Conditions: HIV Infections
Keywords: HIV infection GSK3640254 Nucleoside Reverse Transcriptase Inhibitor Dolutegravir Abacavir (ABC)/Lamivudine (3TC) Emtricitabine (FTC)/tenofovir alafenamide (TAF) Maturation Inhibitor
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 161
Healthy volunteers: no

Brief summary:
This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses \[100, 150 and 200 milligrams {mg}\]), active controlled clinical trial. It aims to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine \[ABC/3TC\] or emtricitabine/tenofovir alafenamide \[FTC/TAF\]).

Detailed description:

Arms:
arm 1: Participants with human immunodeficiency virus type 1 (HIV-1), orally received one 100 mg tablet per day of GSK3640254 and two tablets per day of matching placebo in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day of 600 mg abacavir (ABC) / 300 mg lamivudine (3TC) OR 200 mg emtricitabine (FTC) / 25 mg tenofovir alafenamide (TAF) orally. arm 2: Participants with HIV-1, orally received 150 mg (one 100 mg tablet + two 25 mg tablets per day) of GSK3640254 in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally. arm 3: Participants with HIV-1, orally received two 100 mg tablets (200 mg) per day of GSK3640254 and one tablet per day of matching placebo in a blinded setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally. arm 4: Participants with HIV-1, orally received one 50 mg tablet per day of DTG in an open label setting. Open label dual NRTI background therapies were given as one tablet per day combination of 600 mg ABC / 300 mg 3TC OR 200 mg FTC / 25 mg TAF orally.

Interventions: intervention 1: GSK3640254 intervention 2: ABC/3TC intervention 3: FTC/TAF intervention 4: Dolutegravir intervention 5: Placebo
Intervention descriptions: intervention 1: GSK3640254 was available as a 25 mg and 100 mg tablets to be administered via oral route. intervention 2: ABC/3TC was available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route. intervention 3: FTC/TAF was available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route. intervention 4: Dolutegravir was available as a 50 mg tablet to be administered via oral route. intervention 5: Placebo matching GSK3640254 was administered in the form of tablets via oral route.

Protocol document:
SAP_004.pdf: 
 
CONFIDENTIAL 
 
 
 
GlaxoSmithKline group of companies 
 
208379 
1 
 
 
RAP Author: 
 
Copyright 2023 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
 
 
RAP Team Review Confirmations  
(Method: E-mail)
5Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: A Phase IIb, randomized, partially blind, active controlled, 
dose-range finding study of GSK3640254 compared to a 
reference arm of dolutegravir, each in combination with 
nucleoside reverse transcriptase inhibitors, in HIV-1 infected 
antiretroviral treatment-naive adults 
Compound Number  
: GSK3640254 
Clinical Study 
Identifier 
: 208379 
Effective Date  
: 21 Jun 2023 
 
Description: 
The purpose of this RAP is to describe the planned analyses and output to be included in the 
Clinical Study Reports for Protocol 208379.  
This RAP is intended to describe the efficacy, safety, PK required for the study at week 24 , 
up to Week 48 and Final End of Study (Eos) Analysis.  
This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable. 
This version of the RAP documents the Sections considered as for this specific study as 
agreed by the study team.  
Author 
Date 
Lead 
 
Senior Statistician (GSK Biostatistics) 
21 Jun 2023 
PPD


 
 
 
 
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Reviewer  
Date 
 
Physician Product Lead, ViiV  
16-JUNE-2023 
 
Medicine Development Leader, ViiV 
20-JUNE-2023 
 
, Clinical Development Clinical Scientists, ViiV 
20-JUNE-2023 
 
, GSK 
20-JUNE-2023 
 
, GSK 
15-JUNE-2023 
 
Clinical Development Investigator, Clinical Virology, ViiV 
20-JUNE-2023 
 
Manager, Data Management, GSK 
20-JUNE-2023 
 
, Data Management, GSK 
20-JUNE-2023 
 
Manager Programming, GSK 
12-JUNE-2023 
Clinical Statistics & Clinical Programming Line Approvals              
(Method: Pharma TMF eSignature) 
Approver 
Date 
 
21 Jun 2023 
Statistics Leader, Biostatistics, GSK 
 
21 Jun 2023 
Programming Leader, Clinical Programming, GSK 
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
 
 
 
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TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 6 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................... 6 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan .................................... 6 
2.2. 
Study Objective(s) and Estimand(s) / Endpoint(s) ............................................... 6 
2.3. 
Study Design .................................................................................................. 8 
2.4. 
Statistical Hypotheses / Statistical Analyses........................................................ 9 
3. 
PLANNED ANALYSES ........................................................................................... 10 
3.1. 
Interim Analyses ........................................................................................... 10 
3.2. 
Final Analyses .............................................................................................. 10 
4. 
ANALYSIS POPULATIONS .................................................................................... 11 
4.1. 
Protocol Deviations ....................................................................................... 13 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ...................................................................................................... 14 
5.1. 
Study Treatment & Sub-group Display Descriptors ........................................... 14 
5.2. 
Baseline Definitions ...................................................................................... 14 
5.3. 
Multicentre Studies ....................................................................................... 15 
5.4. 
Examination of Covariates, Other Strata and Subgroups ..................................... 15 
5.4.1. 
Covariates and Other Strata ............................................................. 15 
5.4.2. 
Examination of Subgroups .............................................................. 16 
5.5. 
NOTES: Underweight = BMI of < 18.5 kg/m2, Normal = BMI of 18.5 – 
24.99 kg/m2, Overweight = BMI of 25 – 29.99 kg/m2, Obese = BMI of ≥ 
30 kg/m2.Multiple Comparisons and Multiplicity .............................................. 17 
5.6. 
Other Considerations for Data Analyses and Data Handling Conventions ............. 17 
6. 
STUDY POPULATION ANALYSES ......................................................................... 18 
6.1. 
Overview of Planned Study Population Analyses .............................................. 18 
7. 
EFFICACY ANALYSES .......................................................................................... 19 
7.1. 
Primary Efficacy Analyses ............................................................................. 19 
7.1.1. 
Endpoint / Variables ....................................................................... 19 
7.1.2. 
Summary Measure ......................................................................... 19 
7.1.3. 
Population of Interest ...................................................................... 20 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events ....................... 20 
7.1.5. 
Statistical Analyses / Methods ......................................................... 20 
7.2. 
Secondary Efficacy Analyses .......................................................................... 24 
7.2.1. 
Endpoint / Variables ....................................................................... 24 
7.2.2. 
Summary Measure ......................................................................... 24 
7.2.3. 
Population of Interest ...................................................................... 24 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events ....................... 24 
7.2.5. 
Statistical Analyses / Methods ......................................................... 24 
8. 
VIROLOGY ............................................................................................................ 28 
8.1. 
Overview of Planned Virology Statistical Analysis ....................................... 28 


 
 
 
 
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9. 
SAFETY ANALYSES .............................................................................................. 29 
9.1. 
Adverse Events Analyses ............................................................................... 29 
9.2. 
Adverse Events of Special Interest Analyses ..................................................... 29 
9.3. 
Clinical Laboratory and Biomarker Analyses .................................................... 30 
9.3.1. 
Lipids ........................................................................................... 30 
9.3.2. 
, Insulin, Glucose and HbA1c Analyses ............................. 30 
9.3.3. 
Bone Biomarkers Analyses .............................................................. 31 
9.3.4. 
Renal Biomarkers Analyses ............................................................. 31 
9.3.5. 
Inflammatory Biomarkers Analyses .................................................. 32 
9.3.6. 
Stomach/Gastric Biomarkers ........................................................... 32 
9.4. 
Other Safety Analyses ................................................................................... 33 
10. PHARMACOKINETIC ANALYSES ......................................................................... 34 
10.1. 
Endpoint / Variables ...................................................................................... 34 
10.1.1. 
Drug Concentration Measures .......................................................... 34 
10.1.2. 
Derived Pharmacokinetic Parameters for Subjects Participating 
in the Intense PK ............................................................................ 34 
10.2. 
Summary Measure ........................................................................................ 35 
11. POPULATION PHARMACOKINETIC (POPPK) ANALYSES .................................... 36 
12. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES .................................. 37 
13. REFERENCES ......................................................................................................... 38 
14. APPENDICES ......................................................................................................... 39 
14.1. 
Appendix 1: Exclusions from Per Protocol Population ....................................... 39 
14.2. 
Appendix 2: Schedule of Activities ................................................................. 40 
14.2.1. 
Protocol Defined Schedule of Events ................................................ 40 
14.3. 
Appendix 3: Assessment Windows .................................................................. 41 
14.3.1. 
Definitions of Assessment Windows for Snapshot Analyses ................ 41 
14.3.2. 
Definitions of Assessment Windows for Other Analyses ..................... 42 
14.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse Events ................... 44 
14.4.1. 
Study Phases.................................................................................. 44 
14.4.2. 
Treatment Emergent Flag for Adverse Events .................................... 45 
14.5. 
Appendix 5: Data Display Standards & Handling Conventions ........................... 46 
14.5.1. 
Reporting Process .......................................................................... 46 
14.5.2. 
Reporting Standards ....................................................................... 46 
14.5.3. 
Reporting Standards for Pharmacokinetic .......................................... 47 
14.6. 
Appendix 6: Derived and Transformed Data ..................................................... 49 
14.6.1. 
General ......................................................................................... 49 
14.6.2. 
Study Population ............................................................................ 49 
14.6.3. 
Efficacy ........................................................................................ 50 
14.6.4. 
Virology ....................................................................................... 56 
14.6.5. 
Safety ........................................................................................... 59 
14.7. 
Appendix 7: Reporting Standards for Missing Data ........................................... 63 
14.7.1. 
Premature Withdrawals ................................................................... 63 
14.7.2. 
Handling of Missing Data ............................................................... 63 
14.8. 
Appendix 8: Values of Potential Clinical Importance ......................................... 67 
14.8.1. 
ECG ............................................................................................. 67 
14.8.2. 
Vital Signs .................................................................................... 67 
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14.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses .............................. 68 
14.10. Appendix 10: Time to Event Details ................................................................ 69 
14.10.1. TRDF Detailed Steps ...................................................................... 69 
14.10.2. TRDF Detailed Steps for the Kaplan-Meier plot ................................. 74 
14.10.3. ERDF Detailed Steps ...................................................................... 76 
14.11. Appendix 11: Abbreviations & Trademarks ...................................................... 77 
14.11.1. Abbreviations ................................................................................ 77 
14.11.2. Trademarks ................................................................................... 78 
14.12. Appendix 12: List of Data Displays ................................................................. 79 
14.12.1. Data Display Numbering ................................................................. 79 
14.12.2. Mock Example Shell Referencing .................................................... 79 
14.12.3. Deliverables .................................................................................. 80 
14.12.4. Study Population Tables .................................................................. 81 
14.12.5. Efficacy Tables .............................................................................. 84 
14.12.6. Efficacy Figures ............................................................................. 88 
14.12.7. Safety Tables ................................................................................. 89 
14.12.8. Safety Figures ................................................................................ 96 
14.12.9. Virology tables .............................................................................. 97 
14.12.10. Pharmacokinetic Tables .................................................................. 99 
14.12.11. Pharmacokinetic Figures ............................................................... 100 
14.12.12. ICH Listings ................................................................................ 101 
14.12.13. Non-ICH Listings ......................................................................... 106 
14.13. Appendix 13: Example Mock Shells for Data Displays .................................... 111 
 
 
 
 
 
 


 
 
 
 
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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 208379. The RAP is based on the 
following 208379 protocol versions Amendment 04 -TMF-13994091 (01-Oct-2021). 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
This study was closed by the Sponsor after the Week 48 endpoint. All analyses associated 
with Weeks 96 and 144 have been removed from the study objectives and endpoints 
2.2. 
Study Objective(s) and Estimand(s) / Endpoint(s) 
Objectives 
Endpoints 
Primary Objective 
Primary Endpoints 
• To evaluate antiviral efficacy of 
GSK3640254 relative to DTG, each 
given in combination with 2 NRTIs, 
enabling the selection of an optimal 
dose for GSK3640254 
• Proportion of participants with plasma 
HIV-1 RNA <50 copies/mL at Week 24 
using the FDA snapshot algorithm 
Secondary Objectives 
Secondary Endpoints 
• To evaluate antiviral efficacy in the 
Randomized Phase of GSK3640254 
relative to DTG, each given in 
combination with 2 NRTIs at Week 
48  
•  
• Proportion of participants with plasma 
HIV-1 RNA <50 copies/mL at Weeks 48 
and 96 using the FDA snapshot algorithm 
• Absolute values and changes from 
baseline in HIV-1 RNA through Weeks 
24, and 48Absolute values and changes 
from baseline in CD4+ cell counts through 
Weeks 24, and 48 
• To evaluate safety and tolerability in 
the Randomized Phase of 
GSK3640254 relative to DTG each 
given in combination with 2 NRTIs 
at Weeks 24 and 48  
•  
• Frequency of SAEs, Deaths and AEs 
leading to Discontinuation through Weeks 
24, and 48 
• Incidence and severity of AEs through 
Weeks 24, and 48 
• AEs in GI, Psych/CNS through Weeks 24, 
and 48 
• To assess the development of viral 
resistance in the Randomized Phase 
to GSK3640254 and 2 NRTI 
backbone in participants 
experiencing virologic failure at 
Weeks 24 and 48. 
 
• Changes in genotypic and/or phenotypic 
profiles of virus compared to baseline 
through Weeks 24, and 48 


 
 
 
 
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Objectives 
Endpoints 
• To characterize the 
pharmacokinetics of GSK3640254 
when given in combination with 
ABC/3TC or FTC/TAF 
• The steady-state plasma PK parameters of 
GSK3640254 will be assessed based on 
Intensive and/or Sparse PK sampling 
through Weeks 24 and 48 
 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
 
Design 
Features 
This trial is a multi-centre, adaptive, Phase IIb, randomized, partially 
blind (only to doses of GSK3640254), active controlled, dose-range 
finding study of GSK3640254 compared to a reference arm of 
dolutegravir, each in combination with nucleoside reverse transcriptase 
inhibitors, in HIV-1 infected antiretroviral treatment-naive adults.  
Dosing 
• Participants will take their randomized treatment once-daily 
throughout the course of the study 
Time & 
Events 
• Refer to Protocol Section 1.3 
Treatment 
Assignment 
• Participants will be randomized to either one of three doses (100 mg, 
150 mg, or 200 mg) of GSK3640254, or DTG (50 mg) plus dual 
NRTI during the randomization phase. After the optimal dose has 
been chosen, and after the last participant completes their Week 48 
visit, participants in the GSK3640254 arm will move into the Non-
Randomised Phase receiving open label optimal dose and they will 
also be switched from the dual NRTI therapy to DTG. Participants in 
the control arm will continue with DTG (50 mg) plus dual NRTI until 
end of the study. 
Interim 
Analysis 
• One interim analysis will occur when 33% of planned enrolment 
(approximately 50 participants) have completed Week 12. This 
interim analysis will be conducted by an independent data monitoring 
committee to determine if any modifications to the trial would benefit 
participant safety. 
 


 
 
 
 
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2.4. 
Statistical Hypotheses / Statistical Analyses 
The study is designed to investigate the antiviral activity, safety, and tolerability of three 
doses (100 mg, 150 mg, and 200 mg) of GSK3640254 given in combination with either 
ABC/3TC or FTC/TAF as compared to the reference treatment (defined as either DTG 
+ ABC/3TC or DTG + FTC/TAF), and to select an optimal GSK3640254 dose for further 
development. Bayesian analyses will be conducted to evaluate the probability that the 
Week 24 response rate, defined as the proportion of participants with plasma HIV-1 RNA 
<50 c/mL as calculated by the FDA snapshot algorithm, of at least one dose of 
GSK3640254 has comparable efficacy to the reference treatment using a 10% margin. 


 
 
 
 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
An independent data monitoring committee (IDMC) will conduct an interim analysis 
after the 50th participant (33% enrolled) has completed their Week 12 visit. This interim 
analysis will be conducted to determine if any of the GSK3640254 doses are suboptimal 
and: 1) should be discontinued from the study or 2) if the entire study should be stopped 
due to futility. Full details of this analysis are contained in the IDMC charter.  
3.2. 
Final Analyses 
This study will have a primary analysis after all participants complete their Week 24 
visit. There will be three additional subsequent analyses: after all participants complete 
their Week 48 Visit, and a End of study analysis at study completion. Each of these 
analyses will be performed after the completion of the following sequential steps: 
All participants have completed their Week 24, 48 and the study (for the End of study 
analysis) as defined in the protocol.  
All required database cleaning activities have been completed and final database lock 
(DBL) has been declared by Data Management. 
For Week 24 all criteria for unblinding the randomization codes have been met.  
For Week 24 analysis, randomization codes have been distributed according to RandAll 
NG procedures. 
 
 


 
 
 
 
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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened  
• Comprises Screened for inclusion in the 
study, including screen-failures. 
• This population will be based on the treatment 
to which the subject was randomized. Screen-
failures will be categorised as “non-
randomized”. 
• Study Population 
Randomized 
 
• Any participant who has been randomized 
(for this study, this means a randomization 
number was assigned), whether or not the 
participant ever took a dose of study 
medication. 
• Study Population 
Safety 
• All randomized participants who were 
exposed to study intervention with the 
exception of any participants with 
documented evidence of not having consumed 
any amount of study intervention 
• This population will be analysed according to 
the actual treatment the participant received. 
 
• Demographic 
• Safety 
Intent-To-
Treat 
Exposed 
(ITT-E) 
• All randomized participants who received at 
least one dose of study treatment. 
• Participants will be analyzed according to the 
randomized treatment regardless of what 
treatment was actually received 
 
• Efficacy 
Per-Protocol 
(PP) 
• This population will consist of subjects in the 
ITT-E Population except for Important 
protocol deviations designated as exclusions 
from the analysis population. (see Section 
14.1). 
• This population will be based on the treatment 
to which the subject was randomized. 
• Protocol deviations before a specified analysis 
timepoint that would exclude participants 
from the PP population are defined in Section 
4.1 (Protocol Deviations) and Appendix 1: 
Exclusions from Per Protocol Population). 
• Efficacy 
(Sensitivity 
analysis) 


 
 
 
 
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Population 
Definition / Criteria 
Analyses Evaluated 
E.g. a subject with an important protocol 
deviation between week 24 and Week48 
would not be excluded due to this deviation 
from week 24 PP population but would be 
excluded from Week 48 PP population. 
Intent-To-
Treat 
Exposed 
Sensitivity 
(ITT-ES) 
• This population will consist of subjects in the 
ITT-E Population excluding any subjects with 
missing Week 24 data as a result of COVID-
19 pandemic (this includes subjects that have 
discontinued due to COVID-19 before 
providing Week 24 data or still on study but 
no Week 24 Virologic data due to COVID-19. 
Note subjects with Week 24 Viral Load data 
and then discontinuing by COVID-19 
subsequently will be included in the above 
table) 
• This population will be based on the treatment 
to which the subject was randomized. 
• Efficacy 
(Sensitivity 
analysis) 
Intensive 
Pharmacoki
netic 
(Intensive 
PK) 
• All participants who received at least one dose 
of GSK3640254 and have evaluable drug 
concentrations reported, where samples are 
collected according to the intensive PK 
sampling scheme Note: PK samples that may 
be affected by protocol deviations will be 
reviewed by the study team to determine 
whether the sample will be excluded. 
• PK  
Sparse 
Pharmacoki
netic 
(Sparse PK) 
• All participants who received at least one dose 
of GSK3640254 and have evaluable drug 
concentrations reported, where samples are 
collected according to the sparse PK sampling 
scheme 
• Note: PK samples that may be affected by 
protocol deviations will be reviewed by the 
study team to determine whether or not the 
sample will be excluded  
• PK 
Viral 
Genotypic  
 
• Comprise of all subjects in the ITT-E 
population who have available On-treatment 
genotypic resistance data.  
• Viral Genotypic 


 
 
 
 
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Population 
Definition / Criteria 
Analyses Evaluated 
Viral 
Phenotypic 
 
• Comprise of all subjects in the ITT-E 
population who have available On-treatment 
phenotypic resistance data.   
• Viral Phenotypic 
PDVF 
• All subjects in the ITT-E population who met 
the PDVF criteria defined in the protocol. 
Please see Section 14.6.3for details of PDVF 
determination. 
 
• Virology 
• Viral Genotypic 
• Viral Phenotypic 
EGD sub 
study 
• All subjects in the safety population who have 
consented to participate in the EGD sub study 
and have the baseline assessment.  
•  
Refer to Appendix 12: List of Data Displays which details the population used 
for each display. 
 
 
4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed. 
Separately, important deviations which result in exclusion from analysis populations and 
events that result in exclusion from analysis populations will be summarised and listed.  
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan v3.0 (Latest version) 
o Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations and deviations which may lead to exclusion from the 
analysis populations are captured and categorised on the protocol deviations 
dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 


 
 
 
 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
RandAll NG  
Data Displays for Reporting  
Code 
Description 
Description 
Order in TLF  
D1 
GSK3640254 100mg 
GSK254 100 mg + 2NRTIs 
1 
D2 
GSK3640254 150mg 
GSK254 150 mg + 2NRTIs 
2 
D3 
GSK3640254 200mg 
GSK254 200 mg + 2NRTIs 
3 
AC 
Dolutegravir 50mg 
DTG 50 mg + 2NRTIs 
4 
 
Treatment comparisons will be displayed as follows using the descriptors as specified: 
• 
GSK254 100 mg + 2NRTIs vs DTG 50 mg + 2NRTIs 
• 
GSK254 150 mg + 2NRTIs vs DTG 50 mg + 2NRTIs 
• 
GSK254 200 mg + 2NRTIs vs DTG 50 mg + 2NRTIs 
 
5.2. 
Baseline Definitions 
For all endpoints (unless otherwise stated) the baseline value will be the latest pre-dose 
assessment with a non-missing value, including those from unscheduled visits. If time is 
not collected, Day 1 assessments are assumed to be taken prior to first dose and used as 
baseline. 
Parameter 
Study Assessments Considered as Baseline 
Baseline Used in 
Data Display 
Screening 
Day 1 (Pre-Dose) 
Safety 
12-lead ECG 
X 
X 
Day 1 (Pre-Dose) 
Vital Signs 
X 
X 
Day 1 (Pre-Dose) 
Laboratory 
Assessments 
X 
X 
Day 1 (Pre-Dose) 
Efficacy 
HIV-1 RNA/ 
CD4+ T cell 
X 
X 
Day 1 (Pre-Dose) 
Virology 
Genotypic/ 
Phenotypic 
X  
X 
Day 1 (Pre-Dose) 


 
 
 
 
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On Day 1 triplicate pre-dose ECGs will be performed. The baseline for every ECG 
parameter should calculated as the average of that parameter’s values from the Day 1 pre-
dose triplicate ECG reading. 
On Day 1 three readings of blood pressure and pulse will be taken. The first reading 
should be rejected. The average of the second and third readings (as recorded in the CRF) 
will serve as baseline. 
For Genotypic and Phenotypic data, Day 1 visit data will serve as baseline, otherwise, 
baseline will be set to missing. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
5.3. 
Multicentre Studies 
In this multicentre global study, enrolment will be presented by country and investigative 
site. For purposes of efficacy analyses, all sites are assumed to be exchangeable and there 
will be no site or country level adjustment.  
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 
Randomization 
Strata using 
Baseline 
Values 
The randomization is stratified by factors which are assessed using 
screening values. The baseline categories are considered to be more 
relevant, hence the randomization strata are re-derived using baseline 
values and will be referred to as the analysis strata. Strata will be based 
on actual data as opposed to data from the randomization system. 
 
The strata are as follows: 
• Screening HIV-1 RNA (<100,000 copies/mL or >=100,000 
copies/mL)  
• 
Initial background dual NRTI (ABC/3TC or FTC/TAF), 
Covariates 
• 
Baseline HIV-1 RNA (<100,000 copies/mL, 100,000 to < 
250,000 copies/mL, 250,000 to < 400,000 copies/mL, 400,000 
to < 500,000 copies/mL, >= 500,000 copies/mL) 
• 
Background dual NRTI (ABC/3TC or FTC/TAF, Others) at 
week 24 or time of IP discontinuation, whichever is earlier 
• 
Baseline CD4+ cell count, (≤200 cells/mm3 or >200 cells/mm3) 


 
 
 
 
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Category 
Details 
• Baseline CDC category (HIV infection stage 0, HIV infection 
stage 1, HIV infection stage 2, HIV infection stage 3 (AIDS), 
HIV infection stage unknown) 
• Race (White, Black, Asian, Other) 
• Sex (Female, Male) 
5.4.2. 
Examination of Subgroups 
The list of subgroups may be used in descriptive summaries and statistical analyses. 
Additional subgroups of clinical interest may also be considered. 
• 
If the percentage of participants is small within a particular subgroup, then the 
subgroup categories may be refined prior to unblinding the trial. 
• 
If the category cannot be refined further, then descriptive rather than statistical 
comparisons may be performed for the particular subgroup. 
• 
Descriptive summaries of subgroups will only include subjects with non-missing 
data. The number of subjects with non-missing data for each subgroup will be 
displayed in the table (n) and be used as the denominator in percent calculations. 
Subgroup 
Categories  
Baseline HIV RNA 
• 
<100,000 copies/mL 
• 
>=100,000 copies/mL 
Baseline NRTI  
• 
ABC/3TC  
• 
FTC/TAF 
Age 
• 
<50 years 
• 
≥50 years 
OR 
• 
<35 
• 
35-<50 
• 
≥50 
Race 
• 
White  
• 
Black 
• 
Asian 
• 
Other 
OR 
• 
White 
• 
Non-White 
Sex 
• 
Female 
• 
Male  
Baseline CD4+ Cell Count 
(cells/mm3) 
• 
<200 
• 
200 to <350 
• 
350 to <500 
• 
≥500 


 
 
 
 
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Subgroup 
Categories  
History of Depression or 
Psychiatric Events at Baseline 
• 
Yes 
• 
No 
BMI 
• 
Underweight  
• 
Normal  
• 
Overweight  
• 
Obese  
5.5. 
NOTES: Underweight = BMI of < 18.5 kg/m2, Normal = BMI of 18.5 – 24.99 kg/m2, 
Overweight = BMI of 25 – 29.99 kg/m2, Obese = BMI of ≥ 30 kg/m2.Multiple 
Comparisons and Multiplicity 
The study is designed to select a dose primarily on the basis of antiviral activity and 
tolerability in conjunction with immunological response, safety, and pharmacokinetic 
measures and is not designed to evaluate formal statistical hypotheses. Hence, 
adjustments for multiplicity are not applicable.  
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 
Section14.1 
Appendix 1: Exclusions from Per Protocol Population 
Section14.2 
Appendix 2: Schedule of Activities 
Section14.3 
Appendix 3: Assessment Windows 
Section14.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
Section14.5 
Appendix 5: Data Display Standards & Handling Conventions 
Section14.6 
Appendix 6: Derived and Transformed Data 
Section14.7 
Appendix 7: Reporting Standards for Missing Data 
Section14.8 
Appendix 8: Values of Potential Clinical Importance 
Section14.9 
Appendix 9: Population Pharmacokinetic  
Section14.10 Appendix 10: Time to Event Details 
Section14.11 Appendix 11: Abbreviations and Trademarks 
Section14.12 Appendix 12: List of Data displays 
Section14.13 Appendix 13: Example Mock shells 


 
 
 
 
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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 “Screened”, “Randomized”, Intent-to-
Treat Exposed population, unless otherwise specified. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and exposure and treatment compliance will be based on GSK Core Data Standards.  
Details of the planned displays are presented in Appendix 12: List of Data Displays. 


 
 
 
 
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7. 
EFFICACY ANALYSES 
7.1. 
Primary Efficacy Analyses 
This study is designed to investigate the antiviral activity of three doses (100 mg, 150 
mg, and 200 mg) of GSK3640254 given in combination with either ABC/3TC or 
FTC/TAF as compared to the reference treatment of DTG+ABC/3TC or 
DTG+FTC/TAF, and to select an optimal dose of GSK3640254 for further development. 
To achieve this objective, a Bayesian analysis will be conducted to evaluate the 
probability that the Week 24 response rate, defined as the proportion of participants with 
plasma HIV-1 RNA < 50 c/mL as calculated by the FDA snapshot algorithm, of at least 
one dose of GSK3640254 has comparable efficacy to the reference treatment using a 
10% margin. A positive efficacy decision will be made if any GSK3640254 dose has a 
high posterior probability (e.g. >= 0.85) of being within the 10% margin. 
7.1.1. 
Endpoint / Variables 
The primary efficacy endpoint is the binary outcome indicating the virologic category of 
plasma HIV-1 RNA <50 copies/mL (c/mL) at Week 24 using the FDA Snapshot 
algorithm (See Section 14.6.3.1). The other Snapshot outcomes (HIV-1 RNA ≥50 
copies/mL (c/mL) and no virologic data at Week 24 Window) will be collapsed into a 
single category for the analysis (non-response category). 
7.1.2. 
Summary Measure 
For each dose of GSK3640254 the following Bayesian statistics will be provided: 
- 
The number and proportion of subjects with plasma HIV 1 RNA <50 copies c/mL 
at Week 24 using the snapshot algorithm. 
- 
Summary statistics of the posterior distribution of response rate for the specified 
dose including: 
o Mean, median, and mode of posterior distribution of response rate for the 
specified dose 
o 95% highest posterior density credible interval of response rate for the 
specified dose 
For the control arm the following Bayesian statistics will be provided: 
- 
The number and proportion of subjects with plasma HIV 1 RNA <50 copies c/mL 
at Week 24 using the snapshot algorithm  
- 
Summary statistics of the posterior distribution of response rate for the control 
including: 
o Mean, median, and mode of posterior distribution of response rate  


 
 
 
 
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o 95% highest posterior density credible interval of response rate  
- 
Posterior Probability that response rate of the specified dose is greater than the 
control arm response rate -10%. That is:  
o Posterior Pr(Response rate GSK3640254 XX mg – Response Rate 
Control) > -0.1 
For each dose, this posterior probability will be compared to 85% to determine if that 
dose achieves internal sponsor go/no-go decision-making criteria for efficacy  
Main analytical approach 
Comparisons between dose arms will be made by calculating differences between the 
posterior distributions of the response rate in each arm with the control arm which will be 
summarized to obtain posterior means and CIs. Samples from the posterior distribution of 
the response rates in each arm will also be used to obtain posterior probabilities of interest 
(e.g. Pr(Response rate GSK3640254 XX mg – Response Rate Control arm > -10% | 
Data)).The point estimates of differences in virologic response rate with 95% credible 
intervals will be calculated for the treatment comparisons described in the estimands. 
Posterior probability for the differences of following comparisons will also be reported. 
1. Response rate GSK3640254 100 mg vs. Response Rate Control arm 
2. Response rate GSK3640254 150 mg vs. Response Rate Control arm 
3. Response rate GSK3640254 200 mg vs. Response Rate Control arm 
 
If success criteria are met for more than one arm, then additional factors would be taken 
into consideration. 
 
7.1.3. 
Population of Interest  
The primary efficacy analyses will be based on the Intent-to-Treat Exposed (ITT-E) and 
Per Protocol Population for sensitivity analysis. 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
Intercurrent events such as discontinuations, missing plasma HIV-1 RNA samples and 
change in background regimen are handled using the Snapshot algorithm (see Section 
14.6.3.1), which details how to assign each participant’s virologic outcome. 
 
7.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles. 


 
 
 
 
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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. 
Primary Endpoint Statistical Methodology Specification 
Endpoint / Variables 
• Binary outcome indicating the virologic category of plasma HIV-1 RNA <50 
copies/mL (c/mL) at Week 24 using the FDA Snapshot algorithm 
Model Specification 
• Posterior distributions of the response rates for each dose, d, of GSK3640254 and the 
reference treatment will be calculated according to the following Bayesian model and 
parameters: 
• 𝑝𝑝𝑑𝑑= 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑜𝑜𝑜𝑜 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 𝑜𝑜𝑜𝑜 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 𝑑𝑑  
𝑝𝑝𝑑𝑑=
𝑒𝑒𝜃𝜃𝑑𝑑
1 + 𝑒𝑒𝜃𝜃𝑑𝑑 
• 𝜃𝜃𝑑𝑑= 𝐿𝐿𝐿𝐿𝐿𝐿 𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜 𝑜𝑜𝑜𝑜 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑜𝑜𝑓𝑓 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 𝑓𝑓𝑓𝑓𝑓𝑓 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 𝑑𝑑 
𝜃𝜃𝑑𝑑= ln ൬
𝑝𝑝𝑑𝑑
1 −𝑝𝑝𝑑𝑑
൰ 
• Prior for the log odds of response on GSK3640254 arms 
𝜃𝜃𝑑𝑑~𝑁𝑁(0,52) 
• Prior for the log odds of response of the DTG reference arm 
𝜃𝜃𝐷𝐷𝐷𝐷𝐷𝐷~𝑁𝑁(2.61, 0.73242) 
Model details: 
A Bayesian hierarchical model will be fitted using MCMC methods, and will be used to 
estimate the posterior probability of virologic response rate(Week 24 response rate, 
defined as the proportion of participants with plasma HIV-1 RNA < 50 c/mL as 
calculated by the FDA snapshot algorithm) for each arm incorporating the baseline 
analysis stratification factors defined belowJones, 2011 
Baseline Analysis Strata  
Stratum 
B1: Baseline HIV-1 
RNA (𝐼𝐼{𝐵𝐵1+}) 
B2: Initial background 
dual NRTI (𝐼𝐼{𝐵𝐵2+}) 
<100,000 copies/mL AND ABC/3TC 
B1-(<100,000 c/mL) 
(0) 
B2- (ABC/3TC) (0) 
≥100,000 copies/mL AND ABC/3TC 
B1+(≥100,000 c/mL) 
(1) 
B2- (ABC/3TC) (0) 
<100,000 copies/mL AND FTC/TAF 
B1-(<100,000 c/mL) 
(0) 
B2+ (FTC/TAF) (1) 
≥100,000 copies/mL AND FTC/TAF 
B1+ (≥100,000 c/mL) 
(1) 
B2+ (FTC/TAF) (1) 


 
 
 
 
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Model for each arm: 
𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 𝑟𝑟𝑔𝑔~𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵൫𝑛𝑛𝑔𝑔, 𝑝𝑝𝑔𝑔൯,
𝑔𝑔= 1, 2, 3, 4 
𝜃𝜃𝑔𝑔= 𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙൫𝑃𝑃𝑔𝑔൯= log ቆ
𝑃𝑃𝑔𝑔
1 −𝑃𝑃𝑔𝑔
ቇ= 𝛾𝛾0 + 𝛾𝛾1𝐼𝐼{𝐵𝐵1+} + 𝛾𝛾2𝐼𝐼{𝐵𝐵2+} + 𝜓𝜓𝑔𝑔,
𝑔𝑔= 1, 2, 3, 4 
Where 𝛾𝛾0, 𝛾𝛾1, 𝛾𝛾2, 𝜓𝜓𝑔𝑔 are all parameters. Thus, 
𝜃𝜃1 = 𝛾𝛾0 + 𝜓𝜓1 
𝜃𝜃2 = 𝛾𝛾0 + 𝛾𝛾1 + 𝜓𝜓2 
𝜃𝜃3 = 𝛾𝛾0 + 𝛾𝛾2 + 𝜓𝜓3 
𝜃𝜃4 = 𝛾𝛾0 + 𝛾𝛾1 + 𝛾𝛾2 + 𝜓𝜓4 
Priors:  
𝛾𝛾𝑘𝑘~𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁ቀ0, 106ቁ, 𝑘𝑘= 0, 1, 2 
𝜓𝜓𝑔𝑔 ~ 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁(0, 𝜔𝜔2 ), 𝑔𝑔= 1, 2, 3, 4 
𝜔𝜔~𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻−𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛(1) 
Where we define rg as the number of Virologic responders among ng participants, pg as 
Virologic response rate 
𝑟𝑟𝑔𝑔
𝑛𝑛𝑔𝑔, θg as the log odds of treatment response log(
𝑝𝑝𝑔𝑔
1−𝑝𝑝𝑔𝑔), index g 
=1,...,4 refers to the analysis stratum number, 𝛾𝛾𝑘𝑘 represent fixed effects of baseline 
analysis stratification factors (see  below),  and 𝜓𝜓𝑔𝑔 denotes a random effect in analysis 
stratum g. 
The four analysis strata and representation of the two baseline analysis stratification factors 
B1 and B2 in the model are shown in Table above. 
For each arm, the posterior distribution of Virologic response rate P(pg|data), g=1,2,3,4 
will be derived for each analysis stratum using the model specified above.  
𝑃𝑃(𝑝𝑝1|𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) = 𝑃𝑃(
𝑒𝑒𝜃𝜃1
1 + 𝑒𝑒𝜃𝜃1 |𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) 
𝑃𝑃(𝑝𝑝2|𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) = 𝑃𝑃(
𝑒𝑒𝜃𝜃2
1 + 𝑒𝑒𝜃𝜃2 |𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) 
𝑃𝑃(𝑝𝑝3|𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) = 𝑃𝑃(
𝑒𝑒𝜃𝜃3
1 + 𝑒𝑒𝜃𝜃3 |𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) 


 
 
 
 
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𝑃𝑃(𝑝𝑝4|𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) = 𝑃𝑃(
𝑒𝑒𝜃𝜃4
1 + 𝑒𝑒𝜃𝜃4 |𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) 
 
The posterior distribution of the arm-level Virologic response rate will be derived using a 
mixture of the posterior distributions of Virologic response rate for each analysis stratum 
in that arm. The weights are proportional to the sample size of each analysis stratum in 
each arm. 
 
𝑃𝑃(𝑝𝑝|𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) = ∑
𝑤𝑤𝑔𝑔𝑃𝑃൫𝑝𝑝𝑔𝑔ห𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑൯
4
𝑔𝑔=1
, where 𝑤𝑤𝑔𝑔=
𝑛𝑛𝑔𝑔
∑
𝑛𝑛𝑔𝑔
4
𝑔𝑔=1
 
 
Model Checking & Diagnostics 
• Specific model checking procedures will be implemented according to the “Bayesian 
Statistics Best Practice at GSK- Clinical Trials Using Bayesian Inference document. 
Model Results Presentation 
• A figure will be produced which displays the posterior distribution of response rate 
for each of the dose of GSK3640254 as well as the posterior distribution of response 
rate for the DTG control arm. 
• The mean of the posterior distribution of Week 24 snapshot response rate as well as 
associated 95% highest posterior density credible interval will be calculated for each 
dose of GSK3640254 and the reference DTG arm and presented in tabular form 
Sensitivity Analyses 
• Per-Protocol population analysis: To assess the impact of significant 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. 
• The binary response indicating the virologic outcome category of plasma HIV-1 RNA 
<50 copies/mL (c/mL) at 24, using the FDA Snapshot algorithm: Adjusted Difference 
using CMH estimate in the percent of subjects with plasma HIV 1 RNA<50 c/mL at 
Week 24, defined by the FDA snapshot algorithm between Active treatment groups 
(Each arm of GSK’254 combination doses) vs Control arm. For the analysis details 
please see Section 7.2.5.1. 
 
Number and percent of participants with plasma HIV-1 RNA <50 copies/mL (c/mL) at 
Week 24, using the FDA Snapshot algorithm, will be also tabulated by treatment with 
Clopper Pearson 95% confidence intervals also presented graphically. 


