or biological cutoffs by 
PhenoSense will be used to define the phenotypic susceptibility of background treatment by 
Monogram.  
 
Replication capacity is generated as part of standard phenotypic assays. 
PhenoSense Algorithm 
Drug 
Abbreviation 
Class 
PhenoSense cutoff 
Abacavir 
ABC 
NRTI 
(4.5 – 6.5)a 
Lamivudine 
3TC 
NRTI 
3.5 a 
Didanosine 
ddI 
NRTI 
(1.3 – 2.2) a 
Stavudine 
d4T 
NRTI 
1.7 a 
Zidovudine 
AZT (ZDV) 
NRTI 
1.9 
Emtricitabine 
FTC 
NRTI 
3.5 
Tenofovir 
TDF (TAF) 
NRTI 
(1.4 – 4) a 
Delavirdine 
DLV 
NNRTI 
6.2 
Efavirenz 
EFV 
NNRTI 
3 
Nevirapine 
NVP 
NNRTI 
4.5 
Etravirine 
ETR 
NNRTI 
(2.9-10) a 
Rilpivirine 
RPV 
NNRTI 
2.0 
Doravirine 
DOR 
NNRTI 
3 
Fosamprenavir/r 
FPV/r 
PI 
(4-11) a 
Atazanavir 
ATV 
PI 
2.2a 
Atazanavir/r 
ATV/r 
PI 
5.2 a 
Indinavir/r 
IDV/r 
PI 
10 a 
Lopinavir/r 
LPV/r 
PI 
(9 – 55) a 
Nelfinavir 
NFV 
PI 
3.6 


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Saquinavir/r 
SQV/r 
PI 
(2.3 – 12) a 
Tipranavir/r 
TPV/r 
PI 
(2 – 8) a 
Darunavir/r 
DRV/r 
PI 
(10 – 90) a 
Ritonavir 
RTV 
PI 
2.5 
Enfuvirtide 
T20 
FI 
6.48 
Cabotegravir 
CAB 
INI 
2.5 
Raltegravir 
RAL 
INI 
1.5 
Elvitegravir 
EVG 
INI 
2.5  
Dolutegravir 
DTG 
INI 
(4-13) a 
Bictegravir 
BIC 
INI 
(2.5- 10) 
a. 
clinical cutoff (lower cutoff – higher cutoff).  
 
Phenotypic Susceptibility  
Phenotypic susceptibility to each drug in a participant’s background regimen is determined by 
applying drug-associated cutoffs as defined by the PhenoSense algorithm to the phenotypic fold 
resistance as below:  
 
Full Sensitivity  
Fold Change 
Interpretation 
> clinical lower cutoff or biological cutoff 
resistant 
 clinical lower cutoff or biological cutoff 
sensitive 
 
Partial Sensitivity  
Fold Change 
Interpretation 
> clinical higher cutoff 
resistant 
 clinical higher cutoff and > clinical lower cutoff partially sensitive 
 clinical lower cutoff 
sensitive 
 
PHENOTYP dataset from Monogram contains the phenotypic susceptibility for each drug derived 
from the cutoff listed above. Thus, phenotypic susceptibility (i.e. full sensitivity and partial sensitivity) 
will not be re-derived for our analysis. 
Genotypic and Net Assessment Susceptibility 
Genotypic and Net assessment susceptibility to all licensed antiretroviral drugs and CAB will be 
determined from Monogram Inc. Net assessment susceptibility will be reported with the categories 
of ‘resistant’, ‘partially sensitive’, and ‘sensitive’ as what will be performed for phenotypic 
susceptibility. Genotypic susceptibility will be reported with the categories of ‘resistant’, ‘resistance 
possible’ and ‘sensitive’. Genotypic and Net assessment susceptibility will be assessed at time of 
CVF using plasma sample, Genotypic susceptibility may be assessed at baseline using PBMC. 
 


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15.7. 
Appendix 7: Reporting Standards for Missing Data 
15.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Participant study completion (i.e. as specified in the protocol) was defined as  
o Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including Week 100 and did not enter the Extension 
Phase; 
o Randomly assigned to either treatment group, completed the randomized 
Maintenance Phase including Week 100, and entered and completed the 
Extension Phase (defined as remaining on study until commercial supplies of 
CAB LA + RPV LA Q4W or Q8W regimen become locally available or 
development of CAB LA + RPV LA is terminated). 
 
Participants who withdraw from CAB LA + RPV LA and go into the LTFU Phase, and 
participants who withdraw from oral lead-in will be considered to have prematurely 
withdrawn from the study treatment. 
 
In addition to the 52-week Follow-Up phase required for participants who receive one or 
more injections with CAB LA or RPV LA, an in-clinic Follow-Up visit will be conducted 
approximately 4 weeks after the last dose of study medication for participants who withdraw 
during the oral lead-in period with ongoing AEs, and serious adverse events (SAEs) and 
also any laboratory abnormalities that are considered to be AEs or potentially harmful to the 
participant, at the last on-study visit.  Assessments at the Follow-up visit should reflect any 
ongoing complaints (e.g., blood draws to follow a laboratory abnormality).  Follow-Up visits 
are not required for successful completion of the study. 
 
• 
Withdrawn participants were not replaced in the study. 
• 
All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.  
• 
Withdrawal visits will be slotted as per Error! Not a valid result for table.: Assessment 
Windows or will be summarised as withdrawal visits. 
 
15.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank fields 
on the collection instrument: 
o These data will be indicated by the use of a “blank” in participant listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Outliers 
• 
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
 


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15.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• Partial dates will be displayed as captured in participant listing displays. 
Adverse 
Events 
• The eCRF allows for the possibility of partial dates (i.e., only month and year) to 
be recorded for AE start and end dates; that is, the day of the month may be 
missing. In such a case, the following conventions will be applied for calculating 
the time to onset and the duration of the event: 
o Missing Start Day: First of the month will be used unless this is before the 
start date of study treatment; in this case the study treatment start date will 
be used and hence the event is considered On-treatment as per Appendix 
4: Study Phases and Treatment State. 
o Missing Stop Day: Last day of the month will be used, unless this is after 
the last contact date; in this case the last contact date will be used. 
• Completely missing start or end dates will remain missing, with no imputation 
applied. Consequently, time to onset and duration of such events will be 
missing. 
ART/Non-
ART 
Medications 
or Medical 
History 
• Partial dates recorded in the eCRF will be imputed using the following 
convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month. 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. If 
medications recorded in the eCRF as prior (e.g. recorded in prior ART or 
prior ATLAS ART forms), the earlier date of the imputed and the day prior 
to the maintenance phase treatment start date will be used, i.e. min 
(imputed stop date, maintenance phase treatment start date - 1). 
• For medications with completely missing start date, they will be considered 
started prior to the maintenance phase treatment start date. 
• For medications with completely missing stop date, they will be considered 
ongoing unless recorded in eCRF as prior (e.g. recorded in prior ART or prior 
ATLAS ART forms). 
• For ART booster medications, the start and stop dates are not recorded in the 
database (i.e. missing), the dates will be imputed to be the same as the dates 
of their parent medications.  
• The recorded partial or missing date will be displayed in listings. 
Health 
outcomes  
• For the health outcomes questionnaire data, please refer to Section 12. 
• For the summary of individual item scores outputs, missing scores will not be 
computed. 


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15.7.2.2. 
Handling of Missing data for Statistical Analysis 
Element 
Reporting Detail 
Snapshot 
• In the Snapshot dataset, participants without HIV-1 RNA data in the assessment 
window for the visit of interest (due to missing data or discontinuation of IP prior 
to the visit window) do not belong to ‘HIV-1 RNA < 50 c/mL (or <200 c/mL)’.  
The nature of this missing data will be further classified in Snapshot summaries 
as either ‘HIV-1 RNA ≥ 50 c/mL’ (or ‘‘HIV-1 RNA ≥ 200 c/mL’) or ‘No Virologic 
Data at Week X’; Appendix 9: Snapshot Algorithm Details for full details 
LOCF 
• In the LOCF dataset, missing values will be carried forward from the previous, 
non-missing available on-treatment assessment. If the baseline value is missing 
any missing values until the first non-missing value will remain missing. 
Lipid LOCF 
Baseline for Lipids LOCF Analyses in main study: 
• Last evaluable lipids assessment up to and including the start of IP, where 
‘evaluable’ is defined as: Lipid-modifying agents not taken within 12 weeks of 
the date of assessment and Lipids are collected in a fasting state.  
 
During the Maintenance or Extension Phase: 
• If participants initiate serum lipid-modifying agents during the Maintenance or 
Extension Phase, then the last available fasted on-treatment lipid values prior to 
the initiation will be used in place of future, observed on-treatment values.  
• Imputation at planned visits will continue even if the participant discontinues the 
lipid-modifying agent.  Missing assessments will not be imputed if there is no 
last available fasting on-treatment lipid value prior to the initiation of serum lipid-
modifying agent. 
• If participants take lipid modifying agents within 12 weeks prior to the start of the 
study treatment, all the post-baseline values will be missing. 
 
Baseline for Lipids LOCF Analyses in sub-study: 
• Last evaluable lipids assessment up to and including the start of thigh injection, 
where ‘evaluable’ is defined as: Lipid-modifying agents not taken within 12 
weeks of the date of assessment and Lipids are collected in a fasting state.  
 
During the Thigh Injection or Return to Gluteal Injection Phase: 
• If participants initiate serum lipid-modifying agents during the Thigh injection or 
Return to Gluteal Injection Phase, then the last available fasted on-treatment 
lipid values prior to the initiation will be used in place of future, observed on-
treatment values in sub-study.  
• Imputation at planned visits will continue even if the participant discontinues the 
lipid-modifying agent.  Missing assessments will not be imputed if there is no 
last available fasting on-treatment lipid value prior to the initiation of serum lipid-
modifying agent. 
• If participants take lipid modifying agents within 12 weeks prior to the start of the 
thigh injection, all the post-baseline values in sub-study will be missing. 
 
Analyses Evaluated with Lipid LOCF Dataset: 


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Element 
Reporting Detail 
 
Week 48 analysis: 
This dataset will be used to summarize fasting lipids parameters in the following 
displays:  
Summary of Fasting TC/HDL ratio Change from Baseline 
Summary of Fasting Lipids Percentage Changes from Baseline 
Summary of Chemistry Changes from Baseline 
Summary of Chemistry Values 
 
All other displays of lipids (e.g. toxicity tables and NCEP tables) will use observed 
fasting data, without LOCF imputation. 
 
Post-Week 48 analysis: 
Lipid LOCF dataset will be used for all lipid analysis except for the Summary of 
Maximum Post-Baseline Emergent Chemistry Toxicities. 
 


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15.8. 
Appendix 8: Values of Potential Clinical Importance 
ECG values of potential clinical importance are defined as QTc > 500 msec or increase 
from baseline in QTc ≥ 60 msec. 
 


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15.9. 
Appendix 9: Snapshot Algorithm Details 
Detailed Algorithm Steps 
• 
Consider an analysis visit window for Week X as defined in Table 10 and Table 13.  
• 
The HIV-1 RNA threshold of 50, 200 c/mL will be analysed, respectively, in this study  
• 
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participants ability to attend clinic visits. The snapshot algorithm is 
modified to allow for the presentation of full scope of COVID-19 relatedness. The analysis 
window ‘Week 48’ and HIV-1 RNA threshold of ’50 c/mL’ are used for the purpose of 
illustration. A participant’s Snapshot response and reason at Week 48 are categorized as 
below. 
 
o 
HIV-1 RNA < 50 c/mL 
o 
HIV-1 RNA ≥ 50 c/mL 
   Data in window not below 50 
  Non-COVID-19 related  
Discontinued for lack of efficacy 
Discontinued for other reason while not below 50 
Change in background therapy* 
  COVID-19 related 
Discontinued for lack of efficacy 
Discontinued for other reason while not below 50 
Change in background therapy* 
 
o 
No Virologic Data at Week 48 Window 
  Non-COVID-19 related 
Discontinued study due to AE or death 
Discontinued study for other reasons 
On study but missing data in window 
              COVID-19 related 
Discontinued study due to AE or death 
Discontinued study for other reasons 
On study but missing data in window 
 
* Note: since permanent change in ART are not permitted in this protocol, all such 
participants who permanently change ART will be considered ‘HIV-1 RNA ≥ 50 c/mL’ if the 
permanent change in ART is made prior to an analysis timepoint. Participants with protocol 
permitted temporary oral bridging treatment (CAB+RPV or SOC, the SOC oral bridging 
medication is permitted during COVID-19 pandemic due to the unavailability of the 
CAB/RPV IM injections and oral CAB+RPV) or a temporary change in ART by mistake prior 
to an analysis timepoint (e.g. participant took the ART different from study treatment during 
oral lead-in by mistake for a short period and then went back to the study treatment) will not 
be considered ‘HIV-1 RNA ≥ 50 c/mL’ due to ‘change in ART’. 


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• 
The steps in determining response and reasons are indicated in the table below, in the 
order stated. 
 
• 
Background therapy is not given to participants while on study. The “change in background 
therapy” in detailed steps below refers to the “change in ART” in this study. 
 
Detailed steps 
Please note that the following scenarios will NOT be penalized Per Snapshot algorithm (i.e. 
please exclude these scenarios from Condition 1-4). 
• Dose reduction, dropping a component, or change in formulation (e.g. ‘Tivicay + Kivexa’ 
to ‘Triumeq’ with the identical ingredients) 
• Protocol permitted temporary oral bridging, or temporary change in ART by mistake 
Condition (‘Week 48’ indicates Week 48 window) 
Response  
Reasons 
1. If non-permitted change in background therapy 
prior to Week 48  
 
 
1.1. If the change in background therapy is not due 
to COVID-19 
HIV-1 RNA ≥ 
50  
Change in 
background therapy 
(non-COVID-19 
related) 
1.2. If the change in background therapy is due to 
COVID-19 
HIV-1 RNA ≥ 
50  
Change in 
background therapy 
(COVID-19 related) 
2. If permitted change[a] in background therapy 
prior to Week 48 AND the latest on-treatment 
VL prior to/on the date of change is ≥ 50 c/mL 
(NA to this study) 
 
 
2.1 If the change in background therapy is not due 
to COVID-19 
HIV-1 RNA ≥ 
50  
Change in 
background therapy 
(Non-COVID-19 
related) 
2.2 If the change in background therapy is due to 
COVID-19 
HIV-1 RNA ≥ 
50 
Change in 
background therapy 
(COVID-19 related) 
3. If non-permitted change in background therapy 
during Week 48    
 
 
• Last on-treatment VL during Week 48 prior 
to/on the date of change ≥ 50 c/mL 
HIV-1 RNA ≥ 
50 
Data in window not 
below 50 
• Last on-treatment VL during Week 48 prior 
to/on the date of change < 50 c/mL 
HIV-1 RNA < 
50 
 
• No VL during Week 48 prior to/on the date 
of change and the change in background 
therapy is not due to COVID-19     
HIV-1 RNA ≥ 
50 
Change in 
background therapy 
(Non-COVID-19 
related) 


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• No VL during Week 48 prior to/on the date 
of change and the change in background 
therapy is due to COVID-19     
HIV-1 RNA ≥ 
50  
Change in 
background therapy 
(COVID-19 related) 
4. If permitted change[a] in background therapy 
during Week 48 AND the last on-treatment VL 
prior to/on the date of change is ≥ 50 c/mL (NA 
to this study) 
 
 
4.1 This last on-treatment VL occurs prior to Week 
48 
 
 
4.1.1 The change in background therapy is not due 
to COVID-19 
HIV-1 RNA ≥ 
50 
Change in 
background therapy 
(Non-COVID-19 
related)  
4.1.2 The change in background therapy is due to 
COVID-19 
HIV-1 RNA ≥ 
50 
Change in 
background therapy 
(COVID-19 related) 
4. 2   This last on-treatment VL occurs during Week 
48 but prior to/on the date of change 
HIV-1 RNA ≥ 
50 
Data in window not 
below 50 
5. If none of the above conditions met 
 
 
5.1 On-treatment VL available during Week 48  
 
 
• Last on-treatment VL during Week 48 
≥ 50 c/mL 
HIV-1 RNA ≥ 
50 
Data in window not 
below 50 
• Last on-treatment VL during Week 48 
< 50 c/mL 
HIV-1 RNA < 
50 
 
5.2 No on-treatment VL during Week 48    
 
 
5.2.1 If participants are still on study, i.e. a 
participant has not permanently discontinued
the study treatment yet, or if a participant 
permanently discontinued the study 
treatment and the upper bound of analysis 
snapshot window is prior to the following 
date:  
Q8W arm:  
Min[max(Date of last injection + 63, Date of 
Last  Dose of Oral Study Treatment 
(CAB+RPV, SOC Bridging + 1), Withdrawal 
Date, LTFU ART Start Date] 
Q4W arm: 
Min[max(Date of last injection + 35, Date of 
Last  Dose of Oral Study Treatment 
(CAB+RPV, SOC Bridging) + 1), Withdrawal 
Date, LTFU ART Start Date] 
, where ‘Withdrawal Date’ refers to the date 
the participant failed to complete or 
completed per study conclusion form. 
 
 


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5.2.1.1 If no on-treatment VL during Week 48 is not 
due to COVID-19 
No virologic 
data at Week 
48 Window 
On study but 
missing data in 
window (Non-
COVID-19 related) 
5.2.1.2 If no on-treatment VL during Week 48 is due 
to COVID-19 
No virologic 
data at Week 
48 Window 
On study but 
missing data in 
window (COVID-19 
related) 
5.2.2 If participants withdraw[b] before/during Week
48 due to 
 
 
5.2.2.1 Non-COVID-19 related safety reasons (e.g.
AE/death, liver chemistry stopping criteria, 
renal toxicity withdrawal criteria, QTc 
withdrawal criteria etc, as recorded in 
eCRF Conclusion form) 
No virologic 
data at Week 
48 Window 
Disc due to 
AE/death (Non-
COVID-19 related) 
5.2.2.2 COVID-19 related safety reasons (e.g. 
AE/death, liver chemistry stopping criteria, 
renal toxicity withdrawal criteria, QTc 
withdrawal criteria etc, as recorded in 
eCRF Conclusion form) 
No virologic 
data at Week 
48 Window 
Disc due to 
AE/death (COVID-
19 related) 
5.2.2.3  Non-safety and Non-COVID-19 related 
reasons (e.g. Lack of efficacy, protocol 
deviation, withdrew consent, loss to 
follow-up, study closed/terminated, 
investigator discretion etc, as recorded in 
eCRF Conclusion Form) 
 
 
• Last on-treatment VL <50 c/mL OR no 
on-treatment VL available during study   
No virologic 
Data at Week 
48 Window 
Disc for other 
reasons (Non-
COVID-19 related) 
• Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to Lack of efficacy 
HIV-1 RNA ≥ 
50 
Disc. for lack of 
efficacy (Non-
COVID-19 related) 
• Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to all other non-safety 
related reasons 
HIV-1 RNA ≥ 
50 
Disc. for other 
reason while not 
below 50 (Non-
COVID-19 related) 
5.2.2.4  Non-safety and COVID-19 related 
reasons (e.g. protocol deviation, 
withdrew consent, loss to follow-up, 
study closed/terminated, investigator 
discretion etc, as recorded in eCRF 
Conclusion Form) 
 
 
• Last on-treatment VL <50 c/mL OR no 
on-treatment VL available during study   
No virologic 
Data at Week 
48 Window 
Disc for other 
reasons (COVID-19 
related) 


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• Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to Lack of efficacy 
HIV-1 RNA ≥ 
50 
Disc. for lack of 
efficacy (COVID-19 
related) 
• Last on-treatment VL ≥ 50 c/mL AND 
withdrawal due to all other non-safety 
related reasons 
HIV-1 RNA ≥ 
50 
Disc. for other 
reason while not 
below 50 (COVID-19 
related) 
a. 
Excluding permitted change in background therapy where change or decision to change is made prior to/on the 
first on-treatment viral result  
b. 
Including participants who either prematurely withdraw or complete the study per study conclusion form. In this 
study, participants who completed the Maintenance phase and decided not to enter the Extension phase 
without the reason beyond the completion of the study commitment are considered completers per study 
conclusion form. 
Examples from FDA guidance 
Data in Window 
Virologic outcome should be determined by the last available measurement while the patient is on 
treatment and continued on trial within the time window: 
• HIV-1 RNA = 580 c/mL at Day 336, HIV-1 RNA below 50 c/mL on Day 350. This should 
be categorized as HIV-1 RNA below 50 c/mL. 
No Data in Window 
Discontinued study due to Adverse Event or Death: 
• Any patient who discontinues because of an AE or death before the window should be 
classified as Discontinued due to AE or Death (as appropriate), regardless of the HIV-1 
RNA result, even if the HIV-1 RNA is below 50 c/mL at the time of discontinuation.  
• However, if a patient has an HIV-1 RNA value in the time window and also discontinues 
in the time window, the viral load data should be used to classify the patient’s response. 
This is the Virology First hierarchy: 
a. HIV-1 RNA below 50 c/mL at Day 336 and discontinues because of AE or even 
dies on Day 360 — this person is categorized as having HIV-1 RNA below 50 
c/mL.  
b. HIV-1 RNA is 552 c/mL on Day 336 and the patient discontinues on Day 360, 
the patient is categorized as having HIV-1 RNA ≥ 50 c/mL. 
Discontinued for Other Reasons: 
• Only patients who have achieved virologic suppression can be counted as Discontinued 
for Other Reasons. 
• If a patient discontinues the study before the time window because of lack of efficacy 
then the patient should be included in the HIV-1 RNA ≥ 50 row and not in the 
Discontinued for Other Reasons row. 
• If a patient discontinues because participant withdrew consent and his or her HIV-1 RNA 
result at the time of discontinuation was equal to or above 50 c/mL, then he or she 
should be categorized as HIV-1 RNA ≥ 50 and NOT as Discontinued for Other 
Reasons.  


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• If a patient discontinued because of Lost to Follow-Up and the last HIV-1 RNA result 
was 49 c/mL, then the patient can be categorized as Discontinued for Other Reasons. 
• If patients changed background treatment — not permitted by protocol— they should be 
considered an efficacy failure and captured in the HIV-1 RNA ≥ 50 c/mL row. 
On study but missing data in window: 
• If there are no data during Days 294 to 377, but there is an HIV-1 RNA below 50 c/mL 
on Day 380, this patient should be considered On Study but Missing Data in Window. 
• If there are no data during Days 294 to 377, but there is an HIV-1 RNA equal to or 
above 50 c/mL on Day 280, this patient also should be classified as On Study but 
Missing Data in Window. 
 


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15.10. 
Appendix 10: Variables Defined for Time to Event Analysis 
Programming Instructions for the Kaplan-Meier analysis of treatment-related 
discontinuation equals failure (TRDF) for Week 24 IDMC / Week 24 / Week 48 / Week 96 
Analyses 
Condition 
Censor 
Status  
Event Description/AVAL 
1. Participant met CVF event 
criteria during the 
Maintenance Phase (based 
on derived CVF) 
CNSR=0 EVNTDESC=CVF 
AVAL=Study Day of SVF*  
*immediately preceding CVF 
2. Participant with 
Maintenance Phase 
withdrawal due to ‘Lack of 
Efficacy’, ‘Treatment 
Related AE’, ‘Intolerability 
due to Injection’, or 
‘Protocol Defined Safety 
Stopping Criteria’ during 
Maintenance Phase 
  
Note: primary reason and/or 
standardized subreason for 
discontinuation based on 
Maintenance Conclusion form 
in the eCRF. ‘Protocol 
Defined Safety Stopping 
Criteria’ includes GSK 
defined liver chemistry 
stopping criteria, renal toxicity 
criteria and QTc withdrawal 
criteria. Treatment Related 
AE’ is defined as participants 
who have primary reason for 
withdrawal =AE and who 
have at least one AE 
considered drug related and 
leading to 
withdrawal/permanent 
discontinuation of 
investigational product. 
CNSR=0 EVNTDESC= terms in italic, respectively. 
 
For Q4W arm: 
AVAL= min [Study Day of Maintenance Phase 
Discontinuation, max (Study Day of Last Injection + 
35, Study Day of Last Dose of Oral Study 
Treatment (CAB+RPV or SOC Bridging) + 1)] 
 
For Q8W arm: 
AVAL= min [Study Day of Maintenance Phase 
Discontinuation, max (Study Day of Last Injection + 
63, Study Day of Last Dose of Oral Study 
Treatment (CAB+RPV or SOC Bridging) + 1)] 
 
Note: Date of Maintenance Phase discontinuation is 
from the Maintenance Phase Conclusion form in the 
eCRF. 
If none of the above 
conditions met 
 
 
3.  Participant with 
Maintenance Phase 
withdrawal due to other 
reasons 
CNSR=1 EVNTDESC=’Censored due to Study 
Discontinuation for Other Reasons’ 
 
AVAL will be defined as the same as above 2 


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Programming Instructions for the Kaplan-Meier analysis of treatment-related 
discontinuation equals failure (TRDF) for Week 24 IDMC / Week 24 / Week 48 / Week 96 
Analyses 
Condition 
Censor 
Status  
Event Description/AVAL 
4. Participant who did not 
have premature withdrawal 
from the Maintenance 
Phase 
CNSR=1 EVNTDESC=’Censored due to data cutoff for 
analysis’ 
 
AVAL = Study Day of last on-treatment date during 
the maintenance phase, which is defined as follows:  
 
For Q4W arm: 
min [Study Day of Nominal Week 100 Visit, Study 
Day of LTFU ART Start Date, Study Day of Last 
Contact Date at time of analysis, max (Study Day of 
Last Injection + 35, Study Day of Last Dose of Oral 
Study Treatment (CAB+RPV or SOC Bridging) + 1)] 
For Q8W arm 
min [Study Day of Nominal Week 100 Visit, Study 
Day of LTFU ART Start Date, Study Day of Last 
Contact Date at time of analysis, max (Study Day of 
Last Q8W IM Dose + 63, Study Day of Last Dose of 
Oral Study Treatment (CAB+RPV or SOC Bridging) 
+ 1)] 
 
Programming Instructions for the Kaplan-Meier analysis of treatment-related 
discontinuation equals failure (TRDF) for Week 152 Analysis 
Condition 
Censor 
Status  
Event Description/AVAL 
1. Participant met CVF event 
criteria during the 
Maintenance and Extension 
Phase (based on derived 
CVF) 
CNSR=0 EVNTDESC=CVF 
AVAL=Study Day of SVF*  
*immediately preceding CVF 
2. Participant with study 
withdrawal due to ‘Lack of 
Efficacy’, ‘Treatment 
Related AE’, ‘Intolerability 
due to Injection’, or 
‘Protocol Defined Safety 
Stopping Criteria’  
  
Note: primary reason and/or 
standardized subreason for 
discontinuation based on 
CNSR=0 EVNTDESC= terms in italic, respectively. 
 
For Q4W arm: 
AVAL= min [Study Day of Study Discontinuation, 
max (Study Day of Last Injection + 35, Study Day of 
Last Dose of Oral Study Treatment (CAB+RPV or 
SOC Bridging) + 1)] 
 
For Q8W arm: 
AVAL= min [Study Day of Study Discontinuation, 
max (Study Day of Last Injection + 63, Study Day of 


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Programming Instructions for the Kaplan-Meier analysis of treatment-related 
discontinuation equals failure (TRDF) for Week 152 Analysis 
Condition 
Censor 
Status  
Event Description/AVAL 
Study Conclusion form in the 
eCRF. ‘Protocol Defined 
Safety Stopping Criteria’ 
includes GSK defined liver 
chemistry stopping criteria, 
renal toxicity criteria and QTc 
withdrawal criteria. Treatment 
Related AE’ is defined as 
participants who have primary 
reason for withdrawal =AE 
and who have at least one AE 
considered drug related and 
leading to 
withdrawal/permanent 
discontinuation of 
investigational product. 
Last Dose of Oral Study Treatment (CAB+RPV or 
SOC Bridging) + 1)] 
 
Note: Date of Study discontinuation is from the 
Study Conclusion form in the eCRF. 
If none of the above 
conditions met 
 
 
3.  Participant with study 
withdrawal due to other 
reasons 
CNSR=1 EVNTDESC=’Censored due to Study 
Discontinuation for Other Reasons’ 
 
AVAL will be defined as the same as above 2 
4. Participant who did not 
have premature withdrawal 
CNSR=1 EVNTDESC=’Censored due to data cutoff for 
analysis’ 
 
AVAL = Study Day of last on-treatment date, which 
is defined as follows:  
 
For Q4W arm: 
min [Study Day of LTFU ART Start Date, Study Day 
of Last Contact Date at time of analysis, max (Study 
Day of Last Injection + 35, Study Day of Last Dose 
of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1)] 
For Q8W arm 
min [Study Day of LTFU ART Start Date, Study Day 
of Last Contact Date at time of analysis, max (Study 
Day of Last Q8W IM Dose + 63, Study Day of Last 
Dose of Oral Study Treatment (CAB+RPV or SOC 
Bridging) + 1)] 
 


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Note that last injection and last dose of oral study treatment (CAB+RPV or SOC bridging) 
mentioned in table above are only applied to participants who permanently discontinued from the 
study treatment. The similar approach will be used to derive for Kaplan-Meier analysis of efficacy-
related discontinuation equals failure (ERDF), except that the reason of withdrawal in Condition 2 
will be restricted to ‘Lack of Efficacy’. 
 
 


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15.11. 
Appendix 11: Identification of Adverse Events of Special 
Interest 
The adverse events of special interest are identified based on MedDRA coded values and/or AE 
data available in the study database. The system organ classes (SOCs), preferred terms (PTs) or 
codes, Standardised MedDRA Queries (SMQs), High Level Group Terms (HLGTs), and High Level 
Terms (HLTs) below are from MedDRA 21.1. SMQs use narrow terms unless otherwise specified. 
In case there is a change to the version of MedDRA at time of reporting, the coded values based 
on the MedDRA version at the time of reporting will be used. The additional events may also be 
added based on the blinded review of AE data collected on study prior to the database freeze. 
1. Hepatic Safety Profile: Assessment of risk of hepatoxicity 
Hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ) 
PT 
PT Code 
Acquired hepatocerebral degeneration 
10080860 
Acute hepatic failure 
10000804 
Acute on chronic liver failure 
10077305 
Acute yellow liver atrophy 
10070815 
Ascites 
10003445 
Asterixis 
10003547 
Bacterascites 
10068547 
Biliary cirrhosis 
10004659 
Biliary fibrosis 
10004664 
Cholestatic liver injury 
10067969 
Chronic hepatic failure 
10057573 
Coma hepatic 
10010075 
Cryptogenic cirrhosis 
10063075 
Diabetic hepatopathy 
10071265 
Drug-induced liver injury 
10072268 
Duodenal varices 
10051010 
Gallbladder varices 
10072319 
Gastric variceal injection 
10076237 
Gastric variceal ligation 
10076238 
Gastric varices 
10051012 
Gastric varices haemorrhage 
10057572 
Hepatectomy 
10061997 
Hepatic atrophy 
10019637 
Hepatic calcification 
10065274 
Hepatic cirrhosis 
10019641 
Hepatic encephalopathy 
10019660 
Hepatic encephalopathy prophylaxis 
10066599 


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PT 
PT Code 
Hepatic failure 
10019663 
Hepatic fibrosis 
10019668 
Hepatic hydrothorax 
10067365 
Hepatic infiltration eosinophilic 
10064668 
Hepatic lesion 
10061998 
Hepatic necrosis 
10019692 
Hepatic steato-fibrosis 
10077215 
Hepatic steatosis 
10019708 
Hepatitis fulminant 
10019772 
Hepatobiliary disease 
10062000 
Hepatocellular foamy cell syndrome 
10053244 
Hepatocellular injury 
10019837 
Hepatopulmonary syndrome 
10052274 
Hepatorenal failure 
10019845 
Hepatorenal syndrome 
10019846 
Hepatotoxicity 
10019851 
Intestinal varices 
10071502 
Intestinal varices haemorrhage 
10078058 
Liver and small intestine transplant 
10052280 
Liver dialysis 
10076640 
Liver disorder 
10024670 
Liver injury 
10067125 
Liver operation 
10062040 
Liver transplant 
10024714 
Lupoid hepatic cirrhosis 
10025129 
Minimal hepatic encephalopathy 
10076204 
Mixed liver injury 
10066758 
Nodular regenerative hyperplasia 
10051081 
Non-alcoholic fatty liver 
10029530 
Non-alcoholic steatohepatitis 
10053219 
Non-cirrhotic portal hypertension 
10077259 
Oedema due to hepatic disease 
10049631 
Oesophageal varices haemorrhage 
10030210 
Peripancreatic varices 
10073215 
Portal fibrosis 
10074726 
Portal hypertension 
10036200 
Portal hypertensive colopathy 
10079446 
Portal hypertensive enteropathy 
10068923 
Portal hypertensive gastropathy 
10050897 


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PT 
PT Code 
Portal vein cavernous transformation 
10073979 
Portal vein dilatation 
10073209 
Portopulmonary hypertension 
10067281 
Primary biliary cholangitis 
10080429 
Regenerative siderotic hepatic nodule 
10080679 
Renal and liver transplant 
10052279 
Retrograde portal vein flow 
10067338 
Reye's syndrome 
10039012 
Reynold's syndrome 
10070953 
Splenic varices 
10067823 
Splenic varices haemorrhage 
10068662 
Steatohepatitis 
10076331 
Subacute hepatic failure 
10056956 
Varices oesophageal 
10056091 
Varicose veins of abdominal wall 
10072284 
White nipple sign 
10078438 
Hepatitis, non-infectious (SMQ) 
PT 
PT Code 
Acute graft versus host disease in liver 
10066263 
Allergic hepatitis 
10071198 
Alloimmune hepatitis 
10080576 
Autoimmune hepatitis 
10003827 
Chronic graft versus host disease in liver 
10072160 
Chronic hepatitis 
10008909 
Graft versus host disease in liver 
10064676 
Hepatitis 
10019717 
Hepatitis acute 
10019727 
Hepatitis cholestatic 
10019754 
Hepatitis chronic active 
10019755 
Hepatitis chronic persistent 
10019759 
Hepatitis fulminant 
10019772 
Hepatitis toxic 
10019795 
Immune-mediated hepatitis 
10078962 
Ischaemic hepatitis 
10023025 
Lupus hepatitis 
10067737 
Non-alcoholic steatohepatitis 
10053219 
Radiation hepatitis 
10051015 
Steatohepatitis 
10076331 
 


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2. Hypersensitivity Reactions (HSR) 
Drug reaction with eosinophilia and systemic symptoms syndrome (SMQ) 
PT 
PT Code 
Drug reaction with eosinophilia and systemic symptoms 
10073508 
Pseudolymphoma 
10037127 
 
PTs (Selective) 
PT 
PT Code 
Drug hypersensitivity 
10013700 
Hypersensitivity 
10020751 
Type IV Hypersensitivity reaction 
10053613 
Eosinophillia 
10014950 
Eye swelling 
10015967 
Eyelid oedema 
10015993 
Lip swelling 
10024570 
Angioedema 
10002424 
Circumoral oedema 
10052250 
Face oedema 
10016029 
Idiopathic angioedema 
10073257 
Lip oedema 
10024558 
Mouth swelling 
10075203 
Oedema mouth 
10030110 
Periorbital oedema 
10034545 
Swelling face 
10042682 
Periorbital swelling 
10056647 
Swelling of eyelid 
10042690 
 
3. Rash 
Severe cutaneous adverse reactions (SMQ) 
PT 
PT Code 
Acute generalised exanthematous pustulosis 
10048799 
Cutaneous vasculitis 
10011686 
Dermatitis bullous 
10012441 
Dermatitis exfoliative 
10012455 
Dermatitis exfoliative generalised 
10012456 
Drug reaction with eosinophilia and systemic symptoms 
10073508 


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PT 
PT Code 
Epidermal necrosis 
10059284 
Erythema multiforme 
10015218 
Exfoliative rash 
10064579 
Oculomucocutaneous syndrome 
10030081 
Skin necrosis 
10040893 
Stevens-Johnson syndrome 
10042033 
Toxic epidermal necrolysis 
10044223 
Toxic skin eruption 
10057970 
 
PTs (Selective) 
PT 
PT Code 
Eyelid rash 
10074620 
Genital rash 
10018175 
Mucocutaneous rash 
10056671 
Nodular rash 
10075807 
Perineal rash 
10075364 
Rash 
10037844 
Rash erythematous 
10037855 
Rash generalised 
10037858 
Rash macular 
10037867 
Rash maculo-papular 
10037868 
Rash maculovesicular 
10050004 
Rash morbilliform 
10037870 
Rash papular 
10037876 
Rash rubelliform 
10057984 
Rash scarlatiniform 
10037890 
Rash vesicular 
10037898 
Rash pruritic 
10037884 
Rash follicular 
10037857 
Rash pustular 
10037888 
Drug eruption 
10013687 
 
4. Prolongation of the Corrected QT Interval of the ECG in Supratherapeutic Doses 
Torsade de pointes/QT prolongation (SMQ) 
PT 
PT Code 
Electrocardiogram QT interval abnormal 
10063748 


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PT 
PT Code 
Electrocardiogram QT prolonged 
10014387 
Long QT syndrome 
10024803 
Long QT syndrome congenital 
10057926 
Torsade de pointes 
10044066 
Ventricular tachycardia 
10047302 
 
PTs (Selective) 
PT 
PT Code 
Electrocardiogram repolarisation abnormality 
10052464 
 
5. Suicidal Ideation/Behaviour 
Suicide/self-injury (SMQ) 
PT 
PT Code 
Assisted suicide 
10079105 
Columbia suicide severity rating scale abnormal 
10075616 
Completed suicide 
10010144 
Depression suicidal 
10012397 
Intentional overdose 
10022523 
Intentional self-injury 
10022524 
Poisoning deliberate 
10036000 
Self-injurious ideation 
10051154 
Suicidal behaviour 
10065604 
Suicidal ideation 
10042458 
Suicide attempt 
10042464 
Suicide threat 
10077417 
Suspected suicide attempt 
10081704 
 
6. Depression 
Depression (excl suicide and self injury) (SMQ) 
PT 
PT Code 
Activation syndrome 
10066817 
Adjustment disorder with depressed mood 
10001297 
Adjustment disorder with mixed anxiety and depressed mood 
10001299 
Agitated depression 
10001496 
Anhedonia 
10002511 


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PT 
PT Code 
Antidepressant therapy 
10054976 
Childhood depression 
10068631 
Decreased interest 
10011971 
Depressed mood 
10012374 
Depression 
10012378 
Depression postoperative 
10012390 
Depressive symptom 
10054089 
Dysphoria 
10013954 
Electroconvulsive therapy 
10014404 
Feeling guilty 
10049708 
Feeling of despair 
10016344 
Feelings of worthlessness 
10016374 
Helplessness 
10077169 
Major depression 
10057840 
Menopausal depression 
10067371 
Mixed anxiety and depressive disorder 
10080836 
Perinatal depression 
10078366 
Persistent depressive disorder 
10077804 
Post stroke depression 
10070606 
Postictal depression 
10071324 
 