 
 
 
 
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7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoint / Variables 
Secondary analyses will be conducted on: 
• The binary outcome indicating the virologic category of plasma HIV-1 RNA <50 
copies/mL (c/mL) at Weeks 48 and 96 using the FDA Snapshot algorithm (See 
Section 14.6.3.1). The other Snapshot outcomes (HIV-1 RNA ≥50 copies/mL 
(c/mL) and no virologic data in the Week 48 and 96 Windows) will be collapsed 
into a single category for the analysis. 
• Absolute values and changes from baseline in HIV-1 RNA through Weeks 24, 48, 
and 96 
• Absolute values and changes from baseline in CD4+ T-cell counts through Weeks 
24, 48, and 96 
• CD4+/CD8+ cell count ratio at weeks 24, 48 and 96. 
• Incidence of disease progression (HIV-associated conditions, AIDS, and death) 
through weeks 24, 48 and 96 
 
7.2.2. 
Summary Measure 
Percent of participants with plasma HIV-1 RNA <50 copies/mL (c/mL) at Weeks 48 and 
96, defined by the FDA Snapshot algorithm (see Section 14.6.3.1), between each 
treatment group (GSK3640254 –DTG). 
Descriptive statistics (mean, median, standard deviation, etc.) of absolute values and 
changes from baseline in HIV-1 RNA, Log10 of HIV-1 RNA, CD4+ T-cell counts, 
CD4+/CD8+ cell count ratio through weeks 24, 48, and 96. Incidence of disease 
progression (HIV-associated conditions, AIDS, and death) through weeks 24, 48 and 96. 
7.2.3. 
 Population of Interest  
The secondary efficacy analyses will be based on the Intent-to-Treat Exposed (ITT-E) , 
unless otherwise specified. 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events 
Intercurrent events such as discontinuations, missing plasma HIV-1 RNA samples and 
change in background regimen are handled using the Snapshot algorithm (see Section 
14.6.3.1), which details how to assign each participant’s virologic outcome. 
7.2.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles. 


 
 
 
 
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Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
There will not be any formal statistical analysis of secondary endpoints. Only descriptive 
statistics will be reported.  


 
 
 
 
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7.2.5.1. 
Statistical Methodology Specification 
Endpoint / Variables 
The binary response indicating the virologic outcome category of plasma HIV-1 RNA 
<50 copies/mL (c/mL) at weeks 48, and 96, using the FDA Snapshot algorithm (see 
Section 14.6.3.1), 
Model Specification 
The efficacy endpoint will be analysed using a stratified analysis for proportions with 
Cochran-Mantel-Haenszel (CMH) weights, adjusting for Baseline HIV-1 RNA 
(<100,000 copies/mL or ≥100,000 copies/mL) and the investigator’s choice of dual 
NRTI background therapy (ABC/3TC or FTC/TAF). Details of the analysis strata can be 
found in the Section 5.4.1. The CMH estimate of the adjusted treatment difference will 
be calculated as a weighted average of strata-specific estimates of the treatment 
difference calculated within each of the following 4 analysis strata: 
• <100,000 copies/mL AND ABC/3TC 
• <100,000 copies/mL AND FTC/TAF 
• ≥100,000 copies/mL AND ABC/3TC 
• ≥100,000 copies/mL AND FTC/TAF 
 
If nk is the number of Treatment treated participants, mk is the number of Comparator 
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 dk are estimates of the differences in proportions of 
participants with plasma HIV-1 RNA <50 copies/mL (c/mL) between the two 
treatment arms (Doses of GSK3640254), rGSK3640254 – rDTG, for the kth strata. 
The corresponding two-sided 95% CI will be calculated as 
 
 
where the variance estimator (Sato, 1989) is consistent in both sparse data and large 
strata and is given below   
(
)
(
)
(
)
(
)
(
)2
2
ˆ
ˆ
ˆ
raˆ
v
∑
∑
∑
∑
∑
∑
+
=
+
=
k
k
k
cmh
k
k
k
k
k
cmh
cmh
W
Q
P
d
N
m
n
Q
P
d
d
 
where 
2
2
2
2
/)
(
k
k
k
k
k
k
k
k
k
k
N
n
m
m
n
x
m
y
n
P
−
+
−
=
 
)
ˆ 
r(
a ˆ 
v 
96
.1
ˆ
cmh
cmh 
d
d 
× 
± 
k 
k 
k 
k 
N 
m 
n 
W = 


 
 
 
 
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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 HIV-1 RNA <50 
copies/mL (c/mL) at weeks 48, ad 96 as determined by the FDA Snapshot algorithm 
(see Section 14.6.3.1), for treatment and comparator, respectively, for the kth 
stratum. 
Model Checking & Diagnostics 
• Not applicable, as no formal statistical modeling is being performed 
Model Results Presentation 
Adjusted CMH estimate of the difference in the percent of participants with plasma 
HIV-1 RNA <50 copies/mL (c/mL) between each treatment group (GSK3640254– 
DTG) and corresponding 95% confidence interval will be presented. 
Subgroup Analyses 
• An analysis for subgroups listed in Section 5.4.2 will be performed. This will show 
the percent of participants with plasma HIV-1 RNA <50 copies/mL (c/mL) at the 
time of analysis (Weeks 24 and 48) based on the Snapshot algorithm (Section 
14.6.3.1) and will be presented by treatment group. Unadjusted percent by subgroup 
and corresponding two-sided 95% (Wilson Score) confidence intervals will be 
tabulated and may also presented graphically in a forest plot. 
Percent of participants with HIV-1 RNA <50 copies/mL (c/mL) will be also tabulated by 
treatment and visit with Wilson 95% confidence intervals.  


 
 
 
 
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8. 
Virology 
8.1. 
Overview of Planned Virology Statistical Analysis 
The virology analyses of genotype and phenotype data will be based on the Viral 
Genotypic, Phenotypic and PDVF populations with subjects having Viral load >= 200 
c/ml.  
The PDVF population will be based on subjects who have experienced a PDVF at any 
point. Refer to protocol Section 7.1.1 and Section 4.1.2.2.1 and RAP Section 14.6.4 for 
the details of the PDVF details. Summary tables will present PDVFs up to and including 
the time point of interest. PDVFs must be confirmed within the phase in which they are 
reported. Listings will present PDVFs occurring at any point. 
Full sequence reverse transcriptase (RT), integrase inhibitors (INI), protease inhibitors 
(PI), and the study drug GSK3640524 maturation inhibitors (MI) available data will be 
analysed at baseline, Week 4, and at time of confirmed protocol-defined virologic failure 
for baseline mutations and for emergent mutations. Additionally, genotypic changes from 
baseline will be identified and listed to potentially identify pathways to resistance. These 
analyses will use the PDVF population. 
Phenotypic changes for approved drugs will be determined at baseline, Week 4, and at 
time of confirmed PDVF. Emergent phenotypic changes will be investigated in the on-
treatment Genotypic and Phenotypic population. 
Details of data displays is presented in Appendix 12: List of Data Displays. 


 
 
 
 
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9. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety population, unless otherwise specified. 
Relevant COVID-19 tables, figures, and listings will be included as described by GSK 
standards.  
9.1. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs) 
and other significant AEs will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 12: List of Data Displays. 
Adverse events will be summarized using descriptive statistics and will not undergo 
formal statistical analysis. Selected adverse events summaries may also be reported by 
NRTI backbone to explore any potential relationship. 
9.2. 
Adverse Events of Special Interest Analyses 
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event in a separate document (AESI MedDRA). Changes to the MedDRA 
dictionary may occur between the start of the study and the time of reporting and/or 
emerging data from ongoing studies may highlight additional adverse events of special 
interest, therefore the list of terms to be used for each event of interest and the specific 
events of interest are defined at a compound level and based on the safety review team 
(SRT) agreements in place at the time of reporting.  
Current AESI categories are as follows: 
- 
QT prolongation 
- 
GI intolerability/toxicity 
- 
Psychiatric Events 
o Suicidal ideation/behavior 
o Depression 
o Bipolar Disorder 
o Psychosis 
o Anxiety 
o Sleep Disorders 
- 
Nervous System Disorders 
- 
Skin and subcutaneous tissue disorders 
 
The details of the planned displays are provided in Appendix 12: List of Data Displays. 
Adverse events of special interest will be summarized using descriptive statistics and will 
not undergo formal statistical analysis.  
 


 
 
 
 
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9.3. 
Clinical Laboratory and Biomarker Analyses 
Laboratory evaluations including the analyses of chemistry laboratory tests, hematology 
laboratory tests, urinalysis, liver function tests, and pregnancy tests will be based on GSK 
Core Data Standards. The details of the planned displays are in Appendix 12: List of Data 
Displays. 
All parameters are listed in Table 13 of Section 10.2 of the protocol. 
The following descriptive summaries for data will be provided: 
N (number of subjects in the population), n (number of subjects used for the analysis), 
arithmetic mean, 95% CI for the arithmetic mean, SD, median, minimum, maximum for 
the untransformed data. 
9.3.1. 
Lipids 
Statistical Analyses 
Endpoints 
• Change from Baseline in Fasting Lipids (Triglycerides, LDL cholesterol, HDL 
cholesterol, Total Cholesterol and TC/HDL ratio) at Weeks 24 and 48 
Analysis Specification 
• The data will not be log transformed for the lipids and will be presented on the 
normal scale. 
Results Presentation 
• N (number of subjects in the population), n (number of subjects used for the 
analysis), arithmetic mean, 95% CI for the arithmetic mean, SD, median, minimum, 
maximum will be presented for the untransformed data. 
 
 
9.3.2. 
, Insulin, Glucose and HbA1c Analyses 
Analyses 
Endpoints 
• Change from baseline in 
, Insulin, Glucose and HbA1c at Weeks 24 and 
48. Please refer to Section 14.6.5for the details. 
Analysis Specification 
• If change in 
, Insulin, Glucose or HbA1c is not normally distributed the 
data will be log transformed  
Results Presentation 
• N (number of subjects in the population), n (number of subjects used for the 
analysis), arithmetic mean, 95% CI for the arithmetic mean, SD, Q1, Q3, median, 
minimum, maximum will be presented for the untransformed data. 
CCI
CCI
CCI


 
 
 
 
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Analyses 
For the log transformed parameters, geometric means will replace arithmetic means, a 
95% CI will replace the standard deviations. 
9.3.3. 
Bone Biomarkers Analyses 
 
Analyses 
Endpoints 
• Change from baseline in the following bone biomarkers at Weeks 24 and 48: 
o bone-specific alkaline phosphatase  
o procollagen type 1 N-propeptide  
o type 1 collagen cross-linked C-telopeptide 
o osteocalcin 
o 25 hydroxy-Vitamin D 
Analysis specification 
• It is anticipated that bone biomarkers will be normally distributed and for those, the 
data will not be log transformed 
Results Presentation 
• N (number of subjects in the population), n (number of subjects used for the 
analysis), arithmetic mean, SD, median, Q1, Q3, minimum, maximum will be 
presented. 
 
9.3.4. 
Renal Biomarkers Analyses 
 
Analyses 
Endpoints 
• Change from baseline in the following renal biomarkers at Weeks 24 and 48: 
o Cystatin C (blood) 
o Retinol Binding Protein (RBP, urine) 
o Beta-2-Microglobulin (B2M, urine)  
o Urine RBP/creatinine ratio 
o Urine B2M/creatinine ratio 
o urine albumin/creatinine ratio  
o urine protein/creatinine ratio  
o urine phosphate  
o serum creatinine 
o eGFR (based on CKD-EPI-creatinine) 
o eGFR (based on CKD-EPI-cystatin C)    
Analysis Specification 
• It is anticipated that at least some biomarkers will not be normally distributed and for 
those, the data will be log transformed 
Model Results Presentation 


 
 
 
 
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Analyses 
• N (number of subjects in the population), n (number of subjects used for the 
analysis), arithmetic mean, SD, Q1, Q3, median, minimum, maximum will be 
presented for the untransformed data. 
• For the log transformed parameters, geometric means will replace arithmetic 
means, a 95% CI will replace the standard deviations. 
 
9.3.5. 
Inflammatory Biomarkers Analyses 
Analyses 
Endpoints 
• Change from baseline in the following inflammatory biomarkers at Weeks 24 and 48: 
o Interleukin-6 (IL-6)  
o High-sensitivity C reactive protein (hs-CRP) 
o D-dimer 
o Soluble CD14 (sCD14) 
o Soluble CD163 (sCD163) 
Analysis Specification  
• It is anticipated that inflammatory biomarkers will not be normally distributed and for 
those, the data will be log transformed and geometric means will replace arithmetic 
means, a 95% CI will replace the standard deviations and mean changes from baseline 
will be presented as geometric mean ratios. 
Results Presentation 
• For the log transformed data, geometric means will replace arithmetic means, a 95% 
CI will replace the standard deviations and median, Q1, Q3, minimum and maximum 
will be presented. 
 
9.3.6. 
Stomach/Gastric Biomarkers 
Statistical Analyses 
Endpoints 
• Absolute and change from baseline in the following gastric biomarkers at Weeks 24 
and 48: 
o Fasting Gastrin 
o Pepsinogen I  
o Pepsinogen II  
Results Presentation 
• Summary statistics (absolute and change from baseline) will be provided by 
treatment arm for each of the serum gastric biomarkers (gastrin and pepsinogen I and 
II) for participants in the EGD sub-study. 
Results Presentation 


 
 
 
 
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Statistical Analyses 
• N (number of subjects in the population), n (number of subjects used for the 
analysis), arithmetic mean, 95% CI for the arithmetic mean, SD, median, Q1, Q3, 
minimum, maximum will be presented. 
 
The details on histopathologic findings on Esophagogastro- duodenoscopy (EGD) with 
biopsy and Gastric Biopsy findings (PRF) will be summarized using Tables and Listings. 
Those have been included in the Appendix 12: List of Data Displays. 
9.4. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs, vital signs, liver 
events, Columbia Suicide Severity Rating Scale (C-SSRS), and gastrointestinal 
intolerability evaluation and monitoring (if available), will be based on GSK Core Data 
Standards, unless otherwise specified. The details of the planned displays are presented in 
Appendix 12: List of Data Displays. 
A summary of subjects meeting hepatobiliary laboratory abnormality criteria at any post-
Baseline emergent visit will also be produced based on FDA Guidance for Drug-Induced 
Liver Injury: Premarketing Clinical Evaluation (July 2009). In addition, a summary and 
listing of subjects with Liver Stopping Events will also be produced. 
 
 


 
 
 
 
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10. 
PHARMACOKINETIC ANALYSES 
10.1. 
Endpoint / Variables 
10.1.1. 
Drug Concentration Measures 
All PK concentration listing displays will be based on the Intensive and Sparse 
Pharmacokinetic populations. Refer to Appendix 5: Data Display Standards & Handling 
Conventions (Section 14.5.3 Reporting Standards for Pharmacokinetic). GSK3640254 
concentration listings for the intensive PK population will be sorted by subject and time 
relative to dose, noting the study visit; summaries will be presented by study visit and 
time relative to dose. 
GSK3640254 concentration listings for the sparse PK population will be sorted by 
subject, study visit and time (or sampling window) relative to dose; summaries will be 
presented by study visit and time (or sampling window) for weeks 4, 8, 12, 24, 36, and 
48.   
10.1.2. 
Derived Pharmacokinetic Parameters for Subjects Participating in the 
Intense PK  
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin. All calculations of non-compartmental parameters will be based on actual 
sampling times. Pharmacokinetic parameters at Week 2 (or week 16 if participants cannot 
take part in week 2 intensive PK) listed will be determined from the concentration-time 
data, as data permits. Ctau will be estimated from pre-dose concentration for all subjects 
in the Sparse PK population.  
Parameter Parameter Description 
AUC(0-tau) 
Area under the concentration-time curve over the dosing interval. AUC will 
be calculated using the linear trapezoidal rule for each incremental 
trapezoid and the log trapezoidal rule for each decremental trapezoid 
Cmax 
Maximum observed plasma concentration 
Ctau 
Observed plasma concentration at the end of the dosing interval, 
determined directly from the concentration-time data 
C0 
Observed pre-dose plasma concentration, determined directly from the 
concentration-time data 
Tmax 
Time to Cmax, determined directly from the concentration-time data 
CL/F 
Oral clearance, the apparent volume of plasma cleared of GSK3640254 per 
unit time following extravascular dosing, calculated as:  
CL/F = Dose / AUC(0-tau) 
 


 
 
 
 
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10.2. 
Summary Measure 
All derived PK parameters detailed in Derived Pharmacokinetic Parameters section will 
be summarized by treatment and subgroups; baseline plasma HIV RNA (<100,000, 
≥100,000 copies/mL) and the investigator’s choice of dual NRTI background therapy 
(ABC/3TCor FTC/TAF) and overall. 
. 


 
 
 
 
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11. 
POPULATION PHARMACOKINETIC (POPPK) 
ANALYSES 
A population-based PK model may be constructed based on the GSK3640254 intensive 
concentration PK data at weeks 2, and the sparse concentrations PK data collected at 
weeks 4, 8, 12, 24, 36, and 48, if the quality of the data permits. Data from the study 
could be merged with some previous data to help the model building process. The 
influence of subject demographics, baseline characteristics, including disease activity, 
and co-medication on the pharmacokinetics of GSK3640254 in this population may be 
explored. The individual subject PK parameters will be estimated and documented for the 
purposes of any subsequent exposure response (PK/PD) analyses. The PopPK analyses 
for GSK3640254 will be performed under a separate RAP and will be reported 
separately. 
Further details to be included in a separate RAP. 


 
 
 
 
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12. 
PHARMACOKINETIC / PHARMACODYNAMIC 
ANALYSES 
The primary goal of this analysis is to characterize the pharmacokinetic / 
pharmacodynamic relationship of GSK3640254 administered orally in HIV-1 infected 
participants. The influence of participant demographics and baseline characteristics, 
including disease activity in this population will be investigated. 
Further details to be included in a separate RAP. 
 


 
 
 
 
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13. 
REFERENCES 
Fleiss J.L. Statistical Methods for Rates and Proportions. 2nd ed. New York:John Wiley; 
1981. 
https://hivdb.stanford.edu/dr-summary/mut-scores/INSTI/,last updated on 2022-06-02 
https://myteams.gsk.com/sites/IDSLLibrary/Lists/DataStandard/DispDataStandard.aspx?I
D=30154&Source=/sites/IDSLLibrary/SitePages/DataStdCoreStdByDataGroup.aspx 
Jones HE, Ohlssen DI, Neuenschwander B, Racine A, Branson M. Bayesian models for 
subgroup analysis in clinical trials. Clin Trials. 2011;8:129–143 
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data.  New York: 
Wiley, 1980 
Klingenberg. A new and improved confidence interval for the Mantel-Haenszel risk 
difference. Statistics in Medicine. 2014; 2968-2983. 
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, 
Corrected Version 2.1. [July 2017]. Available from: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
 
 


 
 
 
 
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14. 
APPENDICES 
14.1. 
Appendix 1: Exclusions from Per Protocol Population 
A participant meeting any of the following criteria will be excluded from the Per-
Protocol population: 
Number 
Exclusion Description 
01 
Subject deviates from any inclusion or exclusion criteria, as recorded in the 
eCRF 
02 
Subject took/received incorrect study treatment (MI254+2NRTI or 
DTG+2NRTI), i.e., other than the one to which they were randomized for 
more than 10% of the total time On-treatment 
03 
Interruption/Dose modification of randomized regimen (MI254+2NRTI or 
DTG+2NRTI) for longer than 10% of the total time on-treatment for reasons 
other than treatment related adverse events/laboratory abnormalities. 
Derivation will be based on concomitant medication and IP eCRF forms. 
04 
Prohibited medications: receiving ART medication other than that 
prescribed/allowed by the study for more than 7 days or receiving prohibited 
Concomitant medication that would impact exposure or response to therapy 
with duration taken into consideration. 
The following, general concomitant medications or therapies are not 
permitted at any time during the study: 
• 
HIV immunotherapeutic vaccines are not permitted at any time during 
the study.  
• 
Other experimental agents, antiretroviral drugs not otherwise specified 
in the protocol, cytotoxic chemotherapy, or radiation therapy may not 
be administered.  
• 
Systemically administered immunomodulators (such as interleukin and 
interferon agents) are prohibited (a list of examples is provided in the 
SRM) 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. 
Note: For treatment specific prohibited meds refer in Section 6.8.1.3. and 
Section 6.8.1.4. of the protocol 
05 
Permanent discontinuation of IP/withdrawal due to a reason of “Protocol 
Deviation” (as recorded in the eCRF). 
 


 
 
 
 
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14.2. 
Appendix 2: Schedule of Activities 
14.2.1. 
Protocol Defined Schedule of Events 
Refer to Protocol Section 1.3. 


 
 
 
 
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14.3. 
Appendix 3: Assessment Windows 
14.3.1. 
Definitions of Assessment Windows for Snapshot Analyses 
Analysis 
Set / 
Domain 
Parameter    
(if applicable) 
Target (Day) 
Analysis Window (Day) 
Analysis 
Timepoint 
Window 
Weeks 
Beginning 
Timepoint 
Ending 
Timepoint 
Efficacy 
Snapshot 
Endpoint 
-63 
 
<-3 
Screen 
NA 
1 
-3 
1 
Day 1 
NA 
15 
2 
21 
Week 2 
Day 2 ~ 
Week 3 
29 
22 
42 
Week 4 
3~6 
57 
43 
70 
Week 8 
6~10 
85 
71 
98 
Week 12 
10~14 
113 
99 
126 
Week 16 
14~18 
169 
127 
210 
Week 24  18-30  
225 
211 
238 
Week 32 
30~34 
253 
239 
266 
Week 36 
34~38 
281 
267 
294 
Week 40 
38~42 
337 
295 
378 
Week 48  42-54  
393 
379 
420 
Week 56 
54~60 
449 
421 
476 
Week 64 
60~68 
505 
477 
532 
Week 72 
68~76 
561 
533 
588 
Week 80 
76~84 
617 
589 
630 
Week 88 
84~90 
673 
631 
714 
Week 96 
90-102  
X*7+1 
(X-6)*7+1 
(X+6)*7 
Week X, 
X=108, 
120, 132, 
etc 
(X-
6)~(X+6
) 
Study Day of 
last dose + 28 
>= (Study 
Day of last 
dose + 28) 
 
Follow-up 
NA 
NOTES: 
1. The Snapshot visit windows are used as part of the Snapshot algorithm to determine a 
participant’s category. 
2. Week 24, 48, and 96 follow FDA Snapshot Algorithm to use +/- 6 weeks as the analysis 
window. Apply Snapshot analysis windows only to viral load data that is on-treatment 
3. Other analyses visits will use analysis windows ½ the distance between the previous and 
subsequent timepoint. 
 
 


 
 
 
 
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14.3.2. 
Definitions of Assessment Windows for Other Analyses 
Other analyses Sets (e.g. lab) will use analysis windows ½ the distance between the 
previous and subsequent timepoint.  
 
Analysis 
Set / 
Domain 
Parameter    
(if applicable) 
Target (Day) 
Analysis Window (Day) 
Analysis 
Timepoint 
Window 
Weeks 
Beginning 
Timepoint 
Ending 
Timepoint 
Efficacy 
(Observe
d)/Safety
(Lab, 
ECG, 
VS)/Viro
logy1 
All 
-63 
 
<-3 
Screen 
NA 
1 
-3 
1 
Day 1 
NA 
15 
2 
21 
Week 2 
Day 2 ~ 
Week 3 
29 
22 
42 
Week 4 
3~6 
X*7+1 
(X-2)*7+1 
(X+2)*7 
Week X, 
X=8, 12, 
… , 52, 
once every 
4 weeks 
from Week 
8 to 52  
(X-2) 
~(X+2) 
393 
379 
420 
Week 56 
54~60 
X*7+1 
(X-4)*7+1 
(X+4)*7 
Week X, 
X=64, 72, 
…, 88, 
every 8 
weeks 
from week 
64 to 88  
(X-
4)~(X+4
) 
673 
645 
714 
Week 96 
92~102 
X*7+1 
(X-6)*7+1 
(X+6)*7 
Week X, 
X=108, 
120, …, 
etc 
(X-
6)~(X+6
) 
Study Day of 
last dose + 28 
> =(Study 
Day of last 
dose + 28) 
 
Follow-up 
NA 
Safety 
CSSRS 
-63 
 
<-3 
Screen 
NA 
1 
-3 
1 
Day 1 
NA 
15 
2 
21 
Week 2 
Day 2 ~ 
Week 3 
X*7+1 
(X-2)*7+1 
(X+2)*7 
Week X,  
X>=4, 
In Clinic 
and Virtual 
Visit 
(X-2) 
~(X+2) 


 
 
 
 
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Analysis 
Set / 
Domain 
Parameter    
(if applicable) 
Target (Day) 
Analysis Window (Day) 
Analysis 
Timepoint 
Window 
Weeks 
Beginning 
Timepoint 
Ending 
Timepoint 
Study Day of 
last dose + 28 
> =(Study 
Day of last 
dose + 28) 
 
Follow-up 
NA 
NOTES: 
1. For safety endpoints and some other results collected for virtual visits, please refer to 
protocol Section 1.3 SOA for details. 
 
 


 
 
 
 
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14.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events 
14.4.1. 
Study Phases  
Assessments and events will be classified according to the time of occurrence relative to 
Insert Study Specific Text Here 
14.4.1.1. 
Study Phase for Laboratory, HIV Associated Conditions, Genotypic and 
Phenotypic Data 
Study Phase 
Definition 
Pre-Treatment  
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 5 days 
Post-Treatment 
Date > Study Treatment Stop Date + 5 days 
 
14.4.1.2. 
Study Phase for Adverse Events and Exposure 
Study Phase 
Definition 
Pre-Treatment  
Date < Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date <= Date ≤ Study Treatment Stop Date + 5 days 
Post-Treatment 
Date > Study Treatment Stop Date + 5 days 
 
14.4.1.3. 
Study Phases for Concomitant Medication 
• Prior medications: Those taken (i.e., started) before the start date of investigational 
product.  
• Concomitant medications: Those taken (i.e., started or continued) at any time between 
the start date and stop date of study treatment, inclusive. Prior medications that were 
continued during this period are also considered as concomitant medications.  
• Post treatment medications: Those started after the stop date of study treatment. 
Concomitant medications that were continued during this period are also considered 
as post-treatment medications. 
It will be assumed that medication has been taken on the date in which it is reported as 
started or stopped. For any medication starting on the same date as study treatment, it will 
be assumed that the medication was taken after the subject started taking study treatment. 
NOTES:  
Please refer to Appendix 7: Reporting Standards for Missing Data for handling of 
missing and partial dates for concomitant medication. Use the rules in this table if 
concomitant medication date is completely missing. 


 
 
 
 
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14.4.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
Study Treatment Start Date ≤ AE Start Date ≤ Study Treatment Stop Date 
+ 5 days. 
• 
For AE happened in subjects with more than one treatment, AE is assigned 
to the most recent treatment to the AE start date.   
NOTES:  
• 
If the study treatment stop date is missing, then the AE will be considered to be On-Treatment. 
• 
Time of study treatment dosing and start/stop time of AEs should be considered, if collected. 
 


 
 
 
 
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14.5. 
Appendix 5: Data Display Standards & Handling Conventions 
14.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software Insert Other Software as Required will be 
used. 
Reporting Area 
HARP Server 
: \us1salx00259  
HARP Compound 
: \arprod\gsk3640254\mid208379\Reporting effort number  
Analysis Datasets  
• 
Analysis datasets will be created according to Legacy GSK A&R dataset standards OR 
CDISC standards (SDTM IG Version 3.2 & ADaM IG Version 2.1. If the Study Data 
Standardization Plan (SDSP) exists for a study, ensure the CDISC versions are consistent. 
Generation of RTF Files 
• 
RTF files will be generated for all reporting efforts. 
14.5.2. 
Reporting Standards 
General 
• 
The current GSK Statistical Display Standards in the GSK Standards Library (IDSL) will 
be applied for reporting, unless otherwise stated (Library Location: 
https://myteams.gsk.com/sites/IDSLLibrary/Lists/DataStandard/DispDataStandard.aspx?ID=30154
&Source=/sites/IDSLLibrary/SitePages/DataStdCoreStdByDataGroup.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include participant level listings in the main body of the GSK Clinical Study 
Report. All participant level listings should be located in the modular appendices as ICH 
or non-ICH listings 
Formats 
• 
GSK Statistical Display Principles (4.24) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the GSK Standard Statistical 
Display Principles but may be adjusted to a clinically interpretable number of DP’s. 
• 
For Insert Endpoint / Parameter the following DP’s places will be applied: 
• 
Summary Statistics: 
• 
Listings:  


 
 
 
 
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Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses 
and calculation of any derived parameters, unless otherwise stated. 
• 
The impact of any major deviation from the planned assessment times and/or 
scheduled visit days on the analyses and interpretation of the results will be assessed as 
appropriate. 
• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer 
to GSK Standard Statistical Display Principle 5.5). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings.  
Unscheduled Visits 
• 
Unscheduled visits will be assigned to a study visit using the all-inclusive windows defined 
in Section 14.3. 
• 
However, data summaries will only report the visits according to the window rules defined 
in Appendix 3. 
• 
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 GSK Standard Statistical Display 
Principal 6 
Categorical Data 
 
N, n, frequency, % 
Graphical Displays 
• 
Refer to GSK Standard Statistical Display Principals 7.1 to 7.13. 
• 
Insert as Required: If any publication related displays have been specified, please provide 
relevant details 
14.5.3. 
Reporting Standards for Pharmacokinetic 
Pharmacokinetic Concentration Data 
PC Windows Non-
Linear (WNL) File 
PC WNL file (CSV format) for the non compartmental analysis by Clinical 
Pharmacology Modelling and Simulation function will be created 
according to Standards for the Transfer and Reporting of PK Data 
document. Note: Concentration values will be imputed as per GUI_51487 
Descriptive 
Summary 
Statistics, 
Graphical Displays 
and Listings 
Refer to the GSK Standard PK Display Standard. 
Refer to the GSK Standard Statistical Display Principle 6.06.1. 
Note: Concentration values will be imputed as per GUI_51487 for 
descriptive summary statistics/analysis and summarized graphical displays 
only.  
NONMEM/Pop 
PK File 
Pop-PK file (CSV format) for the POP-PK analysis by Clinical 
Pharmacology Modelling and Simulation function will be created 
according to the data specification detailed in separate RAP 
NONMEM/PK/PD 
File 
PK/PD file (CSV format) for the PK/PD analysis by Clinical 
Pharmacology Modelling and Simulation function will be created 
according to the data specification detailed in separate RAP. 


 
 
 
 
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Pharmacokinetic Parameter Derivation 
PK Parameter to be 
Derived by 
Programmer 
The PK parameters will be calculated by standard non-
compartmental analysis according to current working practices and 
using WinNonLin v 5.2 or above. All calculations of non-
compartmental parameters will be based on actual sampling times 
Pharmacokinetic Parameter Data 
Is NQ impacted PK 
Parameters Rule 
Being Followed 
If any PK parameter is not calculable because of NQs, it will be 
noted as NC (non-calculable) for the PKPar file and excluded (set to 
missing) from the PK parameter summary statistics. Refer to PK 
One document (Standards for the Transfer and Reporting of PK Data 
using HARP) for handling of non-numeric values in the parameter 
data. 
Descriptive 
Summary 
Statistics, 
Graphical Displays 
and Listings 
If any PK parameter is not calculable because of NQs, it will be 
noted as NC (non-calculable) for the PKPar file and excluded (set to 
missing) from the PK parameter summary statistics. Refer to PK 
One document (Standards for the Transfer and Reporting of PK Data 
using HARP) for handling of non-numeric values in the parameter 
data. 
 
 


 
 
 
 
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14.6. 
Appendix 6: Derived and Transformed Data 
14.6.1. 
General 
Multiple Measurements at One Analysis Time Point 
• If there are multiple assessments within Screening window, the last assessment 
before Day 1 will be used 
• If there are multiple assessments within Day 1 window, the latest pre-dose 
assessment will be used 
• With the exception of the Snapshot endpoints, if after window assignment (see 
Section 14.3), 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: 
• the assessment closest to the window target Study Day; 
• if there are multiple assessments equidistant from the target Study Day, then for 
continuous variables the mean of these values will be used and for categorical 
variables the worse assessment. For HIV-1 RNA, the geometric mean of the number 
of copies will be used as opposed to the arithmetic mean 
• Assessments not chosen for use in summary statistics by this algorithm will still 
appear in the associated listings. Also, such valid assessments will be used when 
determining values of potential clinical concern for the ‘any time On-treatment’ time 
point, and for any algorithm that has specific rules for which observation to use (e.g., 
SNAPSHOT). 
•  
Study Day 
• Calculated as the number of days from First Dose Date: 
• Ref Date = Missing              → Study Day = Missing  
• Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date 
• Ref Data ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1     
 
14.6.2. 
Study Population 
Treatment Compliance 
• Treatment compliance will be calculated based on the formula:   
Treatment Compliance = Number of Actual Doses*100 / (Planned Treatment 
Duration in Days * Frequency) 
• Frequency is 2 for BID and 1 for QD. Treatment compliance could be greater than 
100% if there are events of overdose. Cumulative compliance (since Day 1) at each 
visit will be calculated. 
• Planned treatment duration will be defined according to the endpoint analyzed. 
Endpoint 
Planned Treatment Duration 
Week 24 Snapshot (Primary) 
24 weeks 
Week 48 Snapshot (Secondary) 
48 weeks 


 
 
 
 
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Treatment Compliance 
 
• For the final end of study treatment reporting effort, Planned Treatment Duration is 
defined as 48 weeks for participants on the DTG reference arm. Participants on a 
GSK3640254 arm who continue to derive benefit will remain on the study until they 
are transitioned onto a local access program.  
 
Extent of Exposure 
• Number of days of on treatment will be calculated based on the formula:   
Duration of Treatment in Days = Treatment Stop Date – (Treatment Start Date) 
+ 1 
This information will also be categorized as: < 12 weeks, 12 to 24 weeks, >24 weeks 
to 48 weeks, > 48 weeks to 108 weeks, > 108 weeks 
• Number of days of exposure to study drug will be calculated based on the formula:   
Duration of Exposure in Days = Sum of Number of Days on Dose 
This information will also be categorized as: < 12 weeks, 12 to 24 weeks, >24 weeks 
to 48 weeks, > 48 weeks to 108 weeks, > 108 weeks 
• Participants who were randomized but did not report a treatment start date will be 
categorised as having zero days of exposure.  
• If there are any treatment breaks during the study, exposure data will be adjusted 
accordingly. 
Demographics 
Age 
• GSK Statistical Display Standard algorithms will be used for calculating age where 
birth date will be imputed as follows: 
o For all subjects, the missing date and month will have this imputed as ‘30th 
June’. 
• Birth date will be presented in listings as ‘YYYY’. 
• Completely missing dates of birth will remain as missing, with no imputation 
applied. Consequently, the age of the subject will not be calculated and will remain 
missing. 
14.6.3. 
Efficacy 
HIV-1 RNA 
Snapshot  
• It is intended to be primarily a virologic assessment of the endpoint, and as such 
follows a “virology first” hierarchy. 
• Plasma HIV1-RNA < 50 c/mL or plasma HIV1-RNA ≥ 50 c/mL within an analysis 
window is typically determined by the last available plasma HIV-1 RNA 
measurement in that window while the subject is On-treatment. 
• When no HIV-1 RNA data is available within a window, a subject cannot be 
classified under HIV1-RNA < 50 c/mL.  Depending on the reason for lack of data, 


 
 
 
 
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HIV-1 RNA 
the subject will be classified as a HIV1-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 subject withdrawn (i) due to AE or, (ii) for another reason 
yet was suppressed at the time, will be counted as ‘No Virologic Data at Week X’.  
Should a subject withdraw for reasons other than AE and was not suppressed at the 
time, they will be a HIV1-RNA ≥ 50 c/mL. 
• For each scheduled assessment time, the snapshot response rate for a given threshold 
(e.g., <50 c/mL) is defined as: 
Snapshot Rate= Number of responders in that analysis window   
Number of subjects in the analysis population  
• Full details of the algorithm, including the handling of special cases, are included in 
Section 14.6.3.1 of note, the date at which the subject ‘discontinue/withdrawn from 
the study’ in the Snapshot algorithm is the date of treatment discontinuation, rather 
than the date of study withdrawal, 
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.   
• Qualitive measures (i.e. “target detected” and “target non-detected”) may also be 
provided by the laboratory vendor for values <40 c/ml. When a measurement of 
plasma HIV-1 RNA is below the limit of quantification (i.e. 40 c/mL) and is 
qualitatively observable that will be denoted as a “Target Detected” measure, while 
HIV-1 RNA below the limit of quantification that is not qualitatively observable that 
will be denoted as “Target Not Detected”. Any measurements <40 c/mL characterised 
as “Target Non-Detected” or “Target Detected” will be captured in the database. 
CDC HIV-1 Classification and HIV-associated conditions 
• HIV associated conditions will be assessed according to the 2014 CDC Revised 
Classification System for HIV Infection in Adults (see protocol Section 10.10).  
• Any 'other’ conditions reported in the eCRFs will be identified programmatically 
before being sent for clinical review to determine whether they should be classed as 
stage 3 associated conditions. Review will be ongoing and as a minimum will take 
place prior to each reporting effort. 
 
14.6.3.1. 
Snapshot Algorithm Details 
• Consider an analysis visit window, Week X (e.g., Week4, …Week 24, ..Week 48 
etc.). The Window for Week X visit is defined in Section 14.3.1. e.g. Week 48 ( +/- 6 
Week:  295 ≤ Study Day ≤ 378) 


 
 
 
 
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• Consider an HIV1-RNA threshold (e.g. 40, 50, 200 copies/mL …) for a given 
analysis. Our study will use 50 copies/mL as threshold.  
• For example: The analysis window ‘Week48’ and HIV1-RNA threshold of ’50 
copies/mL’ are used for the purposes of illustration. A participant’s Snapshot 
response and reason at Week48 are categorized as below. 
o 
HIV1-RNA < 50 copies/mL 
o 
HIV1-RNA >= 50 copies/mL 
Data in window not below 50 
Discontinued for lack of efficacy 
Discontinued for other reason while not below 50 
Change in background therapy* 
o 
No Virologic Data at Week48 Window 
Discontinued study due to AE or death 
Discontinued study for other reasons 
On study but missing data in window 
*All changes are considered non-permitted except a one-time switch to the other option 
of the NRTI background prior to Week 2 for reasons of tolerability/toxicity. 
• The steps in determining response and reasons are indicated in Table below, in the 
order stated. 
Detailed steps 
Please note that the following scenarios will NOT be penalized Per Snapshot algorithm 
(i.e. please exclude these scenarios from Condition 1-4).  
• 
Dose reduction, dropping a component, or change in formulation (e.g. ‘Tivicay + 
Kivexa’ to ‘Triumeq’ with the identical ingredients)  
• 
Permitted Change in ART where date of change or date of decision to make 
permitted change (whichever is earlier) occurs prior to/on the first on-treatment viral 
load result 
 
 


 
 
 
 
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Condition  
(Note that: “Week XX” indicates Week XX window. 
Week48 is used as an example below) 
Response  
Reasons 
1. If non-permitted change in background therapy 
prior to Week48  
HIV1-RNA ≥ 50  
Change in 
background 
therapy 
2.  If permitted change in background therapy prior 
to Week48 AND the latest on-treatment VL 
prior to/on the date of change is ≥ 50 c/mL [a] 
HIV1-RNA ≥ 50  
Change in 
background 
therapy 
3. If non-permitted change in background therapy 
during Week48    
 
 
3.1 Last on-treatment VL during Week48 prior 
to/on the date of change ≥ 50 c/mL 
HIV1-RNA ≥ 50  
Data in 
window 
not below 
50 
3.2 Last on-treatment VL during Week48 prior 
to/on the date of change <50   c/mL 
HIV1-RNA < 50  
 
3.3 No VL during Week48 prior to/on the     
date of change     
HIV1-RNA ≥ 50  
Change in 
background 
therapy 
4. If permitted change in background therapy 
during Week48 AND the last on-treatment VL 
prior to/on the date of change is ≥ 50 c/mL [a] 
 
 
4.1  This last on-treatment VL occurs prior to 
Week48  
HIV1-RNA ≥ 50  
Change in 
background 
therapy  
4. 2  This last on-treatment VL occurs during 
Week48 but prior to/on the date of change 
HIV1-RNA ≥ 50  
Data in 
window 
not below 
50 
5.  If none of the above conditions met 
 
 
5.1   VL available during Week48  
 
 
      5.1.1 Last on-treatment VL duringWeek48 ≥ 
50 c/mL 
HIV1-RNA ≥ 50  
Data in 
window 
not below 
50 
      5.1.2 Last on-treatment VL during Week48 
<50 c/mL 
HIV1-RNA < 50  
 
5.2   No VL during Week48    
 
 
 
5.2.1     If participants still on study (i.e. The 
on-treatment period continues beyond the 
upper bound of Week48 window. For 
example, for oral treatment, a participant 
with IP stop date+1> Day 378 of the upper 
No virologic data 
at Week48 
Window  
On study 
but missing 
data in 
window 


 
 
 
 
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Condition  
(Note that: “Week XX” indicates Week XX window. 
Week48 is used as an example below) 
Response  
Reasons 
bound of Week48 window, would be 
considered ‘on study’ for Week48 
snapshot assessment) 
5.2.2     If participants withdraw before/during 
Week48 due to : 
 
 
5.2.2.1  Safety reasons (e.g. AE/death, liver 
chemistry stopping criteria, renal toxicity 
withdrawal criteria, QTc withdrawal 
criteria,  as recorded in eCRF Conclusion 
form) 
No virologic data 
at Week48 
Window 
Disc. due 
to 
AE/death 
5.2.2.2  Non-safety related reasons (e.g. Lack of 
efficacy, protocol deviation, withdrew 
consent, loss to follow-up, study 
closed/terminated, investigator discretion 
et al, as recorded in eCRF Conclusion 
Form) 
 
 
5.2.2.2.1 Last on-treatment VL <50 c/mL OR 
no on-treatment VL available during study   
No virologic Data 
at Week48 
Window 
Disc. for 
other 
reasons 
5.2.2.2.2 Last on-treatment VL ≥ 50 c/mL 
AND withdrawal due to Lack of efficacy 
HIV1-RNA ≥ 50  
Disc. for 
lack of 
efficacy 
5.2.2.2.3 Last on-treatment VL ≥ 50 c/mL 
AND withdrawal due to all other non-safety 
related reasons 
HIV1-RNA ≥ 50  
Disc. for 
other 
reason 
while not 
below 50 
[a]: Excluding permitted change in background therapy where change or decision to 
change is made prior to/on the first on-treatment viral result  
 
A dataset will be created based on the Snapshot algorithm, where the dataset contains the 
following information, as a minimum: 
• 
Study identification 
• 
Participant identification  
• 
Study day and date of last blinded treatment  
• 
Virologic outcome based on the snapshot approach (i.e., HIV-1 RNA below 50 
copies/mL (c/mL), HIV-1 RNA equal to or above 50 copies/mL, discontinued due to AE 
or death, discontinued for other reasons, on study but missing data during window)  


 
 
 
 
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• 
The HIV-1 RNA measurement and the corresponding study day and date used to 
determine the above virologic outcome if the measurement was not missing 
• 
Study day and date when the participant switched to open-label treatment due to 
lack or loss of virologic suppression, if applicable 
• 
Discontinuation study day and date, reason for discontinuation, and last blinded 
treatment measurement before discontinuation for participants who discontinued study 
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14.6.4. 
Virology 
PDVF 
PDVF is defined as any of the following (and confirmed by a repeat and consecutive 
plasma HIV-1 RNA measurement between two and four weeks (approx.) after the initial 
suspected virologic failure sample):  
Virologic Non-response  
1. Decrease from Baseline (Day 1) in plasma HIV-1 RNA of ˂1.0 log10 c/mL unless 
plasma HIV-1 RNA is <200 c/mL by Week 12; 
a. SVF: If there is a decrease < 1 log10 from Baseline at Week 12 and HIV-1 
RNA >=200 c/mL, then -> Suspected Virologic Failure 
b. PDVF: If there is a confirmatory sample after 1a, then check if there is a 
decrease <1 log10 from Baseline and the HIV-1 RNA >=200 c/mL then -> 
Protocol Defined Virologic Failure 
Note: In addition, subjects having SVF who discontinued at week 12 or have no Viral 
load after week 12, those subjects would be considered PDVF. 
 
2. Confirmed plasma HIV-1 RNA levels ≥200 c/mL at or after Week 24. 
c. SVF: If a patient has a sample on/after Week 24 and the result is >=200 c/mL 
then -> Suspected Virologic Failure 
d. PDVF: If after 2c, a patient then has a 2nd consecutive sample >=200 c/mL 
on/after Week 24 then -> Protocol Defined Virologic Failure. 
3. Plasma HIV-1 RNA ≥50 c/mL on repeat testing of Week 24 results and prior to 
Week 28. 
e. SVF: If a patient has a sample at Week 24 and the result is >=50 c/mL then -> 
Suspected Virologic Failure 
f. PDVF: If after 3e, a patient then has repeat (retest) sample prior to Week 28 
then -> Protocol Defined Virologic Failure. 
4. Virologic Non-response: If a subject met criteria 1b or 2d or 3f then -> PDVF 
(Virologic Non-response) 
 
Virologic Rebound  
5. Confirmed plasma HIV-1 RNA ≥200 c/mL after confirmed consecutive plasma HIV-
1 RNA <50 c/mL. 
o Patient must have 2 consecutive values <50 c/mL, followed at any time 
(not necessarily immediately) by 2 consecutive values >=200 c/mL 
g. SVF: If a patient has two consecutive samples <50 c/mL, if any following 
value is >=200 c/mL then -> Suspected Virologic Failure 
h. PDVF: If after 5g, a patient then has a 2nd consecutive sample >=200 c/mL 
then -> Protocol Defined Virologic Failure. 
6.  Virologic Rebound: If a subject met criteria 5h then -> PDVF (Virologic 
Rebound) 
 


 
 
 
 
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Genotype 
General considerations 
• Nominal and analysis window will be included in the listings.  
• For summary purposes analysis window will be used.  
• Note: Resistance testing will be performed on samples collected at the SVW 
timepoint (i.e. the timepoint of the initial HIV-1 RNA result which meets one of the 
Virologic Withdrawal criteria and will be subsequently confirmed in a repeat HIV-1 
RNA test. The SVW timepoint is noted as the PDVF timepoint in listings and 
summaries. 
Amino Acid Changes 
• A mutation is considered present whenever the encoded amino acid residue differs 
from the amino acid that would have been encoded by the wild-type (e.g., HXB2, 
NL43) comparator gene; e.g., Q148K.  
• If the encoded amino acid is seen as a mixture of wild-type and mutant amino acid, 
e.g., Q148Q/K, the mutated amino acid is considered present at the codon of interest.  
• If the encoded amino acid is seen as a mixture of two or more amino acids, which 
may or may not include wild type, e.g., Q184K/H or Q184K/H/Q, etc., for the 
purposes of calculating the number of mutated amino acids, only one mutation is 
considered to be present at the codon of interest. 
• Treatment emergent mutations:  need to meet below three criteria: 
1. New mutation:  observed during treatment comparing to baseline at the same 
codon with the class/region. 
2. Mutations are based on prespecified lists usually identified in the RAP.   
a. Integrase:  may use a list generated by Virology that may include non-
IAS guidance mutations derived using the Stanford database (e.g., 
mutations with penalty score >=15; https://hivdb.stanford.edu/dr-
summary/mut-scores/INSTI/), or other reliable sources.  Note the list may 
change over time. Usually the major mutations are the ones with evidence 
of strong resistance to the ART drug.   
b. All other classes:  defined by the International Antiviral Society-USA 
(IAS-USA).  
3. ART Drug class related: based on the class of the ART the subjects are taking 
during the treatment and the new major mutation within that class will be 
considered.  
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' 


 
 
 
 
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_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' 
Prespecified Lists – Resistance Associated Mutations 
• Summaries and listings of resistance associated mutations in the Integrase Strand 
Transfer Inhibitor (INSTI) class will use the following pre-defined INSTI list of 
mutations associated with the development of resistance to BIC, RAL, EVG or DTG.  
 
Category 
Mutations 
Pre-defined INSTI 
mutations 
H51Y, T66A/I/K, L74M, E92Q/V/G, Q95K, T97A, 
G118R, F121Y, E138A/K, G140A/C/S, 
Y143C/H/R/K/S/G/A, P145S, Q146P, S147G, 
Q148N/H/K/R, V151I/L/A, S153F/Y, N155H/S/T, 
E157Q, G163R/K, S230R, R263K, L68V/I*, L74I*, 
E138T*, G193E* 
NOTES: 
• Current list includes INSTI mutations identified via the Stanford HIV 
Resistance database, or identified during in vitro passage of DTG, or as seen in 
previous DTG studies in INSTI-experienced subjects (i.e. ING112574) and may 
be modified in case of additional substantive data availability.    
• INSTI mutations in bold have the maximum score of 60 and are for any INSTI 
drug in the Stanford database v9.1 (https://hivdb.stanford.edu/dr-summary/mut-
scores/INSTI/,last updated on 2022-06-02); the rest have a maximum score <60. 
 
1. Major resistance mutations to other classes (i.e., NRTI, NNRTI, PI) as defined by the 
International Antiviral Society-USA (IAS-USA). The most up to date IAS-USA 
guidelines available at the time of DBF will be used in the analysis.  Note that 
NRTIs A62V, V75I, F77L, and F116Y all need to be present together with Q151M to 
be resistant, so are not major mutations alone. 
Class 
Mutations 
NRTIs 
M41L, K65R/E/N, D67N, K70E/R, L74V, Y115F, M184V/I, L210W, 
T215Y/F, K219Q/E;  [A62V, V75I, F77L, F116Y, Q151M] 
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 
 
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 
2. Note: 2017 Drug Resistance Mutations Update Volume 24, Issue 4, December 
2016/January 2017 


 
 
 
 
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Phenotype 
Fold change (FC) in IC50 (concentration of drug required to inhibit the sample virus to 
50% of its maximum) relative to wild-type control virus is reported from the assays. i.e., 
FC of sample virus = IC50 of sample virus/IC50 of control virus. 
Summary statistics for FC will be reported at Baseline and at the PDVF timepoint (time 
of suspected failure, that was subsequently confirmed) for subjects meeting PDVF 
criteria.  
Fold change ratio (Fold change at the time of PDVF/baseline Fold change) will also be 
summarised.  
 
14.6.5. 
Safety 
ECG Parameters 
RR Interval 
• IF RR interval (msec) is not provided directly, then RR can be derived as: 
[1] If QTcB is machine read & QTcF is not provided, then: 
𝑅𝑅𝑅𝑅= ቈ൬𝑄𝑄𝑄𝑄
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄൰
2
቉ ∗1000 
[2] If QTcF is machine read and QTcB is not provided, then:  
𝑅𝑅𝑅𝑅= ቈ൬𝑄𝑄𝑄𝑄
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄൰
3
቉ ∗1000 
 
• If ECGs are manually read, the RR value preceding the measurement QT interval 
should be a collected value THEN do not derive. 
Corrected QT Intervals 
• When not entered directly in the eCRF, corrected QT intervals by Fredericia’s (QTcF) 
formula will be calculated, in msec, depending on the availability of other 
measurements. 
• IF RR interval (msec) is provided then missing QTcF and/or QTcB will be derived as:  
 
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄= 
𝑄𝑄𝑄𝑄
3ට𝑅𝑅𝑅𝑅
1000
 
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄= 
𝑄𝑄𝑄𝑄
ට𝑅𝑅𝑅𝑅
1000
 


 
 
 
 
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Category of QTc Values 
Absolute QTc Value 
<=450 
451-480 
481-500 
>=501 
Increase in QTc Values 
Increase of <=30 msec 
Increase of 31-60 msec 
Increase of >60 msec 
 
 
Adverse Events 
AE Severity – DAIDS Grading 
• The DAIDS grading (VERSION 2.1, March 2017) for severity of clinical adverse 
events will be performed. 
• See protocol for DAIDS grading criteria. 
Adverse Events of Special Interest (AESI) 
The preferred terms for each AESI will be review by safety and clinical team and updated 
before each formal analysis in a separate document. The following table below shows 
the AESI categories. 
AESI  
- 
QT prolongation 
- 
GI intolerability/toxicity 
- 
Psychiatric Events 
o Suicidal ideation/behavior 
o Depression 
o Bipolar Disorder 
o Psychosis 
o Anxiety 
o Sleep Disorders 
- 
Nervous System Disorders 
- 
Skin and subcutaneous tissue disorders 
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 smallest unit of one more significant 
digit than the number of significant digits in the observed values will be added or 
subtracted (whichever is applicable) in order to impute the corresponding number. For 
example: 
o Example 1: 2 significant digits (as in “<2.2”) will be imputed as 2.19 
o Example 2: 1 significant digit (as in “>5”) will be imputed as 5.1 
o Example 3: 0 significant digits (as in “<0”) will be imputed as -1”.  
• There will be no imputation in the data listings; all values will be displayed as recorded 
in the database. 


 
 
 
 
C O N FI D E N TI A L
 
 
2 0 8 3 7 9  
 
6 1  
 
L a b T o xicities –  D AI D S Gr a di n g  
•  T o xicities will be base d o n t he Di visi o n of AI D S ( D AI D S) gra di n g s yste m, as s pecifie d 
i n t he pr ot oc ol.   
•  T o xicit y gra des pr o vi de d b y t he ce ntral la b orat or y d o n ot disti n g uis h bet wee n 
a b n or mall y hi g h or l o w criteria, w he n b ot h are rel e va nt f or a partic ular p ara meter.  
•  W he n s u m marisi n g t o xicit y gra des f or s u c h para meters, t he y will be cate g orise d as t o 
w het her t he y are a b o ve or bel o w t he mi d p oi nt of n or mal ra n ge. 
P ar a m eter  
Bel o w Mi d p oi nt  
A b o ve Mi d p oi nt  
Calci u m  
H y p ocalcae mia  
H y percalcae mia  
Faste d gl uc os e  
H y p o gl ycae mia  
H y per gl ycae mia  
S o di u m  
H y p o natre mia  
H y per natre mia  
P otassi u m  
H y p o kale mia  
H y per kale mia  
 
 
•  
= (fasti n g plas ma i ns uli n ( m U/ L) * fasti n g plas ma gl uc ose ( m m ol/ L)) / 2 2. 5.  
•  
 cate g ories will be cate g oris e d as f oll o ws: 
o  < 2  
o  2 t o < 3 
o  3 t o < 4 
o  > = 4  
   
All 
 a nal ys es will be base d o n fasti n g val ues a n d o nl y patie nts wit h p ost-
baseli ne val ues will be i n cl u de d i n a nal yses (i. e. p atie nts wit h missi n g p ost -baseli ne 
 will n ot be i ncl u de d i n s u m mar y ta bles or fi g ures). A d diti o nall y, patie nts 
w h o are dia b etic as ca pt ure d o n t he me dical hist or y f or m at scree ni n g will be e xcl u de d 
fr o m all 
 a nal yses. Fi nall y, a n y patie nt w h o has ta ke n a n a nti-dia betic 
me dicati o n ( A T C c o de “ A 1 0” ( D R U G S U S E D I N DI A B E T E S )) as ca pt ure d o n t he 
me dical hist or y f or m u p t o scree ni n g will be re m o ve d fr o m t he a n al ysis.  
Gl o m er ul ar Filtr ati o n R ate ( G F R)  
•  C hr o nic Ki d ne y Diseas e E pi de mi ol o g y C olla b orati o n ( C K D -E PI) e q u ati o n [ Le ve y et 
al.] will be use d b y t he ce ntral la b orat or y t o pr o vi de a n esti mate of G F R, i n m L/ mi n per 
1. 7 3 m 2, as f oll o ws f or t he C K D- E PI creati ni ne e q uati o n: 
 
w here a ge (i n y ears) is at ti me of assess me nt, κ = 0. 7 if fe male or 0. 9 if male, α = - 0. 3 2 9 if 
fe male an d - 0. 4 1 1 if mal e, mi n() i n dicates t he mi ni m u m of C R T/ κ or 1, ma x() i n dicat es t he 
ma xi m u m of C R T/ κ or 1, a n d C R T m g/ d L is ser u m creati ni ne c o nce ntrati o n i n m g/ d L. T he 
ser u m creati ni ne c o nce ntrati o n i n m g/ d L is o btai ne d fr o m G S K sta n dar d u nits of m ol/ L 
as CR T m g/ d L = 0. 0 1 1 3 x C R T m ol/ L.  
 
C CI
C CI
C CI
C CI
C CI
C CI


 
 
 
 
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• 
Cockcroft-Gault formula:  
eClcr= {((140-age) x weight)/(72 SCr)} x 0.85 if female  
where eClcr is expressed in milliliters per minute, age in years, weight in kilograms, and 
serum creatinine (SCr) in milligrams per deciliter. 
CKD-EPI Cystatin C Equation (2012) 
The following will be used for the CKD-EPI Cystatin C Equation: 
eGFR = 133 x min(Scys/0.8, 1)-0.499 x max (Scys/0.8, 1)-1.328 x 0.996Age x 0.932 [if 
female] 
Abbreviations / Units  
eGFR (estimated glomerular filtration rate) = mL/min/1.73 m2 
Scys (standardized serum cystatin C) = mg/l 
min = indicates the minimum of Scys/0.8 or 1 
max = indicates the maximum of Scys/0.8 or 1 
age = years 
Assays 


 
 
 
 
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14.7. 
Appendix 7: Reporting Standards for Missing Data 
14.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
Participant study completion (i.e. as specified in the protocol) was defined as 
complete if they attend the last on treatment visit at the end of study for 
participants in the GSK3640254 arm, and at Week48 (for participants in the 
DTG reference arm). The Follow-Up visit is not required for successful 
completion of the study. The study will be completed when either the 
development of GSK3640254 is discontinued or until GSK3640254 is locally 
approved and commercially available (anticipated to be in the year 2027). 
 
Alternatively, this study could be completed at an earlier date and 
participants would continue in a rollover study that would be anticipated to 
be complete in 2023 
 
• An in-clinic Follow-Up visit will be conducted 2-4 weeks after the last 
dose of study medication for participants with ongoing AEs, serious 
adverse events (SAEs) regardless of attributability, and any laboratory 
abnormalities that are considered to be AEs or potentially harmful to the 
participant, at the last on-study visit. Assessments at the Follow-up visit 
should reflect any ongoing complaints (e.g., blood draws to follow a 
laboratory abnormality). Withdrawn participants will not be 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.  
 
 
14.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• Missing data occurs when any requested data is not provided, leading to 
blank fields on the collection instrument: 
o These data will be indicated by the use of a “blank” in 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. 


 
 
 
 
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Element 
Reporting Detail 
Snapshot 
• In the Snapshot dataset, subjects 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) are classified as either 
‘HIV-1 RNA ≥50 c/mL’) or ‘No Virologic Data’. For full details of the 
Snapshot algorithm see Section 14.6.3 
Observed 
Case (OC) 
• This dataset uses only the data that is available at a particular timepoint, 
with no imputation for missing values. 
Outliers 
• Any participants excluded from the summaries and/or statistical analyses 
will be documented along with the reason for exclusion in the clinical 
study report. 
 
14.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• Partial dates will be displayed as captured in participant listing displays.  
• Where necessary, display macros may impute dates as temporary 
variables for sorting data in listings only. In addition, partial dates may be 
imputed for ‘slotting’ data to study phases (see Section 14.4.1) or for 
specific analysis purposes as outlined below. 
• Imputed partial dates will not be used to derive study day, time to onset or 
duration (e.g., time to onset or duration of adverse events), or elapsed 
time variables (e.g., time since diagnosis). In addition, imputed dates are 
not used for deriving the last contact date in overall survival analysis 
dataset. 
Exposure 
• If study treatment stop date is missing, then for the purposes of 
calculating exposure, it will be imputed using the date of last visit or the 
recorded date of withdrawal/completion whichever is earlier.  
• Partially Missing Stop Day: Last day of the month or last month of the 
year will be used, unless this is after the stop date of study treatment or 
withdrawal date; in this case the earliest of the two dates will be used. 
Treatment 
End Date 
• If subject is still on-going at data cut-off date, we assume the subject is 
still on-treatment, treatment end date will the last visit date. 
Adverse 
Events 
• Imputations in the adverse events dataset are used for slotting events to 
the appropriate study time periods and for sorting in data listings. 
• Partial dates for AE recorded in the CRF will be imputed using the 
following conventions: 
 
Missing start 
day 
• 
If study treatment start date is missing (i.e. 
participant did not start study treatment), then 
set start date = 1st of month. 
• 
Else if study treatment start date is not missing: 


 
 
 
 
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Element 
Reporting Detail 
o If month and year of start date = month and 
year of study treatment start date then 
 
If stop date contains a full date and stop 
date is earlier than study treatment start 
date then set start date= 1st of month. 
 
Else set start date = study treatment start 
date. 
o Else set start date = 1st of month. 
Missing start 
day and month 
• 
If study treatment start date is missing (i.e. 
participant did not start study treatment), then 
set start date = January 1. 
• 
Else if study treatment start date is not missing: 
o If year of start date = year of study 
treatment start date then 
 
If stop date contains a full date and stop 
date is earlier than study treatment start 
date then set start date = January 1. 
 
Else set start date = study treatment start 
date.       
o Else set start date = January 1. 
Missing stop 
day  
Last day of the month will be used. 
Missing stop 
day and month 
No Imputation 
Completely 
missing 
start/end date 
No imputation 
 
• Completely missing start or end dates will remain missing, with no 
imputation applied.  
Concomita
nt 
Medicatio
ns/Medica
l History 
• Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
 
Missing start 
day 
• 
If study treatment start date is missing (i.e. 
participant did not start study treatment), then 
set start date = 1st of month. 
• 
Else if study treatment start date is not missing: 
o If month and year of start date = month and 
year of study treatment start date then 
 
If stop date contains a full date and stop 
date is earlier than study treatment start 
date then set start date= 1st of month. 
 
Else set start date = study treatment start 
date. 


 
 
 
 
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Element 
Reporting Detail 
o Else set start date = 1st of month. 
Missing start 
day and month 
• 
If study treatment start date is missing (i.e. 
participant did not start study treatment), then 
set start date = January 1. 
• 
Else if study treatment start date is not missing: 
o If year of start date = year of study 
treatment start date then 
 
If stop date contains a full date and stop 
date is earlier than study treatment start 
date then set start date = January 1. 
 
Else set start date = study treatment start 
date.       
• 
Else set start date = January 1. 
Missing end 
day 
A '28/29/30/31' will be used for the day (dependent 
on the month and year)  
Missing end 
day and month 
A '31' will be used for the day and 'Dec' will be 
used for the month. 
Completely 
missing 
start/end date 
No imputation 
 
• The recorded partial date will be displayed in listings. 
 
 


 
 
 
 
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14.8. 
Appendix 8: Values of Potential Clinical Importance 
14.8.1. 
ECG 
ECG Parameter 
Units 
Potential Clinically Important Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
 
>450 
Absolute PR Interval 
msec 
<110 
>200 
Absolute QRS Interval 
msec 
<75 
>110 
Change from Baseline 
Increase from Baseline 
QTc 
msec 
 
>60 
 
14.8.2. 
Vital Signs 
 
Vital Sign Parameter 
(Absolute) 
Units 
Potential Clinically Important Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
<85 
>140 
Diastolic Blood Pressure 
mmHg 
<45 
>90 
Heart Rate 
bpm 
<40 
>100 
 


 
 
 
 
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14.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses 
Details will be provided in a separate RAP. 
 
 


 
 
 
 
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14.10. 
Appendix 10: Time to Event Details 
14.10.1. 
TRDF Detailed Steps 
TRDF Detailed steps 
The steps below are for the derivation of TRDF at specific timepoints when the 
upper bound of the analysis window is used as a cut-off i.e. for the table only.  
Final step of the derivation is made in following order:  
[1] When one EVENT (1.2, 2.2, 3.2, 4.2) criterion is satisfied, select. In situations where 
more than one EVENT criteria satisfied, select the earliest event. If the earliest event date 
satisfies more than one criteria (e.g. subject had PDVF and discontinuation), select PDVF. 
[2] When one CENSOR (1.1, 2.1, 3.1, 4.1, 5.x) criterion is satisfied, select. Else in 
situations where more than one CENSOR criteria satisfied, select the latest censor day. If 
the latest event date satisfies more than one criteria, apply the ordering below. 
  
Condition 
Censor 
Status  
Event Description/AVAL 
1. Subjects met PDVF event criteria 
during the randomized period.  
(Based on derived PDVF confirmed 
prior to cut-off used for the analysis) 
 
Then set tempAVAL= Study Day of 
PDVF 
 
 
1.1 PDVF event date is after the upper 
bound of the analysis visit window  
i.e tempAVAL > upper bound of the 
analysis visit window for Week X 
 
CNSR=1 EVNTDESC=Censored due to data 
cutoff. 
AVAL=Upper bound of analysis 
visit window. 
 
1.2 PDVF event date is on or before 
the upper bound of the analysis visit 
window 
CNSR=0 EVNTDESC=PDVF. 
AVAL= tempAVAL. 


 
 
 
 
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TRDF Detailed steps 
i.e tempAVAL ≤ upper bound of the 
analysis visit window for Week X 
 
 
2. Subjects with study withdrawal due 
to treatment related adverse events 
during the randomized period  
(defined as subjects that have reason 
for withdrawal =AE on disposition 
page and that the subject has at least 
one AE considered both: i) drug related 
(AEREL=Y) and ii) result in 
withdrawal from study (AEWD=Y))  
Then set tempAVAL= Earliest of (Day 
of Study Discontinuation [from 
Disposition page]), date of Withdrawal 
Visit [from Study Visit domain], Study 
day of permanent treatment 
discontinuation [from Exposure and 
Concomitant ART domains]). 
Assumption: Study day of permanent 
treatment discontinuation is included in 
the definition to account for cases 
where discontinuation information is 
recorded later. This is a conservative 
approach consistent with treatment 
discontinuation preceding withdrawal.  
 
 
2.1 Study withdrawal is after the upper 
bound of the analysis visit window 
i.e tempAVAL > upper bound of the 
analysis visit window 
CNSR=1 EVNTDESC=Censored due to data 
cutoff. 
AVAL=Upper bound of analysis 
visit window. 
2.2 Study withdrawal is on or before 
the upper bound of the analysis visit 
window 
i.e tempAVAL ≤ upper bound of the 
analysis visit window 
CNSR=0 EVNTDESC=Study Withdrawal 
Due to Treatment Related AE. 
AVAL= tempAVAL 


 
 
 
 
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TRDF Detailed steps 
 
3:  Subjects met protocol defined 
stopping criteria during the randomized 
period.,  
(Based on disposition page) 
 
Then set tempAVAL=Earliest of (Day 
of Study Discontinuation [from 
Disposition page]), date of Withdrawal 
Visit [from Study Visit domain], Study 
day of permanent treatment 
discontinuation [from Study Treatment 
or CONART eCRF pages]). 
 
 
 
3.1 Protocol defined stopping criteria 
were met after the upper bound of the 
analysis visit window 
i.e tempAVAL > upper bound of the 
analysis visit window 
 
CNSR=1 EVNTDESC=Censored due to data 
cutoff. 
AVAL=Upper bound of analysis 
visit window. 
3.2 Protocol defined stopping criteria 
were met on or before the upper bound 
of the analysis visit window 
i.e tempAVAL ≤ upper bound of the 
analysis visit window 
 
CNSR=0 EVNTDESC=Study Withdrawal 
Due to Protocol Defined Criteria. 
AVAL=tempAVAL 
4: Subjects with study withdrawal due 
to lack of efficacy during the 
randomized period. 
(Based on disposition page) 
 
 
 


 
 
 
 
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TRDF Detailed steps 
Then set tempAVAL= Earliest of (Day 
of Study Discontinuation [from 
Disposition page]), date of Withdrawal 
Visit [from Study Visit domain], Study 
day of permanent treatment 
discontinuation [from Study Treatment 
or CONART eCRF pages]) 
4.1 Study withdrawal is after the upper 
bound of the analysis visit window 
i.e tempAVAL > upper bound of the 
analysis visit window 
 
CNSR=1 EVNTDESC=Censored due to data 
cutoff. 
AVAL=Upper bound of analysis 
visit window. 
4.2 Study withdrawal is on or before 
the upper bound of the analysis visit 
window 
i.e tempAVAL ≤ upper bound of the 
analysis visit window 
 
CNSR=0 EVNTDESC=Study Withdrawal 
Due to Lack of Efficacy 
AVAL= tempAVAL  
If none of the above conditions met 
 
 
5: Subjects with study withdrawal for other 
reasons during the randomized period. 
(Based on disposition page) 
 
Then set tempAVAL= Earliest of (Day 
of Study Discontinuation [from 
Disposition page]), date of Withdrawal 
Visit [from Study Visit domain], Study 
day of permanent treatment 
discontinuation [from Study Treatment 
eCRF pages]) 
 
 
5.1 Study withdrawal is after the upper 
bound of the analysis visit window 
CNSR=1 EVNTDESC=Censored due to data 
cutoff. 


 
 
 
 
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TRDF Detailed steps 
i.e tempAVAL > upper bound of the 
analysis visit window 
 
AVAL=Upper bound of analysis 
visit window. 
 
5.2 Study withdrawal is on or before 
the upper bound of the analysis visit 
window 
i.e tempAVAL ≤ upper bound of the 
analysis visit window 
 
CNSR=1 EVNTDESC=Censored due to 
Study Discontinuation for Other 
Reasons. 
AVAL=tempAVAL 
6: Subject completed the randomized 
period of the study. 
(Based on disposition page) 
 
 
CNSR=1 EVNTDESC= Censored as 
completed the Randomized Period. 
AVAL= Date of end of Treatment 
Phase 
7: Subject is ongoing in the study during 
the randomized period and have not yet 
completed the randomized period  
 
Assumption: this will only be in cases 
where the reporting effort/analysis is 
performed midway through the 
randomized period 
CNSR=1 EVNTDESC= Censored due to data 
cutoff. 
AVAL=Upper bound of analysis 
visit window. 


 
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14.10.2. 
TRDF Detailed Steps for the Kaplan-Meier plot 
TRDF Detailed steps 
The steps below are for the derivation of TRDF overall i.e. for the Kaplan-Meier 
plot only.  
Final step of the derivation is made in following order:  
[1] When one EVENT (conditions 1-4) criterion is satisfied, select. In situations where 
more than one EVENT criteria satisfied, select the earliest event. If the earliest event date 
satisfies more than one criteria (e.g. subject had PDVFand discontinuation), select PDVF. 
[2] When one CENSOR (conditions 5.x) criterion is satisfied, select. Else in situations 
where more than one CENSOR criteria satisfied, select the latest censor day. If the latest 
event date satisfies more than one criteria, apply the ordering below. 
  
Condition 
Censor 
Status  
Event Description/AVAL 
1. Subjects met PDVF event 
criteria during the randomized 
period.  
(Based on derived PDVF 
confirmed prior to cut-off 
used for the analysis) 
CNSR=0 EVNTDESC=PDVF. 
AVAL=Study Day of PDVF. 
 
2. Subjects with study 
withdrawal due to treatment 
related adverse events during 
the randomized period  
 (defined as subjects that have 
reason for withdrawal =AE on 
disposition page and that the 
subject has at least one AE 
considered both: i) drug 
related (AEREL=Y) and ii) 
result in withdrawal from 
study (AEWD=Y))  
CNSR=0 EVNTDESC=Study Withdrawal Due to 
Treatment Related AE. 
AVAL=Earliest of (Day of Study 
Discontinuation [from Disposition page]), 
date of Withdrawal Visit [from Study Visit 
domain], Study Day of permanent treatment 
discontinuation [from Study Treatment eCRF 
pages]). 
3:  Subjects met protocol 
defined stopping criteria 
during the randomized 
CNSR=0 EVNTDESC=Study Withdrawal Due to 
Protocol Defined Criteria. 
AVAL=Earliest of (Day of Study 


 
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TRDF Detailed steps 
period.,  
(Based on disposition page) 
Discontinuation [from Disposition page]), 
date of Withdrawal Visit [from Study Visit 
domain], Study Day of permanent treatment 
discontinuation [from Study Treatment eCRF 
pages]). 
4: Subjects with study 
withdrawal due to lack of 
efficacy during the 
randomized period. 
(Based on disposition page) 
CNSR=0 EVNTDESC=Study Withdrawal Due to Lack 
of Efficacy 
AVAL= Earliest of (Day of Study 
Discontinuation [from Disposition page]), 
date of Withdrawal Visit [from Study Visit 
domain], Study Day of permanent treatment 
discontinuation [from Study Treatment eCRF 
pages]) 
If none of the above 
conditions met 
 
 
5: Subjects with study 
withdrawal for other reasons 
on or before the end of 
randomized period. 
(Based on disposition page) 
CNSR=1 EVNTDESC=Censored due to Study 
Discontinuation for Other Reasons. 
AVAL=Earliest of (Day of Study 
Discontinuation [from Disposition page]), 
date of Withdrawal Visit [from Study Visit 
domain], Study Day of permanent treatment 
discontinuation [from Study Treatment eCRF 
pages]) 
6: Subject completed the 
randomized period of the 
study. 
(Based on disposition page) 
CNSR=1 EVNTDESC= Censored as completed the 
Randomized Period. 
AVAL= Date of completion of randomized 
study period 
7: Subject is ongoing in the 
study during the randomized 
period and have not yet 
completed the randomized 
period 
CNSR=1 EVNTDESC= Ongoing in the Study. 
AVAL=Last visit date 
 
 
Notes: 
Randomized Period = Randomized Phase  
Efficacy visit windows should be used throughout for the upper bound of the analysis visit window 
Subjects are considered to have completed the randomized period if they completed the Randomized Phase. 


 
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By definition, a subject must be on-treatment for a PDVF to be recorded therefore inclusion of study date 
of treatment discontinuation in the derivation is not required  
EVNTDESC, AVAL & CNSR variables created for the following timepoints:  
Week 24 or 48 – for the table analysis 
Overall – for the Kaplan-Meier plot  
 
14.10.3. 
ERDF Detailed Steps 
Similar algorithm will be applied for ERDF analyses and  Kaplan-Meier figure, where 
condition 2 and 3 in Section 14.10.1 and Section 14.10.2 will not be considered.  
 
 


 
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14.11. 
Appendix 11: Abbreviations & Trademarks 
14.11.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AIC 
Akaike's Information Criteria 
A&R 
Analysis and Reporting  
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
CTR 
Clinical Trial Register 
CVb / CVw 
Coefficient of Variation (Between) / Coefficient of Variation (Within) 
DBF 
Database Freeze 
DBR 
Database Release 
DOB 
Date of Birth 
DP 
Decimal Places 
eCRF 
Electronic Case Record Form 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure Requirements 
GSK 
GlaxoSmithKline 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee  
IDSL 
Integrated Data Standards Library (GSK Standards Library) 
IMMS 
International Modules Management System 
IP 
Investigational Product 
ITT 
Intent-To-Treat 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamic 
PDMP 
Protocol Deviation Management Plan 
PK 
Pharmacokinetic 
PP 
Per Protocol 
PopPK 
Population PK 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
RAMOS 
Randomization & Medication Ordering System  
SAC 
Statistical Analysis Complete 
SDSP 
Study Data Standardization Plan 


 
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Abbreviation 
Description 
SDTM 
Study Data Tabulation Model 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings  
14.11.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
Tivicay 
 
NONMEM 
 
 
SAS 
 
 
WinNonlin 
 
 


 
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14.12. 
Appendix 12: List of Data Displays 
All data displays will use the term “subject” rather than “participant” in accordance with 
CDSIC and GSK Statistical Display Standards. 
14.12.1. 
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 
Population Pharmacokinetic (PopPK) 
5.1 to 5.n 
5.1 to 5.n 
Pharmacodynamic and / or Biomarker 
6.1 to 6.n 
6.1 to 6.n 
Pharmacokinetic / Pharmacodynamic 
7.1 to 7.n 
7.1 to 7.n 
Section 
Listings 
ICH Listings 
1 to x 
Other Listings 
y to z 
 
14.12.2. 
Mock Example Shell Referencing 
Nonstandard specifications will be referenced as indicated and if required example mock-
up displays provided in Appendix 13: Example Mock Shells for Data Displays. 
 
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 
Population Pharmacokinetic (PopPK) 
POPPK_Fn 
POPPK_Tn 
POPPK_Ln 
Pharmacodynamic and / or Biomarker 
PD_Fn 
PD_Tn 
PD_Ln 
Pharmacokinetic / Pharmacodynamic 
PKPD_Fn 
PKPD_Tn 
PK/PD_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘GSK Statistical Display Standard / Example Shell’ or 
‘Programming Notes’ column as ‘[Non-Standard] + Reference.’ 
 
 


 
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14.12.3. 
Deliverables 
Delivery [Priority] 1 
Description 
Week 24/ 
Week48/EoS 
End of study reporting. 
NOTES:  
1. Indicates priority (i.e. order) in which displays will be generated for the reporting effort 
 


 
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14.12.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
ITT-E 
ES1 
Summary of Subject Status and Subject Disposition for the 
Study Conclusion Record 
ICH E3, 
FDAAA, 
EudraCT 
WEEK 24/ 
WEEK 
48/EOS 
1.2. 
ITT-E 
SD1 
Summary of Treatment Sitatus and Reasons for 
Discontinuation of Study Treatment 
ICH E3 
 
WEEK 24/ 
WEEK 
48/EOS 
1.3. 
ITT-E 
ES4 
Summary of Subject Disposition at Each Study Epoch 
ICH E3 
WEEK 24/ 
WEEK 48 
1.4. 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen 
Failure 
Journal 
Requirements 
WEEK 24/ 
WEEK 48 
1.5. 
Randomized 
NS1 
Summary of Number of Subjects by Country and Site ID 
EudraCT/Clinical 
Operations 
WEEK 24/ 
WEEK 48 
Protocol Deviation 
1.6. 
ITT-E 
DV1 
Summary of Important Protocol Deviations 
ICH E3 
WEEK 24/ 
WEEK 
48/EOS, 


 
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Study Population Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Population Analysed 
1.7. 
Screened 
SP1  
 
Summary of Study Populations  
GSK Statistical 
Display Standard 
 WEEK 24/ 
WEEK 
48/EOS 
1.8. 
ITT-E 
SP2 
 
Summary of Exclusions from the Per Protocol Population 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48 
Demographic and Baseline Characteristics 
1.9. 
ITT-E 
DM1  
Summary of Demographic Characteristics 
ICH E3, 
FDAAA, 
EudraCT 
WEEK 24/ 
WEEK 48 
1.10. 
Screened 
DM11 
Summary of Age Ranges 
EudraCT 
WEEK 24/ 
WEEK 48 
1.11. 
ITT-E 
DM5 
Summary of Race and Racial Combinations 
ICH E3, FDA, 
FDAAA, 
EudraCT 
WEEK 24/ 
WEEK 48 
Prior and Concomitant Medications 
1.12. 
ITT-E 
MH1 /  
MH4 
Summary of Current/Past Medical Conditions 
ICH E3  
WEEK 24/ 
WEEK 
48/EOS 
1.13. 
ITT-E 
CM1 
Summary of Concomitant Medications 
ICH E3 
WEEK 24/ 
WEEK 
48/EOS 


 
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Study Population Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
See GSK 
Statistical 
Display Standard 
Exposure and Treatment Compliance 
1.14. 
ITT-E 
EX1 
Summary of Exposure to Study Treatment for Daily Dosed 
Drugs 
ICH E3 
 
  WEEK 24/ 
WEEK 
48/EOS 
 


 
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14.12.5. 
Efficacy Tables 
Efficacy Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Plasma HIV-RNA < 50 
2.1. 
ITT-E 
Shell 5 
Summary of Posterior Probability of Treatment Difference of 
Plasma HIV-1 RNA <50 copies/mL at Week 24 - Snapshot 
 
WEEK 24 
2.2. 
ITT-E 
Shell 1.1 
Summary of Analysis of Proportion of Subjects with Plasma HIV-
1 RNA <50 copies/mL at WEEK 48- Snapshot 
 
WEEK 24/ 
WEEK 48 
2.3. 
2.4. 
PP 
Shell 5 
Summary of Posterior Probability of Treatment Difference of 
Plasma HIV-1 RNA <50 copies/mL at WEEK 48 - Snapshot 
 
WEEK 24 
2.5. 
2.6. 
PP 
Shell 1 
Summary of Analysis of Proportion of Subjects with Plasma HIV-
1 RNA <50 copies/mL at WEEK 48 - Snapshot 
 
WEEK 24/ 
WEEK 48 
2.7. 
ITT-E 
Shell 1 
Proportion of Subjects with Plasma HIV-1 RNA <50 copies/mL 
by Visit - Observed 
 
WEEK 24/ 
WEEK 
48/EOS 
2.8. 
ITT-E 
Shell 2 
Summary of Study Outcomes (<50 c/mL) at WEEK 48 Snapshot 
Analysis 
 
WEEK 24/ 
WEEK 48  
2.9. 
ITT-E 
 Shell 1 
 Summary of Proportion of Subjects with Plasma HIV-1 RNA 
<50 copies/mL at WEEK 48- Snapshot 
 
WEEK 24/ 
WEEK 48 
2.10. 
ITT-E 
Shell 4 
Proportion of Subjects with Plasma HIV-1 RNA <50 copies/mL 
by Visit and Subgroups - Snapshot 
Only include 
timepoints up 
WEEK 24/ 
WEEK 48 


 
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Efficacy Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
to Week 24 
2.11. 
PP 
Shell 2 
Summary of Study Outcomes (<50 c/mL) at WEEK 48 Snapshot 
Analysis 
 
WEEK 24/ 
WEEK 48 
2.12. 
ITT-E 
Shell 4 
Percent of Subjects with Plasma HIV-1 RNA <50c/mL at WEEK 
48 By Subgroups- Snapshot Analysis  
 
WEEK 24/ 
WEEK 48 
2.13. 
 