7. Bipolar Disorder 
HLGT Manic and Bipolar mood disorders and disturbances 
PT 
PT Code 
Bipolar I disorder 
10004939 
Bipolar II disorder 
10004940 
Bipolar disorder 
10057667 
Cyclothymic disorder 
10011724 
Hypomania 
10021030 
Mania 
10026749 
 
8. Psychosis 
Psychosis and psychotic disorders (SMQ) 
PT 
PT Code 
Acute psychosis 
10001022 
Alcoholic psychosis 
10001632 


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PT 
PT Code 
Alice in wonderland syndrome 
10001666 
Brief psychotic disorder with marked stressors 
10048549 
Brief psychotic disorder without marked stressors 
10056395 
Brief psychotic disorder, with postpartum onset 
10006362 
Charles Bonnet syndrome 
10063354 
Childhood psychosis 
10061040 
Clang associations 
10009232 
Cotard's syndrome 
10059591 
Delusion 
10012239 
Delusion of grandeur 
10012241 
Delusion of reference 
10012244 
Delusion of replacement 
10012245 
Delusional disorder, erotomanic type 
10012249 
Delusional disorder, grandiose type 
10012250 
Delusional disorder, jealous type 
10012251 
Delusional disorder, mixed type 
10012252 
Delusional disorder, persecutory type 
10053195 
Delusional disorder, somatic type 
10012254 
Delusional disorder, unspecified type 
10012255 
Delusional perception 
10012258 
Dementia of the Alzheimer's type, with delusions 
10012295 
Depressive delusion 
10063033 
Derailment 
10012411 
Epileptic psychosis 
10059232 
Erotomanic delusion 
10015134 
Flight of ideas 
10016777 
Hallucination 
10019063 
Hallucination, auditory 
10019070 
Hallucination, gustatory 
10019071 
Hallucination, olfactory 
10019072 
Hallucination, synaesthetic 
10062824 
Hallucination, tactile 
10019074 
Hallucination, visual 
10019075 
Hallucinations, mixed 
10019079 
Hypnagogic hallucination 
10020927 
Hypnopompic hallucination 
10020928 
Hysterical psychosis 
10062645 
Ideas of reference 
10021212 
Illusion 
10021403 


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PT 
PT Code 
Jealous delusion 
10023164 
Loose associations 
10024825 
Mixed delusion 
10076429 
Neologism 
10028916 
Neuroleptic-induced deficit syndrome 
10075295 
Paranoia 
10033864 
Paranoid personality disorder 
10033869 
Parkinson's disease psychosis 
10074835 
Paroxysmal perceptual alteration 
10063117 
Persecutory delusion 
10034702 
Postictal psychosis 
10070669 
Post-injection delirium sedation syndrome 
10072851 
Posturing 
10036437 
Psychosis postoperative 
10065617 
Psychotic behaviour 
10037249 
Psychotic disorder 
10061920 
Psychotic disorder due to a general medical condition 
10061921 
Reactive psychosis 
10053632 
Rebound psychosis 
10074833 
Schizoaffective disorder 
10039621 
Schizoaffective disorder bipolar type 
10068889 
Schizoaffective disorder depressive type 
10068890 
Schizophrenia 
10039626 
Schizophreniform disorder 
10039647 
Schizotypal personality disorder 
10039651 
Senile psychosis 
10039987 
Shared psychotic disorder 
10040535 
Somatic delusion 
10041317 
Somatic hallucination 
10062684 
Substance-induced psychotic disorder 
10072388 
Tangentiality 
10043114 
Thought blocking 
10043495 
Thought broadcasting 
10052214 
Thought insertion 
10043496 
Thought withdrawal 
10043497 
Transient psychosis 
10056326 
Waxy flexibility 
10047853 
 


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9. Mood Disorders 
HLGT Mood disorders and disturbances NEC, Psychiatric disorders SOC 
PT 
PT Code 
Crying 
10011469 
Mood swings 
10027951 
Boredom 
10048909 
Mood altered 
10027940 
Apathy 
10002942 
Affective ambivalence 
10077173 
Emotional poverty 
10014557 
Euphoric mood 
10015535 
Premenstrual dysphoric disorder 
10051537 
Alexithymia 
10077719 
Laziness 
10051602 
Blunted affect 
10005885 
Constricted affect 
10010778 
Affect lability 
10054196 
Anger 
10002368 
Affective disorder 
10001443 
Lethargy 
10024264 
Listless 
10024642 
Inappropriate affect 
10021588 
Dysphoria 
10013954 
Mood disorder due to a general medical 
condition 
10027944 
Morose 
10027977 
Screaming 
10039740 
Steroid withdrawal syndrome 
10042028 
Emotional disorder 
10014551 
Irritability 
10022998 
Moaning 
10027783 
Premenstrual syndrome 
10036618 
Neuroleptic-induced deficit syndrome 
10075295 
Substance-induced mood disorder 
10072387 
Flat affect 
10016759 
Diencephalic syndrome of infancy 
10012774 
Emotional distress 
10049119 
Frustration tolerance decreased 
10077753 
Seasonal affective disorder 
10039775 
 


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10. Anxiety 
HLGT Anxiety disorders and symptoms 
PT 
PT Code 
Acrophobia 
10000605 
Activation syndrome 
10066817 
Acute stress disorder 
10001084 
Aerophobia 
10080300 
Agitation 
10001497 
Agitation neonatal 
10001500 
Agitation postoperative 
10049989 
Agoraphobia 
10001502 
Akathisia 
10001540 
Algophobia 
10078056 
Animal phobia 
10002518 
Anniversary reaction 
10074066 
Anticipatory anxiety 
10002758 
Anxiety 
10002855 
Anxiety disorder 
10057666 
Anxiety disorder due to a general medical condition 
10002859 
Arachnophobia 
10051408 
Astraphobia 
10078372 
Autophobia 
10071070 
Body dysmorphic disorder 
10052793 
Burnout syndrome 
10065369 
Claustrophobia 
10009244 
Compulsions 
10010219 
Compulsive cheek biting 
10076510 
Compulsive handwashing 
10071263 
Compulsive hoarding 
10068007 
Compulsive lip biting 
10066241 
Compulsive shopping 
10067948 
Dermatillomania 
10065701 
Dysmorphophobia 
10049096 
Emetophobia 
10070637 
Fear 
10016275 
Fear of animals 
10016276 
Fear of closed spaces 
10016277 
Fear of crowded places 
10050365 
Fear of death 
10066392 


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PT 
PT Code 
Fear of disease 
10016278 
Fear of eating 
10050366 
Fear of falling 
10048744 
Fear of injection 
10073753 
Fear of open spaces 
10016279 
Fear of pregnancy 
10067035 
Fear of weight gain 
10016280 
Fear-related avoidance of activities 
10080136 
Generalised anxiety disorder 
10018075 
Glossophobia 
10080077 
Haemophobia 
10073458 
Haphephobia 
10067580 
Hydrophobia 
10053317 
Hyperarousal 
10080831 
Immunisation anxiety related reaction 
10075205 
Kinesiophobia 
10078430 
Limited symptom panic attack 
10024511 
Mysophobia 
10078769 
Nail picking 
10066779 
Nervousness 
10029216 
Neurosis 
10029333 
Noctiphobia 
10057946 
Nocturnal fear 
10057948 
Nosophobia 
10063546 
Obsessive need for symmetry 
10077179 
Obsessive rumination 
10056264 
Obsessive thoughts 
10029897 
Obsessive-compulsive disorder 
10029898 
Obsessive-compulsive symptom 
10077894 
Ochlophobia 
10050095 
Osmophobia 
10060765 
Paediatric autoimmune neuropsychiatric disorders associated 
with streptococcal infection 
10072147 
Panic attack 
10033664 
Panic disorder 
10033666 
Panic reaction 
10033670 
Paruresis 
10069024 
Performance fear 
10034432 
Phagophobia 
10050096 
Pharmacophobia 
10069423 


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PT 
PT Code 
Phobia 
10034912 
Phobia of driving 
10056676 
Phobia of exams 
10034913 
Phobic avoidance 
10034918 
Phonophobia 
10054956 
Photaugiaphobia 
10064420 
Post-traumatic stress disorder 
10036316 
Postpartum neurosis 
10036419 
Postpartum stress disorder 
10056394 
Procedural anxiety 
10075204 
Pseudoangina 
10056610 
Selective mutism 
10039917 
Separation anxiety disorder 
10040045 
Sitophobia 
10080170 
Social anxiety disorder 
10041242 
Social fear 
10041247 
Stress 
10042209 
Tension 
10043268 
Terminal agitation 
10077416 
Thanatophobia 
10064723 
Thermophobia 
10075147 
Trichotemnomania 
10072752 
Trichotillomania 
10044629 
 
11. Sleep Disorders 
HLGT Sleep Disorders and Disturbances 
PT 
PT Code 
Behavioural insomnia of childhood 
10072072 
Hyposomnia 
10067530 
Initial insomnia 
10022035 
Insomnia 
10022437 
Middle insomnia 
10027590 
Terminal insomnia 
10068932 
Breathing-related sleep disorder 
10006344 
Dyssomnia 
10061827 
Hypersomnia 
10020765 
Periodic limb movement disorder 
10064600 
Pickwickian syndrome 
10035004 


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PT 
PT Code 
Poor quality sleep 
10062519 
Sleep apnoea syndrome 
10040979 
Somnolence 
10041349 
Somnolence neonatal 
10041350 
Stupor 
10042264 
Upper airway resistance syndrome 
10063968 
Cataplexy 
10007737 
Hypnagogic hallucination 
10020927 
Hypnopompic hallucination 
10020928 
Narcolepsy 
10028713 
Sleep attacks 
10040981 
Sleep paralysis 
10041002 
Abnormal dreams 
10000125 
Abnormal sleep-related event 
10061613 
Confusional arousal 
10067494 
Exploding head syndrome 
10080684 
Loss of dreaming 
10065085 
Nightmare 
10029412 
Parasomnia 
10061910 
Rapid eye movement sleep behaviour disorder 
10077299 
Rapid eye movements sleep abnormal 
10037841 
Sleep inertia 
10067493 
Sleep sex 
10067492 
Sleep talking 
10041009 
Sleep terror 
10041010 
Sleep-related eating disorder 
10067315 
Somnambulism 
10041347 
Hypersomnia related to another mental condition 
10020767 
Hypersomnia-bulimia syndrome 
10053712 
Insomnia related to another mental condition 
10022443 
Sleep disorder 
10040984 
Sleep disorder due to a general medical condition 
10063910 
Sleep disorder due to general medical condition, 
hypersomnia type 
10040985 
Sleep disorder due to general medical condition, 
insomnia type 
10040986 
Sleep disorder due to general medical condition, 
mixed type 
10040987 
Sleep disorder due to general medical condition, 
parasomnia type 
10040988 
Sopor 
10058709 


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PT 
PT Code 
Advanced sleep phase 
10001423 
Circadian rhythm sleep disorder 
10009191 
Delayed sleep phase 
10012209 
Irregular sleep phase 
10022995 
Irregular sleep wake rhythm disorder 
10080301 
Non-24-hour sleep-wake disorder 
10078086 
Shift work disorder 
10078088 
 
HLGT Sleep disturbances (incl subtypes) 
PT 
PT Code 
Abnormal dreams 
10000125 
Abnormal sleep-related event 
10061613 
Confusional arousal 
10067494 
Loss of dreaming 
10065085 
Sleep inertia 
10067493 
Sleep paralysis 
10041002 
Sleep sex 
10067492 
Sleep talking 
10041009 
Sleep terror 
10041010 
Sleep-related eating disorder 
10067315 
Somnambulism 
10041347 
Behavioural insomnia of childhood 
10072072 
Hyposomnia 
10067530 
Initial insomnia 
10022035 
Insomnia 
10022437 
Middle insomnia 
10027590 
Terminal insomnia 
10068932 
Advanced sleep phase 
10001423 
Circadian rhythm sleep disorder 
10009191 
Delayed sleep phase 
10012209 
Irregular sleep phase 
10022995 
Irregular sleep wake rhythm disorder 
10080301 
Non-24-hour sleep-wake disorder 
10078086 
Shift work disorder 
10078088 
Cataplexy 
10007737 
Hypersomnia 
10020765 
Narcolepsy 
10028713 
Central-alveolar hypoventilation 
10007982 
Sleep apnoea syndrome 
10040979 


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PT 
PT Code 
Breathing-related sleep disorder 
10006344 
Dyssomnia 
10061827 
Fatal familial insomnia 
10072077 
Microsleep 
10076954 
Periodic limb movement disorder 
10064600 
Pickwickian syndrome 
10035004 
Poor quality sleep 
10062519 
Rapid eye movement sleep behaviour disorder 
10077299 
Rapid eye movements sleep abnormal 
10037841 
Sleep deficit 
10080881 
Sudden onset of sleep 
10050014 
Upper airway resistance syndrome 
10063968 
 
12. Injection Site Reactions (ISR) from Study Drug Injections 
Study drug ISR data available in the database, i.e. data collected from non-serious ISR AE eCRF 
form and collected serious adverse events with ‘STUDY DRUG INJECTION SITE’ included in the 
AE term. 
13. Seizures and Seizure-like Events 
Convulsions (SMQ) 
PT 
PT Code 
2-Hydroxyglutaric aciduria 
10078971 
Acquired epileptic aphasia 
10052075 
Acute encephalitis with refractory, repetitive partial 
seizures 
10076948 
Alcoholic seizure 
10056347 
Aspartate-glutamate-transporter deficiency 
10079140 
Atonic seizures 
10003628 
Atypical benign partial epilepsy 
10056699 
Automatism epileptic 
10003831 
Autonomic seizure 
10049612 
Baltic myoclonic epilepsy 
10054895 
Benign familial neonatal convulsions 
10067866 
Benign rolandic epilepsy 
10070530 
Biotinidase deficiency 
10071434 
Change in seizure presentation 
10075606 
Clonic convulsion 
10053398 
Convulsion in childhood 
10052391 


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PT 
PT Code 
Convulsion neonatal 
10010911 
Convulsions local 
10010920 
Convulsive threshold lowered 
10010927 
CSWS syndrome 
10078827 
Deja vu 
10012177 
Double cortex syndrome 
10073490 
Dreamy state 
10013634 
Drug withdrawal convulsions 
10013752 
Early infantile epileptic encephalopathy with burst-
suppression 
10071545 
Eclampsia 
10014129 
Epilepsy 
10015037 
Epilepsy surgery 
10079824 
Epilepsy with myoclonic-atonic seizures 
10081179 
Epileptic aura 
10015049 
Epileptic psychosis 
10059232 
Febrile convulsion 
10016284 
Febrile infection-related epilepsy syndrome 
10079438 
Focal dyscognitive seizures 
10079424 
Frontal lobe epilepsy 
10049424 
Generalised non-convulsive epilepsy 
10018090 
Generalised tonic-clonic seizure 
10018100 
Glucose transporter type 1 deficiency syndrome 
10078727 
Gray matter heterotopia 
10080533 
Hemimegalencephaly 
10078100 
Hyperglycaemic seizure 
10071394 
Hypocalcaemic seizure 
10072456 
Hypoglycaemic seizure 
10048803 
Hyponatraemic seizure 
10073183 
Idiopathic generalised epilepsy 
10071081 
Infantile spasms 
10021750 
Juvenile myoclonic epilepsy 
10071082 
Lafora's myoclonic epilepsy 
10054030 
Lennox-Gastaut syndrome 
10048816 
Migraine-triggered seizure 
10076676 
Molybdenum cofactor deficiency 
10069687 
Multiple subpial transection 
10079825 
Myoclonic epilepsy 
10054859 
Myoclonic epilepsy and ragged-red fibres 
10069825 
Partial seizures 
10061334 


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PT 
PT Code 
Partial seizures with secondary generalisation 
10056209 
Petit mal epilepsy 
10034759 
Polymicrogyria 
10073489 
Post stroke epilepsy 
10076982 
Post stroke seizure 
10076981 
Postictal headache 
10052470 
Postictal paralysis 
10052469 
Postictal psychosis 
10070669 
Postictal state 
10048727 
Post-traumatic epilepsy 
10036312 
Schizencephaly 
10073487 
Seizure 
10039906 
Seizure anoxic 
10039907 
Seizure cluster 
10071350 
Seizure like phenomena 
10071048 
Severe myoclonic epilepsy of infancy 
10073677 
Simple partial seizures 
10040703 
Status epilepticus 
10041962 
Sudden unexplained death in epilepsy 
10063894 
Temporal lobe epilepsy 
10043209 
Tonic clonic movements 
10051171 
Tonic convulsion 
10043994 
Tonic posturing 
10075125 
Topectomy 
10073488 
Transient epileptic amnesia 
10081728 
Tuberous sclerosis complex 
10080584 
Uncinate fits 
10045476 
 
PTs (Selective) 
PT 
PT Code 
Confusional state 
10010305 
Loss of consciousness 
10024855 
Syncope 
10042772 
Sopor 
10058709 
Stupor 
10042264 
Altered state of consciousness 
10050093 
Depressed level of consciousness 
10012373 
Consciousness fluctuating 
10050093 


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14. Weight Gain 
HLT General nutritional disorders NEC (Selective) 
PT 
PT Code 
Abdominal fat apron 
10077983 
Overweight 
10033307 
Abnormal weight gain 
10000188 
Central obesity 
10065941 
Obesity 
10029883 
 
HLT Physical examination procedures and organ system status (Selective) 
PT 
PT Code 
Weight abnormal 
10056814 
Weight increased 
10047899 
Waist circumference increased 
10064863 
Body mass index abnormal 
10074506 
Body mass index increased 
10005897 
 
General signs and symptoms NEC (Selective) 
PT 
PT Code 
Fat tissue increased 
10016251 
 
15. Rhabdomyolysis 
Rhabdomyolysis/myopathy (SMQ) 
PT 
PT Code 
Muscle necrosis 
10028320 
Myoglobin blood increased 
10028625 
Myoglobin blood present 
10059888 
Myoglobin urine present 
10028631 
Myoglobinaemia 
10058735 
Myoglobinuria 
10028629 
Myopathy 
10028641 
Myopathy toxic 
10028648 
Necrotising myositis 
10074769 


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PT 
PT Code 
Rhabdomyolysis 
10039020 
Thyrotoxic myopathy 
10081524 
 
PTs (Selective) 
PT 
PT Code 
Myalgia 
10028411 
Myositis 
10028653 
 
16. Pancreatitis 
Acute pancreatitis (SMQ) 
PT 
PT Code 
Cullen's sign 
10059029 
Grey Turner's sign 
10075426 
Haemorrhagic necrotic pancreatitis 
10076058 
Hereditary pancreatitis 
10056976 
Ischaemic pancreatitis 
10066127 
Oedematous pancreatitis 
10052400 
Pancreatic abscess 
10048984 
Pancreatic haemorrhage 
10033625 
Pancreatic necrosis 
10058096 
Pancreatic phlegmon 
10056975 
Pancreatic pseudoaneurysm 
10081762 
Pancreatic pseudocyst 
10033635 
Pancreatic pseudocyst drainage 
10033636 
Pancreatitis 
10033645 
Pancreatitis acute 
10033647 
Pancreatitis haemorrhagic 
10033650 
Pancreatitis necrotising 
10033654 
Pancreatitis relapsing 
10033657 
Pancreatorenal syndrome 
10056277 
17. Impact on Creatinine 
Acute renal failure (SMQ) 
PT 
PT Code 
Acute kidney injury 
10069339 
Acute phosphate nephropathy 
10069688 


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PT 
PT Code 
Anuria 
10002847 
Azotaemia 
10003885 
Continuous haemodiafiltration 
10066338 
Dialysis 
10061105 
Foetal renal impairment 
10078987 
Haemodialysis 
10018875 
Haemofiltration 
10053090 
Hyponatriuria 
10077515 
Neonatal anuria 
10049778 
Nephropathy toxic 
10029155 
Oliguria 
10030302 
Peritoneal dialysis 
10034660 
Prerenal failure 
10072370 
Renal failure 
10038435 
Renal failure neonatal 
10038447 
Renal impairment 
10062237 
Renal impairment neonatal 
10049776 
 
Renal Failure and Impairment HLT 
PT 
PT Code 
Acute Kidney injury 
10069339 
Anuria 
10002847 
Atypical haemolytic uraemic syndrome 
10079840 
Cardiorenal syndrome 
10068230 
Chronic kidney disease 
10064848 
Crush syndrome 
10050702 
Diabetic end stage renal disease 
10012660 
End stage renal disease 
10077512 
Foetal renal impairment 
10078987 
Haemolytic uraemic syndrome 
10018932 
Hepatorenal failure 
10019845 
Hepatorenal syndrome 
10019846 
Nail-patella syndrome 
10063431 
Neonatal anuria 
10049778 
Oliguria 
10030302 
Pancreatorenal syndrome 
10056277 
Postoperative renal failure 
10056675 
Postrenal failure 
10059345 
Prerenal failure 
10072370 


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PT 
PT Code 
Propofol infusion syndrome 
10063181 
Renal failure 
10038435 
Renal failure neonatal 
10038447 
Renal impairment 
10062237 
Renal impairment neonatal 
10049776 
Renal injury 
10061481 
Scleroderma renal crisis 
10062553 
Traumatic anuria 
10044501 
18. Safety in Pregnancy 
Use AE terms co-reported in pregnancy exposures to CAB and/or RPV. 
19. Hyperglycaemia 
Medical concept of Hyperglycaemia/new onset diabetes mellitus - SMQs (1) 
'Hyperglycaemia/new onset diabetes mellitus (SMQ) Narrow SMQ code 20000041 
PT 
PT Code 
Blood 1,5-anhydroglucitol decreased 
10065367 
Blood glucose increased 
10005557 
Diabetes complicating pregnancy 
10012596 
Diabetes mellitus 
10012601 
Diabetes mellitus inadequate control 
10012607 
Diabetes with hyperosmolarity 
10012631 
Diabetic arteritis 
10077357 
Diabetic coma 
10012650 
Diabetic coronary microangiopathy 
10080788 
Diabetic hepatopathy 
10071265 
Diabetic hyperglycaemic coma 
10012668 
Diabetic hyperosmolar coma 
10012669 
Diabetic ketoacidosis 
10012671 
Diabetic ketoacidotic hyperglycaemic coma 
10012672 
Diabetic ketosis 
10012673 
Diabetic metabolic decompensation 
10074309 
Diabetic wound 
10081558 
Euglycaemic diabetic ketoacidosis 
10080061 
Fructosamine increased 
10017395 
Fulminant type 1 diabetes mellitus 
10072628 
Gestational diabetes 
10018209 
Glucose tolerance impaired 
10018429 
Glucose tolerance impaired in pregnancy 
10018430 


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PT 
PT Code 
Glucose urine present 
10018478 
Glycated albumin increased 
10082836 
Glycosuria 
10018473 
Glycosuria during pregnancy 
10018475 
Glycosylated haemoglobin abnormal 
10018481 
Glycosylated haemoglobin increased 
10018484 
Hyperglycaemia 
10020635 
Hyperglycaemic hyperosmolar nonketotic 
syndrome 
10063554 
Hyperglycaemic seizure 
10071394 
Hyperglycaemic unconsciousness 
10071286 
Impaired fasting glucose 
10056997 
Insulin resistance 
10022489 
Insulin resistant diabetes 
10022491 
Insulin-requiring type 2 diabetes mellitus 
10053247 
Ketoacidosis 
10023379 
Ketonuria 
10023388 
Ketosis 
10023391 
Ketosis-prone diabetes mellitus 
10023392 
Latent autoimmune diabetes in adults 
10066389 
Monogenic diabetes 
10075980 
Neonatal diabetes mellitus 
10028933 
New onset diabetes after transplantation 
10082630 
Pancreatogenous diabetes 
10033660 
Steroid diabetes 
10081755 
Type 1 diabetes mellitus 
10067584 
Type 2 diabetes mellitus 
10067585 
Type 3 diabetes mellitus 
10072659 
Urine ketone body present 
10057597 
Hepatogenous diabetes 
10085610 
Maternally inherited diabetes and deafness 
10086189 
Neonatal hyperglycaemia 
10086425 
Acquired generalised lipodystrophy 
10087376 
Glycated serum protein increased 
10087214 
Hyperglycaemic crisis 
10087319 
 


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15.12. 
Appendix 12: Identification of COVID-19 Adverse Events 
COVID-19 adverse events are identified based on MedDRA coded values and/or AE 
referenced in the COVID-19 Coronavirus Infection assessment. The Lowest Level Terms 
(LLTs) and codes, Preferred Terms (PTs), High Level Terms (HLTs), High Level Group 
Terms (HLGTs), and System Organ Classes (SOCs), below are from MedDRA 23.0. In 
case there is a change to the version of MedDRA at time of reporting, the coded values 
based on the MedDRA version at the time of reporting will be used. The additional 
events may also be added based on the blinded review of AE data collected on study prior 
to the database freeze. 
SOC: Infections and infestations 
LLT code LLT 
PT 
HLT 
HLGT 
10084459 Asymptomatic COVID-19 
Asymptomatic 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084467 
Asymptomatic SARS-
CoV-2 infection 
Asymptomatic 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10053983 Corona virus infection 
Coronavirus 
infection 
Coronavirus 
infections 
Viral infectious 
disorders 
10051905 Coronavirus infection 
Coronavirus 
infection 
Coronavirus 
infections 
Viral infectious 
disorders 
10084382 
Coronavirus disease 
2019 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084268 COVID-19 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084401 
COVID-19 respiratory 
infection 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084270 
SARS-CoV-2 acute 
respiratory disease 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084272 SARS-CoV-2 infection 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084381 Coronavirus pneumonia 
COVID-19 
pneumonia 
Coronavirus 
infections 
Viral infectious 
disorders 
10084380 COVID-19 pneumonia 
COVID-19 
pneumonia 
Coronavirus 
infections 
Viral infectious 
disorders 
10084383 
Novel COVID-19-
infected pneumonia 
COVID-19 
pneumonia 
Coronavirus 
infections 
Viral infectious 
disorders 
10084451 Suspected COVID-19 
Suspected 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084452 
Suspected SARS-CoV-2 
infection 
Suspected 
COVID-19 
Coronavirus 
infections 
Viral infectious 
disorders 
10084461 SARS-CoV-2 carrier 
SARS-CoV-2 
carrier 
Infectious 
disorders carrier 
Ancillary infectious 
topics 
 


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15.13. 
Appendix 13: IDMC 
Independent review will be provided by an IDMC to ensure external objective medical 
and/or statistical review of efficacy and safety in order to protect the ethical interests and 
well-being of participants and to protect the scientific validity of this study. An ad-hoc 
review of data by the IDMC will be triggered whenever the number of confirmed 
virologic failures in the Q8W arm exceeds thresholds pre-specified in the IDMC charter. 
Further, analyses including futility checking will be performed for the IDMC to evaluate 
the efficacy and safety when approximately 50% of participants have completed their 
visit at Week 24. 
The list of required outputs is provided in the IDMC Charter, Section 12.3, Appendix C. 
Data handing methods and derived data definitions will be the same as detailed in this 
RAP, unless otherwise stated. 
15.13.1. 
Adhoc CVF IDMC Analyses 
The number of participants meeting Confirmed Virologic Failure (CVF) Criterion per the 
protocol will be monitored and may result in ad-hoc IDMC data reviews. 
The Statistics Data Analysis Centre (SDAC) will be notified by the study virologist in 
writing every time a CVF occurs in the study. The SDAC will track the number of 
participants on Q8W arm past Week 4. The rate of CVF will be monitored against the 
thresholds specified in IDMC Charter Table 1 (See IDMC Charter, Section 3.5.2).  
15.13.2. 
Week 24 IDMC Analyses  
Analyses including futility checking will be performed when approximately 50% of 
participants have completed their Week 24 visit. 
A futility rule will assess the evidence that the CAB LA + RPV LA Q8W arm is non-
inferior to the Q4W control arm. This rule will use the interim data (~ 50% participants 
completing Week 24) to calculate the Bayesian predictive probabilities that the CAB LA 
+ RPV LA Q8W arm is non-inferior to the Q4W arm at Week 24. A 4% non-inferiority 
margin will be used. The details of statistical methods can be found in IDMC Charter, 
Section 12.6.1. The list of outputs is also provided in Section 15.15.4. 


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15.14. 
Appendix 14: Abbreviations & Trademarks 
15.14.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
BMI 
Body Mass Index 
CAB 
Cabotegravir 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel 
COVID 
Coronavirus Disease 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
eC-SSRS 
Electronic Columbia Suicide Severity Rating Scale  
CVb 
Coefficient of Variation (Between) 
CVD 
Cardiovascular Disease  
CVF 
Confirmed Virologic Failure 
DAIDS 
Division of AIDS  
DBF 
Database Freeze 
DBL 
Database Lock 
DBR 
Database Release 
DOB 
Date of Birth 
DP 
Decimal Place 
DTG 
Dolutegravir 
eCRF 
Electronic Case Record Form 
eGFR 
Estimated Glomerular Filtration Rate 
EMA 
European Medicines Agency 
ERDF 
Efficacy Related Discontinuation Failure 
FDA 
Food and Drug Administration  
FSFV 
First Subject First Visit 
GSK 
GlaxoSmithKline 
GUI 
Guidance 
HAT-QoL 
Health-related Quality of Life  
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus  
HIVTSQc 
Change Version of HIV Treatment Satisfaction Questionnaire 
HIVTSQs 
Status Version of HIV Treatment Satisfaction Questionnaire  
HLGT 
High Level Group Term 
HLT 
High Level Term 
HSR 
Hypersensitivity Reaction 
ICH 
International Conference on Harmonisation 


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IDMC 
Independent Data Monitoring Committee 
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
INI 
Integrase Inhibitors 
IP 
Investigational Product 
ITT 
Intent-To-Treat 
ITT-E 
Intent-To-Treat Exposed 
LA 
Long Acting 
LOCF 
Last Observation Carries Forward 
MMRM 
Mixed Model Repeated Measures 
NA 
Not Applicable 
NCEP 
National Cholesterol Education Program  
NNRTI 
Non-Nucleoside Reverse Transcriptase Inhibitors  
NQ 
Non Quantifiable 
NRTI 
Nucleoside Reverse Transcriptase Inhibitors  
OC 
Observed Case 
PBMC 
Peripheral Blood Mononuclear Cell 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamic 
PDMP 
Protocol Deviation Management Plan 
PI 
Protease Inhibitors 
PIN 
Perception of Injection 
PK 
Pharmacokinetic 
PP 
Per Protocol 
PT 
Preferred Term 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAM 
Resistance Associated Mutation 
RAMOS 
Randomization & Medication Ordering System 
RAP 
Reporting & Analysis Plan 
RPV 
Rilpivirine 
SAE 
Serious Adverse Event 
SAC 
Statistical Analysis Complete 
SD 
Standard Deviation 
SDAC 
Statistics Data Analysis Centre  
SDTM 
Study Data Tabulation Model 
SMQ 
Standardised MedDRA Query 
SOC 
System Organ Class 
SOP 
Standard Operation Procedure 
TFL 
Tables, Figures & Listings 
TRDF 
Treatment Related Discontinuation Failure  
 


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15.14.2. 
Trademarks 
 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
Tivicay 
 
Edurant 
Triumeq 
 
NONMEM 
 
 
SAS 
 
 
WinNonlin 
 
 


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15.15. 
Appendix 15: List of Data Displays 
15.15.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.n 
1.1 to 1.n 
Efficacy 
2.1 to 2.n 
2.1 to 2.n 
Safety 
3.1 to 3.n 
3.1 to 3.n 
Pharmacokinetic 
4.1 to 4.n 
4.1 to 4.n 
Pharmacokinetic / Pharmacodynamic 
5.1 to 5.n 
5.1 to 5.n 
Health Outcomes 
6.1 to 6.n 
6.1 to 6.n 
Virology 
7.1 to 7.n 
7.1 to 7.n 
Section 
Listings 
ICH Listings 
1 to x 
Other Listings 
y to z 
 
15.15.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays will be provided in a separate document. 
The example mock-up displays from other reporting efforts will be named in the format: 
Study Number/HARP Reporting Effort/Output Type (T/ F/L)/Display Number, where T 
stands for Table, F stands for Figure and L stands for Listing. For example, the Table 1.1 
from primary_02 reporting effort for Study 201585 will be named by 
201585/primary_02/T1.1. 
Other example mock-up displays will be named using the following format. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
Pharmacokinetic / Pharmacodynamic 
PKPD_Fn 
PKPD_Tn 
PK/PD_Ln 
Health Outcomes 
HO_Fn 
HO_Tn 
HO_Ln 
Virology 
VIR_Fn 
VIR_Tn 
VIR_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column. 
 


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15.15.3. 
Deliverables 
Delivery [1] 
Description 
IW24 
IDMC analyses when approximately 50% participants have completed 
their Week 24 visits 
W24 
Week 24 when 100% participants have completed their Week 24 visits 
HL 
Headline at Week 48 or Week 96 
W48 
Week 48 
W96 
Week 96  
W152 
Week 152 
Sub-study 
Sub-study 
EOS 
End of study 
NOTES:  
1. 
Indicates order in which displays will be generated for the reporting effort 
 
15.15.4. 
List of Data Displays for Week 24 IDMC and Week 24 Planned 
Analyses 
For Week 24 planned analyses, the Week 24 Futility population will be replaced by the 
Intent-to-Treat Exposed population. In addition, unless otherwise specified, present the 
listings by prior exposure to CAB+RPV (i.e. rederived randomization strata, 0, 1-24, >24 
weeks, refer to Section 15.6.2 for calculation details) except for study population listings. 