 
 
 
 
PDVF 
2.14. 
ITT-E 
GSK35158
64 
Table 2.18 
mid204861
/Primary 1 
Cumulative Proportion of Subjects Meeting PDVF by Visit by 
Type of Criteria 
 
WEEK 24/ 
WEEK 
48/EOS 
2.15. 
ITT-E 
table 2.19 
mid204861
/Primary 1 
Distribution of Quantitative Plasma HIV-1 RNA Results at PDVF 
Data only for 
the subjects 
that meet 
PDVF.   
WEEK 24/ 
WEEK 
48/EOS 
  Post-baseline HIV-1 Disease Progression 
2.16. 
ITT-E 
Table 2.24 
mid204861
/Primary 1 
Summary of Post-Baseline HIV-1 Associated Conditions 
Including Recurrences 
 
WEEK 24/ 
WEEK 
48/EOS 
2.17. 
ITT-E 
Table 2.25 
Summary of Post-Baseline HIV-1 Associated Conditions 
 
WEEK 24/ 


 
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Efficacy Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
mid204861
/Primary 1 
Excluding Recurrences 
WEEK 
48/EOS 
2.18. 
ITT-E 
Table 2.26 
mid204861
/Primary 1 
Summary of Post-Baseline HIV-1 Disease Progressions 
 
WEEK 24/ 
WEEK 
48/EOS 
Change from Baseline in Log10 HIV-1 RNA and CD4 
2.19. 
ITT-E 
LB1 
Summary of Change from Baseline in Log Plasma HIV-1 RNA by 
Visit 
 
WEEK 24/ 
WEEK 
48/EOS 
2.20. 
ITT-E 
LB1 
Summary of Change from Baseline in CD4+ TCell Count 
(cells/mm^3) by Visit 
 
 WEEK 24/ 
WEEK 
48/EOS 
2.21. 
ITT-E 
LB1 
Summary of Change from Baseline in in CD4+/CD8+ count ratio 
by Visit 
 
WEEK 24/ 
WEEK 
48/EOS 
Kaplan – Meier 
2.22. 
ITT-E 
Shell 7 
Summary of Kaplan-Meier Estimates of Proportion of Subjects 
Without PDVF at WEEK 48 - Treatment Related Discontinuation 
= Failure 
Refer to: 
GSK3515864/
208090/primar
y_01 Table 
2.24 
WEEK 24/ 
WEEK 48 
2.23. 
ITT
Shell 7 
Summary of Kaplan-Meier Estimates of Proportion of Subjects 
Refer to: 
WEEK 24/ 


 
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Efficacy Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
-E 
Without PDVFat WEEK 48 - Efficacy Related Discontinuation = 
Failure 
GSK3515864/
208090/primar
y_01 Table 
2.25 
WEEK 48 
2.24. 
ITT-E 
GSK35158
64 
Table 2.17 
mid204861
/primary_0
1  
Statistical Analysis of Kaplan-Meier Estimates of Time to Viral 
Suppression Overall and by Baseline HIV-1 RNA Subgroups 
Add 
categories: 
Baseline HIV-
1 RNA (c/mL) 
< 100,000 vs. 
≥100,000  
 
WEEK 24/ 
WEEK 48 
 


 
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14.12.6. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Insert Endpoint Category 
2.1. 
ITT-E 
Shell 7 
Unadjusted Treatment Difference in Proportion (95% CI) of 
Subjects with HIV-1 RNA <50 c/mL at WEEK 48 by 
Subgroup - Snapshot Analysis 
  
WEEK 24/ 
WEEK 48 
2.2. 
ITT-E 
Figure 2.4 
mid20486
1/Primary 
1  
Kaplan-Meier Plot of Time to Failure - Treatment related 
discontinuation = Failure (TRDF) 
 
WEEK 24/ 
WEEK 48 
2.3. 
ITT-E 
Figure 2.5 
mid20486
1/Primary 
1 
Kaplan-Meier Plot of Time to Failure - Efficacy related 
discontinuation = Failure (ERDF) 
 
WEEK 24/ 
WEEK 48 
2.4. 
ITT-E 
Figure 2.6 
mid20486
1/Primary 
1 
Kaplan-Meier Plot of Time to Viral Suppression Overall 
and by Baseline HIV-1 RNA Subgroups  
categories: 
Baseline HIV-1 
RNA (c/mL) <= 
100,000 vs. > 
100,000 for WK 48 
Time to Viral 
Suppression means 
the first time 
HIVRNA<50 c/mL. 
WEEK 24/ 
WEEK 48 


 
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14.12.7. 
Safety Tables 
Safety: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
3.1. 
 
Safety 
AE1     Summary of All Adverse Events by System Organ 
Class and Preferred Term 
ICH E3 
 WEEK 24/ 
WEEK 48/EOS 
3.2. 
 
Safety 
AE5B 
Summary of All Adverse Events by Maximum 
Grade / Intensity by System Organ Class and 
Preferred Term 
 
WEEK 24/ 
WEEK 48/EOS 
3.3. 
 
Safety 
AE3 
Summary of Common (>=2%) Adverse Events by 
Overall Frequency 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
3.4. 
 
Safety 
AE3 
Summary of Common (>=2%) Grade 2-4 Adverse 
Events by Overall Frequency 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
3.5. 
 
Safety 
AE1     
Summary All Drug-Related Adverse Events by 
System Organ Class and Preferred Term/by Overall 
Frequency 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
3.6. 
 
Safety 
AE15 
Summary of Common (>=2%) Non-serious Adverse 
Events by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) 
FDAAA, EudraCT 
 
  WEEK 24/ 
WEEK 48/EOS 


 
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90 
 
Safety: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
3.7. 
 
Safety 
AE3 
Summary of Non-Serious Drug-Related Adverse 
Events by Overall Frequency 
Plain Language 
Summary 
requirements. 
WEEK 24/ 
WEEK 48/EOS 
Serious and Other Significant Adverse Events 
3.8. 
 
Safety 
AE16 
Summary of Serious Adverse Events by System 
Organ Class and Preferred Term (Number of 
Subjects and Occurrences) 
FDAAA, EudraCT 
 
  WEEK 24/ 
WEEK 48/EOS 
3.9. 
 
Safety 
AE1 
 
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal 
from Study by System Organ Class and Preferred 
Term /by Overall Frequency 
GSK Statistical 
Display Standard 
 
  WEEK 24/ 
WEEK 48/EOS 
Laboratory: Chemistry  
3.10.  
Safety 
LB1 
Summary of Chemistry Changes from Baseline  
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
3.11.  
Safety 
LB16 
Summary of Worst Case Chemistry Results by 
Maximum Grade Increase at Post-Baseline Relative 
to Baseline 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
Laboratory: Haematology 
3.12.  
 Safety 
LB1 
Summary of Hematology Changes from Baseline 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 


 
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Safety: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
3.13.  
Safety 
LB16 
Summary of Worst Case Hematology Results by 
Maximum Grade Increase at Post-Baseline Relative 
to Baseline 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
Laboratory: Urinalysis 
3.14.  
Safety 
UR1 
Summary of Worst Case Urinalysis Results (Discrete 
or Character Values) Post-Baseline Relative to 
Baseline 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
Laboratory: Hepatobiliary (Liver) 
3.15.  
 Safety 
LIVER1 
Summary of Liver Monitoring/Stopping Event 
Reporting 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
3.16.  
 Safety 
LIVER10 
Summary of Hepatobiliary Laboratory 
Abnormalities 
GSK Statistical 
Display Standard  
 
  WEEK 24/ 
WEEK 48/EOS 
ECG 
3.17.  
 Safety 
EG1 
Summary of ECG Findings  
GSK Statistical 
Display Standard  
  WEEK 24/ 
WEEK 48/EOS 
3.18.  
Safety 
EG10  
Summary of Maximum QTc Values Post-Baseline 
Relative to Baseline by Category 
GSK Statistical 
Display Standard  
  WEEK 24/ 
WEEK 48/EOS 
3.19.  
Safety 
EG2 
Summary of Change from Baseline in ECG Values 
by Visit 
GSK Statistical 
Display Standard 
 
  WEEK 24/ 
WEEK 48/EOS 


 
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92 
 
Safety: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
3.20.  
Safety 
EG11  
Summary of Maximum Increase in QTc Values 
Post-Baseline Relative to Baseline by Category 
GSK Statistical 
Display Standard   
  WEEK 24/ 
WEEK 48/EOS 
Vital Signs 
3.21.  
Safety 
VS1 
Summary of Change from Baseline in Vital Signs 
ICH E3 
 
  WEEK 24/ 
WEEK 48/EOS 
3.22.  
Safety 
VS3  
Summary of Worst Case Vital Signs Results by Post-
Baseline Relative to Baseline 
GSK Statistical 
Display Standard  
 
  WEEK 24/ 
WEEK 48/EOS 
CSSRS 
3.23.  
Safety 
CSSRS1 
Summary of Subjects with Post Baseline eCSSRS 
Suicidal Ideation or Behaviour 
Only include 
participants who 
have suicidal 
ideation or 
behaviour 
WEEK 24/ 
WEEK 48/EOS 
COVID-19 Related AE 
3.24.  
Safety 
PAN1A 
Summary of COVID-19 Assessment 
 
WEEK 24/ 
WEEK 48 
3.25.  
Safety 
PAN3A 
Summary of COVID-19 Symptoms for Subjects with 
Adverse Events 
Conditional 
Display 
WEEK 24/ 
WEEK 48 
Adverse Events of Special interest 


 
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93 
 
Safety: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
3.26.  
Safety 
SAF_T10 
Summary of Characteristics of Post Baseline QT 
prolongation Adverse events of Special interest 
 
WEEK 24/ 
WEEK 48/EOS 
3.27.  
Safety 
SAF_T10 
Summary of Characteristics of Post Baseline 
Gastrointestinal intolerability/gastric toxicity 
Adverse events of Special interest 
 
WEEK 24/ 
WEEK 48/EOS 
3.28.  
Safety 
SAF_T10 
Summary of Characteristics of Post Baseline 
Psychiatric Adverse events of Special interest 
 
WEEK 24/ 
WEEK 48/EOS 
3.29.  
Safety 
SAF_T10 
Summary of Characteristics of Post Baseline 
Nervous system disorders Adverse events of Special 
interest 
 
WEEK 24/ 
WEEK 48/EOS 
3.30
Safety 
SAF_T10 
Summary of Characteristics of Post Baseline Skin 
and subcutaneous tissue disorder Adverse events of 
Special interest 
 
WEEK 24/ 
WEEK 48/EOS 
Biomarkers (Bone, Renal and Inflammatory) 
3.31 
Safety 
LB1 
Summary of Change from Baseline in Bone 
Biomarkers by Visit 
 
WEEK 24/ 
WEEK 48 
3.32 
Safety 
LB1 
Summary of Change from Baseline in Renal 
Biomarkers by Visit 
 
WEEK 24/ 
WEEK 48 
3.33 
Safety 
LB1 
Summary of Change from Baseline in Renal 
Biomarkers by Visit- Loge Transformed Data  
 
WEEK 24/ 
WEEK 48 
3.34 
Safety 
LB1 
Summary of Change from Baseline in Inflammatory 
Biomarkers - Loge Transformed Data 
 
WEEK 24/ 
WEEK 48 


 
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Safety: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
3.35 
Safety 
LB1 
Summary of Change from Baseline in 
Stomach/Gastric Biomarkers 
 
WEEK 24/ 
WEEK 48 
3.36 
Safety 
LB1 
Summary of Change from Baseline in 
 by 
Visit - Loge Transformed Data 
 
WEEK 24/ 
WEEK 48 
3.37 
Safety 
LB1 
Summary of Change from Baseline in HbA1c by 
Visit 
 
WEEK 24/ 
WEEK 48 
3.38 
Safety 
LB1 
Summary of Change from Baseline in Fasting Lipids 
by Visit 
display both 
mmol/L and 
mg/DL 
WEEK 24/ 
WEEK 48 
3.39 
Safety 
LB1 
Summary of Change from Baseline in Bone 
Biomarkers by Subgroup and Visit 
 
WEEK 24/ 
WEEK 48 
3.40 
Safety 
LB1 
Summary of Change from Baseline in Renal 
Biomarkers by Subgroup and Visit 
 
WEEK 24/ 
WEEK 48 
3.41 
Safety 
LB1 
Summary of Change from Baseline in Renal 
Biomarkers by Subgroup and Visit - Loge 
Transformed Data  
 
WEEK 24/ 
WEEK 48 
3.42 
Safety 
LB1 
Summary of Change from Baseline in Inflammatory 
Biomarkers by Subgroup and Visit - Loge 
Transformed Data 
 
WEEK 24/ 
WEEK 48 
3.43 
EGD Sub 
Study 
LB1 
Summary of Change from Baseline in 
Stomach/Gastric Biomarkers Subgroup and Visit 
 
WEEK 24/ 
WEEK 48 
CCI


 
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Safety: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
3.44 
Safety 
gsk3515864/
mid204862/p
rimary_01 
T1.27 
Summary of Current Cardiovascular System 
Conditions 
 
WEEK 24/ 
WEEK 48/EOS 
3.45 
EGD Sub 
Study 
PRF1 
Summary of Gastric Biopsy Findings by Stomach 
Region and EGD Grading  
 
WEEK 24/EOS 
3.46 
EGD Sub 
Study 
PRF2 
Summary of Treatment Emergent Gastric Biopsy 
Findings by Stomach Region and EGD Grading
 
 
 
 
 
WEEK 24/EOS 
3.47 
EGD Sub 
Study 
PRF3 
Summary of Staining Methods by Visit 
 
WEEK 24/EOS 
3.48 
EGD Sub 
Study 
EGD1 
Summary of Esophagus and Stomach Visualization 
and Savary-Miller Grades 
 
 
 
 
WEEK 24/EOS 
3.49 
EGD Sub 
Study 
EGD2 
Summary of EGD Findings by Esophagus and 
Stomach Regions and Location of greatest impact by 
Grade  
 
WEEK 24/EOS 
3.50 
EGD Sub 
Study 
EGD3 
Summary of Treatment Emergent EGD Findings by 
Esophagus and Stomach Regions and Location of 
greatest impact by Grade 
 
 
WEEK 24/EOS 
 


 
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14.12.8. 
Safety Figures 
Safety: Figures 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events 
3.1. 
Safety 
AE10 
Plot of Common (>=2%) Adverse Events and 
Relative Risk / Other Statistics 
GSK Statistical Display 
Standard  
 WEEK 24/ 
WEEK 48 
Laboratory 
3.2. 
Safety 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT 
GSK Statistical Display 
Standard  
 WEEK 24/ 
WEEK 
48/EOS 
3.3. 
Safety 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total 
Bilirubin 
GSK Statistical Display 
Standard  
 WEEK 24/ 
WEEK 
48/EOS 
 


 
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14.12.9. 
Virology tables  
Virology: Tables 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.1. 
PDVF 
PFG1 
Summary of Major Mutations of NRTI, NNRTI and 
PI Classes at Baseline and Time of PDVF  
Template: 
gsk3515864/mid20486
1/primary_09/table 
4.4. 
 
  WEEK 
24/ WEEK 
48/EOS 
4.2. 
PDVF 
VIR_T4 
Summary of Phenotypic Susceptibility by Drug and 
Drug Class at the Time of PDVF for subjects meeting 
PDVF criteria 
Template: 
gsk3515864/mid20486
1/primary_01/table 
4.8. 
 
  WEEK 
24/ WEEK 
48/EOS 
4.3. 
PDVF 
VIR_T6 
Summary of Fold Change of IC50 at - Time of PDVF   
  WEEK 
24/ WEEK 
48/EOS 
4.4. 
PDVF 
PFG2 
Summary of Emergent INSTI Mutations at Time of 
PDVF  
Please follow template 
from 
gsk3515864/mid20486
1/primary_01/table 4.3 
  WEEK 
24/ WEEK 
48/EOS 
4.5. 
Geno/Pheno 
PFG2 
Summary of Emergent NRTI, NNRTI and PI Classes 
at Time of PDVF  
 
  WEEK 
24/ WEEK 
48/EOS 


 
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Note : Please add a footnote in the tables saying the PDVF subjects with Viral load >=400 are considered at PDVF timepoint. 


 
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14.12.10. Pharmacokinetic Tables 
 
Pharmacokinetic: Tables 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Intensive PK - PK Concentration Data 
5.1 
Intensive PK 
PK01 
Summary of Plasma GSK3640254 PK Concentration-
Time Data by Nominal Time Relative to Dose 
Sorted by Study 
Visit and Time 
relative to Dose 
  WEEK 24 
Intensive PK Derived Parameters 
    
5.2 
Intensive PK 
PK06 
Summary of untransformed and loge-transformed 
Derived Plasma GSK3640254PK Parameters  
 
WEEK 24 
Sparse PK - PK Concentration Data  
5.3 
Sparse PK  
PK01 
Summary of Plasma GSK3640254PK Concentration-
Time Data by Visit and Nominal Time Relative to Dose 
Sorted by Study 
Visit and/or 
Time (window) 
relative to Dose 
WEEK 24/ 
WEEK 48 


 
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14.12.11. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Intensive PK - PK Concentration Data 
5.1. 
Intensive PK 
PK24 
Individual Plasma GSK3640254 Concentration-Time 
Plots (linear and Semi-log) 
Overlay all 
individual profiles 
WEEK 24 
5.2. 
Intensive PK 
PK19 
Mean and SD Plasma GSK3640254 Concentration-Time 
plots (linear and semi-log)  
 
WEEK 24 
5.3. 
Intensive PK 
PK18 
Median Plasma GSK3640254 Concentration-Time plots 
(linear and semi-log)  
 
WEEK 24 
 


 
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14.12.12. ICH Listings 
ICH: Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
ITT-E 
ES2  
Listing of Reasons for Study Withdrawal 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 
2.  
ITT-E 
SD2 
Listing of Reasons for Study Treatment Discontinuation 
ICH E3 
 
 WEEK 24/ 
WEEK 
48/EOS 
3.  
ITT-E 
BL1 
Listing of Subjects for Whom the Treatment Blind was Broken 
ICH E3 
 
 WEEK 24/ 
WEEK 48 
4.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
CS CORE; add 
subreason, i.e 
# of IE criteria 
WEEK 24/ 
WEEK 48 
Protocol Deviations 
5.  
ITT-E 
DV2 
Listing of Important Protocol Deviations  
ICH E3 
 
 WEEK 24/ 
WEEK 
48/EOS 
6.  
ITT-E 
IE3  
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations 
ICH E3 
 WEEK 24/ 
WEEK 48 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Populations Analysed 
7.  
ITT-E 
SP3  
Listing of Subjects Excluded from Any Population 
ICH E3 For PP 
population and 
ITTES 
 WEEK 24/ 
WEEK 48 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Demographic and Baseline Characteristics 
8.  
ITT-E 
DM2  
Listing of Demographic Characteristics 
ICH E3 
 WEEK 24/ 
WEEK 48 
9.  
ITT-E 
DM9 
Listing of Race 
ICH E3 
 WEEK 24/ 
WEEK 48 
Prior and Concomitant Medications 
10.  
ITT-E 
CM3 
Listing of Concomitant Medications 
Based on GSK 
Drug 
Dictionary 
 WEEK 24/ 
WEEK 
48/EOS 
Exposure and Treatment Compliance 
11.  
Safety 
EX3  
Listing of Exposure Data 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 
Adverse Events 
12.  
Safety 
AE8CP 
Listing of All Adverse Events 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 
13.  
Safety 
AE7 
Listing of Subject Numbers for Individual Adverse Events 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 
Serious and Other Significant Adverse Events 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
14.  
Safety 
AE8CP  
Listing of All Drug-related Adverse Events 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 
15.  
Safety 
AE8CP 
 
Listing of Serious Adverse Events (Fatal and Non-Fatal) 
ICH E3 
 
 WEEK 24/ 
WEEK 
48/EOS 
16.  
Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 
17.  
Safety 
AE8CP 
Listing of Adverse Events Leading to Withdrawal from Study / 
Permanent Discontinuation of Study Treatment 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 


 
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105 
 
ICH: Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
All Laboratory 
18.  
Safety 
LB5A  
Listing of All Laboratory Data for Subjects with Any Value of 
Toxicity Grade 1 or Above 
ICH E3 
 
 WEEK 24/ 
WEEK 
48/EOS 
19.  
Safety 
LB5A  
Listing of Laboratory Values of Toxicity Grade 1 or Above 
ICH E3 
 
 WEEK 24/ 
WEEK 
48/EOS 
20.  
Safety 
LB14 
Listing of Laboratory Data with Character Results 
ICH E3 
 WEEK 24/ 
WEEK 
48/EOS 
21.  
Safety 
LB5A 
Listing of Urinalysis Data for Subjects  
ICH E3, The 
columns 
related to 
normal range 
and flags can 
be excluded. 
 WEEK 24/ 
WEEK 
48/EOS 


 
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14.12.13. Non-ICH Listings 
Non-ICH Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Adverse Events 
22.  
Safety 
AE2 
Listing of Relationship Between Adverse Event System 
Organ Classes, Preferred Terms, and Verbatim Text 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
Hepatobiliary (Liver) 
23.  
Safety 
MH2 
Listing of Medical Conditions for Subjects with Liver 
Stopping Events 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
ECG 
24.  
Safety 
EG3  
Listing of All ECG Values for Subjects with Any 
Value of Potential Clinical Importance 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
25.  
Safety 
EG3  
Listing of ECG Values of Potential Clinical Importance GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
26.  
Safety 
EG5 
Listing of All ECG Findings for Subjects with an 
Abnormal ECG Finding 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
27.  
Safety 
EG5 
Listing of Abnormal ECG Findings 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
Vital Signs 
28.  
Safety 
VS4 
Listing of All Vital Signs Data for Subjects with Any 
Value of Potential Clinical Importance 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48 


 
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Non-ICH Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
29.  
Safety 
VS4 
Listing of All Vital Signs Data  
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
COVID-19 Related AE 
30.  
Safety 
PAN12 
Listing of COVID-19 Assessments and Symptom 
Assessment 
 
WEEK 24/ 
WEEK 48 
Other 
31.  
Safety 
PREG1 
Listing of Subjects Who Became Pregnant During the 
Study 
GSK Statistical 
Display Standard 
  WEEK 24/ 
WEEK 48/EOS 
32.  
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event 
 
WEEK 24/ 
WEEK 48/EOS 
PK Endpoints 
33.  
PK 
PK07  
Listing of GSK3640254 Pharmacokinetic 
Concentration-Time Data  
 
WEEK 24/ 
WEEK 48 
Efficacy 
34.  
ITT-E 
VF4 
Listing of Plasma HIV-1 RNA data for subjects with 
PDVF 
 
WEEK 24/ 
WEEK 48/EOS 


 
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Non-ICH Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
35.  
ITT-E 
gsk351586
4/mid2080
90/primary
_01 Listing 
10 
Listing of Quantitative and Qualitative Plasma HIV-1 
RNA Data 
 
WEEK 24/ 
WEEK 48/EOS 
36.  
ITT-E 
gsk351586
4/mid2080
90/primary
_01 Listing 
44 
Listing of CD4+ Cell Count Data 
 
WEEK 24/ 
WEEK 48/EOS 
37.  
ITT-E 
gsk351586
4/mid2080
90/primary
_01 Listing 
45 
Listing of CD8+ and CD4+/CD8+ Cell Count Ratio 
Data 
 
WEEK 24/ 
WEEK 48/EOS 
38.  
ITT-E 
HIV4 
Listing of Stage 3 HIV-1 Associated Conditions 
 
WEEK 24/ 
WEEK 48/EOS 
Virology 


 
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Non-ICH Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
39.  
Geno/Pheno 
VIR_L1 
Listing of All Genotypic Data 
Includes IC50 and 
Fold change. Fold 
change ratio to be 
included in the 
Listing of 
Genotypic and 
Phenotypic data in 
PDVF subjects 
WEEK 24/ 
WEEK 48/EOS 
40.  
Geno/Pheno 
VIR_L1 
Listing of All Pheotypic Data 
Includes IC50 and 
Fold change. Fold 
change ratio to be 
included in the 
Listing of 
Genotypic and 
Phenotypic data in 
PDVF subjects 
WEEK 24/ 
WEEK 48/EOS 
41.  
Safety 
gsk351586
4/mid2048
62/primary
_01 Listing 
62 
Listing of Cardiovascular Events 
 
WEEK 24/ 
WEEK 48/EOS 
42.  
EGD Sub 
Study 
PRF4 
Listing of Gastric Biopsy findings  
 
WEEK 24/EOS 


 
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Non-ICH Listings 
No. 
Population 
GSK 
Standard/ 
Example 
Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
43.  
EGD Sub 
Study 
EGD4 
Listing of EGD findings  
 
WEEK 24/EOS 
 
 


 
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14.13. 
Appendix 13: Example Mock Shells for Data Displays 
Note: All the tables will be presented for the following 4 treatment groups:  
• 
GSK254 100 mg + 2NRTIs 
• 
GSK254 150 mg + 2NRTIs 
• 
GSK254 200 mg + 2NRTIs 
• 
DTG 50 mg + 2NRTIs 
 
Shell 1:  
Protocol: 208379                                                                               Page 1 of 1 
Population: Intent-To-Treat Exposed 
                            
Percent of Subjects with Plasma HIV-1 RNA < 50 c/mL by Visit 
- Snapshot Analysis 
 
                                             Trt A                   Trt B 
                   Actual Relative Time     (N=246)                 (N=247) 
                   ---------------------------------------------------------------------- 
                   Baseline                   XX / XX (XX%)        XX / XX  (XX%) 
                   Week 4                     XX / XX (XX%)        XX / XX  (XX%) 
                   Week 12                       .                      . 
                   Week 24                       .                      . 
                   Week 36                    XX / XX (XX%)        XX / XX  (XX%) 
                    
 
 
 


 
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Shell 1.1  
Protocol: 208379                                                                                       Page 1 of 
n                                                                                                                                
Population: Intent-to-Treat Exposed 
Table T_EFF2 
Summary of Analysis for Proportion of Subjects with Plasma HIV-1 RNA < 50 c/mL at Week 24 – Snapshot Analysis 
 
 
 
 
Treatment 
 
 
N 
Number of HIV-
1 RNA <50 
c/mL/Total 
Assessed      
Percent 
(95% CI) [1] 
Difference in 
Percent  
(95% CI) [2] 
Adjusted 
Difference in 
Percent 
(95% CI) [3] 
 
 
 
 
 
 
Trt. A 
XXX 
X/XXX (XX%) 
(X.X, X.X) 
X.X (X.X, X.X) 
X.X (X.X, X.X) 
 
 
 
 
 
 
Trt. B 
XXX 
X/XXX (XX%) 
(X.X, X.X) 
X.X (X.X, X.X) 
X.X (X.X, X.X) 
 
 
 
 
 
 
Trt. C 
XXX 
X/XXX (XX%) 
(X.X, X.X) 
X.X (X.X, X.X) 
X.X (X.X, X.X) 
 
 
 
 
 
 
Control 
XXX 
X/XXX (XX%) 
(X.X, X.X) 
 
 
 
 
Note: [1] Confidence Intervals estimated using the Wilson (Score) method 
Note: [2] Difference: Proportion on GSK254 + 2 NRTIs - Proportion on DTG + 2 NRTIs 
Note: [3] Based on the Cochran-Mantel Haenszel stratified analysis for adjusting the following baseline 
stratification factors: Screening HIV-1 RNA (<100,000 copies/mL or >=100,000 copies/mL) and 
Initial background dual NRTI (ABC/3TC or FTC/TAF) 
 
 
 
 
 


 
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Shell 2:  
Protocol: 208379   
 
 
 
 
 
 
 
 
       Page 1 of n                                           
Population: Intent-To-Treat Exposed 
 
Table 2.xx 
Summary of Study Outcomes (Plasma HIV-1 RNA >=/< 50 c/mL) at Week X 
- Snapshot  Analysis 
 
Trt A 
Trt B 
Outcome 
(N=xx) 
(N=xx) 
HIV1-RNA < 50 copies/mL  
xx (xx%) 
xxx (xx%) 
HIV1-RNA >= 50 copies/mL  
xx (xx%) 
xx (xx%) 
  Data in window and HIV-1 RNA >= 50 copies/mL 
  Discontinued for lack of efficacy   
  Discontinued for other reason while HIV-1 RNA >= 50 copies/mL 
  Change in background therapy 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
No Virologic Data at Week X Window 
xx (xx%) 
 
xx (xx%) 
  Discontinued study due to AE or Death 
xx (xx%) 
xx (xx%) 
  Discontinued study for Other Reasons 
xx (xx%) 
xx (xx%) 
  On study but missing data in window 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
 


 
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Shell 4: 
Protocol: 208379                                                                      Page 1 of xx 
Population: Intent-to-Treat Exposed 
Table 2.6 
Percent of Subjects with Plasma HIV-1 RNA <threshold c/mL by Visit and Subgroup - Snapshot Analysis 
 
 
Subgroup  
Act. Rel.  
Time 
Trt. A  
(N=XXX) 
Trt. B  
(N=XXX) 
 
 
 
 
 
Sex  
Female 
Baseline             
xxx/XXX 
xxx/XXX 
 
  
Week 2 
xxx/XXX 
xxx/XXX 
 
 
Week 4 
xxx/XXX 
xxx/XXX 
 
 
Week 12 
xxx/XXX 
xxx/XXX 
 
 
... 
xxx/XXX 
xxx/XXX 
 
 
Week 48 
xxx/XXX 
xxx/XXX 
 
 
... 
xxx/XXX 
xxx/XXX 
 
Male 
Baseline             
xxx/XXX 
xxx/XXX 
 
 
Week 2 
xxx/XXX 
xxx/XXX 
 
 
Week 4 
xxx/XXX 
xxx/XXX 
 
 
Week 12 
xxx/XXX 
xxx/XXX 
 
 
... 
xxx/XXX 
xxx/XXX 
 
 
Week 48 
xxx/XXX 
xxx/XXX 
 
 
... 
xxx/XXX 
xxx/XXX 
 
 
 
 


 
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Shell 5 
Protocol: 208379 
Population: Intent-to-Treat Exposed (ITT-E) 
Table 2.1 
Summary of Posterior Probability of Treatment Difference of Plasma HIV-1 RNA <50 copies/mL at Week 24 - Snapshot 
 
 
Arm 1 to 3: 
GSK254 XX mg + 
2NRTIs 
Arm 4: 
DTG 50 mg + 
2NRTIs 
Result 
(N=XXX) 
(N=XXX) 
Overall 
 
 
   Number of Subjects 
XX 
XX 
   Number (%) with HIV-1 RNA <50 c/mL 
XX (XX%) 
XX (XX%) 
   (95% CI) [1] 
(XX%, XX%) 
(XX%, XX%) 
 
 
 
Overall Treatment Difference compared to 
Arm 4 
 
 
   % with HIV-1 RNA <50 c/mL 
XX% 
NE 
   (95% CI)[3] 
(XX%, XX%) 
NE 
 
 
 
Point Estimate (%) of rate of HIV-1 RNA 
<50 c/mL [2] 
 
 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
   (95% CI) 
(XX%, XX%) 
(XX%, XX%) 
 
 
 
Point Estimate (%) of Treatment Difference 
[2] 
 
 
   Mean (SD) 
XX.X (XX.XX) 
NE 
   Median 
XX.X 
NE 
   (95% CI) 
(XX%, XX%) 
NE 
 
 
 


 
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Posterior Probability P(True difference of  
   Arm 1:3 - Arm 4 >= -10% | data)[4] 
0.XXXX 
NE 
 
 
 
[1] Confidence interval is based on frequentist estimate using Clopper-Pearson. 
[2] The point estimate of HIV-1 RNA <50 c/mL and its 95% credible interval are estimated from a Bayesian hierarchical  
model that incorporates the analysis stratification factors. The posterior distribution of the rate for each arm  
is derived using a mixture of the posterior distributions of the rate for each stratum with weight proportional  
to the sample size for each stratum. 
[3] Confidence interval of the frequentist estimate of response rate difference is based on Newcombe. 
[4] Success with complete data is defined as the posterior probability P(Arm1:3 - Arm 4 >= -10% | data) > 85% 
NE = Not estimable 
 


 
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Shell 6 
Protocol: 208379                                                                                      Page 1 of n 
Population: Safety                               
Table 3.xx 
Summary of Characteristics of Adverse Events of Special Interest 
Preferred Term: Depression 
 
Trt. A 
(N=100) 
Trt. B 
(N=100) 
Number of Subjects with Event 
xx (xx%) 
xx (xx%) 
 
 
 
    Number of Events 
xx 
xx 
 
 
 
Event Characteristics [1] 
 
 
    n 
xx 
xx 
    Serious 
xx (xx%) 
xx (xx%) 
    Drug-related 
xx (xx%) 
xx (xx%) 
    Leading to Withdrawal 
xx (xx%) 
xx (xx%) 
    Severe/Potentially life threatening or Grade 3/4 
xx (xx%) 
xx (xx%) 
    Fatal of Grade 5 
xx (xx%) 
xx (xx%) 
 
 
 
Number of occurences 
 
 
    n 
xx 
xx 
    One 
xx (xx%) 
xx (xx%) 
    Two 
xx (xx%) 
xx (xx%) 
    Three or more 
xx (xx%) 
xx (xx%) 
 
 
 
Outcome [2] 
 
 
    n 
xx 
xx 
    Recovered/resolved 
xx (xx%) 
xx (xx%) 
    Recovering/resolving 
xx (xx%) 
xx (xx%) 
    Not recovered/not resolved 
xx (xx%) 
xx (xx%) 
    Recovered/resolved with sequalae 
xx (xx%) 
xx (xx%) 
    Fatal 
xx (xx%) 
xx (xx%) 
 
 
 
Maximum Grade or Intensity 
 
 


 
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    N 
xx 
xx 
    
 or Grade 1 
xx (xx%) 
xx (xx%) 
    
 or Grade 2 
xx (xx%) 
xx (xx%) 
    
 or Grade 3 
xx (xx%) 
xx (xx%) 
    
 or Grade 4 
xx (xx%) 
xx (xx%) 
    
 or Grade 5 
xx (xx%) 
xx (xx%) 
 
 
 
Action Taken [3] 
 
 
    n 
xx 
xx 
    Dose Not Changed 
xx (xx%) 
xx (xx%) 
    Drug Interrupted 
xx (xx%) 
xx (xx%) 
    Drug Withdrawn 
xx (xx%) 
xx (xx%) 
    Dose Increased 
xx (xx%) 
xx (xx%) 
    Dose Reduced 
xx (xx%) 
xx (xx%) 
    Not Applicable 
xx (xx%) 
xx (xx%) 
 
 
Note: Division of AIDS (DAIDS) version 2.1, March 2017 is used for severity grading. 
Note: AEs are coded using MedDRA vxx.x 
Note: [1] Subjects may be included in more than one category for ’Event Characteristics’. 
Note: [2] Outcome worst case hierarchy: Fatal > Not Recovered/Not Resolved > Recovered/Resolved with sequelae> 
Recovering/Resolving > Recovered/Resolved 
Note: [3] Subjects are counted once under each action that was taken. 
Programming note: Repeat for all AESI:  
 
 
CCI
CCI
CCI
CCI
CCI


 
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Shell HIV 4 
Protocol:                                                                                             Page 1 of n 
Population: Intent-to-Treat Exposed 
Listing X 
Listing of Stage 3 HIV-1 Associated Conditions 
Treatment:  
Site ID/ 
Unique 
Subject 
ID 
Category/ 
Condition 
Actual 
Treatment 
State  
Start Date/ 
Days Since  
1st Dose 
Progression 
Previous 
Condition?      
 
 
 
 
 
 
HIV Infection Stage 
3/ 
Candidiasis, 
esophageal 
On-
treatment 
/8
3 d 
HIV Infection 
Stage 2 to HIV 
Infection 
Stage 3 Event 
Yes 
 
 
 
 
 
 
HIV Infection Stage 
3/ 
*DIFFUSE LARGE B CELL 
NON HODGKIN’S 
LYMPHOMA 
On-
treatment 
/7 
d 
HIV Infection 
Stage 2 to HIV 
Infection 
Stage 3 Event 
No 
Note: *Clinically reviewed and determined to be HIV Infection Stage 3 Event. 
 
 
PPD
PPD
PPD
PPD


 
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Shell 7 
Population: Intent-to-Treat Exposed  
Table 2.xx 
Summary of Kaplan- Meier Estimates of Proportion of Subjects Without Protocol Defined Virologic Failure at Week X - 
Treatment Related Discontinuation = Failure 
 
 
Trt A 
(N=xXx) 
Trt B 
(N=xxx) 
Number of Subjects 
 
 
  Protocol Defined Virologic 
  Failure or discontinuation due to 
  treatment related reason at or prior 
  to Week 24 
xx  (xx%) 
Xx (xx%) 
  Censored [1] 
Xx (xx%) 
Xx (xx%) 
 
 
 
Proportion of Subjects Without Protocol 
Defined Virologic Failure or not 
discontinued due to treatment related 
reasons at or prior to Week 48  
 
 
  Estimate 
xx.x% 
xx.x% 
  95% CI 
(xx.x%, xx.x%) 
(x.x%, x.x%) 
 
 
 
Difference in Proportions[2]  
 
 
  Estimated Difference 
x.x% 
 
  95% CI [3] 
(x.x%, x.x%) 
 
 
 
Note: [1] Subjects who have not met the PDVF criteria and are ongoing in the study, or who have discontinued for 
non-treatment related reasons are censored.  
Note: [2] Difference: Proportion on GSK’254 xxmg + 2NRTI’s - Proportion on DTG 50mg + 2NRTIs.  
Note: [3] Based on Greenwood's formula.  


 
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Shell VIR_T1 
 
Protocol: 208379                                                                                               Page 1 of n 
Population:  PDVF 
Table 4.xx 
Summary of INI Mutations at Baseline and Time of PDVF or prior to week X 
 
Treatment: Trt. A 
Codon 
Mutation 
 
 
Baseline 
Time of 
PDVF 
 
 
 
 
  
 (N=xx) 
 (N=xx) 
 
 
 
 
 
 
 
 
A1 
A1A (wild type) 
 
 
xx (xx%) 
xx (xx%) 
 
 
Any mutation 
 
 
xx (xx%) 
xx (xx%) 
 
 
  Any A1B 
 
 
xx (xx%) 
xx (xx%) 
 
 
  Any A1C 
 
 
xx (xx%) 
xx (xx%) 
 
 
    A1B 
 
 
xx (xx%) 
xx (xx%) 
 
 
    A1C 
 
 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
 
 
 
H2 
H2H (wild type) 
 
 
xx (xx%) 
xx (xx%) 
 
 
Any mutation 
 
 
xx (xx%) 
xx (xx%) 
 
 
  Any H2B 
 
 
xx (xx%) 
xx (xx%) 
 
 
  Any H2C 
 
 
xx (xx%) 
xx (xx%) 
 
 
    H2B 
 
 
xx (xx%) 
xx (xx%) 
 
 
    H2C 
 
 
xx (xx%) 
xx (xx%) 
 
 
    H2C/B 
 
 
xx (xx%) 
xx (xx%) 
 
 
    H2H/B 
 
 
xx (xx%) 
xx (xx%) 
 
... 
 
 
 
 
 
 
 
 
Treatment:  
 
... 
 
 
Note: Baseline resistance testing was carried out on whole blood samples collected at Day 1 or subsequent 
visit using Monogram GenoSure Archive assay, which provides genotypic data only. On study resistance testing 


 
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used standard plasma based genotypic and phenotypic resistance testing assays. Testing on Confirmed 
Virologic Withdrawal subjects used the initial elevated viral load ("SVW") sample. Any codon at which there 
is only wild-type has been omitted from this table. "Any mutation" refers to Pre-specified IN Substitutions 
Associated with Development of Resistance to INSTI Class. 
Note: Refer to decision table "Listing of All Genotypic and Phenotypic Data" that shows what data is in 
scope for analyses. 
 
Programming Note: Ordered by frequency of the “Any mutation” values within codon.  “Any mutation” included refers to the 
list of prespecified IN substitutions in RAP. 
 
 


 
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Shell VIR_T2 
Protocol: 208379                                                                                               Page 1 of n 
Population: PDVF 
Table 4.xx 
Summary of Major Mutations of NRTI, NNRTI and PI Classes  
by region at Baseline and Time of PDVF 
 
Region: NRTI 
Treatment: Trt. A 
 
Codon 
Mutation 
 
Baseline 
Time of 
PDVF 
 
 
 
  (N=xx) 
 (N=xx) 
 
 
 
  
 
 
A1 
A1A (wild type)  xx (xx%) 
xx (xx%)  
 
Any mutation 
 xx (xx%) 
xx (xx%)  
 
  Any A1B 
 xx (xx%) 
xx (xx%)  
 
  Any A1C 
 xx (xx%) 
xx (xx%)  
 
    A1B 
 xx (xx%) 
xx (xx%)  
 
    A1C 
 xx (xx%) 
xx (xx%)  
 
 
  
 
 
H2 
H2H (wild type)  xx (xx%) 
xx (xx%)  
 
Any mutation 
 xx (xx%) 
xx (xx%)  
 
  Any H2B 
 xx (xx%) 
xx (xx%)  
 
  Any H2C 
 xx (xx%) 
xx (xx%)  
 
    H2B 
 xx (xx%) 
xx (xx%)  
 
    H2C 
 xx (xx%) 
xx (xx%)  
 
    H2C/B 
 xx (xx%) 
xx (xx%)  
 
    H2H/B 
 xx (xx%) 
xx (xx%)  
... 
 
  
 
 
 
Treatment: Trt. B 
... 
 
Class: NRTI 
 
 
Class: NNRTI  
 
Class: PI  
 


 
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Note: Baseline resistance testing was carried out on whole blood samples collected at Day 1 or subsequent 
visit using Monogram GenoSure Archive assay, which provides genotypic data only. On study resistance testing 
used standard plasma based genotypic and phenotypic resistance testing assays. Testing on Confirmed 
Virologic Withdrawal subjects typically uses the initial elevated viral load "SVW" sample. Any codon at 
which there is only wild-type has been omitted from this table. 
Note: Major resistance mutations to classes NRTI, NNRTI, and PI are defined by the 
International Antiviral Society-USA (IAS-USA). 
Note: Refer to decision table "Listing of All Genotypic and Phenotypic Data" that shows what data is in 
scope for analyses. 
 
Programming Note: Repeat for other drug classes; ordered by frequency of the “Any mutation” values within codon. 
 
 


 
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Shell VIR_T4 
Protocol: 208379 
 
 
 
 
 
 
 
 
 
 
Page 1 of n 
Population: PDVF  
Table 4.xx 
Summary of Phenotypic Susceptibility by Drug and Drug Class at the Time of PDVF for subjects meeting PDVF criteria 
Class 
  Drug                                                            Trt A           Trt B 
    Phenotype                                                    (N=XX)          (N=XX) 
-------------------------------------------------------------------------------------- 
INSTI 
  DTG 
    n                                                               xx              xx 
    Sensitive                                                     xx (xx%)        xx (xx%) 
    Resistant                                                     xx (xx%)        xx (xx%) 
 
  BIC 
    n                                                              xx              xx 
    Sensitive                                                     xx (xx%)        xx (xx%) 
    Resistant                                                     xx (xx%)        xx (xx%) 
 
  EVG 
    n                                                              xx              xx 
    Sensitive                                                     xx (xx%)        xx (xx%) 
    Resistant                                                     xx (xx%)        xx (xx%) 
   
  RAL 
    n                                                              xx              xx 
    Sensitive                                                     xx (xx%)        xx (xx%) 
    Resistant                                                     xx (xx%)        xx (xx%) 
 
NRTI 
  DLV 
    n                                                              xx              xx 
    Sensitive                                                     xx (xx%)        xx (xx%) 
    Resistant                                                     xx (xx%)        xx (xx%) 
 
Note: Time of PDVF is at the time of on-treatment initial suspected viral load sample, which was subsequently confirmed. 


 
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Shell VIR_T6  
 
Protocol: 208379  
 
 
 
 
 
 
 
 
 
 
Page 1 of n    
Population: PDVF                                                                                       
 
Table 4.xx 
Summary of Fold Change of IC50 at - Time of PDVF at or prior to Week 24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Trt A 
Trt B 
Drug 
(N=xx) 
(N=xx) 
GSK254 Fold Change (class) 
 n 
xxx 
xxx 
 0-<1 
xx (xx%) 
xx (xx%) 
 2-<4 
xx (xx%) 
xx (xx%) 
 4-<8 
xx (xx%) 
xx (xx%) 
 >=8 
xx (xx%) 
xx (xx%) 
Fold Change 
 n 
xxx 
xxx 
 Geom. Mean 
 x.xx 
 x.xx 
 CV (%) 
 x.xxx 
 x.xxx 
 Median 
 x.xx 
 x.xx 
 Q1 
 x.xx 
 x.xx 
 Q3 
 x.xx 
 x.xx 
 Min. 
 x.xx 
 x.xx 
 Max. 
 x.xx 
 x.xx 
3TC 
Fold Change (class) 
 n  
xxx 
xxx 
0-<1 
           ... 
xx (xx%) 
xx (xx%) 


 
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Note: CV (Coefficient of Variation) = 100*sqrt(exp((SD on log scale)^2)-1). 
Note: Time of PDVF is at the time of on-treatment initial suspected viral load sample, which was subsequently confirmed. 
Note: Refer to decision table “Listing of All Genotypic and Phenotypic Data” that shows what data is in scope. 
 
 


 
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Shell VIR_L1 
Protocol: 208379                                                                                               Page 
1 of n 
Population: 
                                                 Listing x 
                        
 
Listing of All Genotypic Data  
 
Treatment: Trt A 
 
                                                      
               Date/ 
               Nominal 
               Visit/ 
Site ID/       Actual 
Unique         Analysis     Time                        Reverse                           PRO/RT    IN 
Subject ID     Visit        Point          Protease     Transcriptase    Integrase   Assay     Assay 
----------------------------------------------------------------------------------------------------------- 
/   Screening      V3I, I15V,    K11R, V35T,                 GenoSure GenoSure 
 SCREEN/                     G17D, E35D,   T39L, I135V, 
               Screening                   M36I, S37N,   D177E, I178V, 
                                           R41K, R57K,   G196E, L214F, 
                                           Q61D, L63H,   V245L, V276I, 
                                           A71T, I72R,   R277K, A288S, 
                                  I93L E297K,   K311R, 
       
/   On-treatment   V3I, K14N,    V35T, T39L,                 VIROSEQ 
 
Treatment: Trt B 
... 
 
 
 
Note: * Major Mutation 
Note: If available use PSGT and GSIN data for PRO/RT and IN regions first. 
Note: If PSGT and GSIN data is not available for PRO/RT and IN regions use the available data from PSGT+IN. 
Note: Refer to decision table "Listing of All Genotypic and Phenotypic Data" that shows what data is in 
scope.  
 
 
PPD
PPD
PPD
PPD


 
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Shell PRF1 
Protocol: 208379 
 
Page 1 of 1 
Population: EGD Sub Study 
Summary of Gastric Biopsy Findings by Stomach Region and EGD Grading at Baseline and Week 24 
  
 
 
  
 
Actual relative 
time 
Stomach region  
Gastric Biopsy Findings 
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
GSK254 XXmg + 
2NRTIs (N=XX) 
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
DTG XXmg + 
2NRTIs 
(N=XX) 
 
Total 
 
Baseline/Week 24  Greater Curvature 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Normal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Abnormal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Single cell necrosis, parietal 
cells 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Chief cell atrophy or cytoplasmic 
alteration                  
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
….. 
 
Dysplasia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Lesser Curvature (Transitional Zone)      
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Normal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Abnormal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 


 
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Single cell necrosis, parietal 
cells 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Chief cell atrophy or cytoplasmic 
alteration                  
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
… 
 
Dysplasia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
  
 
 
 
 
 
Note: Spasmolytic Polypeptid
essing Meta
ia (SPEM), E
astroduodenosco
D)  
Note: EGD Grading: Grade 0 (
),Grade 1 (
), Grade 2 (
) and Grade 3 (
).     
Note: EGD Findings Data base
ndependent 
ologyst's Re
Progarmming Note: This table would incude all the stomach regions in Planned and Unplanned Biopsy  
 
 
 
CCI
CCI
CCI
CCI


 
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Page 1 of 1 
Population: EGD Sub Study 
Summary of Treatment Emergent Gastric Biopsy Findings by Stomach Region and EGD Grading at Week 24 
  
 
 
 
 
 
 
 
 
  
Stomach region  
 
 Gastric Biopsy Findings 
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
DTG XXmg + 
2NRTIs 
(N=XX) 
Total 
             Greater Curvature 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Normal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Abnormal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Single cell necrosis, parietal cells 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Chief cell atrophy or cytoplasmic   
alteration                  
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
….. 
 
Dysplasia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
 
Lesser Curvature (Transitional Zone)        
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Normal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 


 
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Abnormal 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Single cell necrosis, parietal cells 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Chief cell atrophy or cytoplasmic 
alteration                  
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
… 
Dysplasia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
   Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Note: Spasmolytic Polypeptide-Expressing Metaplasia (SPEM),  Esophagogastroduodenoscopy (EGD)  
Note: EGD Grading: Grade 0 (
),Grade 1 (
), Grade 2 (
) and Grade 3 (
.     
Note: Emergent refers to Gastric Biopsy Findings severity that develops or increases in intensity after baseline.   
Note: EGD Findings  Data  based on Independent Pathologyst's Report 
Progarmming Note: This table would incude all the stomach regions in Planned and Unplanned Biopsy  
Progarmming Note: Ensure only  Emergent cases are include in this table.  if  the same finding remains the same grade at 
baseline and week 24 then it will be excluded.  
  
 
 
CCI
CCI
CCI
CCI


 
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Protocol: 208379 
 
Page 1 of 1 
Population: EGD Sub Study 
 
Summary of Staining Methods by Visit 
Actual 
Relative time Staining Methods 
GSK254 XXmg + 
2NRTIs (N=XX) 
GSK254 XXmg + 
2NRTIs (N=XX) 
GSK254 XXmg + 
2NRTIs (N=XX) 
DTG XXmg + 
2NRTIs (N=XX) Total 
Baseline/ Week 
24 
Periodic Acid Schiff-Alcian 
Blue (PAS-AB) 
Acceptable 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Not 
Acceptable 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Control Periodic Acid 
Schiff-Alcian Blue (PAS-AB) Acceptable 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Not 
Acceptable 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Hematoxylin and eosin (H&E) Acceptable 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Not 
Acceptable 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Reason why H&E Not 
acceptable 
 
 
 
 
 
Any Reason 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Acceptable 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Crushing 
Artefact 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Inadequate 
Fixation 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Insufficient 
Tissue 
Note: EGD  Data  based on Independent Pathologyst's Report 
Progarmming Note: This table would incude all the stomach regions in Planned and Unplanned Biopsy  
Progarmming Note: Ensure only  Emergent cases are include in this table.  if  the same finding remains the same grade at 
baseline and week 24 then it will be excluded.  


 
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of 1 
Population: EGD Sub Study 
Summary of Esophagus and Stomach Vizualisation and Savary-Miller Grades 
 
 
  
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
GSK254 XXmg 
+ 2NRTIs 
(N=XX) 
DTG XXmg + 
2NRTIs 
(N=XX) 
Total 
Savary-Miller 
Grades 
Grade 1: Single Erosion Above The 
Gastroesophageal Mucosal Junction 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Grade 2: Multiple Noncirumferential 
Erosions Above The Gastroesophageal 
Mucosal Junction 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Grade 3: Circumferential Erosion 
Above The Mucosal Junction 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Grade 4: Chronic Change With 
Esophageal Ulceration And 
Associated Stricture 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Grade 5: Barretts Esophagus With 
Histologically Confirmed Intestinal 
Differentiation Within The Columnar 
Epithelium 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Esophagus 
Vizualisation 
Adequate 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Inadequate 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 Reason for inadequate 
visualization of esophagus: 
Reason #1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Reason #2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Reason #3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Stomach  
Vizualisation 
Adequate 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 


 
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Inadequate 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 Reason for inadequate 
visualization of stomach: 
Reason #1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Reason #2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Reason #3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Note:  Data based on Investigator's EGD eCRF data 
 
 
 


 
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Protocol: 208379 
Population: EGD Sub Study 
Page 1 of1 
Summary of EGD Findings by Esophagus and Stomach Regions and Location of greatest impact by Grade at Baseline and Week 24 
 
Treatment: GSK254 XXmg + 2NRTIs (N=XX) 
 
 
 
 
 
EGD Findings 
 
Actual relative 
time 
Region 
Location of greatest impact: 
Mild 
Moderate 
Severe 
Total 
 
Baseline/Week 
24 
Esophagus  Any Finding 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Nodules               
 
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 Upper Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 Middle Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 Lower Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
… 
 
 
 
 
 
Early neoplastic finding             
 
 
 
 
 
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 Upper Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 Middle Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 Lower Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
 
 
 
Stomach 
 Any Finding 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Erythema 
 
 
 
 
 
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Gastric Cardia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Fundus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Lesser Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Greater Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Body of Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 


 
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Pylorus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
… 
 
 
 
 
 
Nodules 
 
 
 
 
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Gastric Cardia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Fundus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Lesser Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Greater Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Body of Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Pylorus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
Note:  Data  based on Investigator's EGD eCRF 
data 
 
 
Progarmming Notes:  
 
This table would incude any other findings reported for Stomach and 
Esophagus in the eCRF. 
 
Repeat for all the 4 treatment arms. 


 
CONFIDENTIAL 
 
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Protocol: 208379 
 
Page 1 of 1 
Population: EGD Sub Study 
Summary of Treatment Emergent EGD Findings by Esophagus and Stomach Regions and Location of greatest impact by Grade at Week 24  
  
 
Treatment: GSK254 XXmg + 2NRTIs (N=XX) 
 
 
 
 
EGD Findings 
 
Region 
Location of greatest impact: 
Mild 
Moderate 
Severe 
Total 
  
Esophagus 
 Any Finding 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Nodules               
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 Upper Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 Middle Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 Lower Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
… 
 
 
 
 
 
Early neoplastic finding             
 
 
 
 
 
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 Upper Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 Middle Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 Lower Third 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
Stomach 
 Any Finding 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Erythema 
 
 
 
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Gastric Cardia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Fundus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Lesser Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Greater Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 


 
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Body of Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Pylorus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
… 
 
 
 
 
Nodules 
 
 
 
 
 
 Any location 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Gastric Cardia 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Fundus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Lesser Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
Greater Curvature of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Body of Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Pylorus of the Stomach 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Note:  Data  based on Investigator's EGD eCRF data 
Progarmming Notes: This table would incude any other findings reported for Stomach and Esophagus in the eCRF. Repeat 
for all the 4 treatment arms. 
Progarmming Note: Ensure only  Emergent cases are include in this table.  if  the same finding remains the same grade at baseline 
and week 24 then it will be excluded.  
 


 
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Page 1 of 1 
Population: EGD sub study 
Listing X 
Listing of Gastric Biopsy (PRF) 
 
 
 
 
 
 
 
 
Site Id.: 
 
Treatment 
Unique Subject 
Id./ 
Subject Id. 
Age (YEARS)/ 
Sex/ 
Race Detail/ 
Weight (kg) 
Stomach 
Region/ 
Gastric 
Biopsy 
Findings 
Actual 
Relative 
time 
(Visit and 
date) 
Emergent 
Flag 
Grade 
Staining 
Method/Decision 
 
 
 
 
 
 
 
 
Trt A 
 
 
 
 
  
PPD
PPD


 
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Page 1 of 1 
Population:  
 
 
Listing X 
 
 
Listing of EGD Findings (CRF) 
 
 
 
 
Treatment 
Unique 
Subject 
Id./ 
Subject 
Id. 
Age (YEARS)/ 
Sex/ 
Race Detail/ 
Weight (kg) 
Region/EGD 
Findings/ 
Location of 
greatest 
impact 
Actual 
Relative 
time 
Emergent 
Flag 
Grade 
Savary-
Miller 
Grades 
Vizualisation
/ Reason if 
Inadequate 
 
 
 
 
 
 
 
 
Trt A 
 
 
 
 
 
PPD


 
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PPD

Prot_002.pdf: 
Protocol Amendment 04 
Study ID:  208379 
Official Title of Study: A Phase IIb, randomized, partially blind, active controlled, dose-
range finding study of GSK3640254 compared to a reference arm of dolutegravir, each in 
combination with nucleoside reverse transcriptase inhibitors, in HIV-1 infected 
antiretroviral treatment-naive adults 
NCT ID: NCT04493216
Date of Document: 01-OCT-2021 


TMF-13994091 
CONFIDENTIAL 
ViiV Healthcare group of companies 
208379 
1 
TITLE PAGE 
Protocol Title: A Phase IIb, randomized, partially blind, active controlled, dose-range 
finding study of GSK3640254 compared to a reference arm of dolutegravir, each in 
combination with nucleoside reverse transcriptase inhibitors, in HIV-1 infected 
antiretroviral treatment-naive adults  
Protocol Number: 208379/ Amendment 04 
Compound 
Number: 
GSK3640254 
Study Phase: Phase 2b 
Short Title: A Phase 2b Dose-Range Finding Clinical Trial in HIV-1 Infected Treatment-
Naive Adults 
Acronym: DOMINO 
Sponsor Name and Legal Registered Address (excluding US): 
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
US IND Sponsor Name and 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.  Unauthorised 
copying or use of this information is prohibited. 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
Vii V H e alt h c ar e gr o u p of c o m p a ni e s  
 
2 0 8 3 7 9  
 
2  
 
Me dic al M o nit or N a me a n d C o nt act I nf or m ati o n   
 D O, M P H 
Fr o m wit hi n t he U S A, dial t he f oll o wi n g:  
U S A m o bile;  
U S A fa x  
Fr o m o utsi de t he U S A, dial t he f oll o wi n g:  
U S A m o bile;  
U S A fa x  
 
 M. D. 
Fr o m wit hi n t he U S A, dial t he f oll o wi n g:  
 Ar ge nti na m o bile 
Fr o m o utsi de t he U S A, dial t he f oll o wi n g:  
+
 Ar ge nti na m o bile 
 
Re g ul at or y A ge nc y I de ntif yi n g N u m ber (s): 
I N D #: 1 3 9, 8 3 8   
E u dr a C T:   2 0 1 9 -0 0 4 4 3 5 -2 3   
A p pr o v al D ate: 0 1 -O C T -2 0 2 1  
 
 
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


TMF-13994091 
CONFIDENTIAL 
 
 
 
208379 
 
3 
 
SPONSOR SIGNATORY 
Protocol Title: A Phase IIb, randomized, partially blind, active controlled, dose-range 
finding study of GSK3640254 compared to a reference arm of dolutegravir, each in 
combination with nucleoside reverse transcriptase inhibitors, in HIV-1 infected 
antiretroviral treatment-naive adults  
Protocol Number: 208379/ Amendment 04 
Compound 
Number: 
GSK3640254  
 
 
 
 
Max Lataillade, DO, MPH  
Vice President, Head of Global Research Strategy 
ViiV Healthcare 
 
Date 
The signed page is a separate document. 
 
Medical Monitor Name and Contact Information can be found in Study Reference 
Manual 
 
 


TMF-13994091 
CONFIDENTIAL 
 
 
 
208379 
 
4 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Global Amendment 04 
01-OCT-2021 
TMF-13994091 
Global Amendment 03 
10-MAY-2021 
TMF-12472318 
Global Amendment 02 
09-APR-2021 
TMF-11948442 
Site Specific Protocol SS 1-244689 
11-DEC-2020 
2019N399207_04 
Global Amendment 01 
25-SEP-2020 
2019N399207_03 
Country Specific Protocol POR-1   
18-SEP-2020 
2019N399207_02 
Country Specific Protocol CAN-1 
18-SEP-2020 
2019N399207_01 
Original Protocol 
29-MAY-2020 
2019N399207_00 
Amendment 04: 01-OCT-2021 
This amendment is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union because it neither significantly impacts the safety or physical/mental 
integrity of participants nor the scientific value of the study. 
Overall Rationale for the Amendment: 
Study 208379 is undergoing this non-substantial amendment primarily to modify further 
the minimum number of CD4+ T-cells needed for study inclusion. Sponsor continues to 
try to find ways to improve the pace of recruitment without compromising safety of the 
participants nor the basics tenets of the research.   
The trial began screening in November in 2020, and Sponsor intially anticipated 
screening 210 participants would complete by 18 May 2021. However, at the time of this 
substantial amendment approximately 275 participants have been screened and 
approximately 85 have been randomized, in the study now looking to recruit only 150 
total. The reasons for the slow pace of recruitment are based upon the multi-factorial 
impact of the global Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) pandemic. 
Qualitative feedback from Investigators shows the incidence of known, newly diagnosed 
Human immunodeficiency virus-1 (HIV-1) infection has decreased. Moreover, 
physicians and newly infected patients have a strong desire to immediately start 
antiretroviral therapy so they are less likely to participate in this Phase 2b study that has a 
screening period of approximately 42 days.  
Additional modifcations are included for accuracy, consistency and transparency. 


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Section # and Name 
Description of Change 
Brief Rationale 
Cover page 
Inserted contact information for the 
additional Medical Monitor  
To meet the needs of an 
expanding GSK3640254 
program. 
1.1, Synopsis, Overall Design  
5.1, Inclusion Criteria, #4 
Modified the CD4+ T-cell count needed to 
meet eligibility, lowered from 300 to 250 
To improve eligibility and 
recruitment without 
compromising safety. 
1.1, Synopsis, Intervention 
Groups and Duration 
Modified the randomization ratio from 
2:2:2:1 to “approximately 1:1:1:1” to align 
with the changes in the number of 
participants in the GSK3640254 treatment 
arms made by Protocol Amendment 03. 
For accuracy. 
This was erroneously 
omitted from Protocol 
Amendment 03. 
4.1.5, Optional Stomach 
Substudy 
(Esophagogastroduodenoscopy 
[EGD] with Biopsy and Serum 
Biomarkers) 
Inserted the word “approximately” in 
reference to the number of substudy 
participants expected from each 
treatment arm (7) as well as the total 
number of participants (28). Because the 
GSK3640254 treatment arms are blinded, 
it will be unknown to the blinded team at 
the time of recruitment end if the arms 
filled evenly.   
Additionally, the total number of 
participants in this substudy may fall short 
of the desired total of 28, even if 
recruitment stays open (as described in 
Section 4.1.5.1). 
For transparency.  Given 
the challenges to date of 
trying to recruit this study 
during the global 
pandemic, protocol 
language is needed to 
address a possible 
substudy recruitment 
shortfall. 
4.1.5.1 Stomach Substudy 
Enrollment Considerations 
Inserted a statement to indicate the 
substudy may be allowed to overenroll if 
needed to account for any prior substudy 
discontinuations.    
For transparency. 
5.2, Exclusion Criteria #35 
Removed Grade 4 ALT from the list of 
parameters that could be considered for 
inclusion. This was in direct conflict with 
the FDA-required ALT exclusion set forth 
in Exclusion Criterion #26: ALT ≥3 x ULN, 
which is the equivalent of Grade 2 or 
higher. 
If a Screening ALT test result ≥ Grade 2, 
it can be repeated within a Screening 
period. 
For accuracy.   
 


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Section # and Name 
Description of Change 
Brief Rationale 
5.3.3, Activity 
Removed unnecessary text regarding the 
limited description of any allowed light 
activity. The first sentence in this section, 
indicating that strenuous activity is 
prohibited within 24 hours of a study clinic 
visit, is sufficient. 
For accuracy. 
6.3, Measures to Minimize 
Bias: Randomization and 
Unblinding 
Inserted details regarding controlled 
access to PK and PKPD data during the 
blinded phase of the study. 
For transparency. 
8.2.3, Cardiac Monitoring with 
Electrocardiograms 
Removed the statement that indicated 
sites could request an overread by an 
ERT cardiologist at any time. This cannot 
be accommodated due to the manner in 
which the study is set up with ERT. 
For accuracy. 
 
8.2.6, Suicidal Ideation and 
Behaviour Risk Monitoring 
Corrected the description of the visit at 
which the Lifetime assessment of the 
eCSSRS is performed.  
For accuracy. 
9.3.3, Pharmacokinetic 
Population 
Inserted a statement that makes 
reference to new details added in Section 
6.3. 
For consistency among 
the 2 related sections of 
the protocol.. 
9.3.4, Safety Population 
Removed the table that provided 
definitions for the Enrolled and 
Randomized populations. This table had 
been misplaced; these 2 populations are 
not part of the Safety population. 
For accuracy.  While 
some systems use the 
word “enrolled” to mean 
those who have 
Screened, an “enrolled” 
population may have a 
different definition in 
guidance for statistical 
analyses. 
9.3.5, Screened Population 
Moved the definition of the Enrolled 
population from Section 9.3.4 to this new 
section, and renamed it to be the 
Screened population. 
For accuracy. 
9.3.6, Randomized Population 
Moved the definition of the Randomized 
population from Section 9.3.4 to this new 
section.   
For accuracy. 
9.5, Interim analyses 
Inserted a statement to indicate when and 
how additional data cuts and analyses 
may occur.  
For transparency, as the 
need for an interim 
analysis can arise at any 
time. 


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Section # and Name 
Description of Change 
Brief Rationale 
10.3.5, Reporting SAE to 
Sponsor 
Removed the requirement for 
Investigators to enter SAE Causality 
within 72 hours.  New instruction was 
inserted.   
To align with GSK/ViiV’s 
removal of this 
requirement.   
10.11.4, COVID-19 Therapeutic 
Agents 
Replaced the word “experimental” with 
the word “therapeutic” to describe the 
agents now available to treat COVID-19. 
To align with research 
and development of 
treatments for COVID-19. 
Throughout 
Minor editorial and document formatting 
revisions. 
Minor, therefore have not 
been summarized. 


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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 4 
1. 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1. 
Synopsis ..................................................................................................... 13 
1.2. 
Schema ...................................................................................................... 18 
1.3. 
Schedule of Activities (SoA) ........................................................................ 19 
2. 
INTRODUCTION .................................................................................................... 31 
2.1. 
Study Rationale .......................................................................................... 31 
2.2. 
Background ................................................................................................ 32 
2.2.1. 
Key Safety Data with a Prior Maturation Inhibitor 
(GSK3532795) ............................................................................. 32 
2.2.2. 
Preclinical Summary with GSK3640254 ....................................... 32 
2.2.3. 
Key Clinical Data on GSK3640254 to date ................................... 34 
2.2.4. 
Key Phase 2a (Study 208132) Clinical Data on 
GSK3640254 ............................................................................... 35 
2.3. 
Benefit/Risk Assessment ............................................................................ 39 
2.3.1. 
Risk Assessment ......................................................................... 41 
2.3.2. 
Benefit Assessment ..................................................................... 53 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 53 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 53 
4. 
STUDY DESIGN .................................................................................................... 55 
4.1. 
Overall Design ............................................................................................ 55 
4.1.1. 
Screening Period ......................................................................... 55 
4.1.1.1. 
Selection of NRTI  Background Therapy: 
ABC/3TC of FTC/TAF ................................................. 56 
4.1.2. 
Treatment Period ......................................................................... 56 
4.1.2.1. 
Day 1 through Week 24 .............................................. 57 
4.1.2.1.1. 
Optional Intensive PK Portion of 
Week 2 Visit – GSK3640254 Arms 
Only ........................................................ 58 
4.1.2.2. 
Week 24 through End of Study ................................... 58 
4.1.2.2.1. 
Virologic Management ............................ 59 
4.1.2.2.2. 
Virtual Visits ............................................ 61 
4.1.2.2.3. 
Primary Analyses and Optimal 
Dose Selection ....................................... 61 
4.1.2.2.4. 
Potential cART Reimbursement 
after Last Dose of Study 
Treatment ............................................... 61 
4.1.2.3. 
Switch to Optimal Dose .............................................. 61 
4.1.3. 
Follow-up ..................................................................................... 62 
4.1.4. 
Study Completion ........................................................................ 63 
4.1.5. 
Optional Stomach Substudy 
(Esophagogastroduodenoscopy [EGD] with Biopsy and 
Serum Biomarkers) ...................................................................... 63 
4.1.5.1. 
Stomach Substudy Enrollment Considerations ........... 65 


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4.1.5.2. 
Stomach Substudy Criteria for Discontinuing 
an Individual Participant ............................................. 65 
4.1.5.3. 
Stomach Substudy Criteria for Stopping the 
Study .......................................................................... 66 
4.2. 
Scientific Rationale for Study Design .......................................................... 66 
4.2.1. 
Community Experts Input into Design .......................................... 66 
4.3. 
Justification for Dose .................................................................................. 66 
4.4. 
End of Study Definition ............................................................................... 73 
5. 
STUDY POPULATION ........................................................................................... 73 
5.1. 
Inclusion Criteria ......................................................................................... 74 
5.2. 
Exclusion Criteria ........................................................................................ 75 
5.3. 
Lifestyle Considerations .............................................................................. 79 
5.3.1. 
Meals and Dietary Restrictions .................................................... 79 
5.3.2. 
Alcohol, Tobacco and Marijuana .................................................. 80 
5.3.3. 
Activity ......................................................................................... 80 
5.3.4. 
Counsel regarding safe sex practices .......................................... 80 
5.4. 
Screen Failures........................................................................................... 80 
5.5. 
Criteria for Temporarily Delaying Randomization ........................................ 80 
5.5.1. 
Delaying Randomization for EGD Scheduling .............................. 81 
5.5.2. 
Delaying Randomization – Other ................................................. 81 
5.5.3. 
Contemporary lab results ............................................................. 81 
6. 
STUDY INTERVENTION ........................................................................................ 82 
6.1. 
Study Intervention(s) Administered ............................................................. 82 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 87 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 87 
6.4. 
Study Intervention Compliance ................................................................... 88 
6.5. 
Dose Modification ....................................................................................... 88 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 89 
6.7. 
Treatment of Overdose ............................................................................... 89 
6.8. 
Concomitant Therapy.................................................................................. 89 
6.8.1. 
Prohibited Medications and Non-Drug Therapies ......................... 90 
6.8.1.1. 
Prohibited Medications: All Participants ...................... 90 
6.8.1.2. 
Medications that need to be stopped in 
Screening ................................................................... 91 
6.8.1.3. 
On Treatment Prohibited Medications: 
GSK3640254 Arms..................................................... 91 
6.8.1.4. 
On Treatment Prohibited Medications: When 
dosing with DTG in any arm ....................................... 91 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 92 
7.1. 
Discontinuation of Study Intervention .......................................................... 92 
7.1.1. 
Protocol-Defined Virologic Failure ................................................ 94 
7.1.1.1. 
Managing Suspected Virologic 
Failure/Endpoint Cases .............................................. 95 
7.1.1.2. 
Managing Confirmed Virologic Failure/Endpoint 
Cases ......................................................................... 95 
7.1.2. 
Liver Chemistry Stopping and Increased Monitoring 
Criteria ......................................................................................... 96 


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7.1.2.1. 
Study Intervention Restart or Rechallenge after 
liver stopping criteria met ............................................ 96 
7.1.3. 
Columbia-Suicide Severity Rating Scale ...................................... 96 
7.1.4. 
QTc Stopping Criteria .................................................................. 96 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 97 
7.3. 
Lost to Follow Up ........................................................................................ 97 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 98 
8.1. 
Efficacy Assessments ................................................................................. 98 
8.1.1. 
Lymphocyte Subsets by Flow Cytometry ..................................... 99 
8.1.2. 
Disease Progression .................................................................... 99 
8.2. 
Safety Assessments ................................................................................... 99 
8.2.1. 
Physical Examinations ................................................................. 99 
8.2.2. 
Vital Signs .................................................................................... 99 
8.2.3. 
Cardiac Monitoring with Electrocardiograms .............................. 100 
8.2.4. 
Clinical Safety Laboratory Assessments .................................... 100 
8.2.5. 
Pregnancy Testing ..................................................................... 101 
8.2.6. 
Suicidal Ideation and Behaviour Risk Monitoring ....................... 101 
8.2.7. 
GI Intolerability Evaluation & Monitoring Plan (with 
Stopping Criteria) ....................................................................... 103 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ....................................................................................... 107 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................. 107 
8.3.2. 
Method of Detecting AEs and SAEs ........................................... 107 
8.3.3. 
Follow-up of AEs and SAEs ....................................................... 108 
8.3.4. 
Regulatory Reporting Requirements for SAEs ........................... 108 
8.3.5. 
Pregnancy ................................................................................. 108 
8.3.6. 
Cardiovascular and Death Events .............................................. 109 
8.3.7. 
Disease-Related Events and/or Disease-Related 
Outcomes (HIV-Associated Conditions) ..................................... 109 
8.3.8. 
Adverse Event of Special Interest .............................................. 110 
8.4. 
Pharmacokinetics ..................................................................................... 110 
8.5. 
Genetics and/or Pharmacogenomics ........................................................ 112 
8.6. 
Biomarkers ............................................................................................... 113 
8.6.1. 
Serum Biomarkers and EGD with Biopsy in the Stomach 
Substudy.................................................................................... 113 
8.6.2. 
Viral Genotyping and Phenotyping Analyses ............................. 115 
8.6.3. 
Renal, Bone and Inflammation Biomarkers ................................ 115 
8.7. 
Immunogenicity Assessments ................................................................... 116 
8.8. 
Health Economics/Medical Resource Utilization ....................................... 116 
9. 
STATISTICAL CONSIDERATIONS ...................................................................... 116 
9.1. 
Statistical Hypotheses............................................................................... 116 
9.2. 
Sample Size Determination ...................................................................... 118 
9.2.1. 
Sample Size Sensitivity .............................................................. 119 
9.3. 
Analysis Sets ............................................................................................ 120 
9.3.1. 
Intent-to-Treat Exposed Population (ITT-E) ............................... 120 
9.3.2. 
Per Protocol Population (PP) ..................................................... 120 
9.3.3. 
Pharmacokinetic Population....................................................... 120 
9.3.4. 
Safety Population ....................................................................... 120 
9.3.5. 
Screened Population ................................................................. 120 


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9.3.6. 
Randomized Population ............................................................. 120 
9.4. 
Statistical Analyses ................................................................................... 121 
9.4.1. 
Efficacy Analyses ....................................................................... 121 
9.4.2. 
Safety Analyses ......................................................................... 121 
9.4.3. 
Health Outcomes Analyses ........................................................ 122 
9.4.4. 
Other Analyses .......................................................................... 122 
9.5. 
Interim Analysis ........................................................................................ 122 
9.5.1. 
Independent Data Monitoring Committee ................................... 123 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 124 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations .......................................................................................... 124 
10.1.1. 
Regulatory and Ethical Considerations ...................................... 124 
10.1.2. 
Financial Disclosure ................................................................... 125 
10.1.3. 
Informed Consent Process ........................................................ 125 
10.1.4. 
Data Protection .......................................................................... 126 
10.1.5. 
Committees Structure ................................................................ 126 
10.1.5.1. Safety Data Review by Safety Review Team 
and IDMC ................................................................. 126 
10.1.6. 
Dissemination of Clinical Study Data ......................................... 126 
10.1.7. 
Data Quality Assurance ............................................................. 127 
10.1.8. 
Source Documents .................................................................... 128 
10.1.9. 
Study and Site Start and Closure ............................................... 128 
10.1.10. Publication Policy ....................................................................... 129 
10.2. 
Appendix 2: Clinical Laboratory Tests ....................................................... 130 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 133 
10.3.1. 
Definition of AE .......................................................................... 133 
10.3.2. 
Definition of SAE ........................................................................ 134 
10.3.3. 
Definition of Cardiovascular Events ........................................... 135 
10.3.4. 
Recording and Follow-Up of AE and SAE .................................. 136 
10.3.5. 
Reporting of SAE to Sponsor ..................................................... 138 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..................................... 139 
10.4.1. 
Definitions .................................................................................. 139 
10.4.2. 
Contraception Guidance ............................................................ 140 
10.5. 
Appendix 5: Genetics ................................................................................ 142 
10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments ............................................................................................ 143 
10.7. 
Appendix 7: Child-Pugh Classification ...................................................... 146 
10.8. 
Appendix 8: Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events Corrected Version 2.1, July 2017 ............... 147 
10.9. 
Appendix 9: Toxicity Management ............................................................ 148 
10.9.1. 
Liver Chemistry Stopping and Follow-up Criteria ....................... 149 
10.9.2. 
Hypersensitivity Reaction ........................................................... 149 
10.9.2.1. Reporting of Hypersensitivity Reactions ................... 149 
10.9.2.2. Abacavir Hypersensitivity Reaction (ABC HSR) ........ 150 
10.9.3. 
Rash & Skin Reactions .............................................................. 151 
10.9.3.1. Rash ......................................................................... 151 
10.9.3.2. Skin reactions without other symptoms that are 
typical of ABC HSR .................................................. 152 
10.9.4. 
Hypertriglyceridemia/Hypercholesterolemia ............................... 153 