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15.15.4.1. Study Population Tables 
Study Population Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Subject Disposition 
1.1 
NA 
Week 24 
Futility 
ES1 
Summary of Subject Accountability: 
Maintenance Phase Conclusion Record - Week 
24 Futility 
ICH E3, GSKCTR, FDAAA, 
EudraCT, see also in 
201585/primary_02/T1.7. 
IW24 
1.2 
1.1 
Intent-to-
Treat 
Exposed 
ES1 
Summary of Subject Accountability: 
Maintenance Phase Conclusion Record - ITT-E 
ICH E3, GSKCTR, FDAAA, 
EudraCT, see also in 
201585/primary_02/T1.7. 
IW24, W24 
Demographic and Baseline Characteristics 
1.3 
NA 
Week 24 
Futility 
201585/primary_02/T1.16 Summary of Demographic Characteristics - 
Week 24 Futility  
ICH E3, FDAAA, EudraCT 
IW24 
1.4 
1.2 
Intent-to-
Treat 
Exposed 
201585/primary_02/T1.16 Summary of Demographic Characteristics - ITT-
E 
ICH E3, FDAAA, EudraCT 
IW24, W24 
1.5 
NA 
Week 24 
Futility 
201584/idmc_03/T1.3 
Summary of Prior Exposure to CAB+RPV - 
Week 24 Futility 
Adjust footnote and row labels as 
appropriate. 
IW24 
1.6 
1.3 
Intent-to-
Treat 
Exposed 
201584/idmc_03/T1.3 
Summary of Prior Exposure to CAB+RPV - ITT-
E 
Adjust footnote and row labels as 
appropriate. 
IW24, W24 
1.7 
1.4 
Intent-to-
Treat 
Exposed 
201584/idmc_03/T1.7 
Summary of Prior Exposure to CAB+RPV by 
Country 
Adjust footnote and row labels as 
appropriate. 
IW24, W24 
1.8 
1.5 
Intent-to-
Treat 
Exposed 
201585/primary_02/T1.19 Summary of Hepatitis Status at Entry 
Add footnote as appropriate for 
subjects classified as Hepatitis B 
positive in analysis. 
IW24, W24 


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15.15.4.2. Efficacy Tables 
Efficacy Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.1 
2.1 
Week 24 
Futility 
201585/primary_02/T2.1 
Summary of Analysis for 
Proportion of Subjects with 
Plasma HIV-1 RNA ≥50 c/mL at 
Week 24 and Posterior 
Predictive Probability of Success 
for the Q8W Arm - Snapshot 
Analysis 
For Week 24 IDMC, add a column on right with 
'Posterior Predictive Probability of Success" and 
adjust the footnotes as appropriate, also add a 
footnote “Target threshold for posterior predictive 
probability is 15%.”. For planned Week 24, remove 
‘and Posterior Predictive Probability of Success for 
the Q8W Arm’ from the title, adjust the footnote as 
appropriate. For proportions, keep one decimal 
place. The adjustment is based on rederived 
randomization strata. 
IW24, W24 
2.2 
2.2 
Week 24 
Futility 
201585/primary_02/T2.4 
Summary of Study Outcomes 
(50 c/mL Threshold) at Week 24 
(Maintenance Phase) - Snapshot 
Analysis 
For proportions, keep one decimal place. 
IW24, W24 
2.3 
2.3 
Week 24 
Futility 
201585/primary_02/T2.6 
Summary of Analysis for 
Proportion of Subjects with 
Plasma HIV-1 RNA ≥50 c/mL at 
Week 24 by Randomization 
Strata (Maintenance Phase) - 
Snapshot Analysis 
Note that only by randomization strata summary is 
provided. Change the footnote to “[1] Difference: 
Proportion on Q8W - Proportion on Q4W. 95% CIs 
were calculated using an unconditional exact 
method with two inverted one-sided tests based on 
the score statistic.” Add Footnote "Note: 
Randomization strata are rederived using the prior 
exposure to CAB+RPV in Study 201585, collected 
from eCRF." For proportions, keep one decimal 
place.  
IW24, W24 


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Efficacy Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.4 
2.4 
Week 24 
Futility 
201585/primary_02/T2.21 
Cumulative Proportion of 
Subjects Meeting Confirmed 
Virologic Failure by Visit (Up to 
Week 24) 
For proportions, keep one decimal place. Non-
snapshot visit window will be used. 
IW24, W24 
2.5 
2.5 
Week 24 
Futility 
201585/primary_02/T2.21 
Cumulative Proportion of 
Subjects Meeting Confirmed 
Virologic Failure by Visit and 
Randomization Strata (Up to 
Week 24) 
Add column for ‘Analysis Strata’, add footnote for 
randomization strata similar to T2.3. For 
proportions, keep one decimal place. Non-snapshot 
visit window will be used. 
IW24, W24 
2.6 
2.6 
Intent-to-
Treat 
Exposed 
201585/primary_02/T2.21 
Cumulative Proportion of 
Subjects Meeting Confirmed 
Virologic Failure during the 
Maintenance Phase 
Note that this is overall summary, not by visit. 
Replace the column ‘Timepoint’ with ‘CVF 
Category’. For proportions, keep one decimal 
place. 
IW24, W24 
2.7 
2.7 
Intent-to-
Treat 
Exposed 
201584/idmc_03/T2.7 
Cumulative Proportion of 
Subjects Meeting Confirmed 
Virologic Failure by 
Randomization Strata during the 
Maintenance Phase 
Adjust footnote and row labels as appropriate. For 
proportions, keep one decimal place. Use rederived 
Randomization strata. 
IW24, W24 
2.8 
2.8 
Week 24 
Futility 
EFF_T1 
Summary of Kaplan-Meier 
Estimates of Proportion of 
Subjects without CVF at Week 
24 - Treatment Related 
Discontinuation = Failure 
The non-snapshot visit window for Week 24 will be 
used. 
IW24, W24 


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Efficacy Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.9 
2.9 
Week 24 
Futility 
EFF_T2 
Summary of Kaplan-Meier 
Estimates of Proportion of 
Subjects without CVF at Week 
24 - Efficacy Related 
Discontinuation=Failure 
The non-snapshot visit window for Week 24 will be 
used. 
IW24, W24 
2.10 
2.10 
Intent-to-
Treat 
Exposed 
201584/idmc_03/T2.10 
Proportion of Subjects with 
Plasma HIV-1 RNA < 50 c/mL by 
Visit - Observed Case Analysis 
Adjust the footnote as appropriate. The non-
snapshot visit window will be used. For W24, add 
‘(Up to Week 24)’ to the title, only display visits up 
to Week 24. 
IW24, W24 
2.11 
2.11 
Intent-to-
Treat 
Exposed 
201584/idmc_03/T2.11 
Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL by 
Visit and Randomization Strata - 
Observed Case Analysis 
Adjust footnote and row labels as appropriate. The 
non-snapshot visit window and rederived 
randomization strata will be used. For W24, add 
‘(Up to Week 24)’ to the title, only display visits up 
to Week 24. 
IW24, W24 


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15.15.4.3. Efficacy Figures 
Efficacy Figures 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
2.1 
2.1 
Week 24 
Futility 
201584/idmc_03/F2.1 
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles 
by Visit for Subjects Who are in the Category of 
‘Viral Load ≥50 c/mL’ at Week 24 per Snapshot 
Algorithm 
Adjust the x-axis label and 
footnote as appropriate. The x-
values are based on study day of 
the assessment. 
IW24, W24 
2.2 
2.2 
Intent-to-Treat 
Exposed 
201584/idmc_03/F2.2 
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles 
by Visit for Subjects with a Viral Load ≥50 c/mL 
during the Maintenance Phase 
Adjust the x-axis label and 
footnote as appropriate. The x-
values are based on study day of 
the assessment. 
IW24, W24 


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15.15.4.4. Safety Tables 
Safety Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverabl
e 
Adverse Events 
3.1 
3.1 
Safety 
AE3 
Summary of All Adverse Events by Overall Frequency 
- Maintenance Phase 
See also in 
201585/primary_02/T3.20. 
IW24, W24 
3.2 
3.2 
Safety 
AE1 
Summary of All Drug-Related Adverse Events by 
System Organ Class - Maintenance Phase 
See also in 
201585/primary_02/T3.16. 
IW24, W24 
3.3 
3.3 
Safety 
AE3 
Summary of Grade 3-5 Adverse Events by Overall 
Frequency - Maintenance Phase 
See also in 
201585/primary_02/T3.20. 
IW24, W24 
Serious and Other Significant Adverse Events 
3.4 
3.4 
Safety 
AE1 
Summary of Serious Adverse Events by System 
Organ Class - Maintenance Phase 
See also in 
201585/primary_02/T3.21. 
IW24, W24 
3.5 
3.5 
Safety 
AE1 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ Class - 
Maintenance Phase 
See also in 
201585/primary_02/T3.31. 
IW24, W24 
Injection Site Reaction Adverse Events 
3.6 
3.6 
Safety 
201585/primary_02/T3.
40 
Summary of Injection Site Reaction Adverse Events 
(Event-Level Summary) - Maintenance Phase 
For W24, add ‘Study Drug’ 
before ‘Injection’ in the title and 
only summarize ISR from study 
drug injections. 
IW24, W24 


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Safety Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverabl
e 
3.7 
3.7 
Safety 
201585/primary_02/T3.
43 
Summary of Subject-Level Characteristics of Injection 
Site Reaction Adverse Events - Overall and Common 
(Maintenance Phase) 
Common ISR adverse events 
includes injection site pain, 
injection site induration, 
injection site nodules and any 
other ISR with ≥5% subjects in 
either treatment arm. For W24, 
add ‘Study Drug’ before 
‘Injection’ in the title and only 
summarize ISR from study drug 
injections. 
IW24, W24 
Laboratory: Chemistry and Hematology 
3.8 
3.8 
Safety 
201584/idmc_03/T3.8 
Summary of Maximum Post-Baseline Emergent 
Clinical Chemistry Toxicities Parameters of Special 
Interest - Maintenance Phase 
Replace “Day 1” with “Study 
Day 1” in the first footnote. Use 
the same parameter list as the 
one in 201584/idmc_03/T3.8. 
IW24, W24 
3.9 
3.9 
Safety 
201584/idmc_03/T3.9 
Summary of Maximum Post-Baseline Emergent 
Hematology Toxicities Parameters of Special Interest 
- Maintenance Phase 
Replace “Day 1” with “Study 
Day 1” in the first footnote. 
Adjust the second footnote to 
be: "Note:  Parameters of 
Special Interest include 
Hemogoblin, Leukocytes, 
Neutrophils, and Platelets." In 
output, change the parameter 
label 'White Blood Cell count' to 
'Leukocytes'. 
IW24, W24 


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15.15.4.5. Safety Figures 
Safety Figures 
No. 
in 
IW24 
No. 
in 
W24 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
Laboratory: Hepatobiliary (Liver) 
3.1 
3.1 
Safety 
201584/idmc_03/F3.2 Scatter Plot of Maximum Maintenance Phase vs. 
Baseline for ALT 
Adjust the legend as needed. 
Change the first footnote to “Axes 
are on a log10 scale”. Remove 
the second footnote. Adjust the 
treatment label from empty 
triangle to solid triangle. 
IW24, W24 
3.2 
3.2 
Safety 
201584/idmc_03/F3.1 Matrix Plot of Maximum Liver Chemistries - 
Maintenance Phase 
Replace “>5.1” with “>5.0” in the 
second footnote. Make treatment 
labels in the plot consistent 
across figures. 
IW24, W24 


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15.15.4.6. Pharmacokinetic Tables 
Pharmacokinetic Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.1 
4.1 
Pharmacokinetic 201585/primary_02/T4.1 
Summary of Plasma CAB PK Concentrations 
(ug/mL) - Time Data by Treatment and Visit - 
Including Log-Transformed Statistics 
Remove the first footnote 
“Note:…”. 
IW24, W24 
4.2 
4.2 
Pharmacokinetic 201585/primary_02/T4.2 
Summary of Plasma RPV PK Concentrations 
(ng/mL) - Time Data by Treatment and Visit - 
Including Log-Transformed Statistics 
Remove the first footnote 
“Note:…”.. 
IW24, W24 
4.3 
NA 
Pharmacokinetic 
201584/idmc_03/T4.3 
Proportion of Subjects with Evaluable PK 
Concentration below Expected Values 
 
IW24 


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15.15.4.7. Pharmacokinetic Figures 
Pharmacokinetic Figures 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.1 
NA 
Pharmacokinetic 
201584/idmc_03/
F4.1 
Scatter Plot of Evaluable PK Concentrations in 
Relation to Occurrence of CVF up to Week 16 for 
Subjects on Q8W Arm by Visit and Randomization 
Strata 
Note that this plot is by visit and 
rederived randomization strata. Add 
footnote for strata as appropriate. 
IW24 


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15.15.4.8. Virology Tables 
Virology Tables 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverabl
e 
7.1 
7.1 
Confirmed 
Virologic Failure 
201585/primary
_02/T8.1 
Summary of the Prevalence of Known INI Resistance 
Mutations at Time of CVF (Maintenance Phase) - 
Plasma Sample 
 
IW24, W24 
7.2 
7.2 
Confirmed 
Virologic Failure 
201585/primary
_02/T8.2 
Summary of the Prevalence of Major Resistance 
Mutations of NNRTI, NRTI, and PI Class at Time of 
CVF (Maintenance Phase) - Plasma Sample 
 
IW24, W24 
7.3 
7.3 
Confirmed 
Virologic Failure 
201585/primary
_02/T8.3 
Summary of Phenotypic Susceptibility at Time of CVF 
(Maintenance Phase) - Plasma Sample 
 
IW24, W24 
7.4 
7.4 
Confirmed 
Virologic Failure 
201585/primary
_02/T8.7 
Summary of Fold Change to CAB and RPV at Time of 
CVF (Maintenance Phase) - Plasma Sample 
 
IW24, W24 
7.5 
7.5 
Confirmed 
Virologic Failure 
201585/primary
_02/T8.8 
Summary of Viral Load, Genotypic and Phenotypic Data 
for Subjects Who Met Confirmed Virologic Failure 
Criteria during the Maintenance Phase 
Remove the Columns ‘ARTs’ and 
‘FC for ARTs’. Remove the 
footnotes [1] and [2]. Adjust the 
footnote as appropriate. 
IW24, W24 


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15.15.4.9. ICH Listings 
Note: Both unique subject ID and latest subject ID for a subject will be included in the listings, unless otherwise specified. 
ICH Listings 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
1 
1 
Randomized 
201584/idmc_03/L1.
3 
Listing of Randomized and Actual Strata 
and Treatment Assignment 
Randomized and Actual Treatments 
will include oral lead-in information 
(e.g. Oral followed by Q4W). For W24 
analyses, remove column for Futility 
Population. 
IW24, W24 
Efficacy 
2 
2 
Week 24 Futility 
201585/primary_02/
L11 
Listing of Study Outcomes (50 c/mL 
Threshold) at Week 24 - Snapshot Analysis 
 
IW24, W24 
Adverse Events 
3 
3 
Safety 
201585/primary_02/
L17 
Listing of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product - Maintenance 
Phase 
Remove “Time Since Last Dose” from 
the column header. 
IW24, W24 
4 
4 
Safety 
201585/primary_02/
L17 
Listing of All Serious Adverse Events - 
Maintenance Phase 
Remove “Time Since Last Dose” from 
the column header. 
IW24, W24 
Laboratory 
5 
NA 
Safety 
201584/idmc_03/L3.
5 
Listing of All Parameters of Special Interest 
Laboratory Data for Subjects with Grade 3 
or 4 Maintenance Phase Emergent 
Toxicities for Parameters of Special Interest 
Replace ‘Day 1’ with ‘Study Day 1’ in 
the second footnote. 
IW24 


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ICH Listings 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
PK 
6 
5 
Pharmacokinetic 
201584/idmc_03/L4.
1 
Listing of Plasma CAB PK Concentration-
Time Data 
Change the first footnote to “Relative 
Time is calculated relative to the date 
and time of last previous dose. If the 
time of the last previous dose (e.g. 
oral lead-in/oral bridging) is missing, 
then the relative time will be set to 
missing and the sample will 
not be considered ‘evaluable’.” 
Remove the second footnote. 
Change column header ‘Visit’ to 
‘Analysis Visit/Nominal Visit’ to 
include both visits. 
IW24, W24 
7 
6 
Pharmacokinetic 
201584/idmc_03/L4.
2 
Listing of Plasma RPV PK Concentration-
Time Data 
Change the first footnote to “Relative 
Time is calculated relative to the date 
and time of last previous dose. If the 
time of the last previous dose (e.g. 
oral lead-in/oral bridging) is missing, 
then the relative time will be set to 
missing and the sample will 
not be considered ‘evaluable’.” 
Remove the second footnote. 
Change column header ‘Visit’ to 
‘Analysis Visit/Nominal Visit’ to 
include both visits. 
IW24, W24 


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15.15.4.10. Non-ICH Listings 
Note: Both unique subject ID and latest subject ID for a subject will be included in the listings, unless otherwise specified. 
Non-ICH Listings 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
8 
7 
Intent-to-Treat 
Exposed 
ES2 
Listing of Reasons for Maintenance Phase 
Withdrawal 
See also in 
201585/primary_02/L30. 
IW24, W24 
9 
8 
Screened 
Shell POP_L2 
Listing of Subjects Who Were Rescreened 
 
IW24, W24 
10 
9 
Intent-to-Treat 
Exposed 
201584/idmc_0
3/L1.1 
Listing of Prior Antiretroviral Therapy 
Remove the column ‘Treatment 
Phase/Treatment State’. Add a 
column for Route. 
IW24, W24 
11 
10 
Intent-to-Treat 
Exposed 
201584/idmc_0
3/L1.2 
Listing of Concomitant Antiretroviral Therapy 
Change column ‘Treatment 
Phase/Actual Treatment State’ to 
‘Phase during Which Concomitant’, 
remove ‘Induction Study Day’ from 
column headers, and remove 
‘Maintenance’ from ‘Maintenance 
Study Day’ in column headers. 
IW24, W24 
Efficacy 
12 
11 
Confirmed Virologic 
Failure 
201585/primary
_02/L40 
Listing of All Plasma HIV-1 RNA Viral Load 
Data for Subjects with Confirmed Virologic 
Failure during the Maintenance Phase 
Non-snapshot visit window will be 
used for deriving the visits in 
Column ‘Actual Relative Time’. 
Replace ‘Period’ in column header 
with ‘Phase’. 
IW24, W24 


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Non-ICH Listings 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
13 
12 
Week 24 Futility 
201585/primary
_02/L40 
Listing of All Plasma HIV-1 RNA Viral Load 
Data for Subjects Who are in the Category of 
‘Viral load ≥50 c/mL’ at Week 24 per Snapshot 
Algorithm 
Non-snapshot visit window will be 
used for deriving the visits in 
Column ‘Actual Relative Time’. 
Replace ‘Period’ in column header 
with ‘Phase’. 
IW24, W24 
Adverse Events 
14 
13 
Safety 
201585/primary
_02/L17 
Listing of All Drug-Related Adverse Events - 
Maintenance Phase 
Remove “Time Since Last Dose” 
from the column header. 
IW24, W24 
15 
14 
Safety 
201585/primary
_02/L17 
Listing of All Grade 3-5 Adverse Events - 
Maintenance Phase 
Remove “Time Since Last Dose” 
from the column header. 
IW24, W24 
16 
15 
Safety 
201585/primary
_02/L17 
Listing of All Adverse Events - Long-term 
Follow-up Phase 
Remove “Time Since Last Dose” 
from the column header. 
IW24, W24 
PK 
17 
NA 
Pharmacokinetic 
201584/idmc_0
3/L4.3 
Listing of Plasma CAB PK Concentration-Time 
Data for Subjects with CAB Concentration 
<1.35 ug/mL (~8 X PAIC90) at Visits up to 
Week 16 
Change the first footnote to 
“Relative Time is calculated relative 
to the date and time of last previous 
dose. If the time of the last previous 
dose (e.g. oral lead-in/oral bridging) 
is missing, then the relative time will 
be set to missing and the sample 
will not be considered ‘evaluable’.” 
Remove the second footnote. 
Change column header ‘Visit’ to 
‘Analysis Visit/Nominal Visit’ to 
include both visits. 
IW24 


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Non-ICH Listings 
No. in 
IW24 
No. in 
W24 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
18 
NA 
Pharmacokinetic 
201584/idmc_0
3/L4.4 
Listing of Plasma CAB PK Concentration-Time 
Data for Subjects with CAB Concentration 
<0.166 ug/mL (PAIC90) at Visits up to Week 
16 
The same note as in Listing 17. 
IW24 
19 
NA 
Pharmacokinetic 
201584/idmc_0
3/L4.5 
Listing of Plasma RPV PK Concentration-Time 
Data for Subjects with RPV Concentration <12 
ng/mL (PAIC90) at Visits up to Week 16 
The same note as in Listing 17. 
IW24 
Virology 
20 
16 
Confirmed Virologic 
Failure 
201584/idmc_0
3/L7.1 
Listing of Genotypic Mutation Data at All 
Timepoints 
 
IW24, W24 
21 
17 
Confirmed Virologic 
Failure 
201584/idmc_0
3/L7.2 
Listing of Phenotypic Data at All Timepoints 
 
IW24, W24 


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15.15.5. 
List of Data Displays for Week 48/96/End-of-Study Planned Analyses 
15.15.5.1. Study Population Tables 
Study Population Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Subject Disposition 
1.1 
1.1 
1.1 
Randomized 
NS1 
Summary of Number of Subjects Enrolled by 
Country and Site ID 
‘No Treatment’ column is not 
needed. 
W48, W96, EOS 
1.2 
1.2 
1.2 
Screened 
ES6 
Summary of Screening Status and Reasons 
for Screening Failures 
 
W48, W96 
1.3 
1.3 
1.3 
Intent-to-
Treat 
Exposed 
ES1 
Summary of Subject Accountability: Study 
Conclusion Record 
For WK 96 and EOS: Add a 
footnote [1] for Subject Status: 
“[1] Subject Status is derived 
based on the data collected 
from the Study Conclusion 
eCRF form. “COMPLETED” 
subjects are those completing 
the study without reasons 
beyond the completion of the 
study commitment. 
“WITHDRAWN” subjects are 
those either withdrawn from 
Maintenance / Extension phase, 
or those who completed 
Maintenance phase and 
decided not to enter Extension 
phase due to reasons beyond 
the completion of the study 
commitment (Subjects xxx, xxx, 
and xxx are in this group and 
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Study Population Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
their primary reasons for 
withdrawal are xxx, xxx and xxx 
respectively.).” Update the 
numbering of other footnotes 
accordingly. Footnotes may be 
adjusted as appropriate. Add a 
section “Type of Adverse 
Events Which Led to Study 
Withdrawal” with categories 
“COVID-19” and “Non-COVID-
19”. 
1.4 
1.4 
NA 
Intent-to-
Treat 
Exposed 
ES1 
Summary of Subject Accountability: 
Maintenance Phase Conclusion Record 
For W96: Add a section “Type 
of Adverse Events Which Led to 
Study Withdrawal” with 
categories “COVID-19” and 
“Non-COVID-19”. 
HL, W48, W96 
NA 
1.5 
1.4 
Intent-to-
Treat 
Exposed 
ES1 
Summary of Subject Accountability: 
Maintenance + Extension Phase Conclusion 
Record 
For subject status, refer to 
201584/primary_07/T1.10 for 
the layout. For W96 and EOS: 
Add a section “Type of Adverse 
Events Which Led to Study 
Withdrawal” with categories 
“COVID-19” and “Non-COVID-
19”. 
W96, EOS 
1.5 
1.6 
1.5 
Long-term 
Follow-up 
ES1 
Summary of Subject Accountability: Long-term 
Follow-up Phase Conclusion Record 
For W96 and EOS: Add a 
section “Type of Adverse 
Events Which Led to Study 
Withdrawal” with categories 
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Study Population Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
“COVID-19” and “Non-COVID-
19”. 
1.6 
1.7 
1.6 
Intent-to-
Treat 
Exposed 
ES4 
Summary of Subject Disposition at Each Study 
Phase 
Replace ‘Epoch’ with ‘Phase’ in 
column header. Screening 
Phase will not be included. Add 
a footnote “Note: Entry into 
Long-Term Follow-up is based 
on presence of a long-term 
follow-up visit in the eCRF (i.e. 
LTFU Month 1, LTFU Month 3, 
etc.) or evidence of filling out 
the long-term follow-up phase 
conclusion form.” For WK96 
and EOS, update the last part 
of the footnote to be “…or 
evidence of filling out the long-
term follow-up phase 
conclusion form or indication of 
continuing into the long-term 
follow-up phase in the subject 
continuation form.” 
W48, W96, EOS 
1.7 
1.8 
1.7 
Intent-to-
Treat 
Exposed 
ES5 
Summary of Reasons for Withdrawal at Each 
Study Phase 
The same comment as above. 
W48, W96, EOS 
1.8 
1.9 
1.8 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T1.9 
Summary of Subject Accountability: 
Withdrawals by Visit (Maintenance + 
Extension Phase) 
 
W48, W96, EOS 


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Study Population Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
1.9 
1.10 
1.9 
Intent-to-
Treat 
Exposed 
ES1 
Summary of Study Drug Discontinuation 
Update the row label to ‘Primary 
Reason[1]/Subreason[2] for 
Study Drug Discontinuation’. 
For W96 and EOS: Add a 
section “Type of Adverse 
Events Which Led to Study 
Drug Discontinuation” with 
categories “COVID-19” and 
“Non-COVID-19”. 
W48, W96, EOS 
1.10 
1.11 
NA 
Intent-to-
Treat 
Exposed 
DV1a 
Summary of Important Protocol Deviations 
 
W48, W96, EOS 
NA 
1.12 
1.10 
Intent-to-
Treat 
Exposed 
DV1a 
Summary of Important Protocol Deviations 
(Maintenance + Extension Phase) 
 
W96, EOS 
1.11 
1.13 
1.11 
Intent-to-
Treat 
Exposed 
IE1 
Summary of Inclusion/Exclusion Criteria 
Deviations 
 
W48, W96 
1.12 
1.14 
1.12 
Screened 
201585/primar
y_02/T1.1 
Summary of Study Populations 
Adjust the footnote as 
appropriate. 
HL, W48, W96, 
EOS 
1.13 
1.15 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.14 
Summary of Protocol Deviations Leading to 
Exclusion from the Per-Protocol Population 
 
W48, W96 
NA 
1.36 
1.32 
Intent-to-
Treat 
Exposed 
DV1a 
Summary of Important COVID-19 Related 
Protocol Deviations 
Update the label for the first row 
to be “ANY IMPORTANT 
COVID-19 RELATED 
PROTOCOL DEVIATIONS”. 
W96, EOS 


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Study Population Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
NA 
1.37 
1.33 
Intent-to-
Treat 
Exposed 
DV1a 
Summary of Important Non-COVID-19 Related 
Protocol Deviations 
Update the label for the first row 
to be “ANY IMPORTANT NON-
COVID-19 RELATED 
PROTOCOL DEVIATIONS”. 
W96, EOS 
Demographic and Baseline Characteristics 
1.14 
1.16 
1.13 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.16 
Summary of Demographic Characteristics 
 
HL, W48, W96, 
EOS 
1.15 
1.17 
1.14 
Randomized 
DM11 
Summary of Age Ranges 
Also refer to 
201585/primary_02/T1.4. 
Follow the footnote in 
201585/primary_02/T1.4. 
W48, W96 
1.16 
1.18 
1.15 
Intent-to-
Treat 
Exposed 
DM5 
Summary of Race and Racial Combinations 
 
W48, W96, EOS 
1.17 
1.19 
1.16 
Intent-to-
Treat 
Exposed 
DM6 
Summary of Race and Racial Combinations 
Details 
 
W48, W96, EOS 
1.18 
1.20 
1.17 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.19 
Summary of Hepatitis Status at Entry 
Add footnote as appropriate for 
subjects classified as Hepatitis B 
positive in analysis. 
W48, W96 
1.19 
1.21 
1.18 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.20 
Summary of Derived Baseline CDC Stages of 
HIV Infection 
 
W48, W96 
1.20 
1.22 
1.19 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.21 
Summary of Baseline Cardiovascular Risk 
Assessments 
 
W48, W96 


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Study Population Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
1.21 
1.23 
1.20 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.22 
Distribution of CD4+ Cell Count Results at 
Screening and Baseline 
 
W48, W96 
1.22 
1.24 
1.21 
Intent-to-
Treat 
Exposed 
Shell POP_T1 
Summary of Prior Exposure to CAB+RPV 
 
W48, W96 
1.23 
1.25 
1.22 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.36 
Summary of HIV Risk Factors 
 
W48, W96 
Medical Conditions and Medications 
1.24 
1.26 
1.23 
Intent-to-
Treat 
Exposed 
MH1 
Summary of Current Medical Conditions 
 
W48, W96, EOS 
1.25 
1.27 
1.24 
Intent-to-
Treat 
Exposed 
MH1 
Summary of Past Medical Conditions 
 
W48, W96, EOS 
1.26 
1.28 
1.25 
Intent-to-
Treat 
Exposed 
MH4 
Summary of Current Cardiac, Gastrointestinal, 
Metabolism and Nutrition, Psychiatric, Renal 
and Urinary, Nervous System Conditions, and 
Hepatobiliary Disorders 
 
W48, W96, EOS 
1.27 
1.29 
1.26 
Intent-to-
Treat 
Exposed 
MH4 
Summary of Past Cardiac, Gastrointestinal, 
Metabolism and Nutrition, Psychiatric, Renal 
and Urinary, Nervous System Conditions, and 
Hepatobiliary Disorders 
 
W48, W96, EOS 
1.28 
1.30 
1.27 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.28 
Summary of Prior ART Medications 
Remove the footnote. Follow 
definitions in Section 6.2 to 
W48, W96 


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Study Population Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
determine the prior ART 
medications.  
1.29 
1.31 
NA 
Intent-to-
Treat 
Exposed 
CM8 
Summary of Concomitant Non-ART 
Medication Ingredient Combinations 
(Maintenance Phase) 
 
W48, W96 
NA 
1.32 
1.28 
Intent-to-
Treat 
Exposed 
CM8 
Summary of Concomitant Non-ART 
Medication Ingredient Combinations 
(Maintenance + Extension Phase) 
 
W96, EOS 
1.30 
1.33 
1.29 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.33 
Summary of Lipid Modifying Agent Use at 
Baseline 
 
W48, W96 
1.31 
1.34 
1.30 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.34 
Summary of Lipid Modifying Agent Use 
Started during the Maintenance Phase 
 
W48, W96 
1.32 
1.35 
1.31 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T1.35 
Summary of Substance Use at Entry 
 
W48, W96 
 


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15.15.5.2. Efficacy Tables 
Note: For subgroup analyses, include rederived randomization strata (i.e. prior exposure to CAB+RPV: 0, 1-24, >24 weeks), all demographic and 
baseline characteristic subgroups as mentioned in EMA Subgroup Category 2 in Section 5.4.2, unless otherwise specified. Not all subjects on Q8W 
arm are planned to have viral load data collected at Week 4 (Week 4A or 4B), so leave Week 4 data blank for Q8W arm in by-visit snapshot analysis. 
Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Primary Efficacy Analyses 
2.1 
2.1 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.1 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA >=50 c/mL at Week 48 
(Maintenance Phase) – Snapshot Analysis – ITT-E 
Adjust the footnotes as 
appropriate. For WK96, 
replace ‘Week 48’ with ‘Week 
96’ in title. 
HL, W48, W96 
2.2 
2.2 
NA 
Per-
Protocol 
201584/primar
y_01/T2.2 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA >=50 c/mL at Week 48 
(Maintenance Phase) – Snapshot Analysis – Per-
Protocol 
Adjust the footnotes as 
appropriate. For WK96: 
replace ‘Week 48’ with ‘Week 
96’ in title. 
HL, W48, W96 
2.3 
2.3 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.3 
Summary of Study Outcomes (50 c/mL Threshold) 
at Week 48 (Maintenance Phase) – Snapshot 
Analysis 
For WK96: replace ‘Week 48’ 
with ‘Week 96’ in title. Use 
shell EFF_T5 for mock-up. 
HL, W48, W96 
2.4 
2.4 
NA 
Intent-to-
Treat 
Exposed 
Shell EFF_T3 
Treatment by Strata Tests of Homogeneity for 
Proportion of Subjects with Plasma HIV-1 RNA 
>=50 c/mL at Week 48 (Maintenance Phase) - 
Snapshot Analysis 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ in title. 
HL, W48, W96 


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Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.5 
2.5 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.5 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA >=50 c/mL at Week 48 by 
Subgroup (Maintenance Phase) - Snapshot Analysis 
Adjust the footnote/column 
header label as appropriate. 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ in title. Do not 
include rederived 
randomization strata in the 
table. 
W48, W96 
2.6 
2.6 
NA 
Intent-to-
Treat 
Exposed 
Shell EFF_T4 
Treatment by Strata Tests of Homogeneity for 
Proportion of Subjects with Plasma HIV-1 RNA 
>=50 c/mL at Week 48 among Subjects with >=1 
Weeks Prior Exposure to CAB+RPV (Maintenance 
Phase) - Snapshot Analysis 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ in title. 
W48, W96 
2.7 
2.7 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.6 
Summary of Study Outcomes (50 c/mL Threshold) 
at Week 48 by Subgroup (Maintenance Phase) – 
Snapshot Analysis 
For WK96: replace ‘Week 48’ 
with ‘Week 96’ in title. Use 
shell EFF_T5 for mock-up of 
each subgroup’s study 
outcomes. 
W48, W96 
Secondary and Exploratory Efficacy Analyses 
2.8 
2.8 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.7 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 48 
(Maintenance Phase) – Snapshot Analysis – ITT-E 
Adjust the footnotes as 
appropriate. For WK96, 
replace ‘Week 48’ with ‘Week 
96’ in title. 
HL, W48, W96 
2.9 
2.9 
NA 
Per-
Protocol 
201584/primar
y_01/T2.8 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 48 
(Maintenance Phase) – Snapshot Analysis – Per-
Protocol 
Adjust the footnotes as 
appropriate. For WK96, 
replace ‘Week 48’ with ‘Week 
96’ in title. 
HL, W48, W96 


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Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.10 
2.10 
NA 
Intent-to-
Treat 
Exposed 
Shell EFF_T3 
Treatment by Strata Tests of Homogeneity for 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL at Week 48 (Maintenance Phase) - Snapshot 
Analysis 
Replace ‘Number of HIV-1 
RNA >=50 c/mL’ with 
‘Number of HIV-1 RNA <50 
c/mL’ in column header. For 
WK96, replace ‘Week 48’ 
with ‘Week 96’ in title. 
HL, W48, W96 
2.11 
2.11 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.10 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 48 by 
Subgroup (Maintenance Phase) - Snapshot Analysis 
Adjust the footnote/column 
header label as appropriate. 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ in title. Do not 
include rederived 
randomization strata in the 
table. 
W48, W96 
2.12 
2.12 
NA 
Intent-to-
Treat 
Exposed 
Shell EFF_T4 
Treatment by Strata Tests of Homogeneity for 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL at Week 48 among Subjects with >=1 Weeks 
Prior Exposure to CAB+RPV (Maintenance Phase) - 
Snapshot Analysis 
Replace ‘Number of HIV-1 
RNA >=50 c/mL’ with 
‘Number of HIV-1 RNA <50 
c/mL’ in column header. For 
WK96, replace ‘Week 48’ 
with ‘Week 96’ in title. 
W48, W96 
2.13 
2.13 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.11 
Proportion of Subjects with Plasma HIV-1 RNA 
>=50 c/mL by Visit (Maintenance Phase) – 
Snapshot Analysis 
 
W48, W96 
2.14 
2.14 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.12 
Proportion of Subjects with Plasma HIV-1 RNA 
>=50 c/mL by Subgroup and Visit (Maintenance 
Phase) – Snapshot Analysis 
 
W48, W96 
2.15 
2.15 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.15 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL by Visit (Maintenance Phase) – Snapshot 
Analysis 
 
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Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.16 
2.16 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.16 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL by Subgroup and Visit (Maintenance Phase) – 
Snapshot Analysis 
 
W48, W96 
2.17 
2.17 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.17 
Proportion of Subjects with Plasma HIV-1 RNA 
<200 c/mL by Visit (Maintenance Phase) – 
Snapshot Analysis 
 
W48, W96 
2.18 
2.18 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.17 
Proportion of Subjects with Plasma HIV-1 RNA 
>=200 c/mL by Visit (Maintenance Phase) – 
Snapshot Analysis 
Adjust column headers as 
appropriate. Keep one 
decimal place for proportion. 
W48, W96 
2.19 
2.19 
NA 
Intent-to-
Treat 
Exposed 
Shell EFF_T1 
Summary of Kaplan-Meier Estimates of Proportion 
of Subjects Without Confirmed Virologic Failure at 
Week 48 - Treatment Related Discontinuation = 
Failure 
Adjust the row labels and 
footnotes as appropriate. For 
WK96, replace ‘Week 48’ 
with ‘Week96’ in title.  
W48, W96 
2.20 
2.20 
NA 
Intent-to-
Treat 
Exposed 
Shell EFF_T2 
Summary of Kaplan-Meier Estimates of Proportion 
of Subjects Without Confirmed Virologic Failure at 
Week 48 - Efficacy Related Discontinuation = 
Failure 
Adjust the row labels and 
footnotes as appropriate. For 
WK96, replace ‘Week 48’ 
with ‘Week96’ in title.  
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Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.21 
2.21 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.19 
Proportion of Subjects with HIV-1 RNA >=50 c/mL at 
Week 48 (Snapshot) by Last Delay in IP Injection 
(Maintenance Phase) 
Display both arms. Change 
the footnote to ‘The last delay 
in IP injection will be the 
delay in IP injection at Week 
48, or the delay in last IP 
injection prior to Week 48 if a 
participant did not receive 
Week 48 injection (i.e. 
missing visit or withdrawal).’. 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ in the title and 
footnote accordingly. 
W48, W96 
2.22 
2.22 
2.1 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.20 
Summary of Plasma HIV-1 RNA (log10 c/mL) by 
Visit (Maintenance + Extension Phase) 
 
W48, W96, 
EOS 
2.23 
2.23 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.21 
Cumulative Proportion of Subjects Meeting 
Confirmed Virology Failure Criteria by Visit during 
the Maintenance Phase (Up to Week 48) 
For WK96, remove ‘Up to 
Week 48’ in title. 
HL, W48, W96 
2.24 
2.24 
2.2 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.21 
Cumulative Proportion of Subjects Meeting 
Confirmed Virology Failure Criteria (Maintenance + 
Extension Phase) 
 
HL, W48, 
W96, EOS 
2.25 
2.25 
NA 
 Confirmed 
Virologic 
Failure 
201584/primar
y_01/T2.24 
Distribution of Quantitative Plasma HIV-1 RNA 
Results at Suspected and Confirmation of 
Confirmed Virologic Failure (Maintenance Phase) 
 
W48, W96 


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Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.26 
2.26 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.34 
Proportion of Subjects with Plasma HIV-1 RNA <2 
c/mL by Visit (Maintenance Phase) 
Change footnote to ‘Note: 
Data come from BioMontr 
low-level assay. Only visits 
with available data from this 
assay are included.’ 
W48, W96 
2.27 
2.27 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.51 
Summary of Study Outcomes (200 c/mL Threshold) 
at Week 48 (Maintenance Phase) – Snapshot 
Analysis 
For WK96: replace ‘Week 48’ 
with ‘Week 96’ in title. Use 
shell EFF_T5 for mock-up. 
W48, W96 
2.28 
2.28 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.37 
Summary of Subjects per Viral Load Category by 
Visit (Maintenance Phase) 
Refer to ‘Summary for 
Participants per Viral Load 
Category by Visit’ in Section 
15.6.3. Remove footnote [2]. 
Add a footnote “Note: The 
visit windows are based on 
snapshot analysis windows’. 
W48, W96 
2.29 
2.29 
2.3 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.25 
Summary of Change from Baseline in CD4+ Cell 
Count (cells/mm^3) by Visit (Maintenance + 
Extension Phase) 
 
W48, W96, 
EOS 
2.30 
2.30 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.38 
Summary of Change from Baseline in CD4+ Cell 
Count (cells/mm^3) at Week 48 by Subgroup 
(Maintenance Phase) 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ in title. 
W48, W96 
2.31 
2.31 
2.4 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.26 
Summary of CD4+ Cell Count (cells/mm^3) by Visit 
(Maintenance + Extension Phase) 
 
W48, W96, 
EOS 
2.32 
2.32 
2.5 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.28 
Summary of Change from Baseline in CD8+ Cell 
Count (cells/mm^3) by Visit (Maintenance Phase) 
 
W48, W96, 
EOS 


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Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.33 
2.33 
2.6 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.27 
Summary of CD8+ Cell Count (cells/mm^3) by Visit 
(Maintenance Phase) 
 
W48, W96, 
EOS 
2.34 
2.34 
2.7 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.29 
Summary of CD4+/CD8+ Ratio Cell Count 
(cells/mm^3) by Visit (Maintenance Phase) 
Ratio will be taken when both 
CD4+ and CD8+ are 
available on the same date. 
W48, W96, 
EOS 
2.35 
2.35 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.30 
Summary of HIV-1 Associated Conditions Including 
Recurrences (Maintenance Phase) 
 
W48, W96 
NA 
NA 
2.8 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.30 
Summary of HIV-1 Associated Conditions Including 
Recurrences (Maintenance +Extension Phase) 
 
EOS 
2.36 
2.36 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.31 
Summary of HIV-1 Associated Conditions Excluding 
Recurrences (Maintenance Phase) 
 
W48, W96 
NA 
NA 
2.9 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T2.31 
Summary of HIV-1 Associated Conditions Excluding 
Recurrences (Maintenance +Extension Phase) 
 
EOS 
2.37 
2.37 
NA 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/T2.47 
Summary of HIV-1 Disease Progression and/or 
Deaths (Maintenance Phase) 
For WK96: add a superscript 
[1] to the first n and add a 
footnote: “Note: It is the 
denominator for all 
percentages.”  
W48, W96 


CONFIDENTIAL 
 
 
 
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215 
 
Efficacy Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
NA 
NA 
2.10 
Intent-to-
Treat 
Exposed 
207966/primar
y_02/T2.37 
Summary of HIV-1 Disease Progression and/or 
Deaths (Maintenance + Extension Phase) 
Replace “maintenance” with 
“maintenance and extension” 
in the footnote; add a 
superscript [1] to the first n 
and add a footnote: “Note: It 
is the denominator for all 
percentages.” 
EOS 
2.38 
2.38 
2.11 
Intent-to-
Treat 
Exposed 
207966/primar
y_02/T2.38 
Summary of Change from Baseline in Plasma HIV-1 
RNA (log10 c/mL) by Visit (Maintenance + 
Extension Phase) 
 
W48, W96, 
EOS 
 


CONFIDENTIAL 
 
 
 
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216 
 
15.15.5.3. Efficacy Figures 
Note: For subgroup analyses, include rederived randomization strata (i.e. prior exposure to CAB+RPV: 0, 1-24, >24 weeks), all demographic and 
baseline characteristic subgroups as mentioned in EMA Subgroup Category 2 in Section 5.4.2, unless otherwise specified. Not all subjects on Q8W 
arm are planned to have viral load data collected at Week 4 (Week 4A or 4B), so leave Week 4 data blank for Q8W arm in by-visit snapshot analysis. 
Efficacy Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
Primary Efficacy Analyses 
2.1 
2.1 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F2.1 
Proportion (95% CI) of Subjects with HIV-1 RNA 
≥50 c/mL by Visit (Maintenance Phase) – 
Snapshot Analysis 
 
HL, W48, W96 
2.2 
2.2 
NA 
Intent-to-
Treat 
Exposed 
201584/primary
_01/F2.2 
Unadjusted Treatment Difference in Proportion 
(95% CI) of Subjects with HIV-1 RNA ≥50 c/mL at 
Week 48 by Subgroup – Snapshot Analysis 
Non-inferiority margin is 4%. 
Adjust the footnotes, 
reference line and labels as 
appropriate. For WK96, 
replace ‘Week 48’ with 
‘Week 96’ in title. 
W48, W96 
Secondary and Exploratory Efficacy Analyses 
2.3 
2.3 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F2.3 
Proportion (95% CI) of Subjects with HIV-1 RNA 
<50 c/mL by Visit (Maintenance Phase) – 
Snapshot Analysis 
 
HL, W48, W96 
2.4 
2.4 
NA 
Intent-to-
Treat 
Exposed 
201584/primary
_01/F2.4 
Unadjusted Treatment Difference in Proportion 
(95% CI) of Subjects with HIV-1 RNA <50 c/mL at 
Week 48 by Subgroup – Snapshot Analysis 
Adjust the footnotes, 
reference line and labels as 
appropriate. For WK96, 
replace ‘Week 48’ with 
‘Week 96’ in title. 
W48, W96 