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10.9.5. 
Creatine Phosphokinase (CPK) Elevation .................................. 153 
10.9.6. 
Decline in Renal Function .......................................................... 153 
10.9.7. 
Proximal Renal Tube Dysfunction .............................................. 154 
10.9.8. 
Proteinuria ................................................................................. 154 
10.10. Appendix 10: CDC Classification for HIV-1 Infection (2014) ...................... 155 
10.11. Appendix 11: COVID-19 Pandemic and Clinical Trial Continuity ............... 157 
10.11.1. Changes to Study Visits and Study Procedures ......................... 157 
10.11.2. Changes to Informed Consent ................................................... 159 
10.11.3. Direct-To-Patient (DTP) Shipment of Study IP ........................... 159 
10.11.4. COVID-19 Therapeutic Agents .................................................. 160 
10.11.5. COVID-19 Specific Data Capture ............................................... 160 
10.11.5.1. Capturing COVID-19 Specific Protocol 
Deviations ................................................................ 160 
10.11.5.2. Capturing COVID-19 Specific AEs and SAEs ........... 160 
10.11.5.2.1. WHO Case Definition (December 
16, 2020 Version): ................................ 161 
10.12. Appendix 12: Country-specific requirements ............................................. 162 
10.13. Appendix 13: Abbreviations and Trademarks ............................................ 163 
10.14. Appendix 14: Protocol Amendment History ............................................... 170 
11. REFERENCES ..................................................................................................... 187 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
A Phase IIb, randomized, partially-blind, active-controlled, dose-range finding study of 
GSK3640254 compared to a reference arm of dolutegravir, each in combination with 
nucleoside reverse transcriptase inhibitors, in HIV-1 infected, antiretroviral treatment-
naive adults 
Brief Title:  
A Phase 2b Dose-Range Finding Clinical Trial in HIV-1 Infected Treatment-Naive 
Adults 
Rationale: 
Infection with HIV-1 continues to be a serious health threat throughout the world, with 
more than 40 million individuals infected worldwide. The current standard of care 
treatment for HIV-1 is combination anti-retroviral therapy (cART) with 
recommendations to start regardless of CD4 T-cell count, committing people living with 
HIV to lifelong, life-saving therapy. However, the chronic exposure to cART has 
identified anti-retroviral (ARV)-associated long-term toxicities (e.g. central nervous 
system (CNS) or cardiovascular (CV)/metabolic effects, renal disease, etc.), creating a 
need to address and prevent these co-morbidities. Also, treatment failure remains a 
continuing concern in clinical care due to the presence and emergence of resistant strains 
and tolerability issues.  The aging HIV-1-infected population drives a need for drugs with 
fewer drug-drug interactions. In this environment, medicines with novel mechanisms of 
action (MoA) that can be used as part of a preferred cART regimen have an important 
role to play. However, to be successful, a new ARV agent must be safe and effective, 
provide a relatively high barrier to resistance, have low toxicity, have minimal drug-drug 
interactions, and preferably be a relatively low-dose, once-a-day drug that can be 
combined with other agents as part of a fixed-dose regimen. GSK3640254, a next 
generation HIV-1 maturation inhibitor (MI), has the potential to meet such valued 
features for a new ARV medicine. 
GSK3640254 is a next-generation HIV-1 MI that binds near a key structural element 
within the group-specific antigen (Gag) polyprotein that is required for virion maturation 
and assembly. MIs block the last protease cleavage event between Gag protein segments 
designated as 24-kilodalton (kDa) HIV capsid (CA) protein p24 (CA [p24]) and spacer 
peptide 1 (SP1). Blockage at this step results in the release of immature non-infectious 
virus particles. Other small molecules within this class have demonstrated a 
Pharmacokinetic (PK)/Pharmacodynamic (PD) relationship and longer-term efficacy 
through Phase 2a-2b trials.  
At the time of this protocol submission, GSK3640254 has completed a short-term, 
monotherapy, proof of concept (POC) Phase 2a study. Additionally, the safety, 
tolerability, and PK have been evaluated in eight other completed Phase 1 studies in 


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healthy volunteers. The totality of the clinical data shows: 1) GSK3640254 is generally 
well-tolerated in short-term studies and 2) GSK3640254 has a short-term PK/PD (decline 
in HIV-1 RNA) relationship.  
The Sponsor proposes conducting this Phase 2b dose-range finding study, the primary 
objective of which is to evaluate the efficacy in a Randomized Phase of GSK3640254 
relative to dolutegravir (DTG), each given in combination with abacavir/lamivudine 
(ABC/3TC) or emtricitabine/tenofovir alafenamide (FTC/TAF) for the selection of an 
optimal dose, by analysing the proportion of Virologic Responders (HIV-1 RNA <50 
copies/mL at Week 24). Secondary objectives are to evaluate: 1) longer term efficacy, 2) 
key safety/tolerability, 3) cumulative PK, and 4) cumulative resistance. These secondary 
objectives will also be evaluated in a Non-Randomized Phase when the NRTI backbone 
is switched to DTG (in the experimental arms only) after the last subject completes their 
Week 48 visit. The totality of this data would inform the basis of subsequent clinical 
trials in HIV-1 infected patients. 
Objectives and Endpoints: 
Objective 
Endpoint 
Primary 
• To evaluate antiviral efficacy of 
GSK3640254 relative to DTG, each given 
in combination with 2 NRTIs, enabling the 
selection of an optimal dose for 
GSK3640254 
• Proportion of participants with plasma HIV-1 
RNA <50 copies/mL at Week 24 using the 
FDA snapshot algorithm 
Secondary Efficacy, Safety and PK 
• To evaluate antiviral efficacy in the 
Randomised Phase of GSK3640254 
relative to DTG, each given in 
combination with 2 NRTIs at Week 48 
• To evaluate antiviral efficacy in the Non-
Randomised Phase of GSK3640254 
optimal dose given in combination with 
DTG relative to the reference arm (DTG 
given in combination with 2 NRTIs) at 
Week 96 
• Proportion of participants with plasma HIV-1 
RNA <50 copies/mL at Weeks 48 and 96 
using the FDA snapshot algorithm 
• Absolute values and changes from baseline 
in HIV-1 RNA through Weeks 24, 48, and 
96 
• Absolute values and changes from baseline 
in CD4+ cell counts through Weeks 24, 48, 
and 96 
• To evaluate safety and tolerability in the 
Randomised Phase of GSK3640254 
relative to DTG, each given in 
combination with 2 NRTIs at Weeks 24 
and 48 
• To evaluate safety and tolerability in the 
Non-Randomised Phase of GSK3640254 
optimal dose given in combination with 
DTG relative to the reference arm (DTG 
• Frequency of SAEs, Deaths and AEs 
leading to Discontinuation through Weeks 
24, 48, and 96 
• Incidence and severity of AEs through 
Weeks 24, 48 and 96 
• AEs in GI, Psych/CNS through Weeks 24, 
48, and 96 


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Objective 
Endpoint 
given in combination with 2 NRTIs) at 
Week 96 
• To assess the development of viral 
resistance in the Randomised Phase to 
GSK3640254 and 2 NRTI backbone in 
participants experiencing virologic failure 
at Weeks 24 and 48. 
• To assess the development of viral 
resistance in the Non-Randomised Phase 
to GSK3640254 and DTG in participants 
experiencing virologic failure at Week 96. 
• Changes in genotypic and/or phenotypic 
profiles of virus compared to baseline 
through Weeks 24, 48, and 96 
• To characterize the pharmacokinetics of 
GSK3640254 when given in combination 
with ABC/3TC or FTC/TAF 
• The steady-state plasma PK parameters of 
GSK3640254 will be assessed based on 
Intensive and/or Sparse PK sampling 
through Weeks 24 and 48. 
 
Overall Design: 
Study 208379 is a Phase 2b, randomized, partially blind (to GSK3640254 dose), active 
controlled clinical trial to investigate the safety, efficacy and dose-response of 
GSK3640254 compared to DTG, each given in combination with 2 NRTIs, in 
approximately 150 treatment-naïve HIV-1 infected adults.  
The Sponsor will be blind to the dose of GSK3640254 treatment (being evaluated for the 
treatment of HIV-1) allocation until the database lock for the Week 24 analysis. The 
primary analysis will evaluate all available data as outlined in the endpoints for primary 
and secondary objectives. The primary analysis will result in the selection of an optimal 
dose of GSK3640254. After an optimal dose is selected by the Sponsor, a communication 
will be sent to Health Authorities/Ethics Committees, where required or requested, for 
their information. Investigators and participants will be unblinded to participant’s initial 
dose as well as to the optimal dose of GSK3640254 after the last participant completes 
their Week 48 visit. The Randomised Phase will be complete after the last participant 
completes their Week 48 visit. In the Non-Randomised Phase, participants in the 
GSK3640254 Arms with their most recent HIV-1 RNA <50 c/mL will change from their 
blinded GSK3640254 dose to the open label, optimal dose of GSK3640254 and, at the 
same time, they will switch from their open label, dual NRTI backbone to open label 
DTG. Participants in the GSK3640254 Arms with their most recent HIV-1 RNA = 50-
199 c/mL may be able to make this change as well, but only after site’s consultation with 
the ViiV medical monitor, else they will be discontinued from the study. This change 
from dual NRTI to DTG will provide additional clinical and scientific data on the 
maintenance of virologic suppression, safety/tolerability, and treatment emergent 
resistance if, in subsequent clinical trials, GSK3640254 is only administered with DTG. 


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All medications in the reference arm will be open label throughout both phases. 
Participants in the reference arm will end their participation in the treatment phase as 
each individual participant reaches their Week 144 visit. 
The most clinically relevant inclusion/exclusion criteria are as follows: Participants must 
have an HIV-1 RNA ≥1000 c/mL and a CD4 T-cell count ≥250 cells/mm3. Participants 
must not have received any ARVs, in combination or monotherapy, after the diagnosis of 
HIV-1. Participants will be excluded if they are co-infected with Hepatitis B or C, have 
significant psychiatric condition, have a significant gastrointestinal (GI) condition 
(including inability to eradicate Helicobacter pylori) or have a cardiac condition which 
places them at greater risk for QT prolongation.  
Brief Summary: 
Approximately 150 treatment-naïve, HIV-1 infected adult will be randomized into this 
Phase 2b dose-range finding study, the primary objective of which is to evaluate the 
efficacy of GSK3640254 relative to DTG, each given in combination with 2 NRTIs, by 
analysing the proportion of virologic responders: participants with HIV-1 RNA <50 c/mL 
at Week 24. Participation will be for at least 24 weeks, then up to 96 weeks or more.  
Participants will be followed at visits every 4 weeks during the first year, then at 
increasing intervals in the years following. Access to the study treatments will be 
maintained in this study, or in a rollover study, until GSK3640254 is locally approved 
and commercially available; participants in the reference arm, however, will end their 
participation in the treatment phase as each individual participant reaches their Week 144 
visit. 
Number of Participants: 
Approximately 300 participants will be screened to achieve approximately 150 randomly 
assigned to one of 4 arms of the study interventions, approximately 40 per GSK3640254 
arm, and approximately 30 in the DTG Reference Arm.  
The enrollment period may be extended if the additional effort is needed to help ensure a 
sufficient number participate in the optional Stomach Substudy.  
Intervention Groups and Duration: 
Participants will enter the Screening period for a maximum of 42 days, and if they 
qualify, will be randomly assigned to receive either GSK3640254 or DTG, plus an 
investigator-selected choice among 2 dual-NRTI background therapies (ratio of 
approximately 1:1:1:1) for a period of at least 48 weeks in the Randomised Phase: 
• Arm 1: Blinded GSK3640254 100 mg + Open Label ABC/3TC or FTC/TAF 
• Arm 2: Blinded GSK3640254 150 mg + Open Label ABC/3TC or FTC/TAF 
• Arm 3: Blinded GSK3640254 200 mg + Open Label ABC/3TC or FTC/TAF 
• Arm 4: Open Label DTG + Open Label ABC/3TC or FTC/TAF   


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Participants will be stratified by Screening plasma HIV-1 RNA, by <100,000 c/mL or 
≥100,000 c/mL, and the investigator’s choice of dual NRTI background therapy (either 
ABC/3TC or FTC/TAF).  
Participants in any arm who are Virologic Responders may continue in the study beyond 
Week 24. 
In the experimental arms, GSK3640254 will be administered in 3 blinded doses until the 
last participant completes their Week 48 study visit (Week 48 Secondary Endpoint study 
milestone). Thereafter, participants whose most recent HIV-1 RNA <50 c/mL in the 
GSK3640254 arms will move into the Non-Randomised Phase and will be switched from 
their blinded dose to the open label optimal dose. Simultaneously, these participants will 
also be switched from their dual NRTI therapy to DTG. Participants in the GSK3640254 
Arms with their most recent HIV-1 RNA = 50-199 c/mL may be able to make this change 
as well, but only after site’s consultation with the ViiV medical monitor, else they will be 
discontinued from the study. 
Thereafter, the trial will be fully open label with just 2 arms: 
• Arms 1, 2 & 3 will switch to the Open Label GSK3640254 Optimal Dose + Open 
Label DTG  
• Participants on the Open Label DTG + ABC/3TC or FTC/TAF arm will continue 
unchanged into the Non-Randomised Phase 
Participants who continue to derive benefit from the treatments will remain on study 
beyond Week 96, in this study or in a rollover study, until GSK3640254 is commercially 
available (projected to be in the year 2027) or they are transitioned onto a local access 
program; participants in the reference arm, however, will end their participation in the 
treatment phase as each individual participant reaches their Week 144 visit.  
Independent Data Monitoring Committee:  
The study will include an Independent Data Monitoring Committee.  
The IDMC will review the totality of clinical data (exclusive of the Stomach Substudy) 
with at least one analysis before the Week 24 Primary Analysis and will be responsible 
for recommending to the Chief Medical Officer (CMO) and the ViiV Safety and 
Labelling Committee (VSLC): 1) discontinuation of any treatment arm, 2) 
discontinuation of the study, or 3) continuation of the study as planned. Moreover, a 
separate IDMC recommendation from a parallel Phase 2b Study 212483 (same doses of 
GSK3640254 + DTG in HIV-1 infected treatment naïve adults) may impact the CMO 
and VH Governance decision-making on any arm(s) within this trial. 


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1.2. 
Schema 


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1.3. 
Schedule of Activities (SoA) 
Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
Clinical Assessments 
 
Informed Consent 
X 
NV 
NV 
NV 
NV 
NV 
NV 
NV 
NV 
NV 
NV 
 
NV 
NV = if a New 
Version is 
available 
Inclusion/Exclusion criteria  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Review during 
Screening; 
Confirm prior to 
Day 1 dose. 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, Weight, and BMI 
X 
W 
W 
W 
W 
W 
W 
W 
W 
W 
W 
 
W 
W = weight only 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Section 8.2.2 


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
Physical Exam 
 
F 
 
 
 
T 
 
 
T 
T at Week 
48, 96  
T at Week 
120 then 
every 6 
months 
 
T 
F = Full 
Physical  
T = Targeted 
Physical  
See Section 
8.2.1 
Medical History3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Current Medical Conditions 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior ARV Check 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Ensure naïve 
status 
CDC HIV-1 Classification 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Section 10.10 
HIV-associated conditions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
Adverse event (AE)/SAE 
assessments 
SAE Only 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.3 
Concomitant medications 
review4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Section 6.8 
Adherence Review5 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
C-SSRS – Baseline/Lifetime 
X 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 
8.2.6 
C-SSRS – Since Last Visit 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X6 
 
See Section 
8.2.6 
Clinical Procedures 
 
ECG: single reading 
X 
 
 
 
 
 
 
 
 
 
at EW only 
 
 


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
ECG: single reading PRE-dose 
 
 
X 
 
 
 
 
 
 
 
 
 
 
See Section 
8.2.3 
 
Post-dose 
ECGs are to be 
done ±15 
minutes of the 
time point 
ECG: triplicate readings PRE-
dose 
 
X 
 
 
 
 
 
 
 
 
 
 
 
ECG: single readings POST-
dose at 2, 4 and 6 hours 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
ECG: single reading POST-
dose any time between 2-6 hrs  
 
 
 
 
 
X 
 
 
X 
Weeks 36 
and 48, 72, 
96 
X    
(not at EW)   
 
 


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Optional Stomach Substudy7 
Esophagogastroduodenoscopy 
(EGD) with biopsy 
 
X7 
 
 
 
 
 
 
X 
Week 968 
 
 
 
See Section 
4.1.5 and 
Section 8.6.1;   
Separate 
Stomach 
Substudy ICF 
The “Day 1” 
EGD with 
biopsy 
procedure, in 
most cases, 
needs to be 
done prior to 
Day 1 within the 
Screening 
period. 
The Day 1 
Substudy 
biomarkers are 
to be drawn at 
the Day 1 visit. 
Clinical Assessments 
 
Urine Drugs of Abuse panel 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Also, for any 
Grade 3-4 
Psychiatric AE. 
See Section 
8.2.6 
HLA-B*5701 allele 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
PT/INR 
X 
 
 
 
 
 
 
 
 
 
 
 
 
For Child-Pugh 
per Section 
10.7 
Rapid Plasma Reagin (RPR) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Local lab breath or stool test 
for Helicobacter pylori4  
X 
 
 
 
 
 
 
 
 
 
EW or Final 
visit only 
 
 
See Section 
4.1.1 
To be done at 
the site’s local 
lab  
Pregnancy test9 
S 
U, 
S 
 
S 
S 
S 
S 
S 
S 
S 
S 
U  
done at home 
X 
POCBP Only 
S = Serum 
U = Urine 
Hematology/Chemistry 
X 
  X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
Fasting Lipids10 
X 
X 
 
 
 
X 
 
 
X 
Week 48, 
72, and 96 
Week 120, 
then every 
6 months  
+ Final/EW 
 
 
6hr minimum 
fast.  
Urinalysis 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Hepatitis B and C serology 
X 
 
 
 
 
 
 
 
 
Week 48 
and 96 
Week 144, 
192, etc. 
 
 
 
HIV-1 RNA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Lymphocyte T-cell subsets 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
CD4 and CD8 
Plasma for Storage 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
Plasma for Geno/Phenotypic 
Resistance Assays11 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
PK – Sparse; GSK arms only 
 
 
 
X 
X 
X 
 
 
X 
Week 36 
and 48 
 
 
 
See Section 8.4 
Separate lab kit 
for Sparse PK 
contains a PRE-
DOSE tube. 
PK – Intensive; subset of 
participants in the GSK arms 
only 
Optional12 
 
 
X 
 
 
 
 
 
 
 
 
 
 
See Section 
4.1.2.1.1 
See Section 8.4 
Separate lab kit 
for Intensive PK 
contains a PRE-
DOSE tube. 


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
Optional PGX sample13 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Separate PGX 
ICF 
Renal, Bone and Inflammatory 
biomarker analytes 
(blood/urine) and HbA1c, 
insulin and glucose14 
 
X 
 
 
 
 
 
 
X 
Week 48 
and 96 
Week 144 
 
 
 
Optional Stomach 
Substudy7,10 Fasting Serum 
Biomarkers 
 
X 
 
 
 
 
 
 
X 
Week 48 
and 968 
 
 
 
See Section 
8.6.1;  
12hr minimum 
fast  
Separate 
Stomach 
Substudy ICF;  
Separate lab kit  


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Activities1 
Screening  
 
 
IN-CLINIC VISITS2 
VIRTUAL 
VISIT2 
IN-
CLINIC 
Follow-
up Visit 
 
 
Notes 
 
42 days 
 
 (or up to 
63 days in 
certain 
situations) 
Day 
1 
Wk  
2 
 
Day 
11-
14 
 
 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Weeks 28, 
32, 36, 40,    
44,  48,  52, 
56, 64, 72, 
80, 88, and 
96 
Week 108 
then every 
12 weeks 
and         
Final Visit / 
Early 
Withdrawal 
(EW) 
Week 60, 68, 
76, 84, 92, 
100 then 
every 4 
weeks 
between in-
clinic visits 
(Wk 104, 112, 
116, etc.) 
2-4 weeks 
after the 
last dose  
 
Study Treatment 
 
RAMOS Enrol  
X 
 
 
 
 
 
 
 
 
  
 
 
 
 
RAMOS Randomization/Study 
Treatment Assignment and 
Dispensation 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
RAMOS Study Treatment 
Dispensation 
 
 
 
X 
X 
X 
X 
X 
X 
X15 
X           
(not at EW) 
 
 
 
RAMOS Final Disposition 
SF 
 
 
 
 
 
 
 
 
 
W at EW 
 
C 
S: Screen Fail   
W: Withdrawn   
C: Complete 
Study Treatment Accountability 
(pill counts) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
1. 
Order of Assessments (pre-dose): CSSRS –  ECG – Vital Signs – Blood Draws (see notes in Section 8.4 regarding order for blood draw and ECG during the Week 2 visit) 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
 
2 0 8 3 7 9  
 
2 9  
 
2.  
T h e acc e pt a bl e wi n d o w ar o u n d a ny visit, W e ek 4 a n d b ey o n d  (i ncl u di n g t h e Virt u al Visits), is ± 2  d ays.  Partici p a nt m ust c o m e i n n o l at er t h a n  + 2 d ays of t h e visit wi n d o w s or 
p artici p a nt will r u n o ut of  dr u g s u p ply.  
3.  
M e dic al Hist ory i ncl u d es s u bst a nc e us a g e  a n d t h e M e dic al C o n diti o ns list e d i n Excl usi o n Crit eri a i n Secti o n 5. 2  , as w ell as ass ess m e nts of c ar di ov asc ul ar, m et a b olic ( e. g., 
Ty p e I or II di a b et es m ellit us), a n d, i n p artic ul ar, b ut n ot li mit e d t o, c ar di ac, psyc hi atric, r e n al ( e. g., n e p hr olit hi asis, n e p hr o p at hy, r e n al f ail ur e), a n d b o n e dis or d ers .  
4.  
T h e C o nc o mit a nt M e dic ati o n r evi e w at Scr e e ni n g i ncl u d es n ot o nly t h os e list e d i n Secti o n 6. 8  t o b e c o nsi d er e d r el ativ e t o d osi n g r e q uir e m e nts, b ut als o a c h eck f or pr o hi bit e d 
m e dic ati o ns ( Se e S ecti o n 6. 8. 1 ) t h at m ay n e e d t o b e st o p p e d i n or d er t o m e et t h e r e q uir e m e nts of t h e l oc al t est f or H. pyl ori . 
5.  
A d h er e nc e r evi e w i ncl u d es pill c o u nt, r evi e w  of a ny r ec or d e d miss e d d os es, a n d a c o nv ers ati o n a b o ut ot h er p ossi bl e miss e d d os es if t h e pill c o u nt d o es n ot m atc h t h os e 
r ec or d e d a n d/ or v er b ally r e p ort e d. 
6.  
O n D ay 1, p artici p a nts will  pr ovi d e r es p o ns e t o t h e C S S R S Bas eli n e f or m pri or t o  t h e R A M O S t ask of R a n d o miz ati o n .  T h e C S S R S will b e i n el ectr o nic f or m at, r es p o ns es 
pr ovi d e d by p artici p a nts eit h er by p h o n e or c o m p ut er, w h et h er t h ey ar e i n cli nic or if t h ey ar e r e m ot e (virt u al visits).  
7.  
Lik ely t o b e d o n e at s el ect c o u ntri es/s el ect sit es. Partici p ati o n i n t h e O pti o n al St o m ac h  su bst u dy i ncl u d es  b ot h  t h e E G D pr oc e d ur e wit h bi o psy  a n d t h e S er u m Bi o m ark er bl o o d 
dr a ws . F or E G D  pr oc e d ur e sc h e d uli n g iss u es, t h e Scr e e ni n g p eri o d c a n b e ext e n d e d  ( Se e S ecti o n 5. 5 ). P ot e nti al p artici p a nts m ust u n d er g o pr e -pr oc e d ur al ev al u ati o n a n d 
c o ns e nt wit h t h e GI f acility  at e ac h ti m e p oi nt . T h e D ay 1 E G D pr oc e d ur e c a n n ot b e d o n e o n t h e s a m e d ay as t h e D ay 1 cli nic visit, s o it s h o ul d b e d o n e d uri n g t h e Scr e e ni n g 
p h as e o nly w h e n all l a b ass ess m e nts a n d pr oc e d ur es i n dic at e t h at t h e p artici p a nts q u alifi es f or t h e st u dy.  S e e m or e d et ails i n Secti o n 4. 1. 5 . It is r e as o n a bly ex p ect e d t h at t h e 
pr oc e d ur e s h o ul d b e p erf or m e d ± 2 w e eks ar o u n d t h e W e ek 2 4 a n d W e ek 9 6 visit mil est o n es . T h e fr e q u e ncy of a d diti o n al S er u m a n d E G D m o nit ori n g ( e. g. W e ek 4 8, W e ek 
1 4 4, etc.) will b e b as e d u p o n e m er gi n g cli nic al a n d sci e ntific d at a s ol ely fr o m t his tri al.    
8.  
Ev al u ati o ns b ey o n d W e ek 9 6 m ay b e p erf or m e d b as e d u p o n e m er gi n g cli nic al / sci e ntific d a t a 
9.  
At Scr e e ni n g, a n d f or P O C B P o nly, sit es will s u b mit s er u m f or F S H  a n d Estr a di ol , a n d f or Pr e g n a ncy  t esti n g. (F O R C A N A D A O N L Y:  If t h e D ay 1 visit d o es n ot occ ur wit hi n 3 0 
d ays of t h e Scr e e ni n g Visit, a s ec o n d s er u m pr e g n a ncy t est [d o n e a p pr oxi m at ely D ay  -7 t o D ay -5 ] s h o ul d b e p erf or m e d s o t h at r es ults ar e k n o w n pri or t o t h e pl a n n e d D ay 1. )  
O n D ay 1, i n a d diti o n t o t h e s er u m s a m pl e s e nt t o t h e c e ntr al l a b, a uri n e pr e g n a ncy t est will b e d o n e i n t h e cli nic t o c o nfir m n e g ativ e st at us pri or t o I P a d mi nistrati o n. If t h e uri n e 
t est r es ult is a m bi g u o us, t h e sit e s h o ul d a w ait t h e r es ults of t h e D ay 1 s er u m t est b ef or e st u dy tr e at m e nt c a n b e i niti at e d. O n Tr e at m e nt, a bl o o d s a m pl e wil l b e c oll ect e d at e ac h 
visit f or s er u m pr e g n a ncy t esti n g.   Uri n e pr e g n a ncy t ests will b e d o n e at ev ery 4 w e eks at h o m e f or t h e virt u al visits (r es ults n e e d t o b e r e p ort e d t o t h e sit e). A ny a m bi g u o us 
uri n e r es ult will n e e d t o b e r et est e d i n s er u m.  Sit e will pr ovi d e t ests kits t o P O C B P t o b e us e d i n t h e i nt erv al ( e.g., at W e ek 5 6, pr ovi d e 1 t est kit t o b e d o n e at h o m e at W e ek 6 0 
Virt u al Visit; at W e ek 1 0 8, pr ovi d e 2 t est kits t o b e d o n e at h o m e at W e ek 1 1 2 a n d W e ek 1 1 6 Virt u al Visits ).  
1 0.  A n ov er ni g ht f ast is pr ef err e d  pri or t o visits t h at i ncl u d e li pi d a n d r e n al/ b o n e/ i nfl a m m ati o n bi o m ark er ass ess m e nts, b ut a mi ni m u m of 6 h o urs is acc e pt a bl e. R e g ar dl ess of li pi d 
c oll ecti o n, p artici p a nts t aki n g p art i n t h e St o m ac h Su bst u dy s h o ul d f ast f or a mi ni m u m of 1 2 h o urs pri or t o t h e c oll ecti o ns a t D ay 1, W e ek 2 4, W e ek 4 8 a n d W e ek 9 6.    
1 1.  U n us e d pl as m a s a m pl es c oll ect e d f or t h e p ot e nti al n e e d of r esist a nc e t esti n g will e nt er l o n g -t er m st or a g e a n d ar e t h e n i ncl u d e d i n t h e p o ol of s a m pl es t h at c a n b e us e d f or 
f urt h er r es e arc h, if p artici p a nt h as c o ns e nt e d. 
1 2.  If t h er e ar e C O VI D-1 9 i m p acts  t h at r estrict t h e a bility f or a p artici p a nt t o c o m e t o t h e cli nic f or t h e d ay-l o n g visit at W e ek 2, t h e n, at t h e l e ast, all s u bj ects s h o ul d att e n d t h e cli nic 
visit f or t h e c oll ecti o n of HI V-1 R N A a n d as m a ny of t h e E C Gs as p ossi bl e, a n d  t h e I nt e nsiv e P K p orti o n of t h e visit f or t h os e i n t h e G S K 3 6 4 0 2 5 4 ar ms w h o o pt e d t o t ak e p art 
c a n b e d o n e at W e ek 1 6.  
1 3.  T h e e arli est visit at w hic h t h e P G X s a m pl e s h o ul d b e c oll ect e d is at W e ek 8, or, if miss e d at W e ek 8, at a visit t h er e aft er.  
1 4.  Bl o o d s a m pl e f or H b A 1c, i ns uli n, gl uc os e, r e n al, b o n e a n d i nfl a m m ati o n bi o m ark er ass ess m e nts: R e n al: Cyst ati n C, B et a -2 -Micr o gl o b uli n ( uri n e), R eti n ol Bi n di n g Pr ot ei n ( R B P; 
uri n e), uri n e B 2 M/cr e ati ni n e r ati o, uri n e R P B/cr e ati ni n e r ati o, uri n e al b u mi n/cr e ati ni n e r ati o, uri n e pr ot e i n/cr e ati ni n e r ati o, uri n e p h os p h at e, s er u m cr e ati ni n e; B o n e:  b o n e 
s p ecific alk ali n e p h os p h at as e, pr oc oll a g e n ty p e 1 -N -pr o p e pti d e, ty p e 1 c oll a g e n cr oss -li nk e d C-t el o p e pti d e, ost e oc alci n a n d 2 5 Hy dr oxy -Vit a mi n D ; I nfl a m m ati o n: I nterl e uki n-6 
(I L-6), Hi g h -s ensitivity C r e activ e pr ot ei n ( hs -C R P), D -di m er, S ol u bl e C D 1 4 (s C D 1 4), Sol u bl e C D 1 6 3 (s C D 1 6 3); i ns uli n a n d gl uc os e f or
c alc ul ati o n. 
C CI


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15. During the Randomized (blinded) Phase, the RAMOS NG system is programmed to dispense only a one-month supply of blinded GSK3640254 (set of 3 bottles). Therefore, 
starting at Week 56 (when the 8-week visit intervals begin), participants will need to come to the clinic monthly between clinic visits purely for a dispensation of blinded 
GSK3640254.  For example, at Week 56, participant will receive a one-month supply, then they will need to come to the clinic near the Week 60 time point for dispensation; 
they will receive another one-month supply at their Week 64 clinic visit, then they will need to come to the clinic near the Week 68 time point for a dispensation, etc.  


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2. 
INTRODUCTION 
Infection with HIV-1 continues to be a serious health threat throughout the world, with 
more than 40 million individuals infected worldwide. The current standard of care (SOC) 
treatment for HIV-1 is combination anti-retroviral therapy (cART) with 
recommendations to start regardless of CD4 cell count, committing people living with 
HIV to lifelong, life-saving therapy [European AIDS Clinical Society Guidelines, 
October 2020]. However, the chronic exposure to cART has identified anti-retroviral 
(ARV)-associated long-term toxicities (e.g. central nervous system (CNS) or 
cardiovascular (CV)/metabolic effects, renal disease, etc.), creating a need to address and 
prevent these co-morbidities. Also, treatment failure remains a continuing concern in 
clinical care due to the presence and emergence of resistant strains and tolerability issues.  
The aging HIV-1-infected population drives a need for drugs with fewer drug-drug 
interactions. In this environment, medicines with novel mechanisms of action (MoA) that 
can be used as part of a preferred cART regimen have an important role to play. 
However, to be successful, a new ARV agent must be safe and effective, provide a 
relatively high barrier to resistance, have low toxicity, have minimal drug-drug 
interactions, and preferably be a relatively low-dose once-a-day drug that can be 
combined with other agents as part of a fixed-dose regimen. GSK3640254, a next 
generation HIV-1 maturation inhibitor (MI), has the potential to meet such valued 
features for a new ARV medicine. 
GSK3640254 is a next-generation HIV-1 MI which binds near a key structural element 
within the group-specific antigen (Gag) polyprotein that is required for virion maturation 
and assembly. MIs block the last protease cleavage event between Gag protein segments 
designated as 24-kilodalton (kDa) HIV capsid (CA) protein p24 (CA [p24]) and spacer 
peptide 1 (SP1). Blockage at this step results in the release of immature non-infectious 
virus particles. Other small molecules within this class have demonstrated a 
Pharmacokinetic (PK)/Pharmacodynamic (PD) relationship and longer-term efficacy 
through Phase 2a-2b trials.  
As of February 2021, GSK3640254 has completed a Phase 2a study (short-term, 
monotherapy, proof of concept [POC]). Additionally, the safety, tolerability, and PK have 
been evaluated in eight other completed Phase 1 studies in healthy volunteers. The 
totality of the clinical data shows: 1) GSK3640254 is generally well-tolerated in short-
term studies, and 2) GSK3640254 has a short-term PK/PD (decline in HIV-1 RNA) 
relationship. Summaries of the pre-clinical and clinical studies are included in the 
Clinical Investigator's Brochure (CIB) [GlaxoSmithKline Document Number 
2018N379610_02].   
2.1. 
Study Rationale 
The Sponsor proposes conducting the Phase 2b dose-range finding study, the primary 
objective of which is to evaluate the efficacy of GSK3640254 relative to dolutegravir 
(DTG), each given in combination with either abacavir/lamivudine (ABC/3TC) or 
emtricitabine/tenofovir alafenamide (FTC/TAF), by analysing the proportion of Virologic 
Responders: participants with HIV-1 RNA <50 c/mL at Week 24.  Secondary objectives 
are to evaluate: 1) longer-term efficacy, 2) key safety/tolerability, 3) cumulative PK, and 


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4) cumulative drug resistance.  These secondary objectives would also be evaluated when 
the NRTI backbone is switched to DTG (in the experimental arms only) after the last 
subject completes their Week 48 visit. The totality of this data would inform the basis of 
subsequent clinical trials in HIV-1 infected patients.  
2.2. 
Background  
2.2.1. 
Key Safety Data with a Prior Maturation Inhibitor (GSK3532795) 
Previously, ViiV Healthcare (VH) studied a structurally similar MI, GSK3532795, in the 
Phase 2b study 205891. The Week 24 primary endpoint analysis showed GSK3532795 
was not optimal for Phase 3 development due to gastrointestinal (GI) intolerability and 
treatment-emergent resistance. Specifically, a relatively higher rate of GI intolerability 
(predominately Grade 1-2 diarrhea in 38-61% of participants and abdominal pain in 8-
22% of participants) and higher rate of nucleoside reverse transcriptase inhibitor (NRTI) 
resistance (6.5%) with clinically significant changes in GSK3532795 susceptibility was 
observed across all three GSK3532795 treatment arms [Morales-Ramirez, 2018]. Given 
these clinical and tolerability issues, the Sponsor terminated study 205891 and did not 
advance GSK3532795 into Phase 3 studies. 
Aside from mild to moderate GI intolerability, 2 serious adverse events (SAEs) occurred 
in the Phase I Thorough QT study AI468044/206220 [BMS Document Control 
Number 930109388] at supra-therapeutic doses: 1 healthy participant had an episode of 
acute psychosis and another had suicidal ideation/homicidal ideation as diagnosed 
through an interview by a psychiatrist. The 2 participants received GSK3532795 240 mg 
twice daily and 240 mg once daily (QD) with food, respectively. These events were 
assessed as related to study drug but were not observed in any other clinical study with 
GSK3532795. The most frequent neuropsychiatric adverse events (AEs) in studies with 
GSK3532795 were headache, dizziness, and sleep abnormalities (e.g., insomnia, 
abnormal dreams). 
Importantly, neither of these GI or psychiatric safety findings have been reproduced in 
the completed or ongoing clinical trials of GSK3640254 in healthy volunteers or HIV-1 
infected treatment-naïve participants. 
2.2.2. 
Preclinical Summary with GSK3640254 
Nonclinical pharmacology and virology 
Activity toward a panel of clinical isolates was similar among subtypes, with median 
50% inhibitory effect (EC50) values of 2.0 and 3.0 nM, for subtypes B and C, 
respectively, and 3 nM for subtypes A and CRF01_AE. GSK3640254 was active against 
1 of 3 human immunodeficiency virus type-2 (HIV-2) isolates (EC50 = 2.5 nM). Based 
upon in vitro potency, GSK3640254 is projected to demonstrate efficacy toward the 
majority of subtype B, C and CRF01_AE isolates at a trough concentration (Ctrough) value 
of 150 nM. Data suggest that GSK3640254 may be used in combination therapies with 
agents from any of the nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside 
reverse transcriptase inhibitors (NNRTI), integrase strand transfer inhibitor (INSTI) and 
protease inhibitor (PI) antiretroviral (ARV) classes.  


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Mechanism studies indicate that GSK3640254 blocks production of infectious virus by 
specifically inhibiting HIV-1 protease-mediated cleavage at the CA (p24)/SP1 junction. 
GSK3640254 specifically binds to purified HIV-1 VLPs (Ki 0.7 nM) and dissociates 
slowly, with a half-life of 6 h. These mechanistic studies confirm that GSK3640254 
inhibits via a novel mechanism of action (MoA) that is distinct from current ARVs.  The 
A364V amino acid substitution was the most common change selected by GSK3640254 
in cell culture resistance selection experiments, appearing in several different group-
specific antigen (Gag) polymorphic backgrounds. 
Pharmacokinetics and product metabolism in animals 
Following intravenous (IV) administration, GSK3640254 exhibited low systemic 
clearance, high volume distribution, and elimination half-lives of 5.06, 4.0, 18.7 and 5.3 h 
in mouse, rats, dogs and monkeys, respectively. GSK3640254 was eliminated mainly by 
direct glucuronidation followed by biliary excretion in bile-duct-cannulated (BDC) rats. 
Following repeat oral administration in the rat and dog, increases in systemic exposure to 
GSK3640254 was generally sub-proportional with dose. There was no or minimal 
accumulation of GSK3640254 after repeat dosing, and no consistent indication of a 
difference in exposure between genders.  
Metabolic pathways observed in vitro included mono-oxidation, N-dealkylation and 
direct glucuronidation, with no unique metabolites generated in human liver microsomes 
or hepatocytes. In rat and dog plasma, GSK3640254 was either the only or the 
predominant drug-related component with minor oxidative metabolites.  
Based on the predicted systemic exposures in human, there is a potential risk for 
GSK3640254 to act as a perpetrator of drug-drug interactions of substrates of OATP1B3 
and MRP2. GSK3640254 was an inhibitor of UGT1A1 and clinical drug-drug 
interactions via this mechanism could be possible. 
Toxicology 
The primary target organ of toxicity in non-clinical studies with GSK3640254 was the 
stomach, with microscopic changes affecting parietal and chief cells in both rats and 
dogs.  Due to microscopic changes in the stomach of rats at the lowest dose tested after 
26 weeks, a no observed adverse effect level (NOAEL) in rats was unable to be 
determined.  Microscopic findings in the stomach of rats were minimal to mild at the 
lowest observed adverse effect level (LOAEL) of 10 mg/kg/day (AUC = 18.9 ug.hr/mL), 
corresponding to 0.63-fold the measured highest mean human exposure in the planned 
Phase 2b clinical trial.  Following 39-weeks of dosing in dogs, the NOAEL for 
microscopic changes in the stomach was 0.2 mg/kg/day, and exposures were 0.28-fold 
the highest clinical exposure.  Microscopic stomach changes were associated with 
increases in serum gastrin when evaluated in the 26- and 39-week studies in rats and 
dogs, respectively. All microscopic findings in the stomach of rats and dogs and changes 
in serum gastrin were shown to be reversible following a 4-week recovery period.  
Microscopic findings in the stomach were minimal to mild at the LOAELs of 
10 mg/kg/day (AUC = 18.9 ug.hr/mL) and 1 mg/kg/day (AUC = 46.4 ug/hr/mL) in rats 
and dogs, respectively, corresponding to 0.63-fold and 1.6-fold highest clinical exposure 


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in the planned Phase 2b clinical trial.  Potential effects in the stomach of humans during 
clinical trials are being investigated in a gastric safety substudy. 
With correction for protein binding, compared to the IC50 for the hERG/IKr potassium 
channel, there is a 15.8-fold margin above the predicted average clinical maximum 
observed concentration (Cmax) exposure for the highest dose planned in the study. 
Exposure where a minimal increase in QT interval was seen in a single dog in the single-
dose safety pharmacology study in telemeterized dogs was 3.6-fold higher than the 
predicted Cmax at the highest planned dose in the Phase 2a study. In addition, there were 
no effects on electrocardiogram (ECG) parameters in dogs given up to 25 mg/kg/day for 
4 weeks at 19.3-fold above the predicted average Cmax at the highest dose in the proposed 
study. 
2.2.3. 
Key Clinical Data on GSK3640254 to date 
A summary of safety data from the completed clinical studies performed to date is 
succinctly described here for convenience.  
• No deaths or treatment-related SAEs have been reported during clinical studies with 
GSK3640254.  
• Treatment-related dermatologic AEs (including AEs leading to study discontinuation) 
included rash, drug eruption, pruritis, urticaria, and maculopapular rash (3 in total: 
two Grade 1 and one Grade 2 [in study 208132]). AEs of uticaria and maculopapular 
rash (2 Grade 1: one in study 207187 and one in study 213567) led to discontinuation.  
• Treatment emergent drug-related Grade 2-4 AEs included: 1) Headache (2 
participants both Grade 2; one participant in Studies 207187 and 208132, each), 2) 
Nausea (2 participants both Grade 2; one participant in Studies 208134 and 208132, 
each), and Abdominal Pain (1 participant with Grade 2 AE in Study 208132). 
• Clinically notable AEs of elevated transaminases occurred in Studies 207187 
(SAD/MAD, n = 1 healthy volunteer) and 208135 (DDI with oral contraceptive Portia 
[Ethinyl Estradiol and Levongestrel], n = 8 healthy volunteers with elevated 
transaminases, 5 of which were reported as AEs). Subsequent analysis in Study 
208135 showed no PK/PD relationship with either GSK3640254 or Portia and 
elevated transaminases. The elevated transaminases were likely due to the recent 
initiation of hormonal contraception in study participants. 
• Treatment-related AEs reported in more than 1 study included headache 
(Studies 207187, 208131, 208135 and 208132) diarrhea (Studies 208132, 207187, 
213567 and 208135), nausea (Studies 207187 and 208132) and maculo-papular rash 
(Studies 208132, 207187 and 213567) abdominal pain (Studies 207187 and 208132). 
• Across studies, low grade GI intolerability has been observed: the majority of AEs 
were mild. Both Studies 207187 (MAD) and 208312 (POC) are relevant to this study 
given dosing of 7-14 days; most AEs in 207187 were unrelated and most AEs in 
208132 were related. 
• Across studies, there were generally no clinically significant changes in vital sign 
measurements, ECG results, or safety laboratory parameters (other than the elevated 


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transaminases due to Portia, noted above). Specifically, no participant has 
demonstrated QT prolongation: absolute value >500 msec, or increase from baseline 
>60 msec. 
A comprehensive description of other clinical data of GSK3640254 can be found in 
Section 5 of the Investigator Brochure and the supporting Clinical Study Reports 
(available upon request). 
2.2.4. 
Key Phase 2a (Study 208132) Clinical Data on GSK3640254  
Study Design and Rationale for Amendment to Shorten Monotherapy in Part 2 
Study 208132 was a two-part, Phase 2a, global, multicenter, randomized, partially-blind 
(Sponsor unblinded), placebo-controlled, adaptive clinical trial to evaluate the antiviral 
effect, safety, tolerability and PK/ PD of GSK3640254 in ART-naïve HIV-1 infected 
adults. Part 1 evaluated placebo (n=2 participants) and two active doses (10 and 200 mg 
QD) of GSK3640254 in two dose arms (n=6 participants in each dose arm) – all given for 
10 days. Due to the mitigation of treatment emergent A364A/V and A364V genotypic 
changes seen in the 200 mg arm (described below), Part 2 evaluated placebo (n=2 
participants) and three active doses (40, 80, and 140 mg QD) of GSK3640254 in three 
dose arms (n=6 participants in each dose arm) – only given for 7 days.  
Primary Objective: Antiviral decline after 7 to 10 days of monotherapy 
Of the 34 randomized participants in Part 1 and 2 combined, the average age was 32 
years. Two females were randomized. The short-term antiviral response is shown in 
Table 1. 
 
Table 1 
Summary of Plasma HIV-1 RNA (log 10 c/mL) Change from Baseline 
and Maximum Decline from Baseline in 208132 
 
GSK3640254 
Placebo 
10 mg 
Part 1 
40 mg 
Part 2 
80 mg 
Part 2 
140 mg 
Part 2 
200 mg 
Part 1 
Part 1 
Part 2 
N = 6 
N = 6 
N = 6 
N = 6 
N = 6 
N = 2 
N = 2 
Baseline  
 
 
 
 
 
 
Mean 
4.187 
4.672 
4.433 
4.533 
4.820 
4.245 
4.750 
Median 
4.180 
4.690 
4.255 
4.455 
4.825 
4.245 
4.750 
Change from Baseline at Day 8, 9, or 10 (Part 1) or Day 8 (Part 2) 
 
Mean 
-0.137 
-1.178 
-1.015 
-1.450 
-1.700 
0.155 
0.150 
Median 
-0.125 
-1.145 
-1.035 
-1.410 
-1.570 
0.155 
0.150 
SD 
0.3730 
0.4358 
0.3299 
0.2353 
0.3447 
0.0354 
0.2263 
Maximum Change from Baseline within Study Period 
 
Mean 
-0.363 
-1.178 
-1.015 
-1.488 
-2.013 
-0.205 
-0.030 
Median 
-0.280 
-1.145 
-1.035 
-1.445 
-1.960 
-0.205 
-0.030 
SD 
0.2519 
0.4358 
0.3299 
0.2671 
0.3292 
0.2616 
0.1273 
 


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Secondary Objective: Assessment of Safety/Tolerability 
There were no deaths. There were two SAEs: 1) unrelated severe dilated congestive 
cardiomyopathy (Grade 3), and 2) anal abscess (Grade 1). The participant with unrelated 
severe dilated congestive cardiomyopathy also had an AE of unrelated idiopathic 
myocarditis (Grade 3). Both SAEs and the AE were unrelated to study medication. Note, 
the participant with congestive cardiomyopathy received GSK3640254 10 mg. An in-
depth discussion of this participant’s clinical course is location in Section 5.3.2.5. of the 
IB. 
There were no AEs which led to discontinuation. There were 9 participants with 14 
related AEs. Of these 14, 11 were Grade 1 (mostly gastrointestinal in nature) and three 
were Grade 2 (rash maculo-papular, abdominal pain and nausea).  
Of the 34 participants randomized, 22 participants developed 50 individual AEs. There 
were 7 participants with seven Grade 2 AEs: abdominal pain (related), nausea (related), 
pyrexia, spine pain, rash maculo-papular (related), headache, and neutropenia. The 
remaining AEs are shown in Table 2. The most frequent AEs occurred in the 
Infections/Infestations SOC (8 participants). The most frequent individual AE was 
headache (4 participants). Although not shown, all GI AEs and Neuro AEs were less than 
1 day in duration except: 1) one participant had a headache (Grade 1) from Study Day 1-
2, 2) one participant had diarrhea and vomiting (both Grade 1) from Study Day 4-9, and 
3) one participant had constipation (Grade 1) from Study Day 1-5.  
Table 2 
Summary of All Adverse Events by Preferred Term (Safety 
Population) 
Preferred Term 
GSK 
10 mg 
(N=6) 
GSK 
40 mg 
(N=6) 
GSK 
80 mg 
(N=6) 
GSK 
140 mg 
(N=6) 
GSK 
200 mg 
(N=6) 
Placebo 
(N=4) 
Total 
(N=34) 
Any Event 
3 (50) 
5 (83) 
4 (67) 
5 (83) 
5 (83) 
0 
22 (65) 
Headache 
0 
1 (17) 
0 
1 (17) 
2 (33) 
0 
4 (12) 
Diarrhoea 
1 (17) 
1 (17) 
0 
0 
1 (17) 
0 
3 (9) 
Oropharyngeal pain 
0 
0 
0 
1 (17) 
2 (33) 
0 
3 (9) 
Nasopharyngitis 
0 
0 
0 
0 
2 (33) 
0 
2 (6) 
Vomiting 
1 (17) 
0 
0 
0 
1 (17) 
0 
2 (6) 
Abdominal pain 
0 
0 
2 (33) 
0 
0 
0 
2 (6) 
Lymphadenopathy 
1 (17) 
0 
0 
0 
1 (17) 
0 
2 (6) 
Anal abscess 
0 
0 
0 
1 (17) 
0 
0 
1 (3) 
Meningococcal 
infection 
1 (17) 
0 
0 
0 
0 
0 
1 (3) 
Pharyngitis 
0 
0 
0 
0 
1 (17) 
0 
1 (3) 
Upper respiratory tract 
infection 
0 
0 
0 
0 
1 (17) 
0 
1 (3) 
Urinary tract infection 
0 
0 
0 
1 (17) 
0 
0 
1 (3) 
Viral infection 
0 
1 (17) 
0 
0 
0 
0 
1 (3) 
Constipation 
0 
0 
0 
1 (17) 
0 
0 
1 (3) 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
 
2 0 8 3 7 9  
 
3 7  
 
Pr ef err e d T er m  
G S K  
1 0 m g  
( N = 6) 
G S K  
4 0 m g  
( N = 6) 
G S K  
8 0 m g  
( N = 6) 
G S K  
1 4 0 m g  
( N = 6) 
G S K  
2 0 0 m g  
( N = 6) 
Pl a ce b o  
( N = 4) 
T otal  
( N = 3 4) 
Na us e a  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
Mi gr ain e  
0  
0  
1 ( 1 7) 
0  
0  
0  
1 ( 3)  
Pr esy nco p e  
0  
1 ( 1 7) 
0  
0  
0  
0  
1 ( 3)  
Ast h e ni a  
0  
0  
0  
0  
1 ( 1 7) 
0  
1 ( 3)  
F ati g u e  
0  
1 ( 1 7) 
0  
0  
0  
0  
1 ( 3)  
No d ul e  
0  
0  
1 ( 1 7) 
0  
0  
0  
1 ( 3)  
Pyr exi a  
0  
0  
0  
0  
1 ( 1 7) 
0  
1 ( 3)  
Cat arr h  
0  
0  
0  
0  
1 ( 1 7) 
0  
1 ( 3)  
E pist axis  
0  
1 ( 1 7) 
0  
0  
0  
0  
1 ( 3)  
Ne utr o p e ni a  
0  
0  
1 ( 1 7) 
0  
0  
0  
1 ( 3)  
P ai n i n extr e mity  
0  
0  
1 ( 1 7) 
0  
0  
0  
1 ( 3)  
S pi n al pai n  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
Der m atitis at o pic  
0  
0  
1 ( 1 7) 
0  
0  
0  
1 ( 3)  
Pr urit us  
0  
0  
0  
1 ( 1 7) 
0  
0  
1 ( 3)  
Ras h m ac ul o -pa p ular  
0  
0  
0  
1 ( 1 7) 
0  
0  
1 ( 3)  
Co n g estiv e 
c ar di o my o pat hy 
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
My ocar ditis  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
A L T i ncr e as e d  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
A S T i ncr e as e d  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
Hy p er glyc a e mi a  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
I ns ulin r esist anc e 
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
Vit a mi n D defici e ncy  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
Chr o m at uri a  
1 ( 1 7) 
0  
0  
0  
0  
0  
1 ( 3)  
S o urc e D at a: T a bl e 3. 2  of C P S R 2 0 8 1 3 2  
 
T here w ere n o a b n or mal cli nicall y si g nifica nt arr h yt h mias or c orrecte d Q T i nter val ( Q Tc) 
pr ol o n gati o ns ( v al ues > 5 0 0 msec or i ncreases > 6 0 msec fr o m bas eli ne) o bser ve d f or a n y 
partici pa nt . T here were n o cli nicall y si g nifica nt tre n ds i n vital si g ns, c he mistry la b orat or y 
val ues, or he mat ol o g y la b orat or y val ues acr oss t h e ar ms.  
C CI


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
 
2 0 8 3 7 9  
 
3 8  
 
Sec o n d ary O bj ective: C h ar acteriz ati o n of P K Pr ofile  
G S K 3 6 4 0 2 5 4 P K para meters deri ve d b ase d o n n o mi nal ti mes f oll o wi n g o nce -dail y 
a d mi nistrati o n of 1 0 m g a n d 2 0 0 m g o n ce dail y f or 1 0 da ys were det er mi ne d o n Da y 1 
( Part 1 a n d 2) a n d eit her Da y 8 -9 ( Part 1) or  Da y 7 ( Part 2)  (Ta ble 3 ). F oll o wi n g o nce-
dail y a d mi n istrati o n of G S K 3 6 4 0 2 5 4 o ver 1 0 m g t o 2 0 0 m g d ose ra n ge wit h a m o derate 
fat meal, Da y 1 m e dia n Tma x  ra n ge d bet w ee n 3. 0 0 –  5. 5 h o urs. Varia bilit y i n t he P K 
para meters [ % bet wee n -p artici pa nt c oefficie nt of v ariati o n ( C V b)] ra n ge d fr o m 1 9 % t o 
5 2 %.  
Stea d y -st ate ( D a y 8 -9 or 7 f or Part 1 a n d Part 2, res pecti vel y) me dia n T ma x  ra n ge d 
bet wee n 4. 0 0 h  a n d 5. 5 0 h . Varia bilit y i n t he P K para meters [ % C V b] was l o w t o 
m o derate, ra n gi n g fr o m 1 9. 5 %  t o 4 7 %.  
Alt h o u g h t he sa m ple siz e is s mall, G S K 3 6 4 0 2 5 4 de m o nstrate d ge n erall y d ose -
pr o p orti o nal P K o ver t he d ose ra n ge st u die d ( 1 0 –  2 0 0 m g). C o nsiste nt wit h a nti viral 
decli ne descri be d a b o v e, t he P K para meters of: a) 4 0 a n d 8 0 m g a p pr o xi mate d eac h ot h er , 
a n d b) 1 4 0 a n d 2 0 0 m g a p pr o xi mate d eac h ot her. T here were t hree p a rtici p a nts i n t he 8 0 
m g ar m w h o ha d e x p os ur e si milar t o t hat o bser ve d at 4 0 m g d ose ( data n ot s h o w n).  
T a bl e 3  
S u m m ar y St ati sti c s of D a y 1 a n d D a y 8 -9  ( P art 1) or D a y 7 ( P art 2) P K 
P ar a m et er s F oll o wi n g M ulti pl e D ail y D o s e A d mi ni str at i o n of 
G S K 3 6 4 0 2 5 4 i n St u d y 2 0 8 1 3 2 
 
P K Para m et er  
1 0 m g  
n = 6  
4 0 m g   
n = 6  
8 0 m g  
n = 6  
1 4 0 m g  
n = 6  
2 0 0 m g  
n = 6 1 
G e o m etri c M e a n [ C V b %] ( 9 5 % CI) 
D a y 1  
A U C( 0 -2 4)   
( µ g*h/ m L) 
0. 6 9 5  [ 1 3. 5] 
( 0. 5 8 8, 0. 8 2 1) 
3. 2 5 [ 3 1. 7]  
( 2. 3 5, 4. 5 0) 
6. 1 2 [ 3 8. 8]  
( 4. 1 3, 9. 0 7) 
1 4. 0 [ 3 6. 6]  
( 9. 6 7, 2 0. 4) 
1 2. 4  [ 9 1. 3] 
( 5. 4 8, 2 8. 0) 
C m ax  ( µ g/ m L) 
0. 0 5 9 [ 1 7 7. 4]  
( 0. 0 1 7, 0. 2 0 7) 
0. 2 3 2 [ 3 0. 5]  
( 0. 1 6 9, 
0. 3 1 7)  
0. 4 3 3 [ 3 3. 6]  
( 0. 3 0 7, 
0. 6 1 0)  
0. 9 1 8 [ 4 1. 5]  
( 0. 6 0 4, 
1. 3 9 5)  
0. 9 3 8   [ 8 2. 3] 
( 0. 4 4 1, 2. 0 0) 
T m ax ( h) 
( m e di a n)[r a n g e] 
2. 9 3  
[ 0. 0 0, 5. 0 0] 
4. 4 2  
[ 3. 9 7, 8. 0 0] 
4. 0 8  
[ 2. 9 5, 6. 1 7] 
5. 5 1  
[ 3. 0 0, 6. 2 5] 
5. 5 3  
[ 3. 9 2, 8. 0 5] 
St e a d y 
St at e 2 
A U C( 0 -2 4)   
( µ g*h/ m L) 
0. 9 0 8 [ 4 4. 7]  
( 0. 5 8 0, 1. 4 2 2) 
7. 4 6 [ 2 6. 8]  
( 5. 6 6, 9. 8 4) 
1 1. 8 [ 2 6. 7]  
( 8. 9 8, 1 5. 6) 
2 9. 3 [ 2 7. 9]  
( 2 2. 0, 3 9. 0) 
2 7. 9 [ 1 8. 4]  
( 2 3. 1, 3 3. 8) 
C m ax  ( µ g/ m L) 
0. 0 5 5 [ 4 1. 3]  
( 0. 0 3 6, 0. 0 8 3)  
0. 4 6 9 [ 2 0. 6]  
( 0. 3 7 9, 
0. 5 8 1)  
0. 7 4 7 [ 2 3. 7]  
( 0. 5 8 5, 
0. 9 5 5)  
1. 8 6 [ 2 6. 0]  
( 1. 4 2, 2. 4 3) 
1. 8 6 [ 1 9. 5]  
( 1. 5 1, 2. 2 7) 
T m ax ( h) 
( m e di a n)[r a n g e] 
4. 0 2  
[ 1. 8 7, 5. 0 0] 
4. 0 6  
[ 2. 0 0, 8. 0 0] 
4. 5 8  
[ 4. 0 0, 5. 1 8] 
4. 0 8  
[ 2. 9 2, 5. 2 0] 
5. 4 8  
[ 3. 0 0, 6. 2 0] 
Ct a u  ( µ g/ m L) 
0. 0 2 7 [ 4 7. 0] 
( 0. 0 1 7, 0. 0 4 3) 
0. 2 1 9 [ 3 0. 1]  
0. 3 6 0 [ 3 1. 1]  
0. 7 9 8 [ 3 4. 1]  
0. 7 0 3 [ 2 9. 6]  
C CI


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PK Parameter 
10 mg 
n=6 
40 mg  
n=6 
80 mg 
n=6 
140 mg 
n=6 
200 mg 
n=61 
Geometric Mean [CVb%] (95% CI) 
(0.161, 
0.298) 
(0.262, 
0.495) 
(0.563, 
1.131) 
(0.519, 
0.953) 
CI = Confidence interval 
1One participant In the 200 mg group has been excluded from PK analysis for day 1 due to vomiting within 1x 
tmax post-dose 
2Steady State was measured at Visit 5/6 (Day 8/9 in Part 1 vs Day 7 in Part 2) [Based on FTIH study, mean half-life 
ranges between 21h – 28h] 
 
The key PK modelling and simulation data from Study 208132 is summarized in the dose 
justification in Section 4.3. 
2.3. 
Benefit/Risk Assessment 
Based upon preclinical and clinical studies (including the prior MI GSK3532795), the 
potential risks for GSK3640254 are GI intolerability (e.g., abdominal pain and diarrhea) 
and gastric toxicity (effects on parietal cell and chief cells), prolongation of the corrected 
QT interval (QTc), neuropsychiatric safety, skin and subcutaneous tissue disorders, and 
treatment emergent virologic resistance.  
First, GI intolerability and gastric toxicity (e.g., single-cell parietal cell necrosis) will be 
assessed using clinical and invasive monitoring as outlined in Section 1.3 and Section 
8.6.1.  
Second, prolongation of the QTc interval is a risk. One preclinical study showed 1 dog 
with an increased QTc interval when given a single dose of GSK3640254. A 
cardiodynamic analysis of healthy participants in Study 207187 was conducted. A final 
model from the MAD data showed a QT effect (∆ΔQTcF) of GSK3640254 could be 
predicted to be 5.38 ms (90% CI: 1.66 to 9.10) and 6.70 ms (90% CI: 2.79 to 10.61) for 
the 200 mg (1779 ng/mL) and 320 mg (2154 ng/mL) doses (administered with a 
moderate fat meal), respectively, on Day 14 (the top two doses in the trial). Based on this 
concentration-QTc analysis, a QTcF effect above 10 ms could be excluded up to 
GSK3640254 plasma concentrations of approximately 2000 ng/mL (corresponding to 
doses approximately 200 mg QD; note, 200 mg QD is the top dose considered for this 
Phase 2b study). Importantly, in GSK3640254 clinical trials to date, there have been no 
abnormal clinically significant arrhythmias, and no participants met the trial based QTc 
stopping criteria for QTcF prolongations: values >500 ms or increases >60 ms from 
Baseline. This study contains specific cardiac exclusion criteria, has ECG monitoring (at 
Tmax once GSK3640254 attains steady state concentration), and has QTcF based stopping 
criteria (See Section 1.3, Section 5.2, and Section 7.1.4). 
Third, given the risk of psychiatric risks seen with GSK3532795 (see Section 2.3.1) the 
protocol will exclude potential participants with any significant pre-existing psychiatric 
condition including the results of an assessment using the Columbia Suicide Severity 
Rating Scale (C-SSRS). Participants will also be required to provide response to the C-


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SSRS during the on-treatment portion of the study – and will be clinically evaluated for 
suicidality as indicated (See Section 1.3, Section 5.2 and Section 8.2.6).  
Fourth, across clinical trials in HIV-1 infected participants and healthy participants, skin 
and subcutaneous tissue disorders have been observed (in some cases leading to 
discontinuation). Participants will be followed regularly for the development of AEs and 
will undergo physical exams throughout the study. 
Last, the risk of treatment emergent resistance (to any ARV) will be addressed by several 
means. First, a HIV-1 RNA at Week 2 will be obtained to demonstrate a decline relative 
to Day 1. Second, the following resistance assays will be obtained from Monogram on 
Day 1 and Week 4 samples from all participants in the GSK3640254 treatment arms: Gag 
genotype (using a Next Generation Sequencing Platform), PhenoSense Gag Assay for 
GSK3640254, PhenoSense GT, GeneSeq Integrase and PhenoSense Integrase. These 
assays will document the emergence of resistance or decreased susceptibility in advance 
of protocol-defined virologic failure (PDVF) – thereby preserving as many ARV options 
for participants. Additionally, participants (in all treatment groups) will have their HIV-1 
RNA monitored at frequent intervals and have criteria for resistance testing based upon 
the development of PDVF (Section 1.3 and Section 7.1.1). 
To ensure the overall safety of participants (including, but not limited to, the risk of GI 
intolerability/reversible gastric toxicity, QTc prolongation, skin and subcutaneous tissue 
disorders, and neuropsychiatric safety), this clinical study will include relatively healthy 
HIV-1 infected treatment-naïve adults who will receive clinical, ECG, and laboratory 
evaluations during their participation.  
This study includes an optional Stomach Substudy that includes the procedure of an EGD 
with biopsy. The procedural risks and mitigation are outlined in Section 2.3.1. 
More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of GSK3640254 may be found in the Investigator’s Brochure 
(IB) [GlaxoSmithKline Document Number 2018N379610_02]. 


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2.3.1. 
Risk Assessment  
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
Investigational Product (IP) GSK3640254   
Cardiovascular (QT prolongation) 
Non-clinically, GSK3640254 inhibited cardiac hERG/IKr 
potassium, cardiac SCN5A sodium and L-type calcium 
channel currents recorded from HEK 293 cells stably 
transfected with complementary DNA from the ion 
channels. In a single-dose safety pharmacology study in 
telemeterized dogs, increases in QT interval (up to 20 ms) 
occurred primarily in 1 dog given 17 mg/kg. Later, there 
were no GSK3640254-related effects on 
electrocardiogram (ECG) parameters in dogs given up to 
25 mg/kg/day for up to 39 weeks. 
 
In Study 207187 (MAD) the concentration-QTc analysis, a 
QTcF effect above 10 ms could be excluded up to 
GSK3640254 plasma concentrations of approximately 
2000 ng/mL (corresponding to doses approximately 
200 mg QD). Importantly, in GSK3640254 clinical trials to 
date, there have been no abnormal clinically significant 
arrhythmias, and no participants have met the trial-based 
Stopping Criteria for QTcF prolongations: values >500 ms 
or increases >60 ms from Baseline. 
Protocol exclusion criteria based on screening 
ECG parameters and cardiac medical history 
(see Section 5.2). 
 
Participants will have regular ECG monitoring 
during the course of the study (see Section 
1.3) with QTc stopping criteria (see Section 
7.1.4). 
 
As noted in Section 7.1.4, if a clinically 
significant finding is identified (including but 
not limited to changes from baseline in QT 
interval corrected using or Fridericia’s formula 
[QTcF]) after enrollment, the investigator or 
qualified designee will determine if the 
participant meets QTc Stopping Criteria, and if 
any change in participant management is 
needed. This review of the ECG printed at the 
time of collection must be documented. Any 
new clinically relevant finding should be 
reported (at a minimum) as an AE. 
Gastrointestinal intolerability  
Non-clinically, signs of gastrointestinal intolerability 
(sporadic vomiting and abnormal faeces beginning on Day 
1 and continuing throughout the dosing periods) occurred 
mainly in dogs at ≥1 mg/kg/day. In humans, GI 
Protocol exclusion criterion based on pre-
existing GI pathology or baseline GI 
signs/symptoms (see Section 5.2) 
 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
 
2 0 8 3 7 9  
4 2  
 
P ot e nti al Ri sk of Cli ni cal Si g nifi c a n ce  
S u m m ar y of D ata/ R ati o n ale f or Ri s k  
Miti g ati o n Str at e g y a , b 
i nt ol er a bility ( pr ed o mi n at ely a b do mi n al pai n an d di arr h ea) 
w as s e en wit h a str uctur ally r el at e d c o m p ou nd 
G S K 35 3 27 95 w hic h w as eval u ate d thr o ug h Ph ase 2 b 
d osi n g.  
 
W hil e s u m m ariz e d i n d et ail in t he I B, t he r ates of all GI 
A Es ( all Gr a de 1 re g ar dless of r el atio ns hip) i n t h e M A D 
p orti o n of St u dy 2 07 18 7 ( Phas e 1 F TI H) w er e 33 %, 0 %, 
2 4 %, a n d 2 9 % i n particip a nts  w h o r ec eive d G S K 36 40 2 54 
5 0, 1 0 0, 20 0, a n d 3 20 m g daily f or 1 4 d ays  (t h e o nly 
c o m pl et ed st u dy wit h t h e gre at est dur ati o n a nd d os e of 
d osi n g) , res p ectively (rel ative t o a r ate of 2 1 % i n 
p articip a nts  w h o r ec eiv ed plac e bo).  
 
T h e r ates of all GI A Es i n Stu dy 2 0 81 3 2 ( P h ase 2 a P O C) 
st u dy ar e s ho w n i n S ecti on 2. 2.4 . 
P articip a nts  will u n der g o conti n uo us 
ev al u ati o n for adv ers e ev e nts d urin g t heir 
p articip ati on i n t h e trial; t her e ar e cli nic al 
st o p pin g crit eria b as ed u p on i nt e nsity of 
tr e at m e nt-e m er g ent A E s (s e e Secti o n 7.1 ). 
A d diti on ally , a GI i ntol er ability ev al uati o n a nd 
m o nit orin g pl a n is av ail abl e t o g ui d e t h e 
i nv esti g ator s ho ul d GI A Es e m er g e (s ee 
S ecti o n 8.2. 7 ) 
 
 
G astric T oxicity  
G astric t oxicity eff ects o n pariet al c ells a n d/or c hi ef c ells 
ass oci at ed wit h ch an g es i n s er u m g astri n lev els w er e 
pr es e nt i n pr ecli nical s p eci es. T h es e fi n din gs w er e 
r ev ersibl e. 
It is u ncl ear if gastric t oxicity occ urs i n 
h u m a ns; a nd if pr es e nt w h at t h e 
hist o pat h ol o gic al fin di ngs are ( w h et h er t hey 
c orrel at e wit h A Es, bi o m arkers, etc). T o 
ex pl or e th e m onit oring of g astric  t oxicity, a 
s u bs et of ~7  particip a nts i n e ac h ar m will t ak e 
p art i n th e O pti on al St o m ach  S ubst u dy a n d 
will u n d er g o 
wit h Bi o psy of th e gr e ater 
a n d less er c urv atur e (f or subs e qu e nt 
hist o pat h ol o gic exa mi n ati on) al o n g with a 
m e as ur e m e nt of S er u m Bi o m ark ers ( S e e 
S ecti o n 1.3  an d Secti on 8.6. 1 ). 
 
C CI


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
Individual and Protocol based discontinuation 
criteria will be based upon treatment emergent 
histologic findings (see Section 4.1.5.2 and 
Section 4.1.5.3).  
Neurologic/psychiatric safety 
 
Two psychiatric SAEs in previous MI GSK3532795 clinical 
program (acute psychosis, homicidal/suicidal ideation) at 
supratherapeutic doses were seen in healthy participants 
in a TQT study. 
 
From a Neurologic and Psychiatric AE summary and 
PK/PD analysis for GSK3532795 across all studies, mild 
G1 headache and G1 sleep abnormalities were the 
predominant AEs, with a trend for increasing neurologic 
and psychiatric AEs with increasing dose (based on TQT 
and P2b studies). No exposure-response relationship 
seen for select neurologic and psychiatric AEs (based on 
TQT and P2b studies) CNS penetration data for 
GSK3532795 and GSK3640254 in rats demonstrate a 
similarly low brain distribution/penetration. 
 
While summarized in the IB, the rates of all Nervous 
system and Psychiatric AEs in the MAD (Study 207187 
FTIH) ranged from 24-57% and 0-17%, respectively 
across doses (50-320 mg x 14 days) without any trend.  
 
 
 
No GSK3640254 clinical trial has observed SAEs of acute 
psychosis or homicidal/suicidal ideation. 
Protocol exclusion criterion based on any pre-
existing psychiatric condition (including results 
of psychological assessment and the 
eCSSRS tool) in participants. 
 
Continuous evaluation for adverse events 
during their participation in the trial including 
direct AE inquiry as noted in Section 1.3.  
 
Participants will also provide responses to the 
C-SSRS throughout the study. Ultimately, in 
the event of a new onset suicidality ideation or 
behavior (SIB), as determined by the 
investigator (in consultation with psychiatry, as 
needed), the participant will discontinue from 
the trial and the Investigator will arrange for 
urgent specialist psychiatric evaluation and 
management.  
 
Guidance for the management of emergent 
psychiatric symptoms are available (see 
Section 8.2.6).  
 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
There are clinical stopping criteria based upon 
intensity of treatment-emergent psychiatric 
AEs (see Section 7.1). 
Skin and subcutaneous tissue disorders 
Across clinical trials, AEs leading to discontinuation have 
included urticaria and maculo-papular rash 
Participants with a history of drug or other 
allergy that, in the opinion of the investigator 
or Medical Monitor, contraindicates their 
participation are excluded.  
Participants will undergo continuous 
evaluation for adverse events during their 
participation in the trial supplemented by the 
use of physical exams. 
Protocol includes individual participant 
stopping criteria, including any Grade 3 or 
higher rash, or Grade 2 rash that is associated 
with any systemic signs, allergic symptoms or 
if mucosal involvement develops. (see Section 
10.9.3). 
 ABC   
Hypersensitivity Reaction 
Serious and sometimes fatal hypersensitivity reactions, 
with multiple organ involvement, have occurred with 
abacavir. Participants who carry the HLA-B*5701 allele 
are at a higher risk of a hypersensitivity reaction to 
abacavir; although, hypersensitivity reactions have 
occurred in patients who do not carry the HLA-B*5701 
allele. 
Testing for the HLA-B*5701 allele will be done 
at Screening so that Investigators can make 
an appropriate choice among the study 
background therapy options.  
Guidelines for the management of HSR are 
provided in Section 10.9.2. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
Both ABC and DTG are associated with a risk for 
hypersensitivity reactions (HSR) and share some common 
features such as fever and/or rash with other symptoms 
indicating multi-organ involvement. 
Also see Section 7.1, Discontinuation of Study 
Intervention. 
The participant informed consent form (ICF) 
includes information on this risk and the 
actions participants should take in the event of 
an HSR or associated signs and symptoms 
DTG 
Hypersensitivity reaction (HSR) and 
rash 
 
HSR has been observed uncommonly with DTG.  Rash 
was commonly reported in DTG Phase IIb/III clinical trials; 
episodes were generally mild to moderate in intensity; no 
episodes of severe rash, such as Stevens-Johnson 
Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and 
erythema multiforme were reported.  
Participants with history of drug or other 
allergy that, in the opinion of the Investigator 
or Medical Monitor, contraindicates their 
participation, are excluded. 
 
Guidelines for the management of HSR are 
provided in Section 10.9.2. 
Also see Section 7.1, Discontinuation of Study 
Intervention. 
Specific/detailed toxicity management 
guidance is provided for rash (Section 
10.9.3.1) 
 
The participant informed consent form (ICF) 
includes information on this risk and the 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
actions participants should take in the event 
of a HSR or associated signs and symptoms. 
Drug induced liver injury (DILI) and 
other clinically significant liver chemistry 
elevations 
Non-clinical data suggested a possible, albeit low, risk for 
hepatobiliary toxicity with DTG.  Drug-related hepatitis is 
considered an uncommon risk for ART containing DTG 
regardless of dose or treatment population.  For 
participants with hepatitis B virus (HBV) and/or hepatitis C 
virus (HCV) co-infection, improvements in 
immunosuppression as a result of HIV virologic and 
immunologic responses to DTG- containing ART, along 
with inadequate therapy for HBV co-infected participants, 
likely contributed to significant elevations in liver 
chemistries.  A review of postmarketing data found that 
the number of cases reporting particularly severe liver 
dysfunction was found to be very low in the context of 
exposure to DTG and DTG/ABC/3TC. The reported cases 
of severe liver dysfunction (including acute hepatic failure) 
are complex with potential confounding factors but in a 
very small number of cases, drug-induced liver injury is 
likely and the role of DTG-containing regimens cannot be 
ruled out particularly in those involving DTG. 
 
Participants meeting any of the following 
criteria during the screening period are 
excluded from participating. 
• Alanine aminotransferase (ALT) 3 times 
the-upper limit of normal (ULN) or ALT 
2xULN and bilirubin 1.5x ULN  
• Infection with Hepatitis B or Hepatitis C, 
as described in the Exclusion Criteria (See 
Section 5.2) 
 
Specific/detailed liver stopping criteria and 
toxicity management guidance is provided for 
suspected DILI or other clinically significant 
liver chemistry elevations (Section 10.9.1). 
 
Psychiatric disorders 
Psychiatric disorders including suicidal ideation and 
behaviours are common in people living with HIV. Events 
of suicidal ideation, attempt, behaviour and completion 
were observed in clinical studies of DTG, primarily in 
participants with a pre-existing history of depression or 
other psychiatric illness.  
Protocol exclusion criterion based on any pre-
existing psychiatric condition (including results 
of psychological assessment and the 
eCSSRS tool) in participants. 
 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
Continuous evaluation for adverse events 
during their participation in the trial including 
direct AE inquiry as noted in Section 1.3.  
 
Participants will also provide responses to the 
C-SSRS throughout the study. Ultimately, in 
the event of a new onset suicidality ideation or 
behavior (SIB), as determined by the 
investigator (in consultation with psychiatry, as 
needed), the participant will discontinue from 
the trial and the Investigator will arrange for 
urgent specialist psychiatric evaluation and 
management.  
 
Guidance for the management of emergent 
psychiatric symptoms are available (see 
Section 8.2.6).  
 
There are clinical stopping criteria based upon 
intensity of treatment-emergent psychiatric 
AEs (see Section 7.1). 
 
The participant informed consent form 
includes information on the risk of depression 
and suicidal ideation and behavior.  
 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
Theoretical serious drug interaction with 
dofetilide and pilsicainide 
Co-administration of DTG may increase 
dofetilide/pilsicainide plasma concentration via inhibition of 
organic cation transporter (OCT-2), resulting in potentially 
life-threatening toxicity. 
The co-administration of DTG with dofetilide 
or pilsicainide is prohibited in the study 
(Section 6.8.1). 
Renal function 
Mild elevations of creatinine have been observed with 
DTG which are related to a likely benign effect on 
creatinine secretion with inhibition of OCT-2.  DTG has 
been shown to have no significant effect on glomerular 
filtration rate (GFR) or effective renal plasma flow. 
Specific/detailed toxicity management 
guidance is provided for participants who 
develop a decline in renal function (Section 
10.9.6). 
 
Creatinine clearance is calculated in all 
participants prior to initiating therapy and 
renal function (creatinine clearance and 
serum phosphate) will be monitored at all 
subsequent study visits. 
Neural tube defects 
In a birth outcome surveillance study in Botswana there 
have been 7 cases of neural tube defects reported in 
3,591 deliveries (0.19%) to mothers taking dolutegravir-
containing regimens from the time of conception, 
compared with 21 cases in 19,361 deliveries (0.11%) to 
mothers taking non-dolutegravir-containing regimens from 
the time of conception (Prevalence Difference 0.09%; 
95% CI 0.03-0.30). 
In the same study, no increased risk of neural tube 
defects was reported in women who started DTG 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 
1. Participants who are female at birth who 
are breastfeeding or plan to become 
pregnant or breastfeed during the study 
are excluded. 
2. Participants who are female at birth who 
become pregnant, or who desire to be 
pregnant while in the study, or who state 
they no longer are willing to comply with 
the approved pregnancy avoidance 
methods, will have study treatment 
discontinued and will be withdrawn from 
the study. 
3. Participants of reproductive potential are 
reminded re: pregnancy avoidance and 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
deliveries (0.07%) to mothers who started non-
dolutegravir-containing regimens during pregnancy. 
A causal relationship of these events to the use of 
dolutegravir 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. As neural tube defects 
occur within the first 4 weeks of foetal development (at 
which time the neural tubes are sealed) this potential risk 
would concern women exposed to dolutegravir at the time 
of conception and in early pregnancy. 
Data analysed to date from other sources including the 
Antiretroviral Pregnancy Registry, clinical trials, and post-
marketing data are insufficient to address the risk of 
neural tube defects with dolutegravir. 
More than 1,000 outcomes from second and third 
trimester exposure in pregnant women indicate no 
evidence of increased risk of adverse birth outcomes. 
In animal reproductive toxicity studies, no adverse 
development outcomes, including neural tube defects, 
were identified. Dolutegravir was shown to cross the 
placenta in animals. 
adherence to contraception requirements 
at every study visit. 
4. Pregnancy status is monitored at every 
study visit 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
FTC/TAF 
New onset or worsening renal 
impairment 
Renal impairment, including cases of acute renal failure 
and Fanconi syndrome (renal tubular injury with severe 
hypophosphatemia), has been reported with the use of 
tenofovir prodrugs in both animal toxicology studies and 
human trials. 
Guidelines for monitoring are provided in 
Appendix 9, Toxicity Management 
(specifically, Section 10.9.6) 
Proximal Renal Tubule Dysfunction 
In clinical trials of FTC+TAF with EVG+COBI in treatment-
naïve subjects and in virally suppressed subjects switched 
to FTC+TAF with EVG+COBI with estimated creatinine 
clearance greater than 50 mL per minute, renal serious 
adverse events or discontinuations due to renal adverse 
reactions were encountered in less than 1% of 
participants treated with FTC+TAF with EVG+COBI. In a 
study of virally suppressed subjects with baseline 
estimated creatinine clearance between 30 and 69 mL per 
minute treated with FTC+TAF with EVG+COBI for a 
median duration of 43 weeks, FTC+TAF with EVG+COBI 
was permanently discontinued due to worsening renal 
function in two of 80 (3%) subjects with a baseline 
estimated creatinine clearance between 30 and 50 mL per 
minute 
Guidelines for monitoring are provided in 
Appendix 9, Toxicity Management 
(specifically, Section 10.9.7) 
Proteinuria 
Prior to or when initiating DESCOVY, and during 
treatment with DESCOVY on a clinically appropriate 
schedule, assess serum creatinine, estimated creatinine 
Guidelines for monitoring are provided in 
Appendix 9, Toxicity Management 
(specifically, Section 10.9.8) 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
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clearance, urine glucose, and urine protein in all 
individuals 
Study Procedures 
Optional EGD with biopsy 
The overall complication rates for EGD range from 
0.009% to 1.9%.% [Wolfsen, 2010]. The mortality rate 
ranges from 0 – 0.05% [Ben-Menachem, 2012]. Risks 
associated with an EGD with biopsy include hypoxia, 
cardiovascular complications 0.14%- 0.9% (e.g. 
hypotension, shock, supraventricular tachycardia, 
vasovagal reaction, myocardial infarction, cerebrovascular 
accidents), aspiration, pneumonia, apnea, respiratory 
arrest, a reaction to medication (e.g. 
methemoglobinemia), infection (0-8%) [Ben-Menachem, 
2012], bleeding (0.15%), incarceration, and/or perforation 
(0.02-0.2%). 
Only qualified medical professionals with 
appropriate supportive staff/environment will 
evaluate potential participants, perform the 
procedure, and provide post-procedure care. 
Additional requirements are detailed in 
Section 4.1.5. 
 