CONFIDENTIAL 
 
 
 
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217 
 
Efficacy Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
2.5 
2.5 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F2.10 
Proportion (95% CI) of Subjects with HIV-1 RNA 
>=200 c/mL by Visit (Maintenance Phase) – 
Snapshot Analysis 
 
W48, W96 
2.6 
2.6 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F2.5 
Proportion (95% CI) of Subjects with HIV-1 RNA 
<200 c/mL by Visit (Maintenance Phase) – 
Snapshot Analysis 
 
W48, W96 
2.7 
2.7 
2.1 
Intent-to-
Treat 
Exposed 
207966/idmc_0
3/F2.1 
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles 
by Visit – for CVF Subjects  
 
HL, W48, 
W96, EOS 
2.8 
2.8 
NA 
Intent-to-
Treat 
Exposed 
207966/idmc_0
3/F2.1 
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles 
by Visit for subjects Who are in the Category of 
‘HIV-1 RNA >=50 c/mL’ at Week 48 per Snapshot 
Algorithm 
For WK96, replace ‘Week 
48’ with ‘Week 96’ in the 
title.  
HL, W48, W96 
 


CONFIDENTIAL 
 
 
 
207966 
 
218 
 
15.15.5.4. Safety Tables 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Exposure 
3.1 
3.1 
3.1 
Safety 
201585/primar
y_02/T3.1 
Summary of Extent of Exposure to 
Investigational Product (Maintenance 
Phase) 
No need for the first two footnotes. 
Update the last footnote to be below: 
Note: The injection at nominal visit of 
Week 100 was not included in the 
summary of Exposure (No. of IP 
injections). For W96 and EOS: 
Replace “Investigational Product” 
with “Study Treatment including SOC 
Oral Bridging” in the title; Add 
sections after Section “Exposure (No. 
of IP injection visits)” for exposure to 
CAB+RPV oral bridging and 
exposure to SOC oral bridging 
similarly to exposure to oral lead-in; 
Add sections for overall exposure to 
IP similarly to overall exposure; the 
levels for categorical summaries will 
be selected as appropriate.   
W48, W96 
NA 
3.2 
3.2 
Safety 
201585/primar
y_02/T3.1 
Summary of Extent of Exposure to 
Investigational Product (Maintenance + 
Extension Phase) 
Remove the footnotes. For W96 and 
EOS: update similarly to the table 
above.   
W96, EOS 
3.2 
3.3 
NA 
Safety 
201585/primar
y_03/T3.102 
Summary of Needle Length and Gauge for 
CAB Injection (Maintenance Phase) 
Display both arms. 
W48, W96 
3.3 
3.4 
NA 
Safety 
201585/primar
y_03/T3.103 
Summary of Needle Length and Gauge for 
RPV Injection (Maintenance Phase) 
Display both arms. 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
219 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
3.4 
3.5 
NA 
Safety 
201585/primar
y_02/T3.6 
Summary of Adherence to CAB/RPV 
Injection Dosing Schedule (Maintenance 
Phase) 
Display both arms. Adjust the 
footnotes as appropriate. For W96, 
present “Missed Injection with 
CAB+RPV Oral Bridging” and 
“Missed Injection with SOC Oral 
Bridging” separately. 
W48, W96 
Adverse Events 
3.5 
3.6 
NA 
Safety 
201585/primar
y_02/T3.7 
Summary of All Adverse Events by System 
Organ Class (Maintenance Phase) 
 
W48, W96 
3.6 
3.7 
NA 
Safety 
201585/primar
y_02/T3.8 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity 
(Maintenance Phase) 
 
HL, W48, 
W96 
NA 
3.8 
3.3 
Safety 
201585/primar
y_02/T3.8 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity 
(Maintenance + Extension Phase) 
 
W96, EOS 
3.7 
3.9 
NA 
Safety 
201585/primar
y_02/T3.8 
Summary of All Adverse Events Excluding 
Study Drug Injection Site Reactions by 
System Organ Class and Maximum 
Toxicity (Maintenance Phase) 
 
HL, W48, 
W96 
NA 
NA 
3.4 
Safety 
201585/primar
y_02/T3.8 
Summary of All Adverse Events Excluding 
Study Drug Injection Site Reactions by 
System Organ Class and Maximum 
Toxicity (Maintenance + Extension Phase) 
 
EOS 
NA 
NA 
3.5 
Long-term 
Follow-up 
201585/primar
y_02/T3.8 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity (Long-
term Follow-up Phase) 
 
EOS 
3.8 
3.10 
NA 
Safety 
201585/primar
Summary of All On-treatment Adverse 
 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
220 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
y_02/T3.11 
Events by System Organ Class and 
Maximum Toxicity (Maintenance Phase) 
3.9 
NA 
NA 
Oral Lead-
in 
201585/primar
y_02/T3.13 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity (Oral 
Lead-in Period during the Maintenance 
Phase) 
Remove the footnote. Display both 
arms. 
W48 
3.10 
3.11 
NA 
Safety 
201585/primar
y_02/T3.14 
Summary of Common Adverse Events 
(>=5%) by Overall Frequency 
(Maintenance Phase) 
 
W48, W96 
3.11 
3.12 
NA 
Safety 
201585/primar
y_02/T3.15 
Summary of Common Grade 2-5 Adverse 
Events (>=1%) by Overall Frequency 
(Maintenance Phase) 
 
W48, W96 
3.12 
3.13 
NA 
Safety 
201585/primar
y_02/T3.16 
Summary of All Drug-related Adverse 
Events by System Organ Class 
(Maintenance Phase) 
 
W48, W96 
3.13 
3.14 
NA 
Safety 
201585/primar
y_02/T3.17 
Summary of All Drug-related Adverse 
Events by System Organ Class and 
Maximum Toxicity (Maintenance Phase) 
 
HL, W48, 
W96 
NA 
3.15 
3.6 
Safety 
201585/primar
y_02/T3.17 
Summary of All Drug-related Adverse 
Events by System Organ Class and 
Maximum Toxicity (Maintenance + 
Extension Phase) 
 
W96, EOS 
3.14 
3.16 
NA 
Safety 
201585/primar
y_02/T3.101 
Summary of All Drug-related Adverse 
Events Excluding Study Drug Injection Site 
Reactions by System Organ Class and 
Maximum Toxicity (Maintenance Phase) 
 
HL, W48, 
W96 
NA 
NA 
3.7 
Safety 
201585/primar
Summary of All Drug-related Adverse 
 
EOS 


CONFIDENTIAL 
 
 
 
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221 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
y_02/T3.101 
Events Excluding Study Drug Injection Site 
Reactions by System Organ Class and 
Maximum Toxicity (Maintenance + 
Extension Phase) 
3.15 
3.17 
NA 
Safety 
201585/primar
y_02/T3.20 
Summary of All Drug-Related Grade 2-5 
Adverse Events by Overall Frequency 
(Maintenance Phase) 
 
W48, W96 
Serious and Other Significant Adverse Events 
3.16 
3.18 
NA 
Safety 
201585/primar
y_02/T3.21 
Summary of Serious Adverse Events by 
System Organ Class (Maintenance Phase) 
 
HL, W48, 
W96 
NA 
3.19 
3.8 
Safety 
201585/primar
y_02/T3.21 
Summary of Serious Adverse Events by 
System Organ Class (Maintenance + 
Extension Phase) 
 
W96, EOS 
3.17 
3.20 
3.9 
Long-term 
Follow-up 
201585/primar
y_02/T3.24 
Summary of Serious Adverse Events by 
System Organ Class (Long-term Follow-up 
Phase) 
 
W48, W96, 
EOS 
3.18 
NA 
NA 
Oral Lead-
in 
201585/primar
y_02/T3.25 
Summary of Serious Adverse Events by 
System Organ Class (Oral Lead-in Period 
during the Maintenance Phase) 
Display both arms. 
W48 
3.19 
3.21 
NA 
Safety 
201585/primar
y_02/T3.26 
Summary of Drug-related Serious Adverse 
Events by System Organ Class 
(Maintenance Phase) 
 
W48, W96 
NA 
3.22 
3.10 
Safety 
201585/primar
y_02/T3.26 
Summary of Drug-related Serious Adverse 
Events by System Organ Class 
(Maintenance + Extension Phase) 
 
W96, EOS 
3.20 
3.23 
NA 
Safety 
201585/primar
y_02/T3.29 
Summary of Non-Fatal Serious Adverse 
Events by Overall Frequency (Maintenance 
 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
222 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Phase) 
3.21 
3.24 
NA 
Safety 
201585/primar
y_02/T3.30 
Summary of Drug-related Non-Fatal 
Serious Adverse Events by Overall 
Frequency (Maintenance Phase) 
 
W48, W96 
3.22 
3.25 
NA 
Safety 
201585/primar
y_02/T3.31 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ 
Class (Maintenance Phase) 
 
HL, W48, 
W96 
NA 
3.26 
3.11 
Safety 
201585/primar
y_02/T3.31 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ 
Class (Maintenance + Extension Phase) 
 
W96, EOS 
3.23 
NA 
NA 
Oral Lead-
in 
201585/primar
y_02/T3.34 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ 
Class (Oral Lead-in Period during the 
Maintenance Phase) 
Remove the footnote. Display both 
arms. 
W48 
3.24 
3.27 
NA 
Safety 
201585/primar
y_02/T3.35 
Summary of Common (>=5%) Non-Serious 
Adverse Events (Maintenance Phase) 
 
W48, W96 
3.25 
3.28 
NA 
Safety 
201585/primar
y_02/T3.36 
Summary of Subjects and Number of 
Occurrences of Common (>=5%) Non-
Serious Adverse Events by System Organ 
Class (Maintenance Phase) 
 
W48, W96 
3.26 
3.29 
NA 
Safety 
201585/primar
y_02/T3.37 
Summary of Subjects and Number of 
occurrences of SAEs, Fatal SAEs, and 
Drug-related SAEs (Maintenance Phase) 
 
W48, W96 
3.27 
3.30 
NA 
Safety 
201585/primar
Summary of Cumulative Adverse Events 
Note that this table only display AEs 
W48, W96 


CONFIDENTIAL 
 
 
 
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223 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
y_02/T3.38 
by Visit (Maintenance Phase) 
occurring >=5% subjects during 
Maintenance Phase. 
Study Drug Injection Site Reaction Adverse Events (display for both arms) 
3.28 
3.31 
NA 
Safety 
201585/primar
y_02/T3.40 
Summary of Study Drug Injection Site 
Reaction Adverse Events (Event-level 
Summary) - Maintenance Phase 
 
HL, W48, 
W96 
NA 
3.32 
3.12 
Safety 
201585/primar
y_02/T3.40 
Summary of Study Drug Injection Site 
Reaction Adverse Events (Event-level 
Summary) - Maintenance + Extension 
Phase 
 
W96, EOS 
3.29 
3.33 
NA 
Safety 
201585/primar
y_02/T3.43 
Summary of Subject-level Characteristics 
of Study Drug Injection Site Reaction 
Adverse Events – Overall and Common 
(Maintenance Phase) 
 
W48, W96 
NA 
3.34 
3.13 
Safety 
201585/primar
y_02/T3.43 
Summary of Subject-level Characteristics 
of Study Drug Injection Site Reaction 
Adverse Events – Overall and Common 
(Maintenance + Extension Phase) 
 
W96, EOS 
3.30 
3.35 
NA 
Safety 
201585/primar
y_02/T3.46 
Summary of Study Drug Injection Site 
Reaction Adverse Events by Visit and 
Maximum Severity – Overall and Common 
(Maintenance Phase) 
Change the second footnote to ‘Note: 
Common ISR includes pain, 
induration, nodules and any other 
ISR with >=5% subjects in either 
treatment arm.’ Footnote may be 
adjusted for clarifications. 
W48, W96 
3.31 
3.36 
NA 
Safety 
201585/primar
y_02/T3.47 
Summary of Drug-related Study Drug 
Injection Site Reaction Adverse Events 
(Event-level Summary) - CAB 
 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
224 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
(Maintenance Phase) 
3.32 
3.37 
NA 
Safety 
201585/primar
y_02/T3.48 
Summary of Drug-related Subject-level 
Characteristics of Study Drug Injection Site 
Reaction Adverse Events (Maintenance 
Phase) - Overall and Common (CAB) 
 
W48, W96 
3.33 
3.38 
NA 
Safety 
201585/primar
y_02/T3.49 
Summary of Overall and Common Drug-
related Study Drug Injection Site Reaction 
Adverse Events by Visit and Maximum 
Severity (Maintenance Phase) - CAB 
Footnote may be adjusted for 
clarifications. 
W48, W96 
3.34 
3.39 
NA 
Safety 
201585/primar
y_02/T3.50 
Summary of Maximum Drug-related Study 
Drug Injection Site Reaction Adverse Event 
Grade by Needle Length (Maintenance 
Phase) – Common (CAB) 
Update the needle length in column 
header to be “<=1.5 inches’, ‘>1.5 to 
<2 inches’ and ‘>=2 inches’ 
respectively. Change the first 
footnote to ‘Note: Common ISR 
includes pain, induration, nodules 
and any other ISR with >=5% 
subjects in either treatment arm.’. 
Remove the second footnote. 
W48, W96 
3.35 
3.40 
NA 
Safety 
201585/primar
y_02/T3.51 
Summary of Drug-related Study Drug 
Injection Site Reaction Adverse Events 
(Event-level Summary) - RPV 
(Maintenance Phase) 
 
W48, W96 
3.36 
3.41 
NA 
Safety 
201585/primar
y_02/T3.52 
Summary of Drug-related Subject-level 
Characteristics of Study Drug Injection Site 
Reaction Adverse Events (Maintenance 
Phase) - Overall and Common (RPV) 
 
W48, W96 
3.37 
3.42 
NA 
Safety 
201585/primar
y_02/T3.53 
Summary of Overall and Common Drug-
related Study Drug Injection Site Reaction 
Footnote may be adjusted for 
clarifications. 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
225 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Adverse Events by Visit and Maximum 
Severity (Maintenance Phase) - RPV 
3.38 
3.43 
NA 
Safety 
201585/primar
y_02/T3.54 
Summary of Maximum Drug-related Study 
Drug Injection Site Reaction Adverse Event 
Grade by Needle Length (Maintenance 
Phase) – Common (RPV) 
Update the needle length in column 
header to be “<=1.5 inches’, ‘>1.5 to 
< 2 inches’ and ‘>=2 inches’ 
respectively. Change the first 
footnote to ‘Note: Common ISR 
includes pain, induration, nodules 
and any other ISR with >=5% 
subjects in either treatment arm.’. 
Remove the second footnote. 
W48, W96 
Laboratory: Chemistry and Hematology 
3.39 
3.44 
3.14 
Safety 
201585/primar
y_02/T3.55 
Summary of Chemistry Changes from 
Baseline by Visit (Maintenance + Extension 
Phase) 
Present GFR, lipids and glucose in 
both conventional and standard units. 
Change ‘Post Baseline’ to ‘Post-
baseline’ in the footnote. 
W48, W96, 
EOS 
3.40 
3.45 
3.15 
Safety 
201585/primar
y_02/T3.59 
Summary of Chemistry Values by Visit 
(Maintenance + Extension Phase) 
Present GFR, lipids and glucose in 
both conventional and standard units. 
Change ‘Post Baseline’ to ‘Post-
baseline’ in the footnote. 
W48, W96, 
EOS 
3.41 
3.46 
3.16 
Safety 
201585/primar
y_02/T3.60 
Summary of Hematology Changes from 
Baseline by Visit (Maintenance + Extension 
Phase) 
Change ‘Post Baseline’ to ‘Post-
baseline’ in the footnote. 
W48, W96, 
EOS 
3.42 
3.47 
3.17 
Safety 
201585/primar
y_02/T3.59 
Summary of Hematology Values by Visit 
(Maintenance + Extension Phase) 
Remove the first footnote. Change 
‘Post Baseline’ to ‘Post-baseline’ in 
the footnote. 
W48, W96, 
EOS 
3.43 
3.48 
NA 
Safety 
201585/primar
Summary of Maximum Post-Baseline 
Add “Emergent is relative to last 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
226 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
y_02/T3.61 
Emergent Chemistry Toxicities 
(Maintenance Phase) 
toxicity up to and including baseline.” 
to the end of the second footnote. 
NA 
3.49 
3.18 
Safety 
201585/primar
y_02/T3.61 
Summary of Maximum Post-Baseline 
Emergent Chemistry Toxicities 
(Maintenance + Extension Phase) 
Adjust the footnote similar to above. 
W96, EOS 
3.44 
NA 
NA 
Oral Lead-
in 
201585/primar
y_02/T3.64 
Summary of Maximum Post-Baseline 
Emergent Chemistry Toxicities - Oral Lead-
in Period during the Maintenance Phase 
Display both arms. Adjust the 
footnote similarly to above. 
W48 
3.45 
3.50 
NA 
Safety 
201585/primar
y_02/T3.65 
Summary of Maximum Post-Baseline 
Emergent Hematology Toxicities 
(Maintenance Phase) 
Adjust the footnote similarly to above. W48, W96 
NA 
3.51 
3.19 
Safety 
201585/primar
y_02/T3.65 
Summary of Maximum Post-Baseline 
Emergent Hematology Toxicities 
(Maintenance + Extension Phase) 
Adjust the footnote similarly to above. W96, EOS 
3.46 
NA 
NA 
Oral Lead-
in 
201585/primar
y_02/T3.68 
Summary of Maximum Post-Baseline 
Emergent Hematology Toxicities - Oral 
Lead-in Period during the Maintenance 
Phase 
Display both arms. Adjust the 
footnote similarly to above. 
W48 
NA 
3.114 
NA 
Safety 
Shell SAF_T2 
Summary of Expected and Missed Visits 
(Maintenance Phase) - Hematology and 
Chemistry 
 
W96 
Laboratory: Urinalysis 
3.47 
3.52 
3.20 
Safety 
201585/primar
y_02/T3.69 
Summary of Urinalysis Dipstick Results by 
Visit (Maintenance Phase) 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 
3.48 
3.53 
3.21 
Safety 
201585/primar
y_02/T3.70 
Summary of Urine Concentrations 
Changes from Baseline by Visit 
(Maintenance Phase) 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
227 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
3.49 
3.54 
NA 
Safety 
201585/primar
y_02/T3.71 
Summary of Changes in Proteinuria 
Baseline Laboratory Result to Maximum 
Post-Baseline Laboratory Result 
(Maintenance Phase) 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 
Laboratory: Lipid 
3.50 
3.55 
NA 
Safety 
201585/primar
y_02/T3.72 
Summary of Changes in Baseline NCEP 
Fasting Lipid Category to Maximum Post-
Baseline Category – Triglycerides 
(Maintenance Phase) 
For WK96, update the title to be “… 
Category (Triglycerides, Lipids 
LOCF) – Maintenance Phase”. 
W48, W96 
3.51 
3.56 
NA 
Safety 
201585/primar
y_02/T3.73 
Summary of Changes in Baseline NCEP 
Fasting Lipid Category to Maximum Post-
Baseline Category – Total Cholesterol 
(Maintenance Phase) 
For WK96, update the title to be “… 
Category (Total Cholesterol, Lipids 
LOCF) – Maintenance Phase”. 
W48, W96 
3.52 
3.57 
NA 
Safety 
201585/primar
y_02/T3.74 
Summary of Changes in Baseline NCEP 
Fasting Lipid Category to Minimum Post-
Baseline Category – HDL Cholesterol 
(Maintenance Phase) 
For WK96, update the title to be “… 
Category (HDL Cholesterol, Lipids 
LOCF) – Maintenance Phase”. 
W48, W96 
3.53 
3.58 
NA 
Safety 
201585/primar
y_02/T3.75 
Summary of Changes in Baseline NCEP 
Fasting Lipid Category to Maximum Post-
Baseline Category – LDL Cholesterol 
(Maintenance Phase) 
For WK96, update the title to be “… 
Category (LDL Cholesterol, Lipids 
LOCF) – Maintenance Phase”. 
W48, W96 
3.54 
3.59 
NA 
Safety 
201585/primar
y_02/T3.58 
Summary of Fasting Lipids Percentage 
Changes from Baseline by Visit 
(Maintenance Phase) - Lipids LOCF 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 
3.55 
3.60 
NA 
Safety 
201585/primar
y_02/T3.76 
Summary of Fasting TC/HDL ratio 
Changes from Baseline (Maintenance 
Phase) – Lipids LOCF 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
228 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Laboratory: Hepatobiliary (Liver) 
3.56 
3.61 
NA 
Safety 
201585/primar
y_02/T3.80 
Summary of Liver Monitoring/Stopping 
Event Reporting (Maintenance Phase) 
For WK96: Remove “Monitoring/” 
from the title, remove liver monitoring 
related text, footnote and section in 
the table. 
W48, W96 
3.57 
3.62 
NA 
Safety 
201585/primar
y_02/T3.81 
Summary of Subjects Meeting 
Hepatobiliary Abnormality Criteria 
(Maintenance Phase) 
 
W48, W96 
NA 
3.63 
3.22 
Safety 
201585/primar
y_02/T3.81 
Summary of Subjects Meeting 
Hepatobiliary Abnormality Criteria 
(Maintenance +Extension Phase) 
 
W96, EOS 
3.58 
NA 
NA 
Oral Lead-
in 
201585/primar
y_02/T3.84 
Summary of Subjects Meeting 
Hepatobiliary Abnormality Criteria – Oral 
Lead-in Period during the Maintenance 
Phase 
Display both arms. 
W48 
ECG 
3.59 
3.64 
3.23 
Safety 
201585/primar
y_02/T3.85 
Summary of ECG Findings (Maintenance 
Phase) 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 
3.60 
3.65 
3.24 
Safety 
201585/primar
y_02/T3.88 
Summary of Change from Baseline in ECG 
values by Visit (Maintenance Phase) 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 
3.61 
3.66 
3.25 
Safety 
201585/primar
y_02/T3.91 
Summary of QTc Values by Category 
(Maintenance Phase) 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 
3.62 
3.67 
3.26 
Safety 
201585/primar
y_02/T3.94 
Summary of Change from Baseline QTc 
Values by Category (Maintenance Phase) 
Change ‘Post Baseline’ to ‘Post-
Baseline’ in the footnote. 
W48, W96 
Vital Signs and eC-SSRS 
3.63 
3.68 
NA 
Safety 
201585/primar
Summary of Change from Baseline in Vital 
Change ‘Post Baseline’ to ‘Post-
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
229 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
y_02/T3.97 
Signs by Visit (Maintenance Phase) 
Baseline’ in the footnote. 
3.64 
3.69 
NA 
Safety 
SAFE_T1 
Summary of BMI Shift from Baseline by 
Visit (Maintenance Phase) 
For WK96: Add “Sex and” before 
“Visit” in the title. 
W48, W96 
NA 
3.70 
NA 
Safety 
207966/primar
y_02/T3.64 
Summary of BMI Shift from Baseline by 
Strata and Visit (Maintenance Phase) 
Display by strata instead of sex (i.e. 
prior exposure to CAB + RPV: All, 0, 
1-24, >24 weeks) and visit, add a 
footnote for strata. 
W96 
NA 
3.71 
NA 
Safety 
207966/primar
y_02/T3.63 
Summary of Change from Baseline in 
Weight and BMI by Strata and Visit 
(Maintenance Phase) 
Display by strata (i.e. prior exposure 
to CAB + RPV: All, 0, 1-24, >24 
weeks) and parameter, add a 
footnote for strata. 
W96 
3.65 
3.72 
NA 
Safety 
201585/primar
y_02/T3.99 
Summary of Subjects with eC-SSRS 
Suicidal Ideation or Behaviour 
(Maintenance Phase) 
Change ‘post baseline’ to ‘post-
baseline’ in the row header. 
W48, W96 
Adverse Event of Special Interest (AESI) 
3.66 
3.73 
NA 
Safety 
201585/primar
y_02/T3.100 
Summary of Depression, Anxiety and 
Suicidal Ideation/Behaviour Adverse 
Events by System Organ Class, Maximum 
DAIDS Toxicity Grade, and Prior History of 
Depression, Anxiety and Suicidal Ideation 
at Screening (Maintenance Phase) 
For WK96, follow display 
207966/primary_13/T3.98. 
W48, W96 
NA 
3.74 
3.27 
Safety 
207966/primar
y_13/T3.98 
Summary of Depression, Anxiety and 
Suicidal Ideation/Behaviour Adverse 
Events by System Organ Class, Maximum 
DAIDS Toxicity Grade, and Prior History of 
Depression, Anxiety and Suicidal Ideation 
at Screening (Maintenance + Extension 
 
W96, EOS 


CONFIDENTIAL 
 
 
 
207966 
 
230 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Phase) 
3.67-
3.83 
3.75-
3.91 
NA 
Safety 
209522/iss_01/
T3.38-3.49, 
T3.51-3.55 
Summary of XXX Adverse Events of 
Special Interest by System Organ Class 
and Preferred Term (Number of Subjects 
and Occurrence) – Maintenance Phase 
Only display data from this study, no 
need for showing study number. For 
‘XXX’, refer to Table 4.  
W48, W96 
NA 
3.92-
3.108 
3.28-
3.44 
Safety 
207966/primar
y_02T3.67-
3.83 
Summary of XXX Adverse Events of 
Special Interest by System Organ Class 
and Preferred Term (Number of Subjects 
and Occurrence) – Maintenance + 
Extension Phase 
 
W96, EOS 
3.84 
3.109 
NA 
Safety 
209522/iss_01/
T3.62 
Summary of Characteristics of Common 
Adverse Events of Special Interest – 
Maintenance Phase 
Only display data from this study, no 
need for showing study number. 
Present by individual common AESI. 
For WK96, add a footnote, “Note: 
Percentages are based on the 
Number of subjects with Event. For 
Event Characteristics, Outcome and 
Action Taken sections, a subject can 
be counted in more than one 
category.” 
W48, W96 
NA 
3.110 
3.45 
Safety 
207966/primar
y_02/T3.84 
Summary of Characteristics of Common 
Adverse Events of Special Interest – 
Maintenance + Extension Phase 
For WK96, add a similar footnote to 
Table 3.109. 
W96, EOS 
NA 
3.111 
3.46 
Safety 
207966/regqry
_2019_01/T3.2
07 
Summary of Syncope and Presyncope 
Adverse Events - Maintenance + Extension 
Phase 
Replace row label “Syncope or 
Presyncope” with “Number of 
Subjects with Syncope or 
Presyncope”. 
W96, EOS 
NA 
3.112 
3.47 
Safety 
207966/regqry
Summary of Syncope and Presyncope 
Row labels and footnotes may be 
W96, EOS 


CONFIDENTIAL 
 
 
 
207966 
 
231 
 
Safety Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
_2019_01/T3.2
08 
Adverse Events and Injection Visits - 
Maintenance + Extension Phase 
adjusted as appropriate. 
COVID-19 Adverse Event 
NA 
3.113 
3.48 
Safety 
207966/primar
y_02/T3.6 
Summary of COVID-19 Adverse Events by 
System Organ Class and Maximum 
Toxicity (Maintenance + Extension Phase) 
 
W96, EOS 
NA 
3.115 
3.49 
Safety 
Shell SAF_T3 
Summary of COVID-19 Assessments 
(Maintenance + Extension Phase) 
 
W96, EOS 
 


CONFIDENTIAL 
 
 
 
207966 
 
232 
 
15.15.5.5. Safety Figures 
Note: Unless otherwise specified, display both arms. 
Safety Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
3.1 
3.1 
NA 
Safety 
201585/primar
y_02/F3.1 
Plot of Common Adverse Events and Relative Risk 
- Q8W vs. Q4W (Maintenance Phase) – Excluding 
Study Drug ISRs 
Remove the second footnote. 
HL, W48, W96 
NA 
NA 
3.1 
Safety 
207966/primar
y_02/F3.1 
Plot of Common Adverse Events and Relative Risk 
- Q8W vs. Q4W (Maintenance + Extension Phase) 
– Excluding Study Drug ISRs 
 
EOS 
3.2 
3.2 
NA 
Safety 
201585/primar
y_02/F3.1 
Plot of Common Study Drug Injection Site Reaction 
Adverse Events and Relative Risk - Q8W vs. Q4W 
(Maintenance Phase) 
Remove the second footnote. 
HL, W48, W96 
NA 
NA 
3.2 
Safety 
207966/primar
y_02/F3.2 
Plot of Common Study Drug Injection Site Reaction 
Adverse Events and Relative Risk - Q8W vs. Q4W 
(Maintenance +Extension Phase) 
 
EOS 
3.3 
3.3 
NA 
Safety 
201585/primar
y_02/F3.5 
Plot of Onset, Duration, and Severity of Overall 
and Common Study Drug Injection Site Reaction 
AEs by Maximum Grade — CAB and/or RPV 
(Maintenance Phase) 
 
W48, W96 
3.4 
3.4 
NA 
Safety 
201585/primar
y_02/F3.6 
Plot of Onset, Duration, and Severity of Overall 
and Common Drug-related Study Drug Injection 
Site Reaction AEs by Maximum Grade — CAB 
(Maintenance Phase) 
 
W48, W96 
3.5 
3.5 
NA 
Safety 
201585/primar
y_02/F3.7 
Plot of Onset, Duration, and Severity of Overall 
and Common Drug-related Study Drug Injection 
Site Reaction AEs by Maximum Grade — RPV 
(Maintenance Phase) 
 
W48, W96 
3.6 
3.6 
NA 
Safety 
201585/primar
Plot of Incidence of Maintenance Phase Study 
Footnote may be adjusted for 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
233 
 
Safety Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
y_02/F3.8 
Drug Injection Site Reaction Adverse Events by 
Visit (Overall and Common) – CAB and/or RPV 
clarifications.  
NA 
NA 
3.3 
Safety 
207966/primar
y_02/F3.6 
Plot of Incidence of Maintenance and Extension 
Phase Study Drug Injection Site Reaction Adverse 
Events by Visit (Overall and Common) – CAB 
and/or RPV 
 
EOS 
3.7 
3.7 
NA 
Safety 
201585/primar
y_02/F3.9 
Plot of Incidence of Maintenance Phase Drug-
Related Study Drug Injection Site Reaction 
Adverse Events by Visit (Overall and Common) – 
CAB 
Footnote may be adjusted for 
clarifications. 
W48, W96 
NA 
NA 
3.4 
Safety 
207966/primar
y_02/F3.7 
Plot of Incidence of Maintenance and Extension 
Phase Drug-Related Study Drug Injection Site 
Reaction Adverse Events by Visit (Overall and 
Common) – CAB 
 
EOS 
3.8 
3.8 
NA 
Safety 
201585/primar
y_02/F3.10 
Plot of Incidence of Maintenance Phase Drug-
Related Study Drug Injection Site Reaction 
Adverse Events by Visit (Overall and Common) – 
RPV 
Footnote may be adjusted for 
clarifications. 
W48, W96 
NA 
NA 
3.5 
Safety 
207966/primar
y_02/F3.8 
Plot of Incidence of Maintenance and Extension 
Phase Drug-Related Study Drug Injection Site 
Reaction Adverse Events by Visit (Overall and 
Common) – RPV 
 
EOS 
3.9 
3.9 
NA 
Safety 
201585/primar
y_02/F3.11 
Plot of Incidence of Grade 3-5 Maintenance Phase 
Study Drug Injection Site Reaction Adverse Events 
by Visit (Overall and Common) - CAB and/or RPV 
Footnote may be adjusted for 
clarifications. 
W48, W96 
3.10 
3.10 
NA 
Safety 
201585/primar
y_02/F3.12 
Plot of Incidence of Grade 3-5 Maintenance Phase 
Drug-related Study Drug Injection Site Reaction 
Footnote may be adjusted for 
clarifications. 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
234 
 
Safety Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Adverse Events by Visit (Overall and Common) - 
CAB 
3.11 
3.11 
NA 
Safety 
201585/primar
y_02/F3.13 
Plot of Incidence of Grade 3-5 Maintenance Phase 
Drug-related Study Drug Injection Site Reaction 
Adverse Events by Visit (Overall and Common) - 
RPV 
Footnote may be adjusted for 
clarifications. 
W48, W96 
3.12 
3.12 
NA 
Safety 
201585/primar
y_02/F3.2 
Scatter Plot of Maximum vs. Baseline for ALT 
(Maintenance Phase) 
Display at log10 scale. 
HL, W48, W96 
NA 
3.13 
3.6 
Safety 
207966/primar
y_02/F3.12 
Scatter Plot of Maximum vs. Baseline for ALT 
(Maintenance + Extension Phase) 
 
W96, EOS 
3.13 
3.14 
NA 
Safety 
201585/primar
y_02/F3.3 
Scatter Plot of Maximum Total Bilirubin vs. 
Maximum ALT (Maintenance Phase) 
 
HL, W48, W96 
NA 
3.15 
3.7 
Safety 
207966/primar
y_02/F3.13 
Scatter Plot of Maximum Total Bilirubin vs. 
Maximum ALT (Maintenance + Extension Phase) 
 
W96, EOS 
3.14 
3.16 
NA 
Safety 
201585/primar
y_02/F3.4 
Matrix Plot of Maximum Liver Chemistries during 
the Maintenance Phase 
 
HL, W48, W96 
NA 
3.17 
3.8 
Safety 
207966/primar
y_02/F3.14 
Matrix Plot of Maximum Liver Chemistries during 
the Maintenance and Extension Phase 
 
W96, EOS 
3.15 
3.18 
NA 
Safety 
201585/primar
y_02/F3.14 
Bar Chart of Lipid NCEP Categories at Week 48 
vs. Baseline – Triglycerides, Total Cholesterol, LDL 
Cholesterol 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ and add 
“(Lipids LOCF)” to the end of 
the title 
W48, W96 
3.16 
3.19 
NA 
Safety 
201585/primar
y_02/F3.15 
Bar Chart of Lipid NCEP Categories at Week 48 
vs. Baseline - HDL Cholesterol 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ and add 
“(Lipids LOCF)” to the end of 
the title. 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
235 
 
Safety Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
3.17 
3.20 
NA 
Safety 
SAFE_F1 
Histogram of Timeliness of Injections (Maintenance 
Phase) 
 
W48, W96 
3.18 
3.21 
NA 
Safety 
207966/primar
y_02/F3.18 
Plot of Incidence of Maintenance Phase Study 
Drug Injection Site Reaction Adverse Events by 
Strata and Visit (Overall and Common) - CAB 
and/or RPV 
 
W48, W96 
NA 
NA 
3.9 
Safety 
207966/primar
y_02/F3.18 
Plot of Incidence of Maintenance and Extension 
Phase Study Drug Injection Site Reaction Adverse 
Events by Strata and Visit (Overall and Common) - 
CAB and/or RPV 
 
EOS 
NA 
3.22 
3.10 
Safety 
207966/regqry
_2019_01/F3.2
03 
Patient Profile for Subjects with Syncope or 
Presyncope Adverse Events (Maintenance + 
Extension Phase) 
Footnotes may be adjusted as 
appropriate. 
WK96, EOS 
 


CONFIDENTIAL 
 
 
 
207966 
 
236 
 
15.15.5.6. Pharmacokinetic Tables 
Note: For WK48 deliverable, data from visits up to Week 48 are included. For WK96 deliverable, except for Table 4.8- Table 4.9, add 
“(Maintenance Phase)” after visit in the title. Table 4.8- Table 4.9 will only be produced if additional LTFU PK storage samples since the last analysis 
data cut are planned to be analysed. 
Pharmacokinetic Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.1 
4.1 
NA 
Pharmacokinetic 
201585/primary_
02/T4.1 
Summary of Plasma CAB PK Concentration (ug/mL) 
-Time Data by Treatment and Visit – Including Log-
transformed Statistics 
Remove the first 
footnote. 
W48, W96 
4.2 
4.2 
NA 
Pharmacokinetic 
201585/primary_
02/T4.2 
Summary of Plasma RPV PK Concentration (ng/mL) 
-Time Data by Treatment and Visit – Including Log-
transformed Statistics 
Remove the first 
footnote. 
W48, W96 
4.3 
4.3 
NA 
Pharmacokinetic 
201585/primary_
02/T4.3 
Summary of Evaluable Plasma CAB PK 
Concentration (ug/mL) -Time Data by Treatment 
and Visit – Including Log-transformed Statistics 
Remove the first 
footnote. 
W48, W96 
4.4 
4.4 
NA 
Pharmacokinetic 
201585/primary_
02/T4.4 
Summary of Evaluable Plasma RPV PK 
Concentration (ng/mL) -Time Data by Treatment 
and Visit – Including Log-transformed Statistics 
Remove the first 
footnote. 
W48, W96 
4.5 
4.5 
NA 
Pharmacokinetic 
201585/primary_
02/T4.3 
Summary of Evaluable Plasma CAB PK 
Concentration (ug/mL) -Time Data by Strata and 
Treatment and Visit – Including Log-transformed 
Statistics 
Display by rederived 
randomization strata and 
add footnote for strata. 
W48, W96 
4.6 
4.6 
NA 
Pharmacokinetic 
201585/primary_
02/T4.4 
Summary of Evaluable Plasma RPV PK 
Concentration (ng/mL) -Time Data by Strata and 
Treatment and Visit – Including Log-transformed 
Statistics 
Display by rederived 
randomization strata and 
add footnote for strata. 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
237 
 
Pharmacokinetic Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.7 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/T4.6 
Summary of Results of Steady State Assessment by 
Strata for Q8W Arm- Evaluable Concentration 
Display by rederived 
randomization strata and 
add footnote for strata. 
For Q8W arm only. 
W48 
NA 
4.7 
NA 
Pharmacokinetic 
Shell PK_T1 
Summary of Expected and Missed Visits by Strata 
and Treatment (Maintenance Phase) – Plasma CAB 
PK Concentration 
 
W96 
NA 
4.8 
NA 
Pharmacokinetic 
Shell PK_T1 
Summary of Expected and Missed Visits by Strata 
and Treatment (Maintenance Phase) – Plasma RPV 
PK Concentration 
 
W96 
NA 
4.9 
4.1 
Long-term 
Follow-up 
207966/primary_
02/T4.1 
Summary of Plasma CAB PK Concentration (ug/mL) 
-Time Data by Treatment and Visit (Long-term 
Follow-up Phase) - Including Log-transformed 
Statistics 
Remove the column ‘Pl. 
Time’ and the second 
footnote. Produce only if 
we have additional LTFU 
storage samples planned 
to be analysed since last 
analysis data cut. 
W96, EOS 
NA 
4.10 
4.2 
Long-term 
Follow-up 
207966/primary_
02/T4.2 
Summary of Plasma RPV PK Concentration (ng/mL) 
-Time Data by Treatment and Visit (Long-term 
Follow-up Phase) - Including Log-transformed 
Statistics 
Remove the column ‘Pl. 
Time’ and the second 
footnote. Produce only if 
we have additional LTFU 
samples planned to be 
analysed since last 
analysis data cut. 
W96, EOS 
 
 


CONFIDENTIAL 
 
 
 
207966 
 
238 
 
15.15.5.7. Pharmacokinetic Figures 
Note: Unless otherwise specified, display both arms. For WK96 deliverable, add “- Maintenance Phase” to the end of the title except for Figure 
4.17; display Week 96 visit next to Week 48 visit in the mean and median summary figures and add a footnote as appropriate. 
Pharmacokinetic Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
4.1 
4.1 
NA 
Pharmacokinetic 
201585/primary_02/
F4.1 
Individual Plasma CAB Concentration-
Time Plots (Linear and Semi-Log) 
Also include prior exposure to 
CAB+RPV (e.g. 0, 1-24, >24 
weeks) for each subject.  
W48, W96 
4.2 
4.2 
NA 
Pharmacokinetic 
201585/primary_02/
F4.2 
Individual Plasma RPV Concentration-
Time Plots (Linear and Semi-Log) 
Also include prior exposure to 
CAB+RPV (e.g. 0, 1-24, >24 
weeks) for each subject. 
W48, W96 
4.3 
4.3 
NA 
Pharmacokinetic 
201585/primary_02/
F4.3 
Mean (SD) Plasma CAB Concentration-
Time Plots (Linear and Semi-Log)  
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.4 
4.4 
NA 
Pharmacokinetic 
201585/primary_02/
F4.5 
Mean (SD) Plasma RPV Concentration-
Time Plots (Linear and Semi-Log) 
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.5 
4.5 
NA 
Pharmacokinetic 
201585/primary_02/
F4.7 
Mean (SD) Evaluable Plasma CAB 
Concentration-Time Plots (Linear and 
Semi-Log) 
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.6 
4.6 
NA 
Pharmacokinetic 
201585/primary_02/
F4.9 
Mean (SD) Evaluable Plasma RPV 
Concentration-Time Plots (Linear and 
Semi-Log) 
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.7 
4.7 
NA 
Pharmacokinetic 
201585/primary_02/
F4.7 
Mean (SD) Evaluable Plasma CAB 
Concentration-Time Plots by Strata 
(Linear and Semi-Log) 
Display by rederived 
randomization strata and add 
footnote for strata. For WK48, 
data from visits up to Week 48 
are included. 
W48, W96 
4.8 
4.8 
NA 
Pharmacokinetic 
201585/primary_02/
Mean (SD) Evaluable Plasma RPV 
Display by rederived 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
239 
 
Pharmacokinetic Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
F4.9 
Concentration-Time Plots by Strata 
(Linear and Semi-Log) 
randomization strata and add 
footnote for strata. For WK48, 
data from visits up to Week 48 
are included. 
4.9 
4.9 
NA 
Pharmacokinetic 
201585/primary_02/
F4.4 
Median (5th and 95th Percentile) Plasma 
CAB Concentration-Time Plots (Linear 
and Semi-Log) 
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.10 
4.10 
NA 
Pharmacokinetic 
201585/primary_02/
F4.6 
Median (5th and 95th Percentile) Plasma 
RPV Concentration-Time Plots (Linear 
and Semi-Log) 
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.11 
4.11 
NA 
Pharmacokinetic 
201585/primary_02/
F4.8 
Median (5th and 95th Percentile) 
Evaluable Plasma CAB Concentration-
Time Plots (Linear and Semi-Log) 
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.12 
4.12 
NA 
Pharmacokinetic 
201585/primary_02/
F4.10 
Median (5th and 95th Percentile) 
Evaluable Plasma RPV Concentration-
Time Plots (Linear and Semi-Log) 
For WK48, data from visits up 
to Week 48 are included. 
W48, W96 
4.13 
4.13 
NA 
Pharmacokinetic 
201585/primary_02/
F4.8 
Median (5th and 95th Percentile) 
Evaluable Plasma CAB Concentration-
Time Plots by Strata (Linear and Semi-
Log) 
Display by rederived 
randomization strata and add 
footnote for strata. For WK48, 
data from visits up to Week 48 
are included. 
W48, W96 
4.14 
4.14 
NA 
Pharmacokinetic 
201585/primary_02/
F4.10 
Median (5th and 95th Percentile) 
Evaluable Plasma RPV Concentration-
Time Plots by Strata (Linear and Semi-
Log) 
Display by rederived 
randomization strata and add 
footnote for strata. For WK48, 
data from visits up to Week 48 
are included. 
W48, W96 
4.15 
4.17 
4.1 
Long-term 
207966/primary_02/
Plasma PK Concentration-Time since 
For W96 and EOS: Plot by 
W48, W96, 


CONFIDENTIAL 
 
 
 
207966 
 
240 
 
Pharmacokinetic Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
Follow-up 
F4.15 
Last Injection Plots by Strata 
treatment instead of by strata 
and change “Strata” to be 
“Treatment” in the title; Color-
code different strata of prior 
exposure; exclude RPV 
concentrations on/after the 
start of LTFU oral RPV and 
add footnote for this exclusion; 
will only be produced if 
additional LTFU PK storage 
samples since the last analysis 
data cut are planned to be 
analysed. 
EOS 
4.16 
4.15 
NA 
Pharmacokinetic 
207966/primary_06/
F4.16 
Median Evaluable Plasma CAB Trough 
PK Concentration (ug/mL) - Time Plots by 
Treatment and Strata (Linear and Semi-
Log) 
 
W48, W96 
4.17 
4.16 
NA 
Pharmacokinetic 
207966/primary_06/
F4.17 
Median Evaluable Plasma RPV Trough 
PK Concentration (ng/mL) - Time Plots by 
Treatment and Strata (Linear and Semi-
Log) 
 
W48, W96 


CONFIDENTIAL 
 
 
 
207966 
 
241 
 
15.15.5.8. Pharmacokinetic / Pharmacodynamic Tables 
Note: Unless otherwise specified, display by treatment arm.  
Pharmacokinetic / Pharmacodynamic Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
PK / PD Efficacy  
5.1 
NA 
NA 
Pharmacokinetic 
201584/primary_0
1/T5.1 
Univariable Logistic Regression Analysis 
of Snapshot ‘HIV-1 RNA ≥50 c/mL’ at 
Week 48 by Trough PK Concentration and 
Subgroup for Subjects without Prior 
Exposure to CAB + RPV 
 
W48 
5.2 
NA 
NA 
Pharmacokinetic 
201584/primary_0
1/T5.2 
Multivariable Logistic Regression Analysis 
of Predictors of Snapshot ‘HIV-1 RNA ≥50 
c/mL’ at Week 48 for Subjects without 
Prior Exposure to CAB + RPV 
 
W48 
5.3 
NA 
NA 
Pharmacokinetic 
201584/primary_0
1/T5.5 
Summary of Week 8 Trough CAB PK 
concentration by Snapshot ‘HIV-1 RNA 
≥50 c/mL’ (Yes vs. No) at Week 48 for 
Subjects without Prior Exposure to CAB + 
RPV – Including Log-transformed 
Statistics 
 
W48 
5.4 
NA 
NA 
Pharmacokinetic 
201584/primary_0
1/T5.6 
Summary of Week 8 Trough RPV PK 
concentration by Snapshot ‘HIV-1 RNA 
≥50 c/mL’ (Yes vs. No) at Week 48 for 
Subjects without Prior Exposure to CAB + 
RPV – Including Log-transformed 
Statistics 
 
W48 
 


CONFIDENTIAL 
 
 
 
207966 
 
242 
 
15.15.5.9. Pharmacokinetic / Pharmacodynamic Figures 
Pharmacokinetic / Pharmacodynamic Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
PK / PD Efficacy Analyses 
5.1 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.3 
Scatter Plot of Week 8 Trough CAB PK 
Concentration by Snapshot ‘HIV-1 RNA 
≥50 c/mL’ (Yes vs. No) at Week 48 for 
Subjects without Prior Exposure to CAB + 
RPV 
 
W48 
5.2 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.4 
Scatter Plot of Week 8 Trough RPV PK 
Concentration by Snapshot ‘HIV-1 RNA 
≥50 c/mL’ (Yes vs. No) at Week 48 for 
Subjects without Prior Exposure to CAB + 
RPV 
 
W48 
5.3 
5.1 
NA 
Pharmacokinetic 
207966/internal_
01/F5.1 
Individual CAB Trough Concentration-time 
Profiles for Subjects with Snapshot 'HIV-1 
RNA ≥50 c/mL' at Week 48 and Median, 
5th & 95th Percentile of CAB Conc-Time 
Profiles for Other Subjects (Semi-Log) 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ and add “- 
Maintenance Phase” to the end 
of the title. Display by 
treatment arm. 
W48, W96 
5.4 
5.2 
NA 
Pharmacokinetic 
207966/internal_
01/F5.2 
Individual RPV Trough Concentration-time 
Profiles for Subjects with Snapshot 'HIV-1 
RNA ≥50 c/mL' at Week 48 and Median, 
5th & 95th Percentile of RPV Conc-Time 
Profiles for Other Subjects (Semi-Log) 
For WK96, replace ‘Week 48’ 
with ‘Week 96’ and add “- 
Maintenance Phase” to the end 
of the title. Display by 
treatment arm.  
W48, W96 
5.5 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.10 
Scatter Plot of Week 8 Trough 
Concentration of CAB and RPV in Relation 
to Occurrence of Snapshot ‘HIV-1 RNA 
≥50 c/mL’ at Week 48 for Subjects without 
Prior Exposure to CAB + RPV 
 
 W48 


CONFIDENTIAL 
 
 
 
207966 
 
243 
 
Pharmacokinetic / Pharmacodynamic Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
PK / PD Safety Analyses 
5.6 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.13 
Scatter Plot of Maximum Change from 
Baseline in ALT versus Last Trough CAB 
PK Concentrations by Strata and 
Treatment during the Maintenance Phase 
Display by strata and treatment 
arm. Add footnote for rederived 
randomization strata. 
W48 
5.7 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.14 
Scatter Plot of Maximum Change from 
Baseline in ALT versus Last Trough RPV 
PK Concentrations by Strata and 
Treatment during the Maintenance Phase 
Display by strata and treatment 
arm. Add footnote for rederived 
randomization strata. 
W48 
5.8 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.15 
Scatter Plot of Maximum Change from 
Baseline in Total Bilirubin versus Last 
Trough CAB PK Concentrations by Strata 
and Treatment during the Maintenance 
Phase 
Display by strata and treatment 
arm. Add footnote for rederived 
randomization strata. 
W48 
5.9 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.16 
Scatter Plot of Maximum Change from 
Baseline in Total Bilirubin versus Last 
Trough RPV PK Concentrations by Strata 
and Treatment during the Maintenance 
Phase 
Display by strata and treatment 
arm. Add footnote for rederived 
randomization strata. 
W48 
5.10 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.17 
Box Plot of Maximum Toxicity Grades of 
Most Frequently Reported Study Drug ISR 
Adverse Events versus Last Trough CAB 
PK Concentrations during the Maintenance 
Phase by Strata and Treatment 
Display by strata and treatment 
arm. Add footnote for rederived 
randomization strata. Adjust 
the footnotes as appropriate. 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
244 
 
Pharmacokinetic / Pharmacodynamic Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
5.11 
NA 
NA 
Pharmacokinetic 
201585/primary_
02/F5.18 
Box Plot of Maximum Toxicity Grades of 
Most Frequently Reported Study Drug ISR 
Adverse Events versus Last Trough RPV 
PK Concentrations during the Maintenance 
Phase by Strata and Treatment 
Display by treatment arm. 
Adjust the footnotes as 
appropriate. 
W48 
 
 
 


CONFIDENTIAL 
 
 
 
207966 
 
245 
 
15.15.5.10. Health Outcomes Tables 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Perception of Injection (PIN) 
6.1 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.1 
Proportion of Subjects with Each Individual Item 
Score in PIN by Visit –LOCF (Maintenance 
Phase) 
Display both arms. 
W48 
6.2 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.2 
Summary of PIN in Domain Scores (Bother of 
ISRs, Leg movement, Sleep, and Acceptance) 
and Individual Items Scores (Anxiety before, Pain, 
Satisfaction, Anxiety After, Willingness) by Visit 
(Maintenance Phase) 
Display both arms. 
W48 
6.3 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.3 
Summary and Statistical Analysis of PIN in 
Domain Scores (Bother of ISRs, Leg movement, 
Sleep, and Acceptance) and Individual Items 
Scores (Anxiety before, Pain, Satisfaction, Anxiety 
After, Willingness) by Visit - LOCF (Maintenance 
Phase) 
Display both arms. Adjust the 
first half of the footnote to “[1] 
Week 24/48 was compared with 
the 1st visit (Week 8) based on 
Wilcoxon signed-rank test, 
respectively.” 
W48 
6.4 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.4 
Summary of PIN Change from Week 8 in Domain 
Scores (Bother of ISRs, Leg movement, Sleep, 
and Acceptance) and Individual Items Scores 
(Anxiety before, Pain, Satisfaction, Anxiety After, 
Willingness) by Visit (Maintenance Phase) 
Display both arms. Adjust the 
footnote to “Note: Actual values 
are shown at Week 8.” 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
246 
 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
6.5 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.5 
Summary of PIN Change from Week 8 in Domain 
Scores (Bother of ISRs, Leg movement, Sleep, 
and Acceptance) and Individual Items Scores 
(Anxiety before, Pain, Satisfaction, Anxiety After, 
Willingness) by Visit – LOCF (Maintenance 
Phase) 
Display both arms. Adjust the 
footnote to “Note: Actual values 
are shown at Week 8.” 
W48 
6.6 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.11 
Statistical Analysis of PIN Change from Week 8 in 
Domain Scores (Bother of ISRs, Leg Movement, 
Sleep, and Acceptance) and Individual Items 
Scores (Anxiety before, Pain, Satisfaction, Anxiety 
After, Willingness) by Visit – LOCF (Maintenance 
Phase) 
Adjust the column header and 
the footnote as appropriate. 
W48 
Health-related Quality of Life (HAT-QoL) 
6.7 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.6 
Proportion of Subjects with Each Individual 
Questionnaire Item Score in HAT-QoL by Visit - 
LOCF (Maintenance Phase) 
 
W48 
6.8 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.7 
Summary of Quality of Life (HAT-QoL) Score in 
Life Satisfaction, HIV Medication, and Disclosure 
worries by Visit (Maintenance phase) 
 
W48 
6.9 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.8 
Summary of Quality of Life (HAT-QoL) Score in 
Life Satisfaction, HIV Medication, and Disclosure 
worries by Visit - LOCF (Maintenance phase) 
 
W48 
6.10 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.9 
Summary of Quality of Life Score (HAT-QoL)-
Change from Baseline in Life Satisfaction, HIV 
Medication, and Disclosure Worries by Prior 
Exposure to CAB+RPV (0 vs. >=1 Weeks) and 
Visit (Maintenance Phase) 
 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
247 
 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
6.11 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.10 
Summary of Quality of Life Score (HAT-QoL)-
Change from Baseline in Life Satisfaction, HIV 
Medication, and Disclosure Worries by Prior 
Exposure to CAB+RPV (0 vs. >=1 Weeks) and 
Visit – LOCF (Maintenance Phase) 
 
W48 
6.12 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.11 
Statistical Analysis of Quality of Life Score (HAT-
QoL)- Change from Baseline in Life Satisfaction, 
HIV Medication, and Disclosure Worries by Visit 
for Subjects without Prior Exposure to CAB+RPV 
– LOCF (Maintenance Phase) 
Adjust the column header and 
the footnote as appropriate. 
W48 
6.13 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.11 
Statistical Analysis of Quality of Life Score (HAT-
QoL)- Change from Baseline in Life Satisfaction, 
HIV Medication, and Disclosure Worries by Visit 
for Subjects with Prior Exposure to CAB+RPV – 
LOCF (Maintenance Phase) 
Adjust the column header and 
the footnote as appropriate. 
W48 
HIV Treatment Satisfaction Questionnaire Status Version (HIVTSQs) 
6.14 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.18 
Proportion of Subjects with HIVTSQs - Individual 
Item Scores by Visit - LOCF (Maintenance Phase) 
 
W48 
6.15 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.19 
Proportion of Subjects with HIVTSQs - Individual 
Item Scores by Visit and Subgroup - LOCF 
(Maintenance Phase) 
The subgroup includes: prior 
exposure to CAB+RPV (0, 1-24, 
>=24 weeks), sex at birth, age 
(<35, 35 - <50, >=50), race 
(white, non-white), Baseline 
CD4+ cell count (<350, 350 – 
<500, >=500) 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
248 
 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
6.16 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.20 
Summary of HIVTSQs - Total Treatment 
Satisfaction Score by Visit (Maintenance Phase) 
 
W48 
6.17 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.21 
Summary of HIVTSQs - Total Treatment 
Satisfaction Score by Visit – LOCF (Maintenance 
Phase) 
 
W48 
6.18 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.22 
Summary of HIVTSQs - Change from Baseline in 
Total Treatment Satisfaction Score by Prior 
Exposure to CAB+RPV (0 vs. >=1 Weeks) and 
Visit (Maintenance Phase) 
 
W48 
6.19 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.23 
Summary of HIVTSQs - Change from Baseline in 
Total Treatment Satisfaction Score by Prior 
Exposure to CAB+RPV (0 vs. >=1 Weeks) and 
Visit – LOCF (Maintenance Phase) 
 
W48 
6.20 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_03/T7.41 
Summary of HIVTSQs - Change from Baseline in 
Individual Item Score by Prior Exposure to 
CAB+RPV (0 vs. >=1 Weeks) and Visit – LOCF 
(Maintenance Phase) 
 
W48 
6.21 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.24 
Statistical Analysis of HIVTSQs - Change from 
Baseline in Total Treatment Satisfaction Score by 
Visit for Subjects without Prior Exposure to 
CAB+RPV - LOCF (Maintenance Phase) 
Adjust column header and 
footnote as appropriate. 
W48 
6.22 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.24 
Statistical Analysis of HIVTSQs - Change from 
Baseline in Total Treatment Satisfaction Score by 
Visit for Subjects with Prior Exposure to 
CAB+RPV - LOCF (Maintenance Phase) 
Adjust column header and 
footnote as appropriate. 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
249 
 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
HIV Treatment Satisfaction Questionnaire Change Version (HIVTSQc) 
6.23 
NA 
NA 
Q4W 
ATLAS 
201584/primar
y_01/T6.25 
Proportion of Subjects with HIVTSQc - Individual 
Item Change Score at Week 48 (Maintenance 
Phase) for Subjects from Q4W ATLAS 
 
W48 
6.24 
NA 
NA 
SOC 
201584/primar
y_01/T6.25 
Proportion of Subjects with HIVTSQc - Individual 
Item Change Score at Week 48 (Maintenance 
Phase) for Subjects from SOC 
 
W48 
6.25 
NA 
NA 
Q4W 
ATLAS 
201584/primar
y_01/T6.26 
Summary of HIVTSQc – Total Treatment 
Satisfaction Change Score at Week 48 
(Maintenance Phase) for Subjects from Q4W 
ATLAS 
 
W48 
6.26 
NA 
NA 
SOC 
201584/primar
y_01/T6.26 
Summary of HIVTSQc – Total Treatment 
Satisfaction Change Score at Week 48 
(Maintenance Phase) for Subjects from SOC 
 
W48 
6.27 
NA 
NA 
Q4W 
ATLAS 
201584/primar
y_02/T6.41 
Summary of HIVTSQc – Individual Item Change 
Score at Week 48 (Maintenance Phase) for 
Subjects from Q4W ATLAS 
 
W48 
6.28 
NA 
NA 
SOC 
201584/primar
y_02/T6.41 
Summary of HIVTSQc – Individual Item Change 
Score at Week 48 (Maintenance Phase) for 
Subjects from SOC 
 
W48 
6.29 
NA 
NA 
Q4W 
ATLAS 
201584/primar
y_01/T6.27 
Statistical Analysis of HIVTSQc – Total Treatment 
Satisfaction Change Score at Week 48 
(Maintenance Phase) for Subjects from Q4W 
ATLAS 
Adjust column header and 
footnote as appropriate. 
W48 
6.30 
NA 
NA 
SOC 
201584/primar
y_01/T6.27 
Statistical Analysis of HIVTSQc – Total Treatment 
Satisfaction Change Score at Week 48 
(Maintenance Phase) for Subjects from SOC 
Adjust column header and 
footnote as appropriate. 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
250 
 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Treatment Acceptance (ACCEPT) 
6.31 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.28 
Proportion of Subjects with ACCEPT - Individual 
Item Score by Visit - LOCF (Maintenance Phase) 
 
W48 
6.32 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.29 
Summary of Acceptance/General Dimension 
Score (ACCEPT Questionnaire) by Visit 
(Maintenance Phase) 
 
W48 
6.33 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.30 
Summary of Acceptance/General Dimension 
Score (ACCEPT Questionnaire) by Visit - LOCF 
(Maintenance Phase) 
 
W48 
6.34 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.31 
Summary of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Prior Exposure to CAB+RPV (0 
vs. >=1 Weeks) and Visit (Maintenance Phase) 
 
W48 
6.35 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.32 
Summary of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Prior Exposure to CAB+RPV (0 
vs. >=1 Weeks) and Visit - LOCF (Maintenance 
Phase) 
 
W48 
6.36 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.33 
Statistical Analysis of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit for Subjects without Prior 
Exposure to CAB+RPV – LOCF (Maintenance 
Phase) 
Adjust column header and 
footnote as appropriate. 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
251 
 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
6.37 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/T7.33 
Statistical Analysis of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit for Subjects with Prior 
Exposure to CAB+RPV – LOCF (Maintenance 
Phase) 
Adjust column header and 
footnote as appropriate. 
W48 
Preference 
6.38 
NA 
NA 
Q4W 
ATLAS 
Shell HO_T1 
Proportion of Subjects with Response to Each 
Individual Question in Preference Questionnaire 
at Week 48 (Maintenance Phase) for Subjects 
from Q4W ATLAS to Q8W ATLAS-2M 
Only display Q8W arm. 
HL, W48 
6.39 
NA 
NA 
Intent-to-
Treat 
Exposed 
Shell HO_T1 
Proportion of Subjects with Response to Each 
Individual Question in Preference Questionnaire 
by Prior Exposure to CAB+RPV (0 vs. >=1 
Weeks) at Week 48 for Subjects in Q8W ATLAS-
2M (Maintenance Phase) 
Only display Q8W arm. 
W48 
6.40 
NA 
NA 
Intent-to-
Treat 
Exposed 
Shell HO_T1 
Proportion of Subjects with Response to Each 
Individual Question in Preference Questionnaire 
at Week 48 for Subjects in Q4W ATLAS-2M 
(Maintenance Phase) 
Only display Q4W arm. 
W48 
Reasons for Switch/Continuation 
6.41 
NA 
NA 
SOC 
201585/primar
y_02/T7.40 
Reasons for Switch at Baseline for Subjects from 
SOC 
Remove columns ‘Analysis Visit’ 
and ‘Total’. For percentages, use 
the format ‘xx / xx (xx%)’ where 
the denominator is the number of 
subjects with available valid data 
from the questionnaire. 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
252 
 
Health Outcomes Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
6.42 
NA 
NA 
Q4W 
ATLAS 
201585/primar
y_02/T7.40 
Reasons for Continuation at Baseline for Subjects 
from Q4W ATLAS 
Remove columns ‘Analysis Visit’ 
and ‘Total’. For percentages, use 
the format ‘xx / xx (xx%)’ where 
the denominator is the number of 
subjects with available valid data 
from the questionnaire. 
W48 
 
 


CONFIDENTIAL 
 
 
 
207966 
 
253 
 
15.15.5.11. Health Outcomes Figures 
Health Outcomes Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
6.1 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.1 
Line Plot of Adjusted Mean (95% CI) Change from 
Baseline in HIVTSQs Total Treatment Satisfaction 
Score over Time(ANCOVA) for Subjects without 
Prior Exposure to CAB+RPV - LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 
6.2 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.1 
Line Plot of Adjusted Mean (95% CI) Change from 
Baseline in HIVTSQs Total Treatment Satisfaction 
Score over Time(ANCOVA) for Subjects with Prior 
Exposure to CAB+RPV - LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 
6.3 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.2 
Line Plot of Difference (95% CI) in Adjusted Mean 
Change from Baseline in HIVTSQs Total Treatment 
Satisfaction Score over Time (ANCOVA) for 
Subjects without Prior Exposure to CAB+RPV - 
LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 
6.4 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.2 
Line Plot of Difference (95% CI) in Adjusted Mean 
Change from Baseline in HIVTSQs Total Treatment 
Satisfaction Score over Time (ANCOVA) for 
Subjects with Prior Exposure to CAB+RPV - LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 
6.5 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.5 
Line Plot of Adjusted Mean (95% CI) Change from 
Baseline in HAT-QoL (Life Satisfaction, HIV 
medication, and Disclosure Worries) by Visit 
(ANCOVA) for Subjects without Prior Exposure to 
CAB+RPV - LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 


CONFIDENTIAL 
 
 
 
207966 
 
254 
 
Health Outcomes Figures 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
6.6 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.5 
Line Plot of Adjusted Mean (95% CI) Change from 
Baseline in HAT-QoL (Life Satisfaction, HIV 
medication, and Disclosure Worries) by Visit 
(ANCOVA) for Subjects with Prior Exposure to 
CAB+RPV - LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 
6.7 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.6 
Line Plot of Difference in Adjusted Mean (95% CI) 
Change from Baseline in HAT-QoL (Life 
Satisfaction, HIV Medication, and Disclosure 
Worries) by Visit (ANCOVA) for Subjects without 
Prior Exposure to CAB+RPV - LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 
6.8 
NA 
NA 
Intent-to-
Treat 
Exposed 
201585/primary
_02/F7.6 
Line Plot of Difference in Adjusted Mean (95% CI) 
Change from Baseline in HAT-QoL (Life 
Satisfaction, HIV Medication, and Disclosure 
Worries) by Visit (ANCOVA) for Subjects with Prior 
Exposure to CAB+RPV - LOCF 
Adjust footnotes as 
appropriate. Include Baseline 
as a timepoint in x axis. 
W48 
 
 


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15.15.5.12. Virology Tables 
Note: If there is one or more CVFs during the Extension Phase, the tables included in “Genotype” and “Phenotype” below will also be 
produced for Maintenance and Extension Phase for Week 96 analysis. 
Virology Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Genotype 
7.1 
7.1 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.1 
Summary of the Prevalence of Known INI 
Resistance Mutations at time of CVF (Maintenance 
Phase) – Plasma Sample 
 
W48, W96 
7.2 
7.2 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.2 
Summary of the Prevalence of Major Resistance 
Mutations of NRTI, NNRTI and PI Class at time of 
CVF (Maintenance Phase) - Plasma Sample 
 
W48, W96 
7.3 
7.3 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.4 
Summary of Genotypic Susceptibility at time of CVF 
(Maintenance Phase) - Plasma Sample 
 
W48, W96 
Phenotype 
7.4 
7.4 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.3 
Summary of Phenotype Susceptibility at time of CVF 
(Maintenance Phase) - Plasma Sample 
 
W48, W96 
7.5 
7.5 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.6 
Summary of Phenotype: Number of Drugs to Which 
Subject is Phenotypic Resistant or Partial Sensitive 
or Sensitive at Time of CVF (Maintenance Phase) - 
Plasma Sample 
 
W48, W96 
7.6 
7.6 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.7 
Summary of Fold Change to CAB and RPV at Time 
of CVF (Maintenance Phase) - Plasma Sample 
 
W48, W96 


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Virology Tables 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
7.7 
7.7 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.5 
Summary of Net Assessment at time of CVF 
(Maintenance Phase) - Plasma Sample 
 
W48, W96 
Miscellaneousness 
7.8 
7.8 
NA 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.8 
Summary of Viral load, Genotypic and Phenotypic 
data for Subjects Who Met Confirmed Virologic 
Failure Criteria during the Maintenance Phase 
Remove columns for ‘ARTs’, 
‘FC for ARTs’. Adjust the 
footnotes as appropriate. For 
W96: Include baseline 
genotypic data from ATLAS 
PBMC samples; label sample 
as appropriate. 
HL, W48, 
W96 
NA 
7.9 
7.1 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/T8.8 
Summary of Viral load, Genotypic and Phenotypic 
data for Subjects Who Met Confirmed Virologic 
Failure Criteria during the Maintenance and 
Extension Phase 
Remove columns for ‘ARTs’, 
‘FC for ARTs’. Adjust the 
footnotes as appropriate. For 
W96 and EOS: Include 
baseline genotypic data from 
ATLAS PBMC samples; label 
sample as appropriate. 
W96, EOS 
7.9 
7.10 
7.2 
Safety 
201585/primar
y_02/T8.8 
Summary of Viral load, Genotypic and Phenotypic 
data for Non-CVF Subjects with Genotypic and/or 
Phenotypic Data 
Remove columns for ‘ARTs’, 
‘FC for ARTs’. Adjust the 
footnotes as appropriate. For 
W96 and EOS: Include 
baseline genotypic data from 
ATLAS PBMC samples; label 
sample as appropriate; 
remove the last footnote from 
the same table in WK48 
analysis. 
W48, W96, 
EOS 


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15.15.5.13. ICH Listings 
Note: Unless otherwise specified, both unique subject ID and latest subject ID for a subject will be included in the listings; display by 
prior exposure to CAB+RPV (0, 1-24, >24 weeks, refer to Section 15.6.2 for calculation details) for all listings except for study 
population listings.  
ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
1 
1 
1 
Randomized 
201585/prima
ry_02/L1 
Listing of Subjects Randomized but 
Not Treated 
 
W48, W96 
2 
2 
2 
Randomized 
201585/prima
ry_02/L2 
Listing of Randomized and Actual 
Strata and Treatment Assignment 
Randomized and Actual Treatments will 
include oral lead-in information (e.g. Oral 
followed by Q4W). Change the footnote # 
for column ‘Dev.’ to be [2]. Add a footnote 
for actual strata: [1] Actual strata are 
derived using the prior exposure to 
CAB+RPV in Study 201585, collected from 
eCRF. 
W48, W96 
3 
3 
3 
Screened 
201585/prima
ry_02/L3 
Listing of Reasons for Screen 
Failure 
 
W48, W96 
4 
4 
4 
Intent-to-
Treat 
Exposed 
ES2 
Listing of Reasons for Study 
Withdrawal 
For WK96 and EOS: Add a footnote: “Note: 
This listing includes withdrawals per the 
data collected from the Study Conclusion 
eCRF form. It includes withdrawals from 
Maintenance or Extension Phase, and 
withdrawals from subjects who completed 
Maintenance phase and did not enter 
Extension phase with reasons beyond the 
HL, W48, W96, 
EOS 


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ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
completion of the study commitment.” 
5 
5 
5 
Intent-to-
Treat 
Exposed 
201585/prima
ry_02/L5 
Listing of Reasons for Study Drug 
Discontinuation 
 
W48, W96, EOS 
6 
6 
6 
Intent-to-
Treat 
Exposed 
DV2 
Listing of Important Protocol 
Deviations 
For W96 and EOS: add a column on the 
right “COVID-19 Related”. The possible 
values in this column are Y and N, where Y 
indicates the deviation is COVID-19 related 
and N indicates the deviation is non-
COVID-19 related. 
W48, W96, EOS 
7 
7 
7 
Intent-to-
Treat 
Exposed 
DV2 
Listing of Protocol Deviations 
Leading to Exclusion from the Per-
Protocol Population 
Remove the last column on the right. 
HL, W48, W96 
8 
8 
8 
Intent-to-
Treat 
Exposed 
201585/prima
ry_02/L8 
Listing of Subjects with 
Inclusion/Exclusion Criteria 
Deviations 
 
W48, W96 
9 
9 
9 
Intent-to-
Treat 
Exposed 
201585/prima
ry_02/L9 
Listing of Demographic 
Characteristics 
 
W48, W96, EOS 
10 
10 
10 
Intent-to-
Treat 
Exposed 
201585/prima
ry_02/L10 
Listing of Race 
 
W48, W96, EOS 
Efficacy 
11 
11 
11 
Intent-to-
Treat 
Exposed 
201585/prima
ry_02/L11 
Listing of Study Outcome (50 c/mL 
Threshold) at Week 48 – Snapshot 
Analysis 
For WK96: replace “48” with “96” in the 
title. Add a column “COVID-19 
Relatedness” between Columns “Study 
HL, W48, W96 


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ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Outcome” and “Subreason”. Add a footnote 
“Note: Subjects XXXXX, XXXXX, and 
XXXXX took SOC oral bridging prior 
to/during Week 96 and their SOC oral 
bridging medications are considered part of 
the study treatment for the purpose of the 
snapshot. No snapshot penalty is applied 
to the temporary permitted switch to SOC 
oral bridging due to COVID-19.”  
Safety: Exposure 
12 
12 
12 
Safety 
201585/prima
ry_02/L12 
Listing of Investigational Product 
Exposure Data 
 
W48, W96, EOS 
Safety: Adverse Events 
13 
13 
13 
Safety 
201585/prima
ry_02/L13 
Listing of Subject Numbers for 
Individual Adverse Events 
(Maintenance + Extension Phase) 
For WK96 and EOS: Remove 
“(Maintenance + Extension Phase)” from 
the title (i.e. no phase restriction); display 
by Phase and prior exposure to CAB+RPV; 
adjust the column lengths for a better 
presentation. 
W48, W96, EOS 
14 
14 
14 
Safety 
201585/prima
ry_02/L14 
Listing of Reasons for Considering 
as a Serious Adverse Event 
(Maintenance + Extension Phase) 
For WK96 and EOS: Remove 
“(Maintenance + Extension Phase)” from 
the title (i.e. no phase restriction). 
W48, W96, EOS 
15 
15 
15 
Safety 
201585/prima
ry_02/L15 
Listing of Fatal Adverse Events 
(Maintenance + Extension Phase) 
Add Study Period to the 5th Column from 
the left. For WK96 and EOS: Remove 
“(Maintenance + Extension Phase)” from 
the title (i.e. no phase restriction). 
W48, W96, EOS 


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ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
16 
16 
16 
Safety 
201585/prima
ry_02/L16 
Listing of Non-Fatal Serious 
Adverse Events (Maintenance + 
Extension Phase) 
Add Study Period to the 5th Column from 
the left. For WK96 and EOS: Remove 
“(Maintenance + Extension Phase)” from 
the title (i.e. no phase restriction). 
W48, W96, EOS 
17 
17 
17 
Safety 
201585/prima
ry_02/L17 
Listing of Adverse Events Leading 
to Withdrawal/Permanent 
Discontinuation of Investigational 
Product (Maintenance + Extension 
Phase) 
Add Study Period to the 5th Column from 
the left. 
HL, W48, W96, 
EOS 
18 
18 
18 
Safety 
201585/prima
ry_02/L18 
Listing of Changes in 
Intensity/Grades of Study Drug 
Injection Site Adverse Events 
(Maintenance + Extension Phase) 
For WK96 and EOS: Remove 
“(Maintenance + Extension Phase)” from 
the title (i.e. no phase restriction). 
W48, W96, EOS 
19 
19 
19 
Safety 
201585/prima
ry_03/L30 
Listing of All Adverse Events 
(Maintenance + Extension Phase) 
Add Study Period to the 5th Column from 
the left. For WK96 and EOS: Remove 
“(Maintenance + Extension Phase)” from 
the title (i.e. no phase restriction). 
W48, W96, EOS 
NA 
66 
66 
Safety 
207966/prima
ry_02/L19 
Listing of COVID-19 Adverse 
Events 
 
W96, EOS 
NA 
67 
67 
Safety 
SAF_L1 
Listing of COVID-19 Assessments 
 
W96, EOS 
NA 
68 
68 
Safety 
SAF_L2 
Listing of COVID-19 Symptoms 
 
W96, EOS 
Safety: Pregnancy 
20 
20 
20 
Safety 
201585/prima
ry_02/L19 
Listing of Subjects Who Became 
Pregnant during the Study 
(Maintenance + Extension Phase) 
For EOS, remove “(Maintenance + 
Extension Phase)” from the title. 
W48, W96, EOS 


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ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Safety: Hepatobiliary (Liver) 
21 
21 
21 
Safety 
201585/prima
ry_02/L20 
Listing of Medical Conditions for 
Subjects with Liver stopping Events  
W48, W96, EOS 
22 
22 
22 
Safety 
201585/prima
ry_02/L21 
Listing of Substance Use for 
Subjects with Liver Stopping 
Events 
 
W48, W96, EOS 
Safety: ECG 
23 
23 
23 
Safety 
201584/prima
ry_01/L24 
Listing of ECG Values for Subjects 
with a Value of Potential Clinical 
Importance 
Remove Phase Treatment from the column 
header. Add change from baseline values 
for each of QTc assessment. Adjust the 
footnote as appropriate. A footnote may be 
added to clarify the classification of PCI 
values. 
W48, W96 
24 
24 
24 
Safety 
201584/prima
ry_01/L25 
Listing of ECG Findings 
Remove the ‘Phase Treatment’ from the 
third column on the left. 
W48, W96 
Safety: eC-SSRS 
25 
25 
25 
Safety 
201585/prima
ry_02/L24 
Listing of Possible Suicidality-
Related Adverse Event Data: Event 
and Description (Section 1-Section 
2) 
 
W48, W96 
26 
26 
26 
Safety 
201585/prima
ry_02/L25 
Listing of Possible Suicidality-
Related Adverse Event Data: 
Possible Cause(s) (Section 3) 
 
W48, W96 
27 
27 
27 
Safety 
201585/prima
ry_02/L26 
Listing of Possible Suicidality-
Related Adverse Event Data 
 
W48, W96 


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ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
(Section 4) 
28 
28 
28 
Safety 
201585/prima
ry_02/L27 
Listing of Possible Suicidality-
Related Adverse Event Data 
(Section 5-Section 8) 
 
W48, W96 
PK 
29 
29 
29 
Pharmacoki
netic 
201584/prima
ry_01/L30 
Listing of Plasma CAB PK 
Concentration-Time Data 
Remove ‘Phase Treatment’ from the 
column header. Add a column “Excluded”. 
W48, W96, EOS 
30 
30 
30 
Pharmacoki
netic 
201584/prima
ry_01/L31 
Listing of Plasma RPV PK 
Concentration-Time Data 
Remove ‘Phase Treatment’ from the 
column header. Add a column “Excluded”. 
W48, W96, EOS 
 
 


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15.15.5.14. Non-ICH Listings 
Note: Unless otherwise specified, both unique subject ID and latest subject ID for a subject will be included in the listings; display by 
prior exposure to CAB+RPV (0, 1-24, >24 weeks, refer to calculation details in Section 15.6.2) for all listings except for study population 
listings.  
Non-ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Study Population 
31 
31 
31 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/L30 
Listing of Reasons for Maintenance Phase 
Withdrawal 
 
W48, W96 
32 
32 
32 
Oral Lead-
in 
201585/primar
y_02/L31 
Listing of Reasons for Oral Lead-in Period 
Withdrawal 
 
W48, W96 
NA 
33 
33 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/L32 
Listing of Reasons for Extension Phase 
Withdrawal 
 
W96, EOS 
33 
34 
34 
Long-term 
Follow-up 
201585/primar
y_02/L33 
Listing of Reasons for Long-term Follow-up 
Phase Withdrawal 
 
W48, W96, EOS 
34 
35 
35 
Screened 
Shell POP_L2 
Listing of Subjects Who were Rescreened 
 
W48, W96 
35 
36 
36 
Intent-to-
Treat 
Exposed 
Shell POP_L1 
Listing of Prior ART Medications 
Remove the column ‘Phase 
during Which Concomitant’ 
W48, W96 
36 
37 
37 
Intent-to-
Treat 
Exposed 
Shell POP_L1 
Listing of Concomitant ART Medications 
In case the same medication is 
concomitant during both 
maintenance and extension 
phases, list each of them in two 
separate rows. For W96 and 
EOS: add a column “SOC Oral 
W48, W96, EOS 


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Non-ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Bridging?” which has values of 
“Yes” and “No”. 
37 
38 
38 
Intent-to-
Treat 
Exposed 
Shell POP_L1 
Listing of ART Medications Received during 
Long-term Follow-up Phase 
Remove the column ‘Phase 
during Which Concomitant’. For 
W96 and EOS: add a column 
“Start Date of the Long-term 
Follow-up ART/Study Day”. 
W48, W96, EOS 
38 
39 
39 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/L39 
Listing of Investigational Product 
Accountability - Oral Regimens 
 
W48, W96, EOS 
39 
40 
40 
Intent-to-
Treat 
Exposed 
201584/primar
y_01/L43 
Listing of Medical History of Seizure 
 
W48, W96 
NA 
65 
65 
Intent-to-
Treat 
Exposed 
DV2 
Listing of COVID-19 Related Missed Visits and 
Missed Assessments Protocol Deviations 
 
W96 
Efficacy 
40 
41 
41 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/L40 
Listing of All Plasma HIV-1 RNA Data for 
Subjects with Confirmed Virologic Failure 
In column headers, replace 
‘Period’ with ‘Phase’, replace 
‘Sample Day’ with ‘Study Day’. 
W48, W96, EOS 
41 
42 
42 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/L41 
Listing of All Plasma HIV-1 RNA Data for 
Subjects with Viral load >=50 c/mL during the 
Maintenance Phase 
In column headers, replace 
‘Period’ with ‘Phase’, replace 
‘Sample Day’ with ‘Study Day’. 
HL, W48, W96, 
EOS 
42 
NA 
NA 
Oral Lead-
in 
201585/primar
y_02/L41 
Listing of All Plasma HIV-1 RNA Data for 
Subjects with Viral load >=50 c/mL during the 
Maintenance Oral Lead-in Period 
In column headers, replace 
‘Period’ with ‘Phase’, replace 
‘Sample Day’ with ‘Study Day’. 
W48 
NA 
64 
64 
Intent-to-
207966/primar
Listing of All Plasma HIV-1 RNA Data 
 
W96, EOS 


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Non-ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Treat 
Exposed 
y_02/L41 
43 
43 
43 
Intent-to-
Treat 
Exposed 
201585/primar
y_02/L43 
Listing of HIV-1 Associated Conditions 
(Maintenance + Extension Phase) 
For WK96 and EOS: Do not 
restrict phases, i.e. remove 
“(Maintenance + Extension 
Phase” from the title; add 
“Phase” to the original 
“Treatment State” column header 
and present it as third column on 
the right. 
W48, W96, EOS 
Safety 
44 
44 
44 
Safety 
ABC_HSR_EX
PO2 
Listing of Abacavir Hypersensitivity Reaction 
Record - Exposure to Abacavir 
 
W48, W96 
45 
45 
45 
Safety 
ABC_HSR_DR
UG2 
Listing of Abacavir Hypersensitivity Reaction 
Record - Subject History of Drug Allergies 
 
W48, W96 
46 
46 
46 
Safety 
ABC_HSR_CO
ND2 
Listing of Abacavir Hypersensitivity Reaction 
Record - Subject and Family Conditions 
 
W48, W96 
47 
47 
47 
Safety 
ABC_HSR_RA
SH2 
Listing of Abacavir Hypersensitivity Reaction 
Record - Skin Rash Details 
 
W48, W96 
48 
48 
48 
Safety 
ABC_HSR_SY
MP4 
Listing of Abacavir Hypersensitivity Reaction 
Record - Symptoms 
 
W48, W96 
49 
49 
49 
Safety 
VS4 
Listing of Abacavir Hypersensitivity Reaction 
Record - Vital Signs 
 
W48, W96 
50 
50 
50 
Safety 
ABC_HSR 
_SYMP6 
Listing of Abacavir Hypersensitivity Reaction 
Record - Individual Symptoms and Diagnostic 
Category Assignments (Excluding Other 
Symptoms) 
 
W48, W96 


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Non-ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
51 
51 
51 
Safety 
ABC_HSR_SY
MP7 
Listing of Abacavir Hypersensitivity Reaction 
Record - Individual Symptoms and Diagnostic 
Category Assignments (Other Symptoms) 
 
W48, W96 
52 
52 
52 
Safety 
201585/primar
y_02/L52 
Listing of Liver Monitoring/Stopping Event 
Reporting 
For WK96, remove “Monitoring/” 
from the title. 
W48, W96, EOS 
53 
53 
53 
Safety 
201585/primar
y_02/L53 
Listing of Liver Event Information for RUCAM 
Score 
 
W48, W96, EOS 
54 
54 
54 
Safety 
201585/primar
y_02/L54 
Listing of Liver Biopsy Details 
 
W48, W96, EOS 
55 
55 
55 
Safety 
201585/primar
y_02/L55 
Listing of Liver Imaging Details 
 
W48, W96, EOS 
56 
56 
56 
Safety 
201585/primar
y_02/L59 
Listing of Subjects Meeting Hepatobiliary Lab 
Criteria  
For WK96 and EOS: Follow 
207966/primary_11/L1; display 
by phase and prior exposure to 
CAB+RPV. Screening and LTFU 
phases are not included. 
W48, W96, EOS 
57 
57 
57 
Safety 
201585/primar
y_02/L57 
Listing of Potential QTc Interval Prolonging 
Events of Interest 
Add Study Period to the 5th 
Column from the left. 
W48, W96, EOS 
58 
58 
58 
Safety 
201585/primar
y_02/L58 
Listing of ECG values for Subjects with 
Potential QTc Interval Prolonging Events of 
Interest 
 
W48, W96, EOS 
59 
59 
59 
Safety 
201584/primar
y_01/L64 
Listing of ALT, AST, Bilirubin (including Total 
and Direct Bilirubin), INR, and ALP for 
Subjects Meeting Hepatobiliary Lab 
Abnormality Criteria 
Remove ‘Only Q4W IM Subjects 
are presented in this listing.’ from 
the footnote. 
HL, W48, W96, 
EOS 
60 
60 
60 
Safety 
201585/primar
Listing of Investigational Product Exposure 
 
W48, W96, EOS 


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Non-ICH Listings 
No. in 
W48 
No. in 
W96 
No. in 
EOS 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
y_02/L63 
Data for Subject Receiving Oral Bridging 
61 
61 
61 
Safety 
201584/primar
y_01/L66 
Listing of Dosing Errors and IP Device 
Malfunctions 
 
W48, W96, EOS 
Virology 
62 
62 
62 
Confirmed 
Virologic 
Failure 
201585/primar
y_02/L64 
Listing of Replication Capacity in IN and 
PR/RT Region 
Remove ‘of Maintenance Phase’ 
from the column header ‘Study 
Day of Maintenance Phase’. 
W48, W96, EOS 
NA 
63 
63 
Safety 
207966/primar
y_03/L1 
Listing of Resistance Associated Mutations 
(Pre-specified INSTI and IAS-USA NNRTI) 
Remove “Excluded from PRC 
(Yes/No) from the first left 
column; remove the second left 
column; remove Study Day; 
mutations are per definition in 
Section 15.6.7. 
W96, EOS 
PK 
63 
69 
69 
Long-term 
Follow-up 
207966/primar
y_02/L63 
Listing of Plasma PK Concentration-Time Data 
since Last Injection 
For WK96 and EOS: Remove 
age and add LTFU oral RPV 
start date; add asterisk to RPV 
concentration taken on/after the 
start of LTFU oral RPV and add 
a footnote explaining the 
asterisk, will be produced only if 
additional LTFU PK storage 
samples since last analysis data 
cut are planned to be analysed. 
W48, W96, EOS 
 


 
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15.15.6. 
List of Data Displays for Week 152 Planned Analyses 
15.15.6.1. Study Population Tables 
Study Population Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Subject Disposition 
1.1 
Randomized 
NS1 
Summary of Number of Subjects Enrolled 
by Country and Site ID 
‘No Treatment’ column is not needed. 
W152 
1.2 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.3 
Summary of Subject Accountability: Study 
Conclusion Record 
Add section for “COVID-19 Relatedness of 
the Withdrawal” with “Yes”, “No” and 
“Unknown” categories. 
W152 
1.3 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.4 
Summary of Subject Accountability: 
Extension Phase Conclusion Record 
Add section for “COVID-19 Relatedness of 
the Withdrawal” with “Yes”, “No” and 
“Unknown” categories. 
W152 
1.4 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.5 
Summary of Subject Accountability: 
Maintenance + Extension Phase 
Conclusion Record 
Add section for “COVID-19 Relatedness of 
the Withdrawal” with “Yes”, “No” and 
“Unknown” categories. 
W152 
1.5 
Long-term 
Follow-up 
207966/primary_15/T1.6 
Summary of Subject Accountability: Long-
term Follow-up Phase Conclusion Record 
Add section for “COVID-19 Relatedness of 
the Withdrawal” with “Yes”, “No” and 
“Unknown” categories. If there are AEs 
leading to withdrawal, add sections for 
outcome and types similarly to 
207966/primary_15/T1.5. 
W152 
1.6 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.7 
Summary of Subject Disposition at Each 
Study Phase 
 
W152 


 
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Study Population Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
1.7 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.8 
Summary of Reasons for Withdrawal at 
Each Study Phase 
Remove the last footnote in example shell. 
W152 
1.8 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.9 
Summary of Subject Accountability: 
Withdrawals by Visit (Maintenance + 
Extension Phase) 
 
W152 
1.9 
Intent-to-
Treat 
Exposed 
201584/primary_15/T1.10 Summary of Study Drug Discontinuation 
Add section for “COVID-19 Relatedness of 
the Study Drug Discontinuation” with “Yes”, 
“No” and “Unknown” categories. 
W152 
1.10 
Screened 
207966/primary_15/T1.14 Summary of Study Populations 
 
W152 
1.11 
Intent-to-
Treat 
Exposed 
DV1a 
Summary of Important Protocol Deviations 
 
W152 
1.12 
Intent-to-
Treat 
Exposed 
DV1a 
Summary of Important Protocol Deviations 
(Maintenance + Extension Phase) 
 
W152 
1.13 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.15 
Summary of Protocol Deviations Leading 
to Exclusion from the Per-Protocol 
Population 
 
W152 
1.14 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.36 Summary of Important COVID-19 Related 
Protocol Deviations 
 
W152 
1.15 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.37 Summary of Important Non-COVID-19 
Related Protocol Deviations 
 
W152 
Demographic and Baseline Characteristics 


 
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Study Population Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
1.16 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.16 Summary of Demographic Characteristics 
 
W152 
1.17 
Intent-to-
Treat 
Exposed 
DM5 
Summary of Race and Racial 
Combinations 
 
W152 
1.18 
Intent-to-
Treat 
Exposed 
DM6 
Summary of Race and Racial 
Combinations Details 
 
W152 
Medical Conditions and Medications 
1.19 
Intent-to-
Treat 
Exposed 
MH1 
Summary of Current Medical Conditions 
 
W152 
1.20 
Intent-to-
Treat 
Exposed 
MH1 
Summary of Past Medical Conditions 
 
W152 
1.21 
Intent-to-
Treat 
Exposed 
MH4 
Summary of Current Cardiac, 
Gastrointestinal, Metabolism and Nutrition, 
Psychiatric, Renal and Urinary, Nervous 
System Conditions, and Hepatobiliary 
Disorders 
 
W152 
1.22 
Intent-to-
Treat 
Exposed 
MH4 
Summary of Past Cardiac, 
Gastrointestinal, Metabolism and Nutrition, 
Psychiatric, Renal and Urinary, Nervous 
System Conditions, and Hepatobiliary 
Disorders 
 
W152 


 
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Study Population Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
1.23 
Intent-to-
Treat 
Exposed 
207966/primary_15/T1.30 Summary of Prior ART Medications 
Use “TENOFOVIR” for TDF and 
“TENOFOVIR ALAFENAMIDE” for TAF. 
Add a footnote “Note: TENOFOVIR refers to 
tenofovir disoproxil fumarate in the table.”. 
W152 
1.24 
Intent-to-
Treat 
Exposed 
CM8 
Summary of Concomitant Non-ART 
Medication Ingredient Combinations 
(Maintenance + Extension Phase) 
 
W152 
1.25 
Intent-to-
Treat 
Exposed 
201585/primary_02/T1.33 Summary of Lipid Modifying Agent Use at 
Baseline 
 
W152 
1.26 
Intent-to-
Treat 
Exposed 
201585/primary_02/T1.34 
Summary of Lipid Modifying Agent Use 
Started during the Maintenance and 
Extension Phase 
 
W152 
Visits Impacted by COVID-19 Pandemic 
1.27 
Intent-to-
Treat 
Exposed 
PAN4 
Summary of COVID-19 Pandemic Visit 
Impacts 
 
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15.15.6.2. Efficacy Tables 
Note: For subgroup analyses, include rederived randomization strata (i.e. prior exposure to CAB+RPV: 0, 1-24, >24 weeks), all demographic and 
baseline characteristic subgroups as mentioned in EMA Subgroup Category 2 in Section 5.4.2, unless otherwise specified. Not all subjects on Q8W 
arm are planned to have viral load data collected at Week 4 (Week 4A or 4B), so leave Week 4 data blank for Q8W arm in by-visit snapshot analysis. 
Efficacy Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.1 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.1 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA >=50 c/mL at Week 152 – Snapshot 
Analysis – ITT-E 
 
W152 
2.2 
Per-
Protocol 
207966/primary_15/T2.2 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA >=50 c/mL at Week 152 – Snapshot 
Analysis – Per-Protocol 
 
W152 
2.3 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.3 
Summary of Study Outcomes (50 c/mL Threshold) at 
Week 152 – Snapshot Analysis 
 
W152 
2.4 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.4 
Treatment by Strata Tests of Homogeneity for Proportion 
of Subjects with Plasma HIV-1 RNA >=50 c/mL at Week 
152 - Snapshot Analysis 
 
W152 
2.5 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.5 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA >=50 c/mL at Week 152 by Subgroup 
- Snapshot Analysis 
 
W152 
2.6 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.6 
Treatment by Strata Tests of Homogeneity for Proportion 
of Subjects with Plasma HIV-1 RNA >=50 c/mL at Week 
152 among Subjects with >=1 Weeks Prior Exposure to 
CAB+RPV - Snapshot Analysis 
 
W152 


 
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Efficacy Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.7 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.7 
Summary of Study Outcomes (50 c/mL Threshold) at 
Week 152 by Subgroup – Snapshot Analysis 
 
W152 
2.8 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.8 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 152 – Snapshot 
Analysis – ITT-E 
 
W152 
2.9 
Per-
Protocol 
207966/primary_15/T2.9 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 152 – Snapshot 
Analysis – Per-Protocol 
 
W152 
2.10 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.10 
Treatment by Strata Tests of Homogeneity for Proportion 
of Subjects with Plasma HIV-1 RNA <50 c/mL at Week 
152 - Snapshot Analysis 
 
W152 
2.11 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.11 
Summary of Analysis for Proportion of Subjects with 
Plasma HIV-1 RNA <50 c/mL at Week 152 by Subgroup - 
Snapshot Analysis 
 
W152 
2.12 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.12 
Treatment by Strata Tests of Homogeneity for Proportion 
of Subjects with Plasma HIV-1 RNA <50 c/mL at Week 
152 among Subjects with >=1 Weeks Prior Exposure to 
CAB+RPV - Snapshot Analysis 
 
W152 
2.13 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.13 
Proportion of Subjects with Plasma HIV-1 RNA >=50 
c/mL by Visit (Up to Week 152, Maintenance + Extension 
Phase) – Snapshot Analysis 
 
W152 
2.14 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.14 
Proportion of Subjects with Plasma HIV-1 RNA >=50 
c/mL by Subgroup and Visit (Up to Week 152, 
Maintenance + Extension Phase) – Snapshot Analysis 
 
W152 


 
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Efficacy Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.15 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.15 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL 
by Visit (Up to Week 152, Maintenance + Extension 
Phase) – Snapshot Analysis 
 
W152 
2.16 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.16 
Proportion of Subjects with Plasma HIV-1 RNA <50 c/mL 
by Subgroup and Visit (Up to Week 152, Maintenance + 
Extension Phase) – Snapshot Analysis 
 
W152 
2.17 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.17 
Proportion of Subjects with Plasma HIV-1 RNA <200 
c/mL by Visit (Up to Week 152, Maintenance + Extension 
Phase) – Snapshot Analysis 
 
W152 
2.18 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.18 
Proportion of Subjects with Plasma HIV-1 RNA >=200 
c/mL by Visit (Up to Week 152, Maintenance + Extension 
Phase) – Snapshot Analysis 
 
W152 
2.19 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.27 Summary of Study Outcomes (200 c/mL Threshold) at 
Week 152 – Snapshot Analysis 
 
W152 
2.20 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.19 
Summary of Kaplan-Meier Estimates of Proportion of 
Subjects Without Confirmed Virologic Failure at Week 
152 - Treatment Related Discontinuation = Failure 
Replace “Week 96” with “Week 
152” in row labels. Change the 
upper bound in the second 
footnote to be “study day 1092”. 
W152 
2.21 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.20 
Summary of Kaplan-Meier Estimates of Proportion of 
Subjects Without Confirmed Virologic Failure at Week 
152 - Efficacy Related Discontinuation = Failure 
Replace “Week 96” with “Week 
152” in row labels. Change the 
upper bound in the first footnote 
to be “study day 1092”. 
W152 


 
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Efficacy Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.22 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.21 Proportion of Subjects with HIV-1 RNA >=50 c/mL at 
Week 152 (Snapshot) by Last Delay in IP Injection 
Replace ‘Week 96’ with ‘Week 
152’, and replace “(i.e. missing 
visit or withdrawal)” with “(e.g. 
missing visit, remote visit or 
withdrawal) in the footnote. 
W152 
2.23 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.38 Summary of Change from Baseline in Plasma HIV-1 RNA 
(log10 c/mL) by Visit (Maintenance + Extension Phase) 
 
W152 
2.24 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.22 Summary of Plasma HIV-1 RNA (log10 c/mL) by Visit 
(Maintenance + Extension Phase) 
 
W152 
2.25 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.23 
Cumulative Proportion of Subjects Meeting Confirmed 
Virology Failure Criteria by Visit (Up to Week 152, 
Maintenance + Extension Phase) 
 
W152 
2.26 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.24 
Cumulative Proportion of Subjects Meeting Confirmed 
Virology Failure Criteria (Maintenance + Extension 
Phase) 
 
W152 
2.27 
 Confirmed 
Virologic 
Failure 
207966/primary_15/T2.25 
Distribution of Quantitative Plasma HIV-1 RNA Results at 
Suspected and Confirmation of Confirmed Virologic 
Failure (Maintenance + Extension Phase) 
 
W152 
2.28 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.26 Proportion of Subjects with Plasma HIV-1 RNA <2 c/mL 
by Visit (Maintenance + Extension Phase) 
 
W152 
2.29 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.28 Summary of Subjects per Viral Load Category by Visit 
(Up to Week 152, Maintenance + Extension Phase) 
 
W152 


 
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Efficacy Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.30 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.29 Summary of Change from Baseline in CD4+ Cell Count 
(cells/mm^3) by Visit (Maintenance + Extension Phase) 
 
W152 
2.31 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.30 
Summary of Change from Baseline in CD4+ Cell Count 
(cells/mm^3) at Week 152 by Subgroup (Extension 
Phase) 
 
W152 
2.32 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.31 Summary of CD4+ Cell Count (cells/mm^3) by Visit 
(Maintenance + Extension Phase) 
 
W152 
2.33 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.32 Summary of Change from Baseline in CD8+ Cell Count 
(cells/mm^3) by Visit (Maintenance + Extension Phase) 
 
W152 
2.34 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.33 Summary of CD8+ Cell Count (cells/mm^3) by Visit 
(Maintenance + Extension Phase) 
 
W152 
2.35 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.34 Summary of CD4+/CD8+ Ratio Cell Count (cells/mm^3) 
by Visit (Maintenance + Extension Phase) 
 
W152 
2.36 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.35 Summary of HIV-1 Associated Conditions Including 
Recurrences (Maintenance + Extension Phase) 
 
W152 
2.37 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.36 Summary of HIV-1 Associated Conditions Excluding 
Recurrences (Maintenance + Extension Phase) 
 
W152 
2.38 
Intent-to-
Treat 
Exposed 
207966/primary_15/T2.37 Summary of HIV-1 Disease Progression and/or Deaths 
(Maintenance + Extension Phase) 
Replace “maintenance” with 
“maintenance and extension” in 
the second footnote. 
W152 


 
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15.15.6.3. Efficacy Figures 
Note: For subgroup analyses, include rederived randomization strata (i.e. prior exposure to CAB+RPV: 0, 1-24, >24 weeks), all demographic and 
baseline characteristic subgroups as mentioned in EMA Subgroup Category 2 in Section 5.4.2, unless otherwise specified. Not all subjects on Q8W 
arm are planned to have viral load data collected at Week 4 (Week 4A or 4B), so leave Week 4 data blank for Q8W arm in by-visit snapshot analysis. 
Efficacy Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.1 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.1 
Proportion (95% CI) of Subjects with HIV-1 RNA ≥50 
c/mL by Visit (Up to Week 152, Maintenance + 
Extension Phase) – Snapshot Analysis 
 
W152 
2.2 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.2 
Unadjusted Treatment Difference in Proportion (95% CI) 
of Subjects with HIV-1 RNA ≥50 c/mL at Week 152 by 
Subgroup – Snapshot Analysis 
 
W152 
2.3 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.3 
Proportion (95% CI) of Subjects with HIV-1 RNA <50 
c/mL by Visit (Up to Week 152, Maintenance + 
Extension Phase) – Snapshot Analysis 
 
W152 
2.4 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.4 
Unadjusted Treatment Difference in Proportion (95% CI) 
of Subjects with HIV-1 RNA <50 c/mL at Week 152 by 
Subgroup – Snapshot Analysis 
 
W152 
2.5 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.5 
Proportion (95% CI) of Subjects with HIV-1 RNA >=200 
c/mL by Visit (Up to Week 152, Maintenance + 
Extension Phase) – Snapshot Analysis 
 
W152 
2.6 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.6 
Proportion (95% CI) of Subjects with HIV-1 RNA <200 
c/mL by Visit (Up to Week 152, Maintenance + 
Extension Phase) – Snapshot Analysis 
 
W152 
2.7 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.7 Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by 
Visit – for CVF Subjects  
 
W152 


 
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Efficacy Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.8 
Intent-to-
Treat 
Exposed 
207966/primary_15/F2.8 
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by 
Visit for subjects Who are in the Category of ‘HIV-1 RNA 
>=50 c/mL’ at Week 152 per Snapshot Algorithm 
 
W152 
 
 
 


 
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15.15.6.4. Safety Tables 
Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Exposure 
3.1 
Safety 
207966/primary_15/T3.2 
Summary of Extent of Exposure to Study 
Treatment including SOC Oral Bridging 
(Maintenance + Extension Phase) 
The levels for categorical summaries 
except for oral lead-in will be selected as 
appropriate.   
W152 
3.2 
Safety 
207966/primary_15/T3.3 
Summary of Needle Length and Gauge for CAB 
Injection (Maintenance + Extension Phase) 
 
W152 
3.3 
Safety 
207966/primary_15/T3.4 
Summary of Needle Length and Gauge for RPV 
Injection (Maintenance + Extension Phase) 
 
W152 
3.4 
Safety 
207966/primary_15/T3.5 
Summary of Adherence to CAB/RPV Injection 
Dosing Schedule (Maintenance + Extension 
Phase) 
Replace rows for missed Injection with 
those specified in Section 15.6.4. Adjust 
the footnote as appropriate. For missed 
reloading rows, leave blank for Q4W. 
W152 
Adverse Events 
3.5 
Safety 
207966/primary_15/T3.6 
Summary of All Adverse Events by System 
Organ Class (Maintenance + Extension Phase) 
 
W152 
3.6 
Safety 
207966/primary_15/T3.8 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity 
(Maintenance + Extension Phase) 
 
W152 
3.7 
Safety 
207966/primary_15/T3.8 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity (Extension 
Phase) 
 
W152 
3.8 
Safety 
207966/primary_15/T3.9 
Summary of All Adverse Events Excluding 
Study Drug Injection Site Reactions by System 
Organ Class and Maximum Toxicity 
 
W152 


 
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Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
(Maintenance + Extension Phase) 
3.9 
Safety 
207966/primary_15/T3.10 
Summary of All On-treatment Adverse Events 
by System Organ Class and Maximum Toxicity 
(Maintenance + Extension Phase) 
 
W152 
3.10 
Safety 
207966/primary_15/T3.11 
Summary of Common Adverse Events (>=5%) 
by Overall Frequency (Maintenance + Extension 
Phase) 
 
W152 
3.11 
Safety 
207966/primary_15/T3.12 
Summary of Common Grade 2-5 Adverse 
Events (>=1%) by Overall Frequency 
(Maintenance + Extension Phase) 
 
W152 
3.12 
Safety 
207966/primary_15/T3.13 
Summary of All Drug-related Adverse Events by 
System Organ Class (Maintenance + Extension 
Phase) 
 
W152 
3.13 
Safety 
207966/primary_15/T3.15 
Summary of All Drug-related Adverse Events by 
System Organ Class and Maximum Toxicity 
(Maintenance + Extension Phase) 
 
W152 
3.14 
Safety 
207966/primary_15/T3.15 
Summary of All Drug-related Adverse Events by 
System Organ Class and Maximum Toxicity 
(Extension Phase) 
 
W152 
3.15 
Safety 
207966/primary_15/T3.16 
Summary of All Drug-related Adverse Events 
Excluding Study Drug Injection Site Reactions 
by System Organ Class and Maximum Toxicity 
(Maintenance + Extension Phase) 
 
W152 
3.16 
Safety 
207966/primary_15/T3.17 
Summary of All Drug-Related Grade 2-5 
Adverse Events by Overall Frequency 
(Maintenance + Extension Phase) 
 
W152 
Serious and Other Significant Adverse Events 


 
CONFIDENTIAL 
 
 
 
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Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.17 
Safety 
207966/primary_15/T3.19 
Summary of Serious Adverse Events by System 
Organ Class (Maintenance + Extension Phase) 
 
W152 
3.18 
Long-term 
Follow-up 
207966/primary_15/T3.20 
Summary of Serious Adverse Events by System 
Organ Class (Long-term Follow-up Phase) 
 
W152 
3.19 
Safety 
207966/primary_15/T3.22 
Summary of Drug-related Serious Adverse 
Events by System Organ Class (Maintenance + 
Extension Phase) 
 
W152 
3.20 
Safety 
207966/primary_15/T3.23 
Summary of Non-Fatal Serious Adverse Events 
by Overall Frequency (Maintenance + Extension 
Phase) 
 
W152 
3.21 
Safety 
207966/primary_15/T3.24 
Summary of Drug-related Non-Fatal Serious 
Adverse Events by Overall Frequency 
(Maintenance + Extension Phase) 
 
W152 
3.22 
Safety 
207966/primary_15/T3.26 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ Class 
(Maintenance + Extension Phase) 
Adjust the footnote as needed, depending 
on the given data. 
W152 
3.23 
Safety 
207966/primary_15/T3.25 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ Class 
(Extension Phase) 
 
W152 
3.24 
Safety 
207966/primary_15/T3.27 
Summary of Common (>=5%) Non-Serious 
Adverse Events (Maintenance + Extension 
Phase) 
 
W152 
3.25 
Safety 
207966/primary_15/T3.28 
Summary of Subjects and Number of 
Occurrences of Common (>=5%) Non-Serious 
Adverse Events by System Organ Class 
 
W152 


 
CONFIDENTIAL 
 
 
 
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Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
(Maintenance + Extension Phase) 
3.26 
Safety 
207966/primary_15/T3.29 
Summary of Subjects and Number of 
occurrences of SAEs, Fatal SAEs, and Drug-
related SAEs (Maintenance + Extension Phase) 
 
W152 
Study Drug Injection Site Reaction Adverse Events 
3.27 
Safety 
207966/primary_15/T3.32 
Summary of Study Drug Injection Site Reaction 
Adverse Events (Event-level Summary) – 
(Maintenance + Extension Phase) 
 
W152 
3.28 
Safety 
207966/primary_15/T3.34 
Summary of Subject-level Characteristics of 
Study Drug Injection Site Reaction Adverse 
Events – Overall and Common (Maintenance + 
Extension Phase) 
 
W152 
3.29 
Safety 
207966/primary_15/T3.35 
Summary of Study Drug Injection Site Reaction 
Adverse Events by Visit and Maximum Severity 
– Overall and Common (Maintenance + 
Extension Phase) 
 
W152 
3.30 
Safety 
207966/primary_15/T3.36 
Summary of Drug-related Study Drug Injection 
Site Reaction Adverse Events (Event-level 
Summary) - CAB (Maintenance + Extension 
Phase) 
 
W152 
3.31 
Safety 
207966/primary_15/T3.37 
Summary of Drug-related Subject-level 
Characteristics of Study Drug Injection Site 
Reaction Adverse Events (Maintenance + 
Extension Phase) - Overall and Common (CAB) 
 
W152 
3.32 
Safety 
207966/primary_15/T3.38 
Summary of Overall and Common Drug-related 
Study Drug Injection Site Reaction Adverse 
Events by Visit and Maximum Severity 
 
W152 


 
CONFIDENTIAL 
 
 
 
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Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
(Maintenance + Extension Phase) - CAB 
3.33 
Safety 
207966/primary_15/T3.39 
Summary of Maximum Drug-related Study Drug 
Injection Site Reaction Adverse Event Grade by 
Needle Length (Maintenance + Extension 
Phase) – Common (CAB) 
Replace “maintenance” with 
“maintenance and extension” in the 
footnote. 
W152 
3.34 
Safety 
207966/primary_15/T3.40 
Summary of Drug-related Study Drug Injection 
Site Reaction Adverse Events (Event-level 
Summary) - RPV (Maintenance + Extension 
Phase) 
 
W152 
3.35 
Safety 
207966/primary_15/T3.41 
Summary of Drug-related Subject-level 
Characteristics of Study Drug Injection Site 
Reaction Adverse Events (Maintenance + 
Extension Phase) - Overall and Common (RPV) 
 
W152 
3.36 
Safety 
207966/primary_15/T3.42 
Summary of Overall and Common Drug-related 
Study Drug Injection Site Reaction Adverse 
Events by Visit and Maximum Severity 
(Maintenance + Extension Phase) - RPV 
 
W152 
3.37 
Safety 
207966/primary_15/T3.43 
Summary of Maximum Drug-related Study Drug 
Injection Site Reaction Adverse Event Grade by 
Needle Length (Maintenance + Extension 
Phase) – Common (RPV) 
Replace “maintenance” with 
“maintenance and extension” in the 
footnote. 
W152 
Laboratory: Chemistry and Hematology 
3.38 
Safety 
207966/primary_15/T3.44 
Summary of Chemistry Changes from Baseline 
by Visit (Maintenance + Extension Phase) 
 
W152 
3.39 
Safety 
207966/primary_15/T3.45 
Summary of Chemistry Values by Visit 
(Maintenance + Extension Phase) 
 
W152 
3.40 
Safety 
207966/primary_15/T3.46 
Summary of Hematology Changes from 
 
W152 


 
CONFIDENTIAL 
 
 
 
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284 
 
Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Baseline by Visit (Maintenance + Extension 
Phase) 
3.41 
Safety 
207966/primary_15/T3.47 
Summary of Hematology Values by Visit 
(Maintenance + Extension Phase) 
 
W152 
3.42 
Safety 
207966/primary_15/T3.49 
Summary of Maximum Post-Baseline Emergent 
Chemistry Toxicities (Maintenance + Extension 
Phase) 
 
W152 
3.43 
Safety 
207966/primary_15/T3.51 
Summary of Maximum Post-Baseline Emergent 
Hematology Toxicities (Maintenance + 
Extension Phase) 
 
W152 
Laboratory: Urinalysis 
3.44 
Safety 
207966/primary_15/T3.52 
Summary of Urinalysis Dipstick Results by Visit 
(Maintenance + Extension Phase) 
 
W152 
3.45 
Safety 
207966/primary_15/T3.53 
Summary of Urine Concentrations Changes 
from Baseline by Visit (Maintenance + 
Extension Phase) 
 
W152 
3.46 
Safety 
207966/primary_15/T3.54 
Summary of Changes in Proteinuria Baseline 
Laboratory Result to Maximum Post-Baseline 
Laboratory Result (Maintenance + Extension 
Phase) 
 
W152 
Laboratory: Lipid 
3.47 
Safety 
207966/primary_15/T3.55 
Summary of Changes in Baseline NCEP Fasting 
Lipid Category to Maximum Post-Baseline 
Category (Triglycerides, Lipids LOCF) - 
Maintenance + Extension Phase 
Replace “Maintenance” with 
“Maintenance and Extension” in the 
second footnote. 
W152 
3.48 
Safety 
207966/primary_15/T3.56 
Summary of Changes in Baseline NCEP Fasting Replace “Maintenance” with 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
285 
 
Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Lipid Category to Maximum Post-Baseline 
Category (Total Cholesterol, Lipids LOCF) - 
Maintenance + Extension Phase 
“Maintenance and Extension” in the 
second footnote. 
3.49 
Safety 
207966/primary_15/T3.57 
Summary of Changes in Baseline NCEP Fasting 
Lipid Category to Minimum Post-Baseline 
Category (HDL Cholesterol, Lipids LOCF) - 
Maintenance + Extension Phase 
Replace “Maintenance” with 
“Maintenance and Extension” in the 
second footnote. 
W152 
3.50 
Safety 
207966/primary_15/T3.58 
Summary of Changes in Baseline NCEP Fasting 
Lipid Category to Maximum Post-Baseline 
Category (LDL Cholesterol, Lipids LOCF) - 
Maintenance + Extension Phase 
Replace “Maintenance” with 
“Maintenance and Extension” in the 
second footnote. 
W152 
3.51 
Safety 
207966/primary_15/T3.59 
Summary of Fasting Lipids Percentage 
Changes from Baseline by Visit (Maintenance + 
Extension Phase) - Lipids LOCF 
 
W152 
3.52 
Safety 
207966/primary_15/T3.60 
Summary of Fasting TC/HDL ratio Changes 
from Baseline (Maintenance + Extension Phase) 
– Lipids LOCF 
 
W152 
Laboratory: Hepatobiliary (Liver) 
3.53 
Safety 
207966/primary_15/T3.61 
Summary of Liver Stopping Event Reporting 
(Maintenance + Extension Phase) 
 
W152 
3.54 
Safety 
207966/primary_15/T3.63 
Summary of Subjects Meeting Hepatobiliary 
Abnormality Criteria (Maintenance +Extension 
Phase) 
 
W152 
ECG 
3.55 
Safety 
207966/primary_15/T3.64 
Summary of ECG Findings (Maintenance + 
Extension Phase) 
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
286 
 
Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.56 
Safety 
207966/primary_15/T3.65 
Summary of Change from Baseline in ECG 
values by Visit (Maintenance + Extension 
Phase) 
 
W152 
3.57 
Safety 
207966/primary_15/T3.66 
Summary of QTc Values by Category 
(Maintenance + Extension Phase) 
 
W152 
3.58 
Safety 
207966/primary_15/T3.67 
Summary of Change from Baseline QTc Values 
by Category (Maintenance + Extension Phase) 
 
W152 
Vital Signs 
3.59 
Safety 
207966/primary_15/T3.68 
Summary of Change from Baseline in Vital 
Signs by Visit (Maintenance + Extension Phase) 
 
W152 
3.60 
Safety 
207966/primary_15/T3.69 
Summary of BMI Shift from Baseline by Sex and 
Visit (Maintenance + Extension Phase) 
 
W152 
3.61 
Safety 
207966/primary_15/T3.70 
Summary of BMI Shift from Baseline by Strata 
and Visit (Maintenance + Extension Phase) 
 
W152 
3.62 
Safety 
207966/primary_15/T3.71 
Summary of Change from Baseline in Weight 
and BMI by Strata and Visit (Maintenance + 
Extension Phase) 
 
W152 
Adverse Event of Special Interest (AESI) 
3.63 
Safety 
207966/primary_15/T3.74 
Summary of Depression, Anxiety and Suicidal 
Ideation/Behaviour Adverse Events by System 
Organ Class, Maximum DAIDS Toxicity Grade, 
and Prior History of Depression, Anxiety and 
Suicidal Ideation at Screening (Maintenance + 
Extension Phase) 
May need to adjust the footnote given the 
data. 
W152 
3.64-
3.80 
Safety 
207966/primary_15/T3.92-
3.108 
Summary of XXX Adverse Events of Special 
Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrence) – 
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
287 
 
Safety Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Maintenance + Extension Phase 
3.81 
Safety 
207966/primary_15/T3.110 
Summary of Characteristics of Common 
Adverse Events of Special Interest – 
Maintenance + Extension Phase 
 
W152 
3.82 
Safety 
207966/primary_15/T3.111 Summary of Syncope and Presyncope Adverse 
Events - Maintenance + Extension Phase 
 
W152 
3.83 
Safety 
207966/primary_15/T3.112 
Summary of Syncope and Presyncope Adverse 
Events and Injection Visits - Maintenance + 
Extension Phase 
 
W152 
COVID-19 Adverse Event 
3.84 
Safety 
207966/primary_15/T3.113 
Summary of COVID-19 Adverse Events by 
System Organ Class and Maximum Toxicity 
(Maintenance + Extension Phase) 
 
W152 
3.85 
Safety 
207966/primary_15/T3.115 Summary of COVID-19 Assessments 
(Maintenance + Extension Phase) 
Place “Within” in front of “14” in the first 
footnote. If COVID-19 assessments are 
collected multiple times during the study, 
a combination of standard displays 
PAN1A and PAN2A with appropriate 
adjustments may be used. 
W152 
 
 
 


 
CONFIDENTIAL 
 
 
 
207966 
 
288 
 
15.15.6.5. Safety Figures 
Safety Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.1 
Safety 
207966/primary_15/F3.1 
Plot of Common Adverse Events and Relative Risk - 
Q8W vs. Q4W (Maintenance + Extension Phase) – 
Excluding Study Drug ISRs 
 
W152 
3.2 
Safety 
207966/primary_15/F3.2 
Plot of Common Study Drug Injection Site Reaction 
Adverse Events and Relative Risk - Q8W vs. Q4W 
(Maintenance +Extension Phase) 
 
W152 
3.3 
Safety 
207966/primary_02/F3.6 
Plot of Incidence of Maintenance and Extension Phase 
Study Drug Injection Site Reaction Adverse Events by 
Visit (Overall and Common) – CAB and/or RPV 
 
W152 
3.4 
Safety 
207966/primary_15/F3.7 
Plot of Incidence of Maintenance and Extension Phase 
Drug-Related Study Drug Injection Site Reaction 
Adverse Events by Visit (Overall and Common) – CAB 
 
W152 
3.5 
Safety 
207966/primary_15/F3.8 
Plot of Incidence of Maintenance and Extension Phase 
Drug-Related Study Drug Injection Site Reaction 
Adverse Events by Visit (Overall and Common) – RPV 
 
W152 
3.6 
Safety 
207966/primary_15/F3.21 
Plot of Incidence of Maintenance and Extension Phase 
Study Drug Injection Site Reaction Adverse Events by 
Strata and Visit (Overall and Common) - CAB and/or 
RPV 
 
W152 
3.7 
Safety 
207966/primary_15/F3.13 Scatter Plot of Maximum vs. Baseline for ALT 
(Maintenance + Extension Phase) 
 
W152 
3.8 
Safety 
207966/primary_15/F3.15 Scatter Plot of Maximum Total Bilirubin vs. Maximum 
ALT (Maintenance + Extension Phase) 
 
W152 
3.9 
Safety 
207966/primary_15/F3.18 Bar Chart of Lipid NCEP Categories at Week 152 vs. 
Baseline – Triglycerides, Total Cholesterol, LDL 
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
289 
 
Safety Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Cholesterol (Lipids LOCF) 
3.10 
Safety 
207966/primary_15/F3.19 Bar Chart of Lipid NCEP Categories at Week 152 vs. 
Baseline - HDL Cholesterol (Lipids LOCF) 
 
W152 
3.11 
Safety 
207966/primary_15/F3.20 Histogram of Timeliness of Injections (Maintenance + 
Extension Phase) 
 
W152 
3.12 
Safety 
207966/primary_15/F3.22 Patient Profile for Subjects with Syncope or Presyncope 
Adverse Events (Maintenance + Extension Phase) 
 
W152 
 
 
 


 
CONFIDENTIAL 
 
 
 
207966 
 
290 
 
15.15.6.6. Pharmacokinetic Tables 
Pharmacokinetic Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.1 
Pharmacokinetic 
207966/primary_15/T4.1 
Summary of Plasma CAB PK Concentration (ug/mL) -
Time Data by Treatment and Visit (Maintenance + 
Extension Phase) – Including Log-transformed Statistics 
Add Week 156 for Q4W, 
Week 160 for Q8W. Add 
following to the second 
footnote: PK samples were 
collected at Week 156 (for 
Q4W subjects) or Week 
160 (for Q8W subjects) if 
Week 152 PK samples 
were missed (e.g. due to 
the delays in protocol 
amendment approvals or 
site errors).  
W152 
4.2 
Pharmacokinetic 
207966/primary_15/T4.2 
Summary of Plasma RPV PK Concentration (ng/mL) -
Time Data by Treatment and Visit (Maintenance + 
Extension Phase) – Including Log-transformed Statistics 
Similar notes to above. 
W152 
4.3 
Pharmacokinetic 
207966/primary_15/T4.3 
Summary of Evaluable Plasma CAB PK Concentration 
(ug/mL) -Time Data by Treatment and Visit (Maintenance 
+ Extension Phase) – Including Log-transformed Statistics 
Similar notes to above. 
W152 
4.4 
Pharmacokinetic 
207966/primary_15/T4.4 
Summary of Evaluable Plasma RPV PK Concentration 
(ng/mL) -Time Data by Treatment and Visit (Maintenance 
+ Extension Phase) – Including Log-transformed Statistics 
Similar notes to above. 
W152 
4.5 
Pharmacokinetic 
207966/primary_15/T4.5 
Summary of Evaluable Plasma CAB PK Concentration 
(ug/mL) -Time Data by Strata and Treatment and Visit 
(Maintenance + Extension Phase) – Including Log-
transformed Statistics 
Similar notes to above. 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
291 
 
Pharmacokinetic Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.6 
Pharmacokinetic 
207966/primary_15/T4.6 
Summary of Evaluable Plasma RPV PK Concentration 
(ng/mL) -Time Data by Strata and Treatment and Visit 
(Maintenance + Extension Phase) – Including Log-
transformed Statistics 
Similar notes to above. 
W152 
4.7 
Long-term Follow-
up 
207966/primary_15/T4.1 
Summary of Plasma CAB PK Concentration (ug/mL) -
Time Data by Treatment and Visit (Long-term Follow-up 
Phase) - Including Log-transformed Statistics 
Remove the column ‘Pl. 
Time’ and the second 
footnote.  
W152 
4.8 
Long-term Follow-
up 
207966/primary_15/T4.2 
Summary of Plasma RPV PK Concentration (ng/mL) -
Time Data by Treatment and Visit (Long-term Follow-up 
Phase) - Including Log-transformed Statistics 
Remove the column ‘Pl. 
Time’ and the second 
footnote.  
W152 
 
 


 
CONFIDENTIAL 
 
 
 
207966 
 
292 
 
15.15.6.7. Pharmacokinetic Figures 
Pharmacokinetic Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.1 
Pharmacokinetic 
207966/primary_15/F4.1 
Individual Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) – Maintenance + 
Extension Phase 
 
W152 
4.2 
Pharmacokinetic 
207966/primary_15/F4.2 
Individual Plasma RPV Concentration-Time 
Plots (Linear and Semi-Log) – Maintenance + 
Extension Phase 
 
W152 
4.3 
Pharmacokinetic 
207966/primary_15/F4.3 
Mean (SD) Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) – Maintenance + 
Extension Phase 
Treat Week 152 similarly to Week 
96 on X axis and update the 
relevant footnote as “To save the 
plotting space, Week 96 is 
displayed next to Week 48 and 
Week 152 is displayed next to 
Week 152, with hashes to indicate 
the X axis break.” 
W152 
4.4 
Pharmacokinetic 
207966/primary_15/F4.4 
Mean (SD) Plasma RPV Concentration-Time 
Plots (Linear and Semi-Log) – Maintenance + 
Extension Phase 
Similar notes to above. 
W152 
4.5 
Pharmacokinetic 
207966/primary_15/F4.5 
Mean (SD) Evaluable Plasma CAB 
Concentration-Time Plots (Linear and Semi-
Log) – Maintenance + Extension Phase 
Similar notes to above. 
W152 
4.6 
Pharmacokinetic 
207966/primary_15/F4.6 
Mean (SD) Evaluable Plasma RPV 
Concentration-Time Plots (Linear and Semi-
Log) – Maintenance + Extension Phase 
Similar notes to above. 
W152 
4.7 
Pharmacokinetic 
207966/primary_15/F4.7 
Mean (SD) Evaluable Plasma CAB 
Concentration-Time Plots by Strata (Linear 
and Semi-Log) – Maintenance + Extension 
Similar notes to above. 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
293 
 
Pharmacokinetic Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Phase 
4.8 
Pharmacokinetic 
207966/primary_15/F4.8 
Mean (SD) Evaluable Plasma RPV 
Concentration-Time Plots by Strata (Linear 
and Semi-Log) – Maintenance + Extension 
Phase 
Similar notes to above. 
W152 
4.9 
Pharmacokinetic 
207966/primary_15/F4.9 
Median (5th and 95th Percentile) Plasma CAB 
Concentration-Time Plots (Linear and Semi-
Log) – Maintenance + Extension Phase 
Similar notes to above. 
W152 
4.10 
Pharmacokinetic 
207966/primary_15/F4.10 
Median (5th and 95th Percentile) Plasma RPV 
Concentration-Time Plots (Linear and Semi-
Log) – Maintenance + Extension Phase 
Similar notes to above. 
W152 
4.11 
Pharmacokinetic 
207966/primary_15/F4.11 
Median (5th and 95th Percentile) Evaluable 
Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) – Maintenance + Extension 
Phase 
Similar notes to above. 
W152 
4.12 
Pharmacokinetic 
207966/primary_15/F4.12 
Median (5th and 95th Percentile) Evaluable 
Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) – Maintenance + Extension 
Phase 
Similar notes to above. 
W152 
4.13 
Pharmacokinetic 
207966/primary_15/F4.13 
Median (5th and 95th Percentile) Evaluable 
Plasma CAB Concentration-Time Plots by 
Strata (Linear and Semi-Log) – Maintenance + 
Extension Phase 
Similar notes to above. 
W152 
4.14 
Pharmacokinetic 
207966/primary_15/F4.14 
Median (5th and 95th Percentile) Evaluable 
Plasma RPV Concentration-Time Plots by 
Strata (Linear and Semi-Log) – Maintenance + 
Extension Phase 
Similar notes to above. 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
294 
 
Pharmacokinetic Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.15 
Pharmacokinetic 
207966/primary_15/F4.15 
Median Evaluable Plasma CAB Trough PK 
Concentration (ug/mL) - Time Plots by 
Treatment and Strata (Linear and Semi-Log) – 
Maintenance + Extension Phase 
Similar notes to above. 
W152 
4.16 
Pharmacokinetic 
207966/primary_15/F4.16 
Median Evaluable Plasma RPV Trough PK 
Concentration (ng/mL) - Time Plots by 
Treatment and Strata (Linear and Semi-Log) – 
Maintenance + Extension Phase 
Similar notes to above. 
W152 
4.17 
Long-term Follow-
up 
207966/primary_02/F4.15 Plasma PK Concentration-Time since Last 
Injection Plots by Overall and Strata 
Add plot for overall. Exclude RPV 
concentrations on/after the start of 
oral RPV that was received after 
the last injection. Add a footnote: 
“Note: For subjects who received 
oral RPV after the last injection, 
the RPV concentrations taken on 
or after the start of such oral RPV 
are excluded from the plot.” 
W152 
 


 
CONFIDENTIAL 
 
 
 
207966 
 
295 
 
15.15.6.8. Pharmacokinetic / Pharmacodynamic Figures 
Pharmacokinetic / Pharmacodynamic Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
PK / PD Efficacy Analyses 
5.1 
Pharmacokinetic 
207966/primary_15/F5.1 
Individual CAB Trough Concentration-time 
Profiles for Subjects with Snapshot 'HIV-1 RNA 
≥50 c/mL' at Week 152 and Median, 5th & 95th 
Percentile of CAB Conc-Time Profiles for Other 
Subjects (Semi-Log) – Maintenance + 
Extension Phase 
 
W152 
5.2 
Pharmacokinetic 
207966/primary_15/F5.2 
Individual RPV Trough Concentration-time 
Profiles for Subjects with Snapshot 'HIV-1 RNA 
≥50 c/mL' at Week 152 and Median, 5th & 95th 
Percentile of RPV Conc-Time Profiles for Other 
Subjects (Semi-Log) – Maintenance + 
Extension Phase 
 
W152 
PK / PD Safety Analyses 
5.3 
Pharmacokinetic 
207966/primary_02/F5.6 
Scatter Plot of Maximum Change from Baseline 
in ALT versus Last Trough CAB PK 
Concentrations by Strata and Treatment during 
the Maintenance and Extension Phase 
Replace “Maintenance” with 
“Maintenance and Extension” in 
the first footnote. 
W152 
5.4 
Pharmacokinetic 
207966/primary_02/F5.7 
Scatter Plot of Maximum Change from Baseline 
in ALT versus Last Trough RPV PK 
Concentrations by Strata and Treatment during 
the Maintenance and Extension Phase 
Replace “Maintenance” with 
“Maintenance and Extension” in 
the first footnote. 
W152 
5.5 
Pharmacokinetic 
207966/primary_02/F5.8 
Scatter Plot of Maximum Change from Baseline 
in Total Bilirubin versus Last Trough CAB PK 
Concentrations by Strata and Treatment during 
the Maintenance and Extension Phase 
Replace “Maintenance” with 
“Maintenance and Extension” in 
the first footnote. 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
296 
 
Pharmacokinetic / Pharmacodynamic Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
5.6 
Pharmacokinetic 
207966/primary_02/F5.9 
Scatter Plot of Maximum Change from Baseline 
in Total Bilirubin versus Last Trough RPV PK 
Concentrations by Strata and Treatment during 
the Maintenance and Extension Phase 
Replace “Maintenance” with 
“Maintenance and Extension” in 
the first footnote. 
W152 
5.7 
Pharmacokinetic 
207966/primary_02/F5.13 
Scatter Plot of Change from Baseline in Pre-
dose QTcF versus CAB Trough PK 
Concentration at Week 152 by Treatment 
Adjust the alignment of the 
footnote. 
W152 
5.8 
Pharmacokinetic 
207966/primary_02/F5.14 
Scatter Plot of Change from Baseline in Pre-
dose QTcF versus RPV Trough PK 
Concentration at Week 152 by Treatment 
Adjust the alignment of the 
footnote. 
W152 
 
 


 
CONFIDENTIAL 
 
 
 
207966 
 
297 
 
15.15.6.9. Health Outcomes Tables 
Health Outcomes Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Perception of Injection (PIN) 
6.1 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.1 
Proportion of Subjects with Each Individual Item 
Score in PIN by Visit - LOCF (Maintenance + 
Extension Phase) 
 
W152 
6.2 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.2 
Summary of PIN in Domain Scores (Bother of 
ISRs, Leg Movement, Sleep and Acceptance) and 
Individual Items Scores (Anxiety before, Pain, 
Satisfaction, Anxiety after and Willingness) by Visit 
(Maintenance + Extension Phase) 
 
W152 
6.3 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.3 
Summary and Statistical Analysis of PIN in Domain 
Scores (Bother of ISRs, Leg Movement, Sleep and 
Acceptance) and Individual Items Scores (Anxiety 
before, Pain, Satisfaction, Anxiety after and 
Willingness) by Visit - LOCF (Maintenance + 
Extension Phase) 
Adjust the first half of the footnote to 
“[1] Week 24/48/152 was compared 
with the 1st visit (Week 8) based on 
Wilcoxon signed-rank test, 
respectively.” 
W152 
6.4 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.4 
Summary of PIN Change from Week 8 in Domain 
Scores (Bother of ISRs, Leg Movement, Sleep and 
Acceptance) and Individual Items Scores (Anxiety 
before, Pain, Satisfaction, Anxiety after and 
Willingness) by Visit (Maintenance + Extension 
Phase) 
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
298 
 
Health Outcomes Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.5 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.5 
Summary of PIN Change from Week 8 in Domain 
Scores (Bother of ISRs, Leg Movement, Sleep and 
Acceptance) and Individual Items Scores (Anxiety 
before, Pain, Satisfaction, Anxiety after and 
Willingness) by Visit - LOCF (Maintenance + 
Extension Phase) 
 
W152 
6.6 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.6 
Statistical Analysis of PIN Change from Week 8 in 
Domain Scores (Bother of ISRs, Leg Movement, 
Sleep and Acceptance) and Individual Items 
Scores (Anxiety before, Pain, Satisfaction, Anxiety 
after and Willingness) by Visit - LOCF 
(Maintenance + Extension Phase) 
Adjust second the footnote per 
modelling result. 
W152 
HIV Treatment Satisfaction Questionnaire Status Version (HIVTSQs) 
6.7 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.14 
Proportion of Subjects with HIVTSQs - Individual 
Item Scores by Visit - LOCF (Maintenance + 
Extension Phase) 
 
W152 
6.8 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.15 
Proportion of Subjects with HIVTSQs - Individual 
Item Scores by Visit and Subgroup - LOCF 
(Maintenance + Extension Phase) 
The subgroup includes: prior 
exposure to CAB+RPV (0, 1-24, >=24 
weeks), sex at birth, age (<35, 35 - 
<50, >=50), race (white, non-white), 
Baseline CD4+ cell count (<350, 350 
– <500, >=500) 
W152 
6.9 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.16 
Summary of HIVTSQs - Total Treatment 
Satisfaction Score by Visit (Maintenance + 
Extension Phase) 
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
299 
 
Health Outcomes Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.10 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.17 
Summary of HIVTSQs - Total Treatment 
Satisfaction Score by Visit - LOCF (Maintenance + 
Extension Phase) 
 
W152 
6.11 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.18 
Summary of HIVTSQs - Change from Baseline in 
Total Treatment Satisfaction Score by Prior 
Exposure to CAB+RPV (0 vs. >=1 Weeks) and 
Visit (Maintenance + Extension Phase) 
 
W152 
6.12 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.19 
Summary of HIVTSQs - Change from Baseline in 
Total Treatment Satisfaction Score by Prior 
Exposure to CAB+RPV (0 vs. >=1 Weeks) and 
Visit - LOCF (Maintenance + Extension Phase) 
 
W152 
6.13 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.20 
Summary of HIVTSQs - Change from Baseline in 
Individual Item Score by Prior Exposure to 
CAB+RPV (0 vs. >=1 Weeks) and Visit - LOCF 
(Maintenance + Extension Phase) 
 
W152 
6.14 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.21 
Statistical Analysis of HIVTSQs - Change from 
Baseline in Total Treatment Satisfaction Score by 
Visit for Subjects without Prior Exposure to 
CAB+RPV - LOCF (Maintenance + Extension 
Phase) 
Adjust the second footnote based on 
the modelling result. 
W152 
6.15 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.22 
Statistical Analysis of HIVTSQs - Change from 
Baseline in Total Treatment Satisfaction Score by 
Visit for Subjects with Prior Exposure to CAB+RPV 
- LOCF (Maintenance + Extension Phase) 
Adjust the second footnote based on 
the modelling result. 
W152 
Treatment Acceptance (ACCEPT) 


 
CONFIDENTIAL 
 
 
 
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300 
 
Health Outcomes Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.16 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.31 
Proportion of Subjects with ACCEPT - Individual 
Item Score by Visit - LOCF (Maintenance + 
Extension Phase) 
 
W152 
6.17 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.32 
Summary of Acceptance/General Dimension Score 
(ACCEPT Questionnaire) by Visit (Maintenance + 
Extension Phase) 
 
W152 
6.18 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.33 
Summary of Acceptance/General Dimension Score 
(ACCEPT Questionnaire) by Visit - LOCF 
(Maintenance + Extension Phase) 
 
W152 
6.19 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.34 
Summary of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Prior Exposure to CAB+RPV (0 
vs. >=1 Weeks) and Visit (Maintenance + 
Extension Phase) 
 
W152 
6.20 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.35 
Summary of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Prior Exposure to CAB+RPV (0 
vs. >=1 Weeks) and Visit - LOCF (Maintenance + 
Extension Phase) 
 
W152 
6.21 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.36 
Statistical Analysis of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit for Subjects without Prior 
Exposure to CAB+RPV - LOCF (Maintenance + 
Extension Phase) 
Adjust the second footnote based on 
the modelling result. 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
301 
 
Health Outcomes Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.22 
Intent-to-
Treat 
Exposed 
207966/primary_02/T6.37 
Statistical Analysis of Change from Baseline in 
Acceptance/General Dimension Score (ACCEPT 
Questionnaire) by Visit for Subjects with Prior 
Exposure to CAB+RPV - LOCF (Maintenance + 
Extension Phase) 
Adjust the second footnote based on 
the modelling result. 
W152 
Reasons for Oral Bridging and Preference 
6.23 
Oral 
Bridging 
Shell HO_T2 
Proportion of Subjects with Response to Each 
Individual Question in Reasons for Oral Bridging 
and Preference Questionnaire at Week 152 
(Extension Phase) 
 
W152 
 
 
 


 
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302 
 
15.15.6.10. Health Outcomes Figures 
Health Outcomes Figures 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.1 
Intent-to-
Treat 
Exposed 
207966/primary_02/F6.1 
Line Plot of Adjusted Mean (95% CI) Change from 
Baseline in HIVTSQs Total Treatment Satisfaction Score 
over Time (ANCOVA) for Subjects without Prior Exposure 
to CAB+RPV - LOCF 
 
W152 
6.2 
Intent-to-
Treat 
Exposed 
207966/primary_02/F6.2 
Line Plot of Adjusted Mean (95% CI) Change from 
Baseline in HIVTSQs Total Treatment Satisfaction Score 
over Time (ANCOVA) for Subjects with Prior Exposure to 
CAB+RPV - LOCF 
 
W152 
6.3 
Intent-to-
Treat 
Exposed 
207966/primary_02/F6.3 
Line Plot of Difference (95% CI) in Adjusted Mean 
Change from Baseline in HIVTSQs Total Treatment 
Satisfaction Score over Time (ANCOVA) for Subjects 
without Prior Exposure to CAB+RPV - LOCF 
 
W152 
6.4 
Intent-to-
Treat 
Exposed 
207966/primary_02/F6.4 
Line Plot of Difference (95% CI) in Adjusted Mean 
Change from Baseline in HIVTSQs Total Treatment 
Satisfaction Score over Time (ANCOVA) for Subjects with 
Prior Exposure to CAB+RPV - LOCF 
 
W152 
 
 
 


 
CONFIDENTIAL 
 
 
 
207966 
 
303 
 
15.15.6.11. Virology Tables 
Virology Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Genotype 
7.1 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.1 
Summary of the Prevalence of Known INI Resistance 
Mutations at time of CVF (Maintenance + Extension 
Phase) – Plasma Sample 
 
W152 
7.2 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.2 
Summary of the Prevalence of Major Resistance 
Mutations of NRTI, NNRTI and PI Class at time of CVF 
(Maintenance + Extension Phase) - Plasma Sample 
 
W152 
7.3 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.3 
Summary of Genotypic Susceptibility at time of CVF 
(Maintenance + Extension Phase) - Plasma Sample 
 
W152 
Phenotype 
7.4 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.4 
Summary of Phenotype Susceptibility at time of CVF 
(Maintenance + Extension Phase) - Plasma Sample 
 
W152 
7.5 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.5 
Summary of Phenotype: Number of Drugs to Which 
Subject is Phenotypic Resistant or Partial Sensitive or 
Sensitive at Time of CVF (Maintenance + Extension 
Phase) - Plasma Sample 
 
W152 
7.6 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.6 
Summary of Fold Change to CAB and RPV at Time of 
CVF (Maintenance + Extension Phase) - Plasma Sample 
 
W152 
7.7 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.7 
Summary of Net Assessment at time of CVF 
(Maintenance + Extension Phase) - Plasma Sample 
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
304 
 
Virology Tables 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Other 
7.8 
Confirmed 
Virologic 
Failure 
207966/primary_15/T7.9 
Summary of Viral load, Genotypic and Phenotypic data 
for Subjects Who Met Confirmed Virologic Failure Criteria 
during the Maintenance and Extension Phase 
 
W152 
7.9 
Safety 
207966/primary_15/T7.10 
Summary of Viral load, Genotypic and Phenotypic data 
for Non-CVF Subjects with Genotypic and/or Phenotypic 
Data 
 
W152 
 
 
 


 
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305 
 
15.15.6.12. ICH Listings 
Note: Unless otherwise specified, both unique subject ID and latest subject ID for a subject will be included in the listings; display by 
prior exposure to CAB+RPV (0, 1-24, >24 weeks, refer to Section 15.6.2 for calculation details) for all listings except for study 
population listings.  
ICH Listings 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
1 
Intent-to-Treat 
Exposed 
207966/primary_15/L4 
Listing of Reasons for Study 
Withdrawal 
 
W152 
2 
Intent-to-Treat 
Exposed 
207966/primary_15/L5 
Listing of Reasons for Study Drug 
Discontinuation 
 
W152 
3 
Intent-to-Treat 
Exposed 
207966/primary_15/L6 
Listing of Important Protocol 
Deviations 
 
W152 
4 
Intent-to-Treat 
Exposed 
207966/primary_15/L7 
Listing of Protocol Deviations 
Leading to Exclusion from the Per-
Protocol Population 
 
W152 
5 
Intent-to-Treat 
Exposed 
207966/primary_15/L9 
Listing of Demographic 
Characteristics 
 
W152 
6 
Intent-to-Treat 
Exposed 
207966/primary_15/L10 Listing of Race 
 
W152 
7 
Intent-to-Treat 
Exposed 
207966/primary_15/L8 
Listing of Subjects with 
Inclusion/Exclusion Criteria 
Deviations 
 
W152 
Efficacy 
8 
Intent-to-Treat 
Exposed 
207966/primary_15/L11 Listing of Study Outcome (50 c/mL 
Threshold) at Week 152 – Snapshot 
Update the footnote per given data. 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
306 
 
ICH Listings 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Analysis 
Safety 
9 
Safety 
207966/primary_15/L12 Listing of Investigational Product 
Exposure Data 
 
W152 
10 
Safety 
207966/primary_15/L13 Listing of Subject Numbers for 
Individual Adverse Events 
 
W152 
11 
Safety 
207966/primary_15/L14 Listing of Reasons for Considering 
as a Serious Adverse Event 
 
W152 
12 
Safety 
207966/primary_15/L15 Listing of Fatal Adverse Events 
 
W152 
13 
Safety 
207966/primary_15/L16 Listing of Non-Fatal Serious Adverse 
Events 
 
W152 
14 
Safety 
207966/primary_15/L17 
Listing of Adverse Events Leading to 
Withdrawal/Permanent 
Discontinuation of Investigational 
Product (Maintenance + Extension 
Phase) 
 
W152 
15 
Safety 
207966/primary_15/L18 
Listing of Changes in 
Intensity/Grades of Study Drug 
Injection Site Adverse Events 
 
W152 
16 
Safety 
207966/primary_15/L19 Listing of All Adverse Events 
 
W152 
17 
Safety 
207966/primary_15/L66 Listing of COVID-19 Adverse Events 
 
W152 
18 
Safety 
207966/primary_15/L67 Listing of COVID-19 Assessments 
 
W152 
19 
Safety 
207966/primary_15/L68 Listing of COVID-19 Symptoms 
 
W152 
20 
Safety 
207966/primary_15/L20 Listing of Subjects Who Became 
Pregnant during the Study  
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
307 
 
ICH Listings 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
21 
Safety 
207966/primary_15/L21 Listing of Medical Conditions for 
Subjects with Liver stopping Events 
 
W152 
22 
Safety 
207966/primary_15/L22 Listing of Substance Use for 
Subjects with Liver Stopping Events 
 
W152 
23 
Safety 
207966/primary_15/L23 
Listing of ECG Values for Subjects 
with a Value of Potential Clinical 
Importance 
 
W152 
24 
Safety 
207966/primary_15/L24 Listing of ECG Findings 
 
W152 
PK 
25 
Pharmacokinetic 207966/primary_15/L29 Listing of Plasma CAB PK 
Concentration-Time Data 
 
W152 
26 
Pharmacokinetic 207966/primary_15/L30 Listing of Plasma RPV PK 
Concentration-Time Data 
 
W152 
 
 
 


 
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207966 
 
308 
 
15.15.6.13. Non-ICH Listings 
Note: Unless otherwise specified, both unique subject ID and latest subject ID for a subject will be included in the listings; display by 
prior exposure to CAB+RPV (0, 1-24, >24 weeks, refer to calculation details in Section 15.6.2) for all listings except for study population 
listings.  
Non-ICH Listings 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
27 
Intent-to-
Treat 
Exposed 
207966/primary_15/L33 Listing of Reasons for Extension Phase Withdrawal 
 
W152 
28 
Long-term 
Follow-up 
207966/primary_15/L34 Listing of Reasons for Long-term Follow-up Phase 
Withdrawal 
 
W152 
29 
Intent-to-
Treat 
Exposed 
207966/primary_15/L36 Listing of Prior ART Medications 
 
W152 
30 
Intent-to-
Treat 
Exposed 
207966/primary_15/L37 Listing of Concomitant ART Medications 
In case the same medication is 
concomitant during both 
maintenance and extension phases, 
list each of them in two separate 
rows. 
W152 
31 
Intent-to-
Treat 
Exposed 
207966/primary_15/L38 Listing of ART Medications Received during Long-
term Follow-up Phase 
 
W152 
32 
Intent-to-
Treat 
Exposed 
207966/primary_15/L39 Listing of Investigational Product Accountability - 
Oral Regimens 
 
W152 
33 
Intent-to-
207966/primary_15/L6 
Listing of Non-important COVID-19 Related 
Remove the column, “COVID-19 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
309 
 
Non-ICH Listings 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Treat 
Exposed 
Protocol Deviations 
Related”. 
34 
Intent-to-
Treat 
Exposed 
PAN5A 
Country Level Listing of Dates of Waves of COVID-
19 Pandemic Measures 
Only include countries that are 
applicable to the study. The covidimt 
dataset from arenv/arcomn/covid 
uses the IMT alerts to determine 
when pandemic measures began. 
Use this dataset as source to obtain 
the start and end dates of pandemic 
measures. Follow the instructions 
available in the same location for 
appropriate data use.  
W152 
Efficacy 
35 
Confirmed 
Virologic 
Failure 
207966/primary_15/L41 Listing of All Plasma HIV-1 RNA Data for Subjects 
with Confirmed Virologic Failure 
 
W152 
36 
Intent-to-
Treat 
Exposed 
207966/primary_15/L42 
Listing of All Plasma HIV-1 RNA Data for Subjects 
with Viral load >=50 c/mL during the Maintenance 
and Extension Phase 
 
W152 
37 
Intent-to-
Treat 
Exposed 
207966/primary_15/L64 Listing of All Plasma HIV-1 RNA Data 
 
W152 
38 
Intent-to-
Treat 
Exposed 
207966/primary_15/L43 Listing of HIV-1 Associated Conditions 
 
W152 
Safety 
39 
Safety 
207966/primary_15/L52 Listing of Liver Stopping Event Reporting 
 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
310 
 
Non-ICH Listings 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
40 
Safety 
207966/primary_15/L53 Listing of Liver Event Information for RUCAM Score 
 
W152 
41 
Safety 
207966/primary_15/L54 Listing of Liver Biopsy Details 
 
W152 
42 
Safety 
207966/primary_15/L55 Listing of Liver Imaging Details 
 
W152 
43 
Safety 
207966/primary_15/L56 Listing of Subjects Meeting Hepatobiliary Lab 
Criteria  
Only Maintenance and Extension 
phases are included. 
W152 
44 
Safety 
207966/primary_15/L57 Listing of Potential QTc Interval Prolonging Events 
of Interest 
 
W152 
45 
Safety 
207966/primary_15/L58 Listing of ECG values for Subjects with Potential 
QTc Interval Prolonging Events of Interest 
 
W152 
46 
Safety 
207966/primary_15/L59 
Listing of ALT, AST, Bilirubin (including Total and 
Direct Bilirubin), INR, and ALP for Subjects Meeting 
Hepatobiliary Lab Abnormality Criteria 
 
W152 
47 
Safety 
207966/primary_15/L61 Listing of Dosing Errors and IP Device Malfunctions 
 
W152 
48 
Safety 
SAF_L3 
Listing of Selected Study Treatment Data for 
Subjects Who Had Planned Reloading Injections 
 
W152 
Virology 
49 
Confirmed 
Virologic 
Failure 
207966/primary_15/L62 Listing of Replication Capacity in IN and PR/RT 
Region 
 
W152 
50 
Safety 
207966/primary_15/L63 Listing of Resistance Associated Mutations (Pre-
specified INSTI and IAS-USA NNRTI) 
 
W152 
PK 
51 
Long-term 
Follow-up 
207966/primary_02/L63 Listing of Plasma PK Concentration-Time Data 
since Last Injection 
Remove age and add “Start Date of 
Oral RPV after Last Injection” after 
“Baseline BMI (kg/m^2)” in the 
W152 


 
CONFIDENTIAL 
 
 
 
207966 
 
311 
 
Non-ICH Listings 
No. in 
W152 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
second column from the left; add 
asterisk to RPV concentration taken 
on/after the start of such oral RPV. 
and add a footnote, “Note: the RPV 
concentrations marked with an 
asterisk were taken on/after the start 
date of the oral RPV.”  
 
 


 
CONFIDENTIAL 
 
 
 
207966 
 
312 
 
15.15.7. 
List of Data Displays for Sub-study Analysis 
Unless otherwise specified, in sub-study analysis, age refers to the age at the sub-study screening, Baseline weight and Baseline BMI refer 
to the weight and BMI at the sub-study baseline respectively, and the listings will not be presented by prior exposure to CAB + RPV as 
the shell.  
15.15.7.1. Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Subject Disposition 
1.1 
Sub-study ITT-E 
207966/primary_34/T1.1 
Summary of Number of Sub-study 
Subjects Enrolled by Country and Site ID 
 
Sub-study 
1.2 
Sub-study 
Screened 
207966/primary_15/T1.2 
Summary of Screening Status and 
Reasons for Sub-study Screening Failures  
Sub-study 
1.3 
Sub-study ITT-E 
207966/primary_34/T1.2 
Summary of Subject Accountability: Sub-
study Conclusion Record 
Remove the first footnote. Re-number the 
footnotes and the corresponding numbers 
in the display. 
Sub-study 
1.4 
Sub-study ITT-E 
207966/primary_34/T1.3 
Summary of Subject Accountability: Thigh 
Injection Phase Conclusion Record 
 
Sub-study 
1.5 
Sub-study ITT-E 
207966/primary_34/T1.3 
Summary of Subject Accountability: 
Return to Gluteal Injection Phase 
Conclusion Record 
 
Sub-study 
1.6 
Sub-study ITT-E 
207966/primary_34/T1.6 
Summary of Subject Disposition at Each 
Study Phase 
Present following phases in order: Thigh 
Injection Phase, Extension Phase (after 
withdrawal from the Thigh Injection phase), 
Long-term Follow-up Phase (after 
withdrawal from the Thigh Injection phase), 
Return to Gluteal Injection Phase, 
Sub-study 


 
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Study Population Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Extension Phase (after withdrawal from the 
Return to Gluteal Injection phase or sub-
study completion), Long-term Follow-up 
Phase (after withdrawal from the Return to 
Gluteal Injection phase or sub-study 
completion). 
1.7 
Sub-study ITT-E 
207966/primary_34/T1.9 
Summary of Study Drug Discontinuation 
 
Sub-study 
1.8 
Sub-study 
Screened 
207966/primary_34/T1.10 Summary of Study Populations 
Only include analysis populations used in 
the sub-study analysis. 
Sub-study 
1.9 
Sub-study ITT-E 
207966/primary_34/T1.11 Summary of Important Protocol Deviations 
in Sub-study 
 
Sub-study 
1.10 
Sub-study ITT-E 
207966/primary_34/T1.11 Summary of Important Protocol Deviations 
(Thigh Injection Phase) 
 
Sub-study 
1.11 
Sub-study ITT-E 
207966/primary_15/T1.13 Summary of Inclusion/Exclusion Criteria 
Deviations in Sub-study 
 
Sub-study 
1.12 
Sub-study ITT-E 
207966/primary_34/T1.14 Summary of Important COVID-19 Related 
Protocol Deviations in Sub-study 
 
Sub-study 
1.13 
Sub-study ITT-E 
207966/primary_34/T1.15 Summary of Important Non-COVID-19 
Related Protocol Deviations in Sub-study 
 
Sub-study 
Demographic and Baseline Characteristics 
1.14 
Sub-study ITT-E 
207966/primary_34/T1.16 Summary of Demographic Characteristics 
Add [1] after "Age (y)" and "Age group (y)"; 
add the footnote "[1] Age is calculated with 
respect to the first sub-study screening 
visit."; for Weight and BMI, change the 
label to be "Weight (kg) at Sub-study 
Baseline" and "BMI (kg/m^2) at Sub-study 
Baseline" respectively. 
Sub-study 


 
CONFIDENTIAL 
 
 
 
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Study Population Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
1.15 
Sub-study ITT-E 
207966/primary_34/T1.17 Summary of Race and Racial 
Combinations 
 
Sub-study 
1.16 
Sub-study ITT-E 
207966/primary_34/T1.18 Summary of Race and Racial 
Combinations Details 
 
Sub-study 
Medications and Smoking Status 
1.17 
Sub-study ITT-E 
Shell POP_T2 
Summary of Extent of Exposure to Study 
Treatment including SOC Oral Bridging 
Prior to the First Thigh Injection 
 
Sub-study 
1.18 
Sub-study ITT-E 
207966/primary_34/T1.24 
Summary of Concomitant Non-ART 
Medication Ingredient Combinations 
(Thigh Injection Phase) 
 
Sub-study 
1.19 
Sub-study ITT-E 
SU1 
Summary of Smoking Status at Sub-study 
Baseline 
Only include “History of smoking use” 
section. 
Sub-study 
Visits Impacted by COVID-19 Pandemic 
1.20 
Sub-study ITT-E 
207966/primary_34/T1.27 Summary of COVID-19 Pandemic Visit 
Impacts in Sub-study 
Only include visits in sub-study. Remove 
the last footnote. 
Sub-study 
 
 
 


 
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15.15.7.2. Efficacy Tables 
Note: The following subgroups will be included in the subgroup analysis: Age (<50 vs >=50), Race (White vs Non-white), Sex at Birth (Female 
vs Male), Sub-study Baseline BMI (<30, >=30). 
Efficacy Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.1 
Sub-study ITT-E 
207966/primary_34/T2.3 
Summary of Study Outcomes (50 c/mL Threshold) at 
Sub-study Week 16 – Snapshot Analysis 
 
Sub-study 
2.2 
Sub-study ITT-E 
207966/primary_34/T2.7 
Summary of Study Outcomes (50 c/mL Threshold) at 
Sub-study Week 16 by Subgroup – Snapshot Analysis 
 
Sub-study 
2.3 
Sub-study ITT-E 
207966/primary_34/T2.13 
Proportion of Subjects with Plasma HIV-1 RNA >=50 
c/mL by Visit (Thigh Injection Phase) – Snapshot 
Analysis 
 
Sub-study 
2.4 
Sub-study ITT-E 
207966/primary_34/T2.14 
Proportion of Subjects with Plasma HIV-1 RNA >=50 
c/mL by Subgroup and Visit (Thigh Injection Phase) – 
Snapshot Analysis 
 
Sub-study 
2.5 
Sub-study ITT-E 
207966/primary_34/T2.15 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL by Visit (Thigh Injection Phase) – Snapshot 
Analysis 
 
Sub-study 
2.6 
Sub-study ITT-E 
207966/primary_34/T2.16 
Proportion of Subjects with Plasma HIV-1 RNA <50 
c/mL by Subgroup and Visit (Thigh Injection Phase) – 
Snapshot Analysis 
 
Sub-study 
2.7 
Sub-study ITT-E 
207966/primary_34/T2.23 
Summary of Change from Sub-study Baseline in 
Plasma HIV-1 RNA (log10 c/mL) by Visit (Thigh 
Injection + Return to Gluteal Injection Phase) 
 
Sub-study 
2.8 
Sub-study ITT-E 
207966/primary_34/T2.24 Summary of Plasma HIV-1 RNA (log10 c/mL) by Visit 
(Thigh Injection + Return to Gluteal Injection Phase) 
 
Sub-study 


 
CONFIDENTIAL 
 
 
 
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316 
 
Efficacy Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.9 
Sub-study ITT-E 
207966/primary_34/T2.25 
Cumulative Proportion of Subjects Meeting Confirmed 
Virology Failure Criteria by Visit (Thigh Injection + 
Return to Gluteal Injection Phase) 
 
Sub-study 
2.10 
 Sub-study CVF 
207966/primary_34/T2.27 
Distribution of Quantitative Plasma HIV-1 RNA Results 
at Suspected and Confirmation of Confirmed Virologic 
Failure (Thigh Injection + Return to Gluteal Injection 
Phase) 
Produce only when data 
available for the population of 
interest. 
Sub-study 
2.11 
Sub-study ITT-E 
207966/primary_34/T2.29 Summary of Subjects per Viral Load Category by Visit 
(Thigh Injection Phase) 
 
Sub-study 
2.12 
Sub-study ITT-E 
207966/primary_34/T2.30 
Summary of Change from Sub-study Baseline in CD4+ 
Cell Count (cells/mm^3) by Visit (Thigh Injection + 
Return to Gluteal Injection Phase) 
 
Sub-study 
2.13 
Sub-study ITT-E 
207966/primary_34/T2.31 
Summary of Change from Sub-study Baseline in CD4+ 
Cell Count (cells/mm^3) at Sub-study Week 16 by 
Subgroup 
Replace “Baseline” with “Sub-
study baseline” in the footnote. 
 
2.14 
Sub-study ITT-E 
207966/primary_34/T2.32 Summary of CD4+ Cell Count (cells/mm^3) by Visit 
(Thigh Injection + Return to Gluteal Injection Phase) 
 
Sub-study 
2.15 
Sub-study ITT-E 
207966/primary_34/T2.33 Summary of Change from Sub-study Baseline in CD8+ 
Cell Count (cells/mm^3) by Visit (Thigh Injection Phase) 
Replace “Baseline” with “Sub-
study baseline” in the footnote. 
Sub-study 
2.16 
Sub-study ITT-E 
207966/primary_34/T2.34 Summary of CD8+ Cell Count (cells/mm^3) by Visit 
(Thigh Injection Phase) 
 
Sub-study 
2.17 
Sub-study ITT-E 
207966/primary_34/T2.35 Summary of CD4+/CD8+ Ratio Cell Count (cells/mm^3) 
by Visit (Thigh Injection Phase) 
 
Sub-study 
2.18 
Sub-study ITT-E 
207966/primary_34/T2.36 
Summary of HIV-1 Associated Conditions Including 
Recurrences (Thigh Injection + Return to Gluteal 
Injection Phase) 
Produce only when data 
available for the population of 
interest. 
Sub-study 


 
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Efficacy Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.19 
Sub-study ITT-E 
207966/primary_34/T2.37 
Summary of HIV-1 Associated Conditions Excluding 
Recurrences (Thigh Injection + Return to Gluteal 
Injection Phase) 
Produce only when data 
available for the population of 
interest. 
Sub-study 
2.20 
Sub-study ITT-E 
207966/primary_34/T2.38 
Summary of HIV-1 Disease Progression from Sub-study 
Baseline and/or Deaths (Thigh Injection + Return to 
Gluteal Injection Phase) 
Replace "maintenance and 
extension phase" in the 
second footnote with "thigh 
injection or return to gluteal 
injection phase". 
Sub-study 
 
 


 
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15.15.7.3. Efficacy Figures 
Efficacy Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
2.1 
Sub-study ITT-E 
207966/primary_34/F2.1 
Proportion (95% CI) of Subjects with HIV-1 RNA ≥50 
c/mL by Visit (Thigh Injection Phase) – Snapshot 
Analysis 
 
Sub-study 
2.2 
Sub-study ITT-E 
207966/primary_34/F2.3 
Proportion (95% CI) of Subjects with HIV-1 RNA <50 
c/mL by Visit (Thigh Injection Phase) – Snapshot 
Analysis 
 
Sub-study 
2.3 
Sub-study CVF 
207966/primary_34/F2.7 Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by 
Visit – for CVF Subjects  
Produce only when data 
available for the population of 
interest. Replace the first 
footnote with "First vertical 
reference line corresponds to 
the date of first thigh 
injection." 
Sub-study 
2.4 
Sub-study ITT-E 
207966/primary_34/F2.8 
Individual Plasma HIV-1 RNA (log10 c/mL) Profiles by 
Visit for subjects Who are in the Category of ‘HIV-1 
RNA >=50 c/mL’ at Sub-study Week 16 per Snapshot 
Algorithm 
Produce only when data 
available for the population of 
interest. Replace the first 
footnote with "First vertical 
reference line corresponds to 
the date of first thigh 
injection." 
Sub-study 
 
 


 
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15.15.7.4. Safety Tables 
Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Exposure 
3.1 
Sub-study 
Safety 
207966/primary_34/T3.1 
Summary of Extent of Exposure to Study 
Treatment (Thigh Injection + Return to Gluteal 
Injection Phase) 
Include both continuous and categorical 
summaries for Exposure (No. of Thigh 
Injection Visits), Exposure (No. of 
Return to Gluteal Injection Visits), 
Exposure (No. of Injection Visits), 
Overall Exposure to Study Treatment 
during the Thigh Injection Phase, 
Overall Exposure to Study Treatment 
during the Thigh Injection + Return to 
Gluteal Injection Phase. The levels for 
categorical summaries will be selected 
as appropriate. Remove the footnote. 
Sub-study 
3.2 
Sub-study 
Safety 
207966/primary_34/T3.2 
Summary of Needle Length and Gauge for 
CAB Injection (Thigh Injection Phase) 
Replace the “at Maintenance + 
Extension Phase” in footnote with 
“during the Thigh Injection phase”. 
Sub-study 
3.3 
Sub-study 
Safety 
207966/primary_34/T3.3 
Summary of Needle Length and Gauge for 
RPV Injection (Thigh Injection Phase) 
Replace the “at Maintenance + 
Extension Phase” in footnote with 
“during the Thigh Injection phase”. 
Sub-study 
3.4 
Sub-study 
Safety 
207966/primary_34/T3.4 
Summary of Adherence to CAB/RPV Injection 
Dosing Schedule (Thigh Injection Phase) 
Remove the missed Injection related 
rows from shell. Add “Missed Injection” 
row. Replace the footnote with "[1] The 
total number of expected thigh injection 
visits following the first thigh injection." 
Add a footnote “Note: Oral bridging is 
not allowed in the sub-study.”. 
Sub-study 


 
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Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.5 
Sub-study 
Safety 
207966/primary_34/T3.4 
Summary of Adherence to CAB/RPV Injection 
Dosing Schedule (Thigh Injection + Return to 
Gluteal Injection Phase) 
Remove the missed Injection related 
rows from shell. Add “Missed Injection” 
row. Replace the footnote with "[1] The 
total number of expected injection visits 
in sub-study following the first thigh 
injection." Add a footnote “Note: Oral 
bridging is not allowed in the sub-
study.”. 
Sub-study 
Adverse Events 
3.6 
Sub-study 
Safety 
207966/primary_34/T3.6 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity (Thigh 
Injection Phase) 
 
Sub-study 
3.7 
Sub-study 
Safety 
207966/primary_34/T3.6 
Summary of All Adverse Events by System 
Organ Class and Maximum Toxicity (Thigh 
Injection + Return to Gluteal Injection Phase) 
 
Sub-study 
3.8 
Sub-study 
Safety 
207966/primary_34/T3.8 
Summary of All Adverse Events Excluding 
Study Drug Injection Site Reactions by System 
Organ Class and Maximum Toxicity (Thigh 
Injection Phase) 
 
Sub-study 
3.9 
Sub-study 
Safety 
207966/primary_34/T3.10 
Summary of Common Adverse Events (>=5%) 
by Overall Frequency (Thigh Injection Phase) 
 
Sub-study 
3.10 
Sub-study 
Safety 
207966/primary_34/T3.11 
Summary of Common Grade 2-5 Adverse 
Events (>=1%) by Overall Frequency (Thigh 
Injection Phase) 
 
Sub-study 
3.11 
Sub-study 
Safety 
207966/primary_34/T3.13 
Summary of All Drug-related Adverse Events 
by System Organ Class and Maximum Toxicity 
(Thigh Injection Phase) 
 
Sub-study 


 
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Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.12 
Sub-study 
Safety 
207966/primary_34/T3.15 
Summary of All Drug-related Adverse Events 
Excluding Study Drug Injection Site Reactions 
by System Organ Class and Maximum Toxicity 
(Thigh Injection Phase) 
 
Sub-study 
3.13 
Sub-study 
Safety 
207966/primary_34/T3.16 
Summary of All Drug-Related Grade 2-5 
Adverse Events by Overall Frequency (Thigh 
Injection Phase) 
 
Sub-study 
Serious and Other Significant Adverse Events 
3.14 
Sub-study 
Safety 
207966/primary_34/T3.17 
Summary of Serious Adverse Events by 
System Organ Class (Thigh Injection Phase) 
 
Sub-study 
3.15 
Sub-study 
Safety 
207966/primary_34/T3.17 
Summary of Serious Adverse Events by 
System Organ Class (Thigh Injection +Return 
to Gluteal Injection Phase) 
 
Sub-study 
3.16 
Sub-study 
Safety 
207966/primary_34/T3.19 
Summary of Drug-related Serious Adverse 
Events by System Organ Class (Thigh 
Injection Phase) 
 
Sub-study 
3.17 
Sub-study 
Safety 
207966/primary_34/T3.22 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product or Withdrawal from 
Study by System Organ Class (Thigh Injection 
Phase) 
Remove the footnote. 
Sub-study 
3.18 
Sub-study 
Safety 
207966/primary_34/T3.22 
Summary of Adverse Events Leading to 
Withdrawal/Permanent Discontinuation of 
Investigational Product by System Organ 
Class (Thigh Injection + Return to Gluteal 
Injection Phase) 
Remove the footnote. 
Sub-study 
3.19 
Sub-study 
207966/primary_34/T3.25 
Summary of Subjects and Number of 
 
Sub-study 


 
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Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Safety 
Occurrences of Common (>=5%) Non-Serious 
Adverse Events by System Organ Class 
(Thigh Injection Phase) 
3.20 
Sub-study 
Safety 
207966/primary_34/T3.26 
Summary of Subjects and Number of 
occurrences of SAEs, Fatal SAEs, and Drug-
related SAEs (Thigh Injection Phase) 
 
Sub-study 
Study Drug Injection Site Reaction Adverse Events 
3.21 
Sub-study 
Safety 
207966/primary_34/T3.27 
Summary of Study Drug Injection Site 
Reaction Adverse Events (Event-level 
Summary) – (Thigh Injection Phase) 
 
Sub-study 
3.22 
Sub-study 
Safety 
207966/primary_34/T3.28 
Summary of Subject-level Characteristics of 
Study Drug Injection Site Reaction Adverse 
Events – Overall and Common (Thigh Injection 
Phase) 
 
Sub-study 
3.23 
Sub-study 
Safety 
207966/primary_34/T3.29 
Summary of Study Drug Injection Site 
Reaction Adverse Events by Visit and 
Maximum Severity – Overall and Common in 
Sub-study 
 
Sub-study 
3.24 
Sub-study 
Safety 
207966/primary_34/T3.30 
Summary of Drug-related Study Drug Injection 
Site Reaction Adverse Events (Event-level 
Summary) - CAB (Thigh Injection Phase) 
 
Sub-study 
3.25 
Sub-study 
Safety 
207966/primary_34/T3.31 
Summary of Drug-related Subject-level 
Characteristics of Study Drug Injection Site 
Reaction Adverse Events (Thigh Injection 
Phase) - Overall and Common (CAB) 
 
Sub-study 
3.26 
Sub-study 
Safety 
207966/primary_34/T3.32 
Summary of Overall and Common Drug-
related Study Drug Injection Site Reaction 
 
Sub-study 


 
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Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Adverse Events by Visit and Maximum 
Severity in Sub-study - CAB 
3.27 
Sub-study 
Safety 
207966/primary_34/T3.33 
Summary of Maximum Drug-related Study 
Drug Injection Site Reaction Adverse Event 
Grade by Needle Length (Thigh Injection 
Phase) – Common (CAB) 
Replace “Mnt + Ext” with “Thigh 
Injection” in the footnote. 
Sub-study 
3.28 
Sub-study 
Safety 
207966/primary_34/T3.34 
Summary of Drug-related Study Drug Injection 
Site Reaction Adverse Events (Event-level 
Summary) - RPV (Thigh Injection Phase) 
 
Sub-study 
3.29 
Sub-study 
Safety 
207966/primary_34/T3.35 
Summary of Drug-related Subject-level 
Characteristics of Study Drug Injection Site 
Reaction Adverse Events (Thigh Injection 
Phase) - Overall and Common (RPV) 
 
Sub-study 
3.30 
Sub-study 
Safety 
207966/primary_34/T3.36 
Summary of Overall and Common Drug-
related Study Drug Injection Site Reaction 
Adverse Events by Visit and Maximum 
Severity in Sub-study - RPV 
 
Sub-study 
3.31 
Sub-study 
Safety 
207966/primary_34/T3.37 
Summary of Maximum Drug-related Study 
Drug Injection Site Reaction Adverse Event 
Grade by Needle Length (Thigh Injection 
Phase) – Common (RPV) 
Replace “Mnt + Ext” with “Thigh 
Injection” in the footnote. 
Sub-study 
Laboratory: Chemistry and Hematology 
3.32 
Sub-study 
Safety 
207966/primary_34/T3.38 
Summary of Chemistry Changes from Sub-
study Baseline by Visit (Thigh Injection + 
Return to Gluteal Injection Phase) 
 
Sub-study 
3.33 
Sub-study 
Safety 
207966/primary_34/T3.39 
Summary of Chemistry Values by Visit (Thigh 
Injection + Return to Gluteal Injection Phase) 
 
Sub-study 


 
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Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.34 
Sub-study 
Safety 
207966/primary_34/T3.40 
Summary of Hematology Changes from Sub-
study Baseline by Visit (Thigh Injection + 
Return to Gluteal Injection Phase) 
 
Sub-study 
3.35 
Sub-study 
Safety 
207966/primary_34/T3.41 
Summary of Hematology Values by Visit 
(Thigh Injection + Return to Gluteal Injection 
Phase) 
 
Sub-study 
3.36 
Sub-study 
Safety 
207966/primary_34/T3.42 
Summary of Maximum Post Sub-study 
Baseline Emergent Chemistry Toxicities (Thigh 
Injection Phase) 
Add “sub-study” before “baseline” in the 
second footnote. 
Sub-study 
3.37 
Sub-study 
Safety 
207966/primary_34/T3.43 
Summary of Maximum Post Sub-study 
Baseline Emergent Hematology Toxicities 
(Thigh Injection Phase) 
Add “sub-study” before “baseline” in the 
footnote. 
Sub-study 
Laboratory: Urinalysis 
3.38 
Sub-study 
Safety 
207966/primary_34/T3.44 
Summary of Urinalysis Dipstick Results by 
Visit (Thigh Injection Phase) 
 
Sub-study 
3.39 
Sub-study 
Safety 
207966/primary_34/T3.45 
Summary of Urine Concentrations Changes 
from Sub-study Baseline by Visit (Thigh 
Injection Phase) 
Add “sub-study” before “baseline” in the 
second footnote. 
Sub-study 
3.40 
Sub-study 
Safety 
207966/primary_34/T3.46 
Summary of Changes in Proteinuria Baseline 
Laboratory Result to Maximum Post Sub-study 
Baseline Laboratory Result (Thigh Injection 
Phase) 
 
Sub-study 
Laboratory: Hepatobiliary (Liver) 
3.41 
Sub-study 
Safety 
207966/primary_34/T3.53 
Summary of Liver Stopping Event Reporting 
(Thigh Injection Phase) 
 
Sub-study 
3.42 
Sub-study 
207966/primary_34/T3.54 
Summary of Subjects Meeting Hepatobiliary 
 
Sub-study 


 
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Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Safety 
Abnormality Criteria (Thigh Injection Phase) 
ECG 
3.43 
Sub-study 
Safety 
207966/primary_34/T3.55 
Summary of ECG Findings (Thigh Injection 
Phase) 
 
Sub-study 
3.44 
Sub-study 
Safety 
207966/primary_34/T3.56 
Summary of Change from Sub-study Baseline 
in ECG values by Visit (Thigh Injection Phase) 
Add “sub-study” before “baseline” in the 
first footnote. 
Sub-study 
3.45 
Sub-study 
Safety 
207966/primary_34/T3.57 
Summary of QTc Values by Category (Thigh 
Injection Phase) 
 
Sub-study 
3.46 
Sub-study 
Safety 
207966/primary_34/T3.58 
Summary of Change from Sub-study Baseline 
QTc Values by Category (Thigh Injection 
Phase) 
 
Sub-study 
Vital Signs 
3.47 
Sub-study 
Safety 
207966/primary_34/T3.59 
Summary of Change from Sub-study Baseline 
in Vital Signs by Visit (Thigh Injection Phase) 
Add “sub-study” before “baseline” in the 
first footnote. 
Sub-study 
Adverse Event of Special Interest (AESI) 
3.48 
Sub-study 
Safety 
207966/primary_34/T3.63 
Summary of Depression, Anxiety and Suicidal 
Ideation/Behaviour Adverse Events by System 
Organ Class, Maximum DAIDS Toxicity Grade, 
and Prior History of Depression, Anxiety and 
Suicidal Ideation at Screening (Thigh Injection 
Phase) 
May need to adjust the first footnote 
given the data. Add a footnote: “Note: 
The prior history of depression, anxiety 
and suicidal ideation was collected at 
the main study screening”. 
Sub-study 
3.49-
3.66 
Sub-study 
Safety 
207966/primary_34/T3.64-
3.80 
Summary of XXX Adverse Events of Special 
Interest by System Organ Class and Preferred 
Term (Number of Subjects and Occurrence) – 
Thigh Injection Phase 
 
Sub-study 
3.67 
Sub-study 
207966/primary_34/T3.81 
Summary of Characteristics of Common 
 
Sub-study 


 
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Safety Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Safety 
Adverse Events of Special Interest – Thigh 
Injection Phase 
COVID-19 Adverse Event 
3.68 
Sub-study 
Safety 
207966/primary_34/T3.84 
Summary of COVID-19 Adverse Events by 
System Organ Class and Maximum Toxicity 
(Thigh Injection Phase) 
 
Sub-study 
3.69 
Sub-study 
Safety 
PAN1A 
Summary of COVID-19 Assessments for 
Subjects with Suspected, Probable or 
Confirmed COVID-19 Case Diagnosis in Sub-
study 
Replace the first footnote with “[1] 
COVID-19 case diagnosis is based on 
WHO definition that was in effect at the 
time of diagnosis.”. Add a footnote 
“Note: only the assessments with the 
associated COVID-19 adverse event (as 
recorded in the COVID-19 Coronavirus 
Infection Assessment eCRF form) 
started in the sub-study are included.”. 
Sub-study 
3.70 
Sub-study 
Safety 
PAN2A 
Summary of COVID-19 Additional 
Assessments for Subjects with Suspected, 
Probable or Confirmed COVID-19 Case 
Diagnosis in Sub-study 
Add a footnote “Note: only the 
assessments with the associated 
COVID-19 adverse event (as recorded 
in the COVID-19 Coronavirus Infection 
Assessment eCRF form) started in the 
sub-study are included.”. 
Sub-study 
 
 
 


 
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15.15.7.5. Safety Figures 
Safety Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
3.1 
Sub-study 
Safety 
213500/primary_03/F3.2 
Plot of Incidence of Sub-study Study Drug Injection Site 
Reaction Adverse Events by Visit (Overall and 
Common)  
Within each page, display CAB 
LA and/or RPV LA, CAB LA-
Drug- Related, RPV LA-Drug- 
Related 
Sub-study 
3.2 
Sub-study 
Safety 
207966/primary_34/F3.7 
Scatter Plot of Maximum vs. Sub-study Baseline for 
ALT (Thigh Injection Phase) 
Add “Sub-study” to the front of 
“Baseline” in the x axis label. 
Sub-study 
3.3 
Sub-study 
Safety 
207966/primary_34/F3.8 
Scatter Plot of Maximum Total Bilirubin vs. Maximum 
ALT (Thigh Injection Phase) 
 
Sub-study 
3.4 
Sub-study 
Safety 
207966/primary_34/F3.11 Histogram of Timeliness of Injections (Thigh Injection 
Phase) 
 
Sub-study 
 
 
 


 
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15.15.7.6. Pharmacokinetic Tables 
Pharmacokinetic Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.1 
Sub-study PK 
Concentration  
207966/primary_34/T4.1 
Summary of Plasma CAB PK Concentration (ug/mL) - 
Time Data by Treatment and Visit in Sub-study - 
Including Log-transformed Statistics 
Remove the last two 
footnotes. 
Sub-study 
4.2 
Sub-study PK 
Concentration 
207966/primary_34/T4.2 
Summary of Plasma RPV PK Concentration (ng/mL) - 
Time Data by Treatment and Visit in Sub-study - 
Including Log-transformed Statistics 
Remove the last two 
footnotes. 
Sub-study 
4.3 
Sub-study PK 
Concentration 
207966/primary_34/T4.3 
Summary of Evaluable Plasma CAB PK Concentration 
(ug/mL) - Time Data by Treatment and Visit in Sub-study 
- Including Log-transformed Statistics 
Remove the last footnote. 
Sub-study 
4.4 
Sub-study PK 
Concentration 
207966/primary_34/T4.4 
Summary of Evaluable Plasma RPV PK Concentration 
(ng/mL) - Time Data by Treatment and Visit in Sub-study 
- Including Log-transformed Statistics 
Remove the last footnote. 
Sub-study 
4.5 
Sub-study PK 
Parameter 
PK06 
Summary of Plasma CAB PK Parameters (non-
transformed and log-transformed) by Treatment and 
Dosing Interval in Sub-study 
Remove Column "{Additional 
time variable}". Replace 
treatment columns with 
columns for dosing intervals 
as specified in Section 
15.6.5. Add Min and Max 
after %CVb for log-
transformed data. Add %CV 
after SD for non-transformed 
data. Add Q1 and Q3 after 
Median to both types of 
data. 
Sub-study 


 
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Pharmacokinetic Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.6 
Sub-study PK 
Parameter 
PK06 
Summary of Plasma RPV PK Parameters (non-
transformed and log-transformed) by Treatment and 
Dosing Interval in Sub-study 
Similar notes to above. 
Sub-study 
4.7 
Sub-study PK 
Parameter 
Shell PK_T2 
Statistical Analysis of Plasma CAB PK Parameters by 
Treatment in Sub-study 
 
Sub-study 
4.8 
Sub-study PK 
Parameter 
Shell PK_T2 
Statistical Analysis of Plasma RPV PK Parameters by 
Treatment in Sub-study 
 
Sub-study 
 
 
 


 
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15.15.7.7. Pharmacokinetic Figures 
Pharmacokinetic Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
4.1 
Sub-study PK 
Concentration 
207966/primary_34/F4.1 
Individual Plasma CAB Concentration-Time 
Plots (Linear and Semi-Log) in Sub-study 
Remove the second footnote. 
Sub-study 
4.2 
Sub-study PK 
Concentration 
207966/primary_34/F4.2 
Individual Plasma RPV Concentration-Time 
Plots (Linear and Semi-Log) in Sub-study 
Remove the second footnote. 
Sub-study 
4.3 
Sub-study PK 
Concentration 
207966/primary_34/F4.5 
Mean (SD) Evaluable Plasma CAB 
Concentration-Time Plots (Linear and Semi-
Log) in Sub-study 
Remove the first footnote. 
Sub-study 
4.4 
Sub-study PK 
Concentration 
207966/primary_34/F4.6 
Mean (SD) Evaluable Plasma RPV 
Concentration-Time Plots (Linear and Semi-
Log) in Sub-study 
Remove the first footnote. 
Sub-study 
4.5 
Sub-study PK 
Concentration 
207966/primary_34/F4.11 
Median (5th and 95th Percentile) Evaluable 
Plasma CAB Concentration-Time Plots (Linear 
and Semi-Log) in Sub-study 
Remove the first footnote. 
Sub-study 
4.6 
Sub-study PK 
Concentration 
207966/primary_34/F4.12 
Median (5th and 95th Percentile) Evaluable 
Plasma RPV Concentration-Time Plots (Linear 
and Semi-Log) in Sub-study 
Remove the first footnote. 
Sub-study 
4.7 
Sub-study PK 
Parameter 
205696/final/F3.6 
Geometric Mean Ratios and 90% CIs of 
Plasma CAB PK Parameters in Sub-study by 
Treatment and Comparison Type 
Use "PK parameter name (n=xx)" 
for y axis label, add "Geometric 
Mean Ratio with 90% CI" for x 
axis label. Remove the footnotes 
from shell. Add Footnote: Note: 
The geometric mean ratios and 
90% CIs come from the statistical 
analysis of the PK parameters 
using a mixed effects model as 
specified in the analysis plan.  
Sub-study 


 
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Pharmacokinetic Figures 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Page by Treatment and 
Parameter. The parameters 
include Ctau, Cmax and AUC(0-
tau). Each page contains 
comparison types First Thigh vs. 
Gluteal and Last Thigh vs. 
Gluteal. 
4.8 
Sub-study PK 
Parameter 
205696/final/F3.6 
Geometric Mean Ratios and 90% CIs of RPV 
PK Parameters in Sub-study by Treatment 
and Comparison Type 
Similar notes to above. 
Sub-study 
 
 
 


 
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15.15.7.8. Health Outcomes Tables 
Health Outcomes Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
HIV Treatment Satisfaction Questionnaire Status or Change Version (HIVTSQs, HIVTSQc) 
6.1 
Sub-study 
ITT-E 
207966/primary_34/T6.7 
Proportion of Subjects with HIVTSQs - Individual 
Item Scores by Visit in Sub-study 
 
Sub-study 
6.2 
Sub-study 
ITT-E 
207966/primary_34/T6.9 
Summary of HIVTSQs - Total Treatment 
Satisfaction Score by Visit in Sub-study 
Add a column “P Value [1]” to the right 
of the Column “Max.” Add the footnote: 
[1] Sub-study Week 16, Sub-study 
Week 24 (for Q8W arm) or 20 (for 
Q4W arm) are compared with the Sub-
study Baseline using Wilcoxon signed-
rank test.” 
Sub-study 
6.3 
Sub-study 
ITT-E 
207966/primary_34/T6.11 
Summary of HIVTSQs - Change in Total Treatment 
Satisfaction Score in Sub-study 
Remove the column 'Prior Exposure to 
CAB+RPV (weeks)'. Replace "Act. 
Rel. Time" With "Change", the new 
"Change" column includes "Change 
from Baseline to Week 16" for both 
arms, "Change from Baseline to Week 
20" for Q4W and "Change from 
Baseline to Week 24" for Q8W, 
"Change from Week 16 to Week 20" 
for Q4W arm and "Change from Week 
16 to Week 20" for Q8W. Remove the 
footnote. 
Sub-study 
6.4 
Sub-study 
ITT-E 
207966/primary_34/T6.13 
Summary of HIVTSQs - Change in Individual Item 
Score in Sub-study 
Similar notes to above. 
Sub-study 


 
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Health Outcomes Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.5 
Sub-study 
ITT-E 
207966/primary_02/T6.23 
Proportion of Subjects with HIVTSQc - Individual 
Item Change Score at Sub-study Week 16 (Thigh 
Injection Phase) 
 
Sub-study 
6.6 
Sub-study 
ITT-E 
207966/primary_02/T6.27 
Summary of HIVTSQc - Individual Item Change 
Score at Sub-study Week 16 (Thigh Injection 
Phase) 
 
Sub-study 
6.7 
Sub-study 
ITT-E 
207966/primary_02/T6.25 
Summary of HIVTSQc - Total Treatment 
Satisfaction Change Score at Sub-study Week 16 
(Thigh Injection Phase) 
 
Sub-study 
Tolerability of Injection (NRS) 
6.8 
Sub-study 
ITT-E 
Shell HO_T3 
Proportion of Subjects with Each Tolerability of 
Injection (NRS) Score by Visit in Sub-study 
 
Sub-study 
6.9 
Sub-study 
ITT-E 
201584/primary_01/T6.35 
Summary of Tolerability of Injection (NRS) Score 
by Visit in Sub-study 
 
Sub-study 


 
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Health Outcomes Tables 
No.  
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
6.10 
Sub-study 
ITT-E 
201584/primary_01/T6.37 
Summary of Change in Tolerability of Injection 
(NRS) Score in Sub-study 
Replace "Actual Relative Time" with 
"Change”. In this column, for Q4W: 
"Change from Week -4 to Day 1", 
"Change from Week -3 to Week 1", 
"Change from Day 1 to Week 12", 
"Change from Week 1 to Week 13", 
Change from Week 12 to Week 16", 
"Change from Week 13 to Week 17", 
for Q8W:  "Change from Week -8 to 
Day 1", "Change from Week -7 to 
Week 1", "Change from Day 1 to 
Week 8", "Change from Week 1 to 
Week 9", "Change from Week 8 to 
Week 16", "Change from Week 9 to 
Week 17". 
Sub-study 
Preference 
6.11 
Sub-study 
ITT-E 
Shell HO_T4 
Proportion of Subjects with Response to Each 
Individual Question in Preference Thigh Injection 
vs Gluteal Injection Questionnaire by Visit in Sub-
study 
 
Sub-study 
 
 
 


 
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15.15.7.9. Virology Tables 
Tables 7.1-7.6 will only be produced when at least one treatment group has >5 subjects in Sub-study CVF population. Tables 7.8-7.9 will 
only be produced when data are available. 
Virology Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Genotype 
7.1 
Sub-study 
CVF 
207966/primary_34/T7.1 
Summary of the Prevalence of Known INI Resistance 
Mutations at time of CVF (Thigh Injection + Return to 
Gluteal Injection Phase) – Plasma Sample 
 
Sub-study 
7.2 
Sub-study 
CVF 
207966/primary_34/T7.2 
Summary of the Prevalence of Major Resistance 
Mutations of NRTI, NNRTI and PI Class at time of CVF 
(Thigh Injection + Return to Gluteal Injection Phase) - 
Plasma Sample 
 
Sub-study 
7.3 
Sub-study 
CVF 
207966/primary_34/T7.3 
Summary of Genotypic Susceptibility at time of CVF 
(Thigh Injection + Return to Gluteal Injection Phase) - 
Plasma Sample 
 
Sub-study 
Phenotype 
7.4 
Sub-study 
CVF 
207966/primary_34/T7.4 
Summary of Phenotype Susceptibility at time of CVF 
(Thigh Injection + Return to Gluteal Injection Phase) - 
Plasma Sample 
 
Sub-study 
7.5 
Sub-study 
CVF 
207966/primary_34/T7.5 
Summary of Phenotype: Number of Drugs to Which 
Subject is Phenotypic Resistant or Partial Sensitive or 
Sensitive at Time of CVF (Thigh Injection + Return to 
Gluteal Injection Phase) - Plasma Sample 
 
Sub-study 
7.6 
Sub-study 
CVF 
207966/primary_34/T7.6 
Summary of Fold Change to CAB and RPV at Time of 
CVF (Thigh Injection + Return to Gluteal Injection Phase) 
- Plasma Sample 
 
Sub-study 


 
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Virology Tables 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
7.7 
Sub-study 
CVF 
207966/primary_34/T7.7 
Summary of Net Assessment at time of CVF (Thigh 
Injection + Return to Gluteal Injection Phase) - Plasma 
Sample 
 
Sub-study 
Other 
7.8 
Sub-study 
CVF 
207966/primary_34/T7.8 
Summary of Viral load, Genotypic and Phenotypic data 
for Subjects Who Met Confirmed Virologic Failure Criteria 
during the Thigh Injection or Return to Gluteal Injection 
Phase 
 
Sub-study 
7.9 
Sub-study 
Safety 
207966/primary_34/T7.9 
Summary of Viral load, Genotypic and Phenotypic data 
for Non-CVF Subjects with Genotypic and/or Phenotypic 
Data in Sub-study 
 
Sub-study 
 
 
 


 
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15.15.7.10. ICH Listings 
ICH Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
1 
Sub-study 
Screened 
207966/primary_15/L3 
Listing of Reasons for Screen Failure 
in Sub-study 
 
Sub-study 
2 
Sub-study ITT-E 
207966/primary_34/L1 
Listing of Reasons for Sub-study 
Withdrawal 
 
Sub-study 
3 
Sub-study ITT-E 
207966/primary_34/L2 
Listing of Reasons for Study Drug 
Discontinuation 
 
Sub-study 
4 
Sub-study ITT-E 
207966/primary_34/L3 
Listing of Important Protocol 
Deviations 
 
Sub-study 
5 
Sub-study ITT-E 
207966/primary_34/L7 
Listing of Subjects with 
Inclusion/Exclusion Criteria 
Deviations 
 
Sub-study 
6 
Sub-study ITT-E 
207966/primary_34/L5 
Listing of Demographic 
Characteristics 
Add "BMI (kg/m^2)" to the right of "Weight 
(kg)". Add the following sentence to footnote 
[1]: Age is calculated with respect to the 
subject’s first sub-study screening visit. Add a 
footnote for BMI and Weight: [2] BMI and 
Weight are derived at Sub-study Baseline. 
Sub-study 
Efficacy 
7 
Sub-study ITT-E 
207966/primary_34/L8 
Listing of Study Outcome (50 c/mL 
Threshold) at Sub-study Week 16 – 
Snapshot Analysis 
Remove the footnote. 
Sub-study 
Safety 
8 
Sub-study 
207966/primary_34/L9 
Listing of Investigational Product 
 
Sub-study 


 
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ICH Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
Safety 
Exposure Data 
9 
Sub-study 
Safety 
207966/primary_34/L10 Listing of Subject Numbers for 
Individual Adverse Events 
 
Sub-study 
10 
Sub-study 
Safety 
207966/primary_34/L11 Listing of Reasons for Considering 
as a Serious Adverse Event 
 
Sub-study 
11 
Sub-study 
Safety 
207966/primary_34/L12 Listing of Fatal Adverse Events 
 
Sub-study 
12 
Sub-study 
Safety 
207966/primary_34/L13 Listing of Non-Fatal Serious Adverse 
Events 
 
Sub-study 
13 
Sub-study 
Safety 
207966/primary_34/L14 
Listing of Adverse Events Leading to 
Withdrawal/Permanent 
Discontinuation of Investigational 
Product or Withdrawal from Study 
 
Sub-study 
14 
Sub-study 
Safety 
207966/primary_34/L15 
Listing of Changes in 
Intensity/Grades of Study Drug 
Injection Site Adverse Events 
 
Sub-study 
15 
Sub-study 
Safety 
207966/primary_34/L16 Listing of All Adverse Events 
 
Sub-study 
16 
Sub-study 
Safety 
207966/primary_34/L17 Listing of COVID-19 Adverse Events 
 
Sub-study 
17 
Sub-study 
Safety 
207966/primary_34/L18 Listing of COVID-19 Assessments 
 
Sub-study 
18 
Sub-study 
Safety 
207966/primary_34/L19 Listing of COVID-19 Symptoms 
 
Sub-study 
19 
Sub-study 
Safety 
207966/primary_34/L20 Listing of Subjects Who Became 
Pregnant during the Study  
Add a footnote: “Note: As pregnancy status is 
not collected in eCRF for the long-term follow-
Sub-study 


 
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ICH Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
up phase, this listing does not include subjects 
who became pregnant during the long-term 
follow-up phase.” 
20 
Sub-study 
Safety 
207966/primary_34/L23 
Listing of ECG Values for Subjects 
with a Value of Potential Clinical 
Importance in Sub-study 
In footnote, add “sub-study” before the 
“baseline”. Add following to the footnote, “The 
changes from baseline provided in this listing 
are with respect to the sub-study baseline.”  
Sub-study 
PK 
21 
Sub-study PK 
Concentration 
207966/primary_34/L25 Listing of Plasma CAB PK 
Concentration-Time Data 
Remove the Column "Excluded" and remove 
the first footnote. Present nominal visit before 
the analysis visit. Replace "Race Detail" with 
"Sub-study Baseline BMI (kg/m^2)" in the 
second column on the left. 
Sub-study 
22 
Sub-study PK 
Concentration 
207966/primary_34/L26 Listing of Plasma RPV PK 
Concentration-Time Data 
Similar notes to above. 
Sub-study 
 
 
 


 
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15.15.7.11. Non-ICH Listings 
Non-ICH Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
Study Population 
23 
Sub-study ITT-E 
207966/primary_3
4/L27 
Listing of Reasons for Thigh Injection Phase 
Withdrawal 
 
Sub-study 
24 
Sub-study ITT-E 
207966/primary_3
4/L27 
Listing of Reasons for Return to Gluteal Injection 
Phase Withdrawal 
 
Sub-study 
25 
Sub-study LTFU 
207966/primary_3
4/L28 
Listing of Reasons for Long-term Follow-up Phase 
Withdrawal 
 
Sub-study 
26 
Sub-study ITT-E 
Shell POP_L2 
Listing of Exposure to Study Treatment including 
SOC Oral Bridging Prior to the First Thigh Injection 
 
Sub-study 
27 
Sub-study ITT-E 
207966/primary_3
4/L30 
Listing of Concomitant ART Medications 
 
Sub-study 
28 
Sub-study ITT-E 
207966/primary_3
4/L31 
Listing of ART Medications Received during Long-
term Follow-up Phase 
 
Sub-study 
29 
Sub-study ITT-E 
207966/primary_3
4/L34 
Country Level Listing of Dates of Waves of COVID-
19 Pandemic Measures for Countries Participating 
in Sub-study 
 
Sub-study 
30 
Sub-study ITT-E 
209493/final_02/L
52 
Listing of Transition to CAB + RPV LA Marketed 
Product Status 
Replace "Subject Id." with "Latest 
Subject Id." in the column header. 
Sub-study 
Efficacy 
31 
Sub-study CVF 
207966/primary_3
4/L35 
Listing of All Plasma HIV-1 RNA Data for Subjects 
with Confirmed Virologic Failure 
Produce only when data are 
available. 
Sub-study 
32 
Sub-study ITT-E 
207966/primary_3
4/L36 
Listing of All Plasma HIV-1 RNA Data for Subjects 
with Viral load >=50 c/mL during the Thigh Injection 
or Return to Gluteal Injection Phase 
 
Sub-study 


 
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Non-ICH Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
33 
Sub-study ITT-E 
207966/primary_3
4/L37 
Listing of All Plasma HIV-1 RNA Data 
 
Sub-study 
34 
Sub-study ITT-E 
207966/primary_3
4/L38 
Listing of HIV-1 Associated Conditions 
Produce only when data are 
available. 
Sub-study 
Safety 
35 
Sub-study 
Safety 
207966/primary_3
4/L43 
Listing of Subjects Meeting Hepatobiliary Lab 
Criteria (Thigh Injection + Return to Gluteal 
Injection Phase) 
Present by phase. 
Sub-study 
36 
Sub-study 
Safety 
207966/primary_3
4/L45 
Listing of ECG values for Subjects with Potential 
QTc Interval Prolonging Events of Interest in Sub-
study 
 
Sub-study 
37 
Sub-study 
Safety 
207966/primary_3
4/L47 
Listing of Dosing Errors and IP Device Malfunctions 
in Substudy 
 
Sub-study 
PK 
38 
Sub-study PK 
Parameter 
Shell PK_L1 
Listing of Plasma PK Parameters in Sub-study 
 
Sub-study 
 


 
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15.16. 
Appendix 16: Example Mock Shells for Data Displays 
Available upon request 


Si g nat ure Pa ge f or  2 0 7 9 6 6 T M F- 1 5 0 2 4 3 0 1 v 1. 0
Si g nat ure Pa ge f or T M F- 1 5 0 2 4 3 0 1 v 1. 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure: 2 3- Se p- 2 0 2 2 1 4: 4 2: 0 3 G M T + 0 0 0 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure: 2 3- Se p- 2 0 2 2 1 4: 4 8: 1 1 G M T + 0 0 0 0
P P D
P P D