HIV-1 Infection/Patient Population 
HIV Resistance to GSK3640254 and 
other on-study treatments 
 
There is an in intrinsic risk of resistance (genotypic 
changes or decreased phenotypic susceptibility) to any 
developmental ARV (or the ARVs which are co-
administered).  
 
Note: Data from Study 208132 (Phase 2a POC) showed a 
decline in HIV-1 RNA and reasonable PK profile. 
However, some participants receiving GSK3640254 had 
treatment emergent resistance mutations associated with 
maturation inhibitors observed on or after Day 11 (after 10 
As described above, this risk will be mitigated 
using the following approaches.  
1) HIV-1 RNA at Week 2 will be obtained to 
demonstrate a decline relative to Day 1. 
2) At Day 1 and Week 4 the following 
resistance assays will be obtained from 
Monogram Biosciences on samples 
collected from participants in the 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategya,b 
days of receiving GSK3640254 monotherapy). However, 
no resistance to existing and commercially available 
classes of antiretroviral medications (e.g., reverse 
transcriptase, protease, integrase) was observed as there 
is no known cross-resistance between maturation 
inhibitors and other classes of ARVs.  
GSK3640254 arms: Gag genotype (using 
a Next Generation Sequencing Platform), 
PhenoSense Gag Assay for 
GSK3640254, and PhenoSense GT, 
GeneSeq Integrase and PhenoSense 
Integrase. These assays will document 
the emergence of resistance or decreased 
susceptibility in advance of PDVF – 
thereby preserving as many ARV options 
for participants.  
3) All participants will have their HIV-1 RNA 
monitored at frequent intervals and have 
criteria for resistance testing based upon 
the development of Protocol Defined 
Virologic Failure (Section 7.1.1) 
 
a. Careful monitoring of events will be conducted using serious adverse event (SAE) reports and alerts for Grade 3/4 laboratory toxicities (per Division of Acquired 
Immune Deficiency Syndrome [DAIDS] toxicity gradings for HIV-infected participants). Serious/severe events will be managed appropriately including, but not 
limited to, withdrawal of study intervention, and will be followed to resolution as per Sponsor’s standard medical monitoring practices.   
b. Clinical Safety Data will be routinely reviewed in GlaxoSmithKline (GSK)/ViiV Safety Review Team meetings. This will include in-stream review of data from this 
clinical trial on a routine basis. 
 


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2.3.2. 
Benefit Assessment 
Participants in this clinical study may benefit from receiving a combination of ARVs 
containing GSK3640254. Data from the Phase 2a study does show a PK/PD (decline in 
HIV-1 RNA) relationship (described in detail in Section 4.3). Thus, GSK3640254 may 
contribute to a decline in HIV-1 RNA (and maintenance of suppression) when 
administered with other ARVs. A decline in HIV-1 RNA is directly associated with a 
reduction in HIV/AIDS related morbidity/mortality. 
There is no clinical benefit to participating in the optional Stomach substudy. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Considering the measures taken to minimize the potential risks to participants in this 
study, the potential risks identified in association with GSK3640254 are justified by the 
anticipated benefits that may be afforded to participants with HIV-1 infection achieving 
and maintaining virologic suppression (when given in combination with other ARVs). 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary Efficacy 
• To evaluate antiviral efficacy of 
GSK3640254 relative to DTG, each given 
in combination with 2 NRTIs, enabling the 
selection of an optimal dose for 
GSK3640254 
• Proportion of participants with plasma HIV-1 
RNA <50 copies/mL at Week 24 using the 
FDA snapshot algorithm 
Secondary Efficacy, Safety and PK 
• To evaluate antiviral efficacy in the 
Randomised Phase of GSK3640254 
relative to DTG, each given in combination 
with 2 NRTIs at Week 48 
• To evaluate antiviral efficacy in the Non-
Randomised Phase of GSK3640254 
optimal dose given in combination with 
DTG relative to the reference arm (DTG 
given in combination with 2 NRTIs) at 
Week 96 
• Proportion of participants with plasma HIV-1 
RNA <50 copies/mL at Weeks 48 and 96 
using the FDA snapshot algorithm 
• Absolute values and changes from baseline 
in HIV-1 RNA through Weeks 24, 48, and 
96 
• Absolute values and changes from baseline 
in CD4+ cell counts through Weeks 24, 48, 
and 96 
• To evaluate safety and tolerability in the 
Randomised Phase of GSK3640254 
relative to DTG each given in combination 
with 2 NRTIs at Weeks 24 and 48 
• To evaluate safety and tolerability in the 
Non-Randomised Phase of GSK3640254 
optimal dose given in combination with 
• Frequency of SAEs, Deaths and AEs 
leading to Discontinuation through Weeks 
24, 48, and 96 
• Incidence and severity of AEs through 
Weeks 24, 48 and 96 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
 
2 0 8 3 7 9  
5 4  
 
O bj e cti ve s  
E n d p oi nt s  
D T G  r el ativ e t o t h e r efer e nce ar m (D T G 
giv e n i n c o m bi nati o n with 2 N R TIs ) at 
W e ek 9 6  
•  A Es i n GI, Psych/ C N S t hro ug h W e eks 2 4, 
4 8, a n d 9 6  
•  T o ass ess t h e d evel o p m ent of vir al 
r esist a nc e in t he R an d o mise d P h as e t o 
G S K 36 4 02 54 a n d 2 N R TI b ack b on e  i n 
p artici p a nts exp eri e nci ng vir ol o gic fail ur e 
at W e eks 2 4 a n d 4 8.  
•  T o ass ess t h e d evel o p m ent of vir al 
r esist a nc e in t he N on-R a n do mis e d Ph as e 
t o G S K 3 64 02 5 4 a nd D T G  in p articipa nts 
ex p eri e ncin g vir ol ogic f ail ure at W eek 9 6.  
•  C h a n ges i n g e noty pic a nd/ or p h e noty pic 
pr ofil es of vir us c o m p are d to b aseli n e 
t hr o u gh W e eks 2 4, 48, a n d 9 6  
•  T o c h ar act eriz e th e p h ar mac oki n etics of 
G S K 36 4 02 54 w h en giv en i n c o m bi n atio n 
wit h A B C/ 3 T C or F T C/ T A F  
•  T h e st ea dy -st at e pl as m a P K p ar a m et ers of 
G S K 36 4 02 54 will b e assesse d b as ed o n 
I nt e nsiv e an d/or S p ars e P K s a m pli n g 
t hr o u gh W e eks 2 4 a nd 4 8  
C CI


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
 
2 0 8 3 7 9  
5 5  
 
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
Pr ot oc ol wai vers or e x e m pti o ns are n ot all o we d wit h t he e x ce pti o n of i m me diate safet y 
c o ncer ns. T h eref ore, a d h ere nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose 
s pecifie d i n t he Sc he d ul e of Acti vities  ta ble ( Secti o n 1. 3 ), are esse ntial a n d re q uire d f or 
st u d y c o n d u ct. 
St u d y 2 0 8 3 7 9  is a P hase 2 b, ra n d o mize d, m ultice ntre, parallel gr o u p, partiall y -bli n d  ( o nl y 
t o t he d ose s of G S K 3 6 4 0 2 5 4)  trial, t o be c o n d uct e d i n a p pr o xi matel y 1 5 0 HI V -1 i nf ecte d 
A R T -naï ve a d ults.    
I n de pe n de nt D at a M o nit ori n g C o m mittee:  
T he st u d y will i ncl u de a n I n d e pe n de nt Data M o nit ori n g C o m mittee (I D M C).  
T he I D M C will re vie w t h e t otalit y of cli nical data (e x cl usi ve of t he St o mac h S u bst u d y) 
wit h at least o ne a nal ysis bef ore t h e Wee k 2 4 Pri mar y A nal ysis a n d will be res p o nsi ble 
f or rec o m me n di n g t o t he C M O a n d V S L C: 1) disc o nti n uati o n of a n y tr eat m e nt ar m, 2) 
disc o nti n uati o n of t he st u d y, or 3) c o nti n uati o n of t he st u d y as pla n n e d.  
4. 1. 1.  
S cr e e ni n g P eri o d  
Ass u mi n g a scree n fail ure rate of 5 0 %, a p pr o xi matel y 3 0 0 partici pa nts  will be scree ne d 
f or t his st u d y t o ra n d o mi ze a p pr o xi matel y 1 5 0 eli gi ble partici pa nt s.  
T he  e nr oll me nt peri o d m a y b e e xte n de d if t he a d diti o nal eff ort is nee d e d t o recr uit 
a d diti o nal partici pa nts  f or t he o pti o nal  St o mac h S u bst u d y ( see Secti o n 4. 1. 5. 1 ). 
Partici pa nts  will e nter a Scree ni n g peri o d of u p t o 4 2 da ys. T his d urati o n is warra nte d 
base d o n t he le n gt h y t ur n ar o u n d ti me f or t he ce ntr al ge n o/ p he n ot y pic assa y  fr o m 
M o n o gra m .  T he Scree ni n g peri o d ( dela yi n g Ra n d o mizati o n) ma y b e e xte n de d t o a 
ma xi m u m of  6 3 da ys i n c ertai n circ u msta nces, as detaile d i n Secti o n 5. 5 . 
At t h e Scree ni n g visit, fasti n g bl o o d sa m ples a n d uri ne will be c ollecte d, a n E C G will be 
d o ne, a n d partici p a nts  will be as ke d t o pr o vi de res p o nses t o t he C -S S R S Baseli ne 
assess me nt a b o ut t h o u g ht s a n d feeli n gs t hr o u g h o ut t heir e ntire lifeti me. I n a d diti o n, 
partici pa nts will pr o vi de breat h or st o ol sa m ples f or t he testi n g of H. pyl ori , t o be d o ne at 
C CI


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a lab that is local to the study site. The local laboratory should be consulted prior to study 
start for any pre-testing requirements. 
Prohibited Medications (Section 6.8.1.2) will be reviewed for any medications the 
participant is taking that need to be stopped as much as 4 weeks prior to the first dose. 
Participants may be rescreened once (See Section 5.4). However, participants who are 
randomized into the trial and subsequently withdrawn from the study, for any reason, 
may not be rescreened.  
4.1.1.1. 
Selection of NRTI  Background Therapy: ABC/3TC of FTC/TAF 
The Investigator will select the ABC/3TC or FTC/TAF NRTI background therapy for 
each participant.  
• The selection of the fixed-dose combination NRTI backbone should be based on 
subject history and current medical conditions. In countries where the therapy is not 
provided centrally, Investigators must refer to local product labeling and treatment 
guidelines for these products. 
• Results for the HLA-B*5701 allele testing will help inform the decision. The use of 
ABC/3TC is contraindicated for those who carry the allele. 
• The use of the ABC/3TC NRTI backbone is contraindicated in subjects with mild 
hepatic impairment (Child-Pugh score 5-6, Class A) [Epzicom USPI, 2019]. 
4.1.2. 
Treatment Period 
Visits, in clinic or virtual, may be conducted within a window of ± 2 days. 
The Week 2 visit must be done from Day 11-14. 
Any interruption in therapy during the treatment period of 3 or more consecutive days, 
for any reason, must be discussed with the ViiV Medical Monitor prior to resumption of 
.therapy, if possible. If therapy was resumed without prior approval (i.e., if the PI was not 
aware at the time of the missed doses), the Investigator should contact the ViiV Medical 
Monitor upon becoming aware. 
Participants will be asked to complete a diary card for at least a portion of the study that 
will capture key dosing times prior to visits that collect PK samples as well as dates of 
any missed doses that can be recalled. Site staff will perform pill counts to check 
compliance.  At every visit, both in clinic and virtual, site staff will discuss the 
importance of adherence, ensuring participants understand the risk for developing 
resistance that comes with non-compliance.  
Dose administration on all arms requires participants to dose in the morning (at least 
through Week 48, due to study PK and/or post-dose ECG requirements and for 
consistency of daily dosing), and at/near the same time each day (see the SRM for 
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Dose administration with the treatments in the GSK3640254 arms requires participants to 
dose with a low-fat meal (see Section 5.3.1). Dose administration with DTG can be done 
without regard to food. 
All subjects in the GSK3640254 arms will provide samples for Sparse PK at visit Weeks 
4, 8, 12, 24, 36 and 48.  At each of these visits, a PK sample is drawn at the beginning of 
the visits, pre-dose, with all of the other blood samples, and then within a window of time 
later that same day, a second PK sample is drawn.  Some visits (See Section 8.4) will 
require the second PK sample to be collected much later in the day, requiring the subject 
to return to the clinic. Subjects in the Reference Arm will not need to provide samples for 
PK.   
The Week 2 visit will be conducted Day 11-14.  The reason for this is two-fold: it allows 
sufficient time for the study drugs to come to steady state for those participating in the 
Intensive PK portion of this visit (see Section 4.1.2.1.1) and it also represents a sufficient 
length of time to see any effect of early decline in HIV RNA. 
The visit at Week 2 is to be done by all study participants (for collection of HIV-1 RNA, 
plasma for storage, a pre-dose ECG and all 3 post-dose ECGs).  Participants on the 
GSK3640254 arms can volunteer to take part in the Intensive PK portion at Week 2 (~45 
volunteers from the GSK3640254 arms are needed; approximately 15 per arm). Subjects 
in the Reference Arm will not do the Intensive PK portion of the visit at Week 2. 
Fasting requirements: 
• Participants who are taking part in the Stomach Substudy will need to fast for a 
minimum of 12 hours prior to the visits at which Serum Biomarkers are collected, 
and for only 6 hours at visits where lipids but not Serum Biomarkers are collected 
• All other participants need to fast for a minimum of 6 hours prior to the visits at 
which lipids and renal/bone/inflammation biomarkers are collected. 
4.1.2.1. 
Day 1 through Week 24  
Participants will be randomized to either: one of the three blinded, QD, oral dose 
GSK3640254 dose regimens (approximately 40 participants per treatment arm, each in 
combination with open label ABC/3TC or FTC/TAF), or to the open label, active control 
Reference Arm of DTG given in combination with open label ABC/3TC or FTC/TAF 
(approximately 30 participants) in the Randomised Phase.  
• Arm 1: Blinded GSK3640254 100 mg + Open Label ABC/3TC or FTC/TAF 
• Arm 2: Blinded GSK3640254 150 mg + Open Label ABC/3TC or FTC/TAF 
• Arm 3: Blinded GSK3640254 200 mg + Open Label ABC/3TC or FTC/TAF 
• Arm 4: Open Label DTG + Open Label ABC/3TC or FTC/TAF 


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On Day 1, there are several pre-dosing assessments and procedures, then ECGs are also 
required 2, 4 and 6 hours post-dose.  
Participants will be stratified by Screening plasma HIV-1 RNA, by <100,000 c/mL or 
≥100,000 c/mL, and the investigator’s choice of dual NRTI background therapy (either 
ABC/3TC or FTC/TAF).  
A one-time switch to the other option of the NRTI background is permitted prior to Week 
2 for reasons of tolerability/toxicity, no other switch will be allowed. The chosen 
background therapy for each participant will be maintained throughout the entire duration 
of trial participation.    
Participants will be seen in-clinic for study visits every 4 weeks through Week 24.  
At these clinic visits, blood and urine will be collected, ECG(s) will be done at some 
visits, and participants will be asked to provide responses to the C-SSRS Since Last Visit 
questions about their thoughts since the last visit. 
4.1.2.1.1. Optional Intensive PK Portion of Week 2 Visit – GSK3640254 Arms Only 
The visit at Week 2 is to be done by all study participants, but the Intensive PK portion of 
the visit is optional, and limited to participants who are on the GSK3640254 arms.  
The study includes an Intensive PK portion at the visit at Week 2 ([Day 11-14]; also 
called the PK Subgroup) to be performed by approximately 45 participants who are 
assigned to any of the GSK3640254 arms (approximately 15 per treatment arm; 25% of 
the total). Participation is optional; a sufficient dataset is needed for the analysis of this 
secondary endpoint. 
The Intensive PK portion of the visit includes a standard, pre-dose blood draw in the 
morning, followed by 8 blood draws of smaller blood volume over the course of the 
subsequent 6 hours, then another approximately 4 hours later, and then a final, small 
blood draw the following morning (See Section 8.4). EGCs will be collected at some of 
the time points.  
If, due to COVID-19, the Week 2 visit is impacted (e.g., the participant is restricted by 
travel or the clinic has restrictions at the time that limit attendance or otherwise prohibit 
the ability to conduct this day-long visit), then the Intensive PK portion of the visit can be 
postponed and done at Week 16, in conjunction with the required assessments and 
procedures required for Visit 16.  See the SRM for the management of tests/assessments 
that would be duplicative and instructions on how to manage the collection using the 2 
lab kits and data entry into the eCRF. 
4.1.2.2. 
Week 24 through End of Study 
Beyond Week 24, participants will be seen in-clinic for visits approximately every 4 
weeks for another 9 months, then approximately every 8 weeks through the remainder of 
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Participant in the DTG reference arm will end their participation in the treatment phase of 
the study as each individual participant reaches Week 144. 
4.1.2.2.1. Virologic Management 
See the decision tree in Figure 1. 
Participants in any arm who are Virologic Responders will continue in the study beyond 
Week 24 without change. 
Participants in any arm who are Virologic Non-Responders must be discontinued from 
the study immediately. These participants will perform the Early Withdrawal visit, and 
then be seen in clinic once more at a Final Follow-Up visit. 
Figure 1 
Assessment by HIV-1 RNA at Week 24 
 
Refer to Table 4 for management by HIV-1 RNA after all participants in the 
GSK3640254 arms transition to open label GSK3640254 optimal dose + DTG. 
For the purposes of clinical management in this study, Investigators will continuously 
assess HIV-1 RNA throughout the Treatment Phase of the trial (from Day 1, at any visit 
either scheduled or unscheduled) using information found in Section 7.1.1 and the 
guidance as seen in Table 4 (during the Non-Randomized Phase of the study). The 
rationale for this specific virologic management in the Non-Randomized Phase is the 
difference in therapy for virologically suppressed participants who will transition to open 
label GSK3640254 optimal dose + DTG. Specifically, DTG has one of the highest 
barriers to resistance and participants will need to be closely evaluated in this portion of 
the study to ensure they do not develop overt resistance to the INI class of medications. 


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Table 4 
Assessment by HIV-1 RNA During the Non-Randomized Phase 
Current HIV-1 RNA <50 c/mL 
Regardless of previous HIV-1 RNA result, proceed with the next visit, per Schedule of Activities (SOA) in Section 1.3. 
Current HIV-1 RNA ≥50 c/mL but <200 c/mL 
If previous HIV-1 RNA result was <50 c/mL, perform a scheduled or unscheduled visit to reassess HIV-1 RNAa in a time frame 
consistent with Section 7.1.1.1. 
If previous HIV-1 RNA result was ≥50 c/mL, discuss results with the ViiV medical monitorb,c  Participant has met criteria for 
additional HIV-1 RNA testing or possible withdrawal. 
If the participant is withdrawn under the above criteria, they will have met “Precautionary Virologic Withdrawal Criteria (PVW)” 
If the 2 previous consecutive HIV-1 RNA results were ≥50 c/mL and <200 c/mL, the participant has not met PVW. 
Current HIV-1 RNA ≥200 c/mL 
If previous HIV-1 RNA result was <50 c/mL, perform a scheduled or unscheduled visit to reassess HIV-1 RNAa in a time frame 
consistent with Section 7.1.1.1. Participant has met “Suspected Virologic Withdrawal Criteria (SVW)”.  
• 
If the repeat HIV-1 RNA is ≥ 200 c/mL, the participant has met Protocol Defined Virologic Failure (PDVF) criteria (Section 
7.1.1).d 
• 
If the repeat HIV-1 RNA is 50-199 c/mL, then discuss results with the ViiV medical monitor. 
If previous HIV-1 RNA result was ≥50 c/mL, the participant has met PDVF criteria (Section 7.1.1). 
a. 
Investigators should not schedule reassessment blood draws in the presence of factors that could be associated with virologic blips, such as intercurrent infection, treatment 
interruption due to toxicity management or non-compliance, or vaccination. Participants should have received full doses of study intervention for at least 2 weeks at the time of 
plasma HIV-1 RNA reassessment. 
b. 
In case of withdrawal, a sample from the initial visit will be used for resistance testing. If resistance testing will not be done, withdrawing participants should be transitioned off 
study intervention as soon as possible.  
c. 
The medical monitor and investigator should consider intercurrent illness, recent immunization, interruption of therapy or other non-virologic reasons associated with transient 
elevated HIV-1 RNA measurements 50 and <200 c/mL. If no non-virologic reasons are identified to explain the lack of virologic suppression, the participant must be withdrawn.  
If the Investigator and the medical monitor agree that the participant is experiencing a slow re-suppression due to one of the above issues, then a retest HIV-1 RNA measurement 
is required in in a time frame consistent with Section 7.1.1.1. If the HIV-1 RNA remains 50 c/mL on a second retest (the third consecutive HIV-1 RNA assessment), the 
participant must be withdrawn. 
d. 
Participants with confirmed HIV-1 RNA results in the range 200 c/mL to <500 c/mL, should be transitioned off study intervention and withdrawn from study immediately. 


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4.1.2.2.2. Virtual Visits 
Virtual visits may be conducted via phone, or via any video app (e.g., Skype, FaceTime, 
WhatsApp, Zoom), as allowed by local regulations.   
Ideally, the participant will complete the CSSRS (via phone or computer) prior to the 
virtual contact by the site staff so that any alert for a positive response can be acted upon 
with the participant – to counsel or refer for additional assessment. 
The discussion between site staff and the participant will include, at a minimum, those 
assessments outlined in the SoA (Section 1.3), as well as reminders regarding dose 
administration, the requirement for those on the GSK3640254 arms that the dose needs to 
be taken with a meal, study-preferred lifestyle restrictions (Section 5.3), instruction for 
the next virtual or in-clinic visit, as well as reminders for POCBP to perform an at-home, 
monthly pregnancy test and report the results to the site. Site staff should ask general 
questions to assess the emotional wellbeing of the participant, listening for cues for 
suicidal ideation and behavior (SIB) or any other unusual changes in behavior. 
4.1.2.2.3. Primary Analyses and Optimal Dose Selection 
The primary analysis will evaluate all available data as outlined in the endpoints for 
primary and secondary objectives. The Week 24 analysis of efficacy, safety/tolerability, 
PK and resistance will allow the Sponsor to determine an optimal dose for GSK3640254. 
The quantitative criteria used to evaluate success or futility based upon the Week 24 
primary analysis (proportion of Virologic Responders, i.e., participants with HIV-1 RNA 
<50 c/mL) are described in Section 9.5.  
After an optimal dose is selected by the Sponsor, a communication will be sent to Health 
Authorities/Ethics Committees for their information, where required or requested.  
4.1.2.2.4. Potential cART Reimbursement after Last Dose of Study Treatment 
Sponsor recognizes that the clinical goal is for all participants to achieve and maintain 
virologic suppression. When a participant is discontinued from the trial early, whether 
they are a Virologic Non-Responder at Week 24 or they are withdrawn early for any 
other reason, there may be situations where sites may be reimbursed for up to a 6-week 
supply of Investigator selected/prescribed antiretroviral medication to facilitate the 
transition of participants to non-study cART. Any brief duration of reimbursement longer 
than 6 weeks, expected to be in individual and rare circumstances, may be considered 
with Sponsor.  
Specific direction will be provided by GSK Local Operating Company (LOC) personnel, 
who will determine for which country(ies) this is not a viable option, e.g., where 
reimbursement is not allowed by local regulations, or where acquisition of cART can be 
obtained without delay.   
4.1.2.3. 
Switch to Optimal Dose 
After the optimal dose has been chosen, and after the last participant completes their 
Week 48 visit, participants will move into the Non-Randomised Phase. Participants on 


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the GSK3640254 arms will change from the blinded dose to the open label optimal dose. 
Simultaneously, these participants will also be switched from the dual NRTI therapy to 
DTG. GSK3640254 participants will qualify to move into the open label, Non-
Randomised phase if their most recent HIV-1 RNA <50 c/mL. Participants in the 
GSK3640254 Arms with their most recent HIV-1 RNA = 50-199 c/mL may be able to 
make this change as well, but only after site’s consultation with the ViiV medical 
monitor, else they will be discontinued from the study. 
Sponsor, with the Investigator, will assess clinical criteria (e.g., assessment of adherence 
by Investigator) and laboratory criteria (e.g., HIV-1 RNA and CD4+ T-cell count) 
relative to the risk/benefit ratio for continuation of each participant into the Non-
Randomised Phase of the trial. 
Thereafter, the trial will be fully open label with just 2 arms: 
• Arms 1, 2 & 3 will switch to the Open Label GSK3640254 Optimal Dose + Open 
Label DTG  
• Participants on the Open Label DTG + ABC/3TC or FTC/TAF arm will continue 
unchanged into the Non-Randomised Phase and their participation in the 
treatment phase will end as each individual participant reaches their Week 144 
visit. 
Participants on the blinded GSK3640254 arms will have their blinded GSK3640254 
treatment switched to the optimal, open label dose of GSK3640254 at their next regular 
visit, or earlier if necessary (e.g., if one of the doses is identified as being suboptimal and 
it is determined that the switch should happen sooner). Investigators and participants will 
then be unblinded to participant’s initial GSK3640254 dose as well as to the optimal dose 
of GSK3640254.   
The trial at this point will be fully open label. 
Data from this fully open, Non-Randomised Phase will provide long-term, comparative, 
descriptive information on durability of response, safety/tolerability, and resistance when 
GSK3640254 is given in combination with DTG. 
4.1.3. 
Follow-up 
When a participant withdraws/discontinues early (at any point prior to the end of the 
study, including Virologic Non-responders at Week 24), participants will be required to 
be seen in-clinic for a follow-up visit between 2 to 4 weeks after their last on-treatment 
visit. These data comprise an essential evaluation that needs to be done before 
discharging any participant from the study. 
For participants who have reached the end of the study (DTG Reference arm = at Week 
144; GSK3640254 Arm = when the study is declared to be at the end), the in clinic 
Follow-up visit will be conducted 2-4 weeks after the last dose of study medications for 
those who, at the last study visit, have ongoing AEs, SAEs regardless of attributability, 
and any laboratory abnormalities that are considered to be AEs or potentially harmful to 


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the participant.  Assessments at the Follow-up visit should reflect any ongoing 
complaints (e.g., blood draws to follow a laboratory abnormality).  
Beyond this follow-up visit (outside of the study), all AEs, SAEs  and clinically relevant 
vitals, ECG findings, and lab abnormalities will be followed towards acceptable clinical 
resolution. 
Participants who are withdrawn for reasons of safety should continue to be followed even 
beyond the study final, follow-up visit (outside of the study) to assess the outcome of the 
safety event that triggered discontinuation of study drug (as determined by the 
Investigator).  
4.1.4. 
Study Completion  
The study will be completed when either the development of GSK3640254 is 
discontinued or until GSK3640254 is locally approved and commercially available 
(anticipated to be in the year 2027).  
Alternatively, this study could be completed at an earlier date and participants would 
continue in a rollover study that would be anticipated to be complete in 2027. 
For study status purposes, a participant is considered to be complete if they attend the last 
on treatment visit at the end of study for participants in the GSK2640254 arm, and at 
Week 144 (for participants in the DTG reference arm). The Follow-Up visit is not 
required for successful completion of the study. 
4.1.5. 
Optional Stomach Substudy (Esophagogastroduodenoscopy 
[EGD] with Biopsy and Serum Biomarkers) 
To explore the monitoring of potential gastric toxicity in the stomach of HIV-1 infected 
participants, a substudy will explore the potential relationship (if any) between Serum 
Biomarkers and the occurrence of any findings on EGD on biopsy (see Exploratory 
Objective in Section 3).  
The Day 1 EGD with Biopsy will likely need to be performed during the Screening 
Period since performing both this procedure and an entire Day 1 visit all on the same day 
is unlikely. 
The Day 1 blood collection for Serum Biomarkers will be collected at the Day 1 visit. 
An EGD with biopsy will be performed for Day 1 (baseline assessment [prior to first 
dose]; to be done in the Screening period once main study eligibility has been 
confirmed), and again for Week 24 and Week 96.  It is reasonably expected that the 
procedure should be performed ± 2 weeks around the Week 24 and Week 96 visit 
milestones (and any other visit at which an EGD could additionally be requested [See 
Section 8.6.1]). 
Specifically, this will be accomplished by participants voluntarily electing to take part in 
a Stomach substudy (e.g., signing a separate additional informed consent form [ICF] 


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agreeing to undergo the procedure at the GI facility). The Stomach substudy will seek to 
recruit approximately 7 participants from each of the 4 treatment arms, approximately 28 
participants in total. 
A gastroenterologist is expected to be a co-Investigator/sub-Investigator (where locally 
allowed and/or possible) with sites that will participate in this substudy. Not only will the 
participant sign a distinct Stomach Substudy Sponsor ICF, but also a consent as required 
by the facility of the gastroenterologist who will inform the participant of the risks, 
benefits, and alternatives of undergoing the procedure to ensure the participant is making 
an informed decision about their willingness to participate. 
A certified endoscopist must determine that the participant is suitable to undergo the 
procedure. This will be accomplished by a separate, pre-procedural evaluation. This may 
include but is not limited to (as dictated by local SOC: history, physical examination 
(including airway examination), and noting allergies or prior adverse reaction to sedation. 
Additional unscheduled laboratory (e.g. pregnancy testing, coagulation studies, 
type/screen) and imaging (e.g. chest radiograph) assessments before or after the EGD are 
at the discretion of the endoscopist based upon patient risk factors [Pasha, 2014] and 
local SOC. The endoscopist must have appropriate facilities, equipment, and clinical staff 
support to ensure the safety of the participant pre-, peri-, and post-procedure. This 
includes but is not limited to: ongoing assessment of the participant’s clinical condition 
and vitals, respiratory support, rescuing from over-sedation, and cardiopulmonary 
resuscitation). 
The endoscopist will provide direction on NPO timing and administration of routine daily 
medications. The choice of pre-, peri-, and post-procedure medications will be left to the 
discretion of the endoscopist and be permitted at any point in the study. Drugs which 
prolong the QTc should be avoided. Participant monitoring may include vitals and level 
of sedation evaluation: pre-procedure, after sedatives/analgesics, at minimum of every 5 
minutes during the procedure, during recovery, and before discharge (or as dictated by 
local SOC). Additional monitoring may include assessment of ventilator status and 
cardiac electrical activity [Early, 2018]. Post-procedure recovery instructions (e.g. 
limitations on driving or operating machinery) are at the discretion of the endoscopist 
[Levitzky, 2010]. 
Procedural details (including but not limited to gross findings, biopsies taken, and any 
intervention) of the EGD will be captured within an eCRF. Redacted endoscopic 
photographs, where allowed by local regulations, will be stored with the Sponsor. For 
additional details, please see the SRM. 
Details of the optional Stomach Substudy biomarker needs are outlined in Section 8.6.1. 
Blood for this purpose will be collected at the regular clinic visits at Day 1 and at Weeks 
24, 48 and 96. 
The screening period may be extended for participants in the EGD substudy (see Section 
5.5.1). 
If a participant withdraws from the Stomach Substudy, they may still continue in the 
main study. 


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4.1.5.1. 
Stomach Substudy Enrollment Considerations 
The Stomach Substudy, with EGD with biopsy and serum biomarkers, seeks to recruit 28 
participants from the pool of 150 randomized. 
Recruitment into the substudy will be monitored on an ongoing basis.  
Given the nature of voluntarily electing to undergo an additional invasive procedure (in 
addition to all routine study evaluations and procedures), there is a probability that, even 
though the study has sufficiently screened enough participants to achieve 150 
randomized, the Stomach substudy may not have recruited the goal of 28 participants 
total. In this event, the clinical study team may decide to leave the Screening period open 
(for approximately another 2 months, or until 30 additional participants have been 
screened, or until the substudy is filled, whichever comes first) to increase the clinical 
probability of recruiting more participants to voluntarily participate in the Stomach 
substudy. This, in an effort to arrive as close to the original target goal of 7 participants 
per treatment arm (28 in total). 
This will be handled in the following manner: 
• If the least number of participants within the substudy is 4-6 in any arm, Sponsor may 
decide to keep the enrollment period open as described above.  
OR  
• If the least number of participants within the Stomach substudy is 1-3 in any arm, the 
study as a whole will not seek to enrol additional participants. This is because there is 
a lower clinical probability that a large proportion of the additional participants would 
volunteer to participate in the Stomach substudy. 
Sponsor may also decide to let the Stomach Substudy over-enroll to account for any 
substudy discontinuations prior to the collection of the Week 24 sample (needed for the 
comparison to Day 1) 
 
4.1.5.2. 
Stomach Substudy Criteria for Discontinuing an Individual Participant 
A participant with the following findings on any EGD Biopsy sample (at any time) will 
be discontinued from the study if any of the following findings are encountered: 
• 
Dysplasia 
• 
Moderate inflammation and moderate intestinal metaplasia 
• 
Severe changes seen in single cell necrosis of parietal cells, chief cell atrophy or 
cytoplasmic alteration, decreased cellularity of parietal cells or chief cells, inflammation, 
or Spasmolytic polypeptide-expressing metaplasia (SPEM). 


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4.1.5.3. 
Stomach Substudy Criteria for Stopping the Study 
Overall trial stopping criteria (for stopping the substudy altogether) will be based upon all 
participants in the experimental arms participating in the Stomach Substudy (regardless 
of any other criteria, e.g. efficacy): 
• 
≥ 1 participant with any degree of Dysplasia in any treatment arm 
• 
≥ 4 participants with moderate inflammation and moderate Intestinal Metaplasia 
• 
≥ 4 participants with severe changes seen in single cell necrosis of parietal cells, 
chief cell atrophy or cytoplasmic alteration, decreased cellularity of parietal cells or chief 
cells, inflammation, or SPEM. 
4.2. 
Scientific Rationale for Study Design 
208379 is a Phase 2b, dose-range finding assessment of 100 mg, 150 mg and 200 mg 
once-daily doses of GSK3640254 administered with food.  Based on available 
GSK3640254 data, including in vitro virology, PK, antiviral activity/resistance, and 
safety/tolerability data from completed clinical trials, doses 100 mg, 150 mg and 200 mg 
are anticipated to provide adequate antiviral activity/efficacy and be well-tolerated (in 
combination with ABC/3TC or FTC/TAF). The primary endpoint will assess efficacy by 
determining the proportion of virologic responders (participants with plasma HIV-1 RNA 
<50 c/mL at Week 24). HIV-1 RNA is highly predictive of meaningful clinical benefit 
[U.S. Food and Drug Administration, Center for Drug Evaluation and Research, 2015].   
The approved ARVs (ABC/3TC, FTC/TAF) and the DTG-based control arm chosen for 
this study are accepted agents for initiation of antiretroviral therapy in treatment 
guidelines [European AIDS Clinical Society Guidelines, 2020; Panel on Antiretroviral 
Guidelines for Adults and Adolescents, 2019] and, as such, are considered appropriate for 
this trial.  
4.2.1. 
Community Experts Input into Design 
Input from community experts revealed their understanding of the clinical and scientific 
justifications for the visit schedule, and for the assessments and procedures that 
participants will undergo.   
Input also revealed the desire to maintain realistic expectations of the patient population 
in a long-term study.  Based on that feedback, this study does not include restrictive 
requirements for alcohol, tobacco and marijuana, rather, suggestions for study-preferred 
limits that should be highly encouraged at each visit.   
4.3. 
Justification for Dose 
The planned doses for this Phase 2b study (100 mg, 150 mg, and 200 mg QD 
administered with food) were selected based on population PK and exposure-response 
(E-R) modelling and clinical trial simulations of antiviral effect as described in this 
section. The doses were targeted to achieve a minimum of 75% of maximum effect 


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predicted at day 8 and to maintain steady-state C above the 3-times protein binding-
adjusted EC90 (3xPBAEC90) target of 0.11 µg/mL (in-vitro EC90 value for in-vitro 
virus containing R361K/V362I/L363M substitutions) in 95% of the subjects.  
A population pharmacokinetic model was developed using the single dose (1 – 400 mg) 
and multiple dose (50-320 mg QD for 14 days) data from healthy subjects from the FTIH 
study 207187, as well as the multiple dose data in HIV-1 infected subjects (10 mg – 200 
mg QD for 7-10 days). All doses were administered with a moderate-fat meal. The 
pharmacokinetics of GSK3640254 (given with food) was described by a two-
compartment model with sequential zero-order absorption (in the depot compartment) 
followed by first order absorption (from depot to the central compartment) and first order 
elimination. Inter-individual variability was estimated on the apparent oral clearance 
(CL/F), apparent volume of distribution of the central compartment (V2/F), 
intercompartmental clearance (Q/F), absorption rate constant (Ka), and duration of the 
zero-order process (D1). The CL/F and V2/F were scaled using fixed allometric 
coefficients of 0.75 and 1, respectively. Weight was found to be a significant covariate on 
Ka. In addition, Study (as a surrogate for subject type and GSK3640254 salt differences) 
was also found to be significant covariates on bioavailability (F was ~27% lower in the 
FTIH study compared to that from the PoC). Evaluation of the post-hoc individual 
estimates of Cmax, AUC and C indicated that model-estimated PK parameters were 
comparable to the observed values. 
The objective of the E-R analysis was to characterize the relationship between antiviral 
activity and exposure of GSK3640254 in HIV-1 infected subjects, and to determine the 
effect of key covariates (including baseline EC50, baseline viral load, baseline CD4 and 
CD8 T-cell counts) on GSK3640254 antiviral activity. The E-R analysis was conducted 
using the data from the Phase 2a study 208132 (up to day 8/9 [Visit 5] in Part 1 and up to 
day 8 [Visit 6] in Part 2. All doses were administered with a moderate-fat meal. The 
decline in HIV-1 RNA over 7 or 10 days (and the treatment emergent genotypic and 
phenotypic changes) in HIV-1 infected treatment naïve adults is described in Section 
2.2.4. 
The E-R was assessed via an inhibitory Emax model using the observed average steady-
state C and maximum viral load decline from baseline. None of the screened covariates 
were found to be significant and therefore were not included in the full covariate model. 
The population PK model of GSK3640254 was integrated with the E-R model and short-
term clinical trials simulations were conducted (500 trials with 60 subjects/ dose level 
mrgsolve_0.8.9 package in R version 3.2.5) by sampling from the multivariate normal 
distribution and covariance matrix to include both uncertainty in parameter estimates and 
inter-subject variability. It was assumed that the bioavailability of GSK3640254 in Ph2b 
will be similar to that from study 208132. For each individual, the anticipated response 
(maximum viral load decline) and percent of maximum effect was estimated. Simulations 
were then summarized by computing the median percent of maximum effect for each 
dose across the trials. The results of the simulations summarized in Table 5 indicate that 
doses ≥100 mg QD administered with food are predicted to result in a median percent of 
maximum effect at day 8 of at least 75%. In addition, a 300 mg QD dose is not predicted 


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to provide a significant increase in predicted % of maximum effect compared to the 200 
mg dose.   
Table 5 
Predicted Median Percent of Maximum Effect [90% PI] at Day 8 for 
GSK3640254 Doses Ranging from 75 mg to 300 mg QD administered 
with food (500 trials with n=60 subjects per dose level) 
Dose (mg) 
Median [5%, 95%] Percent of Maximum Effect 
75 
70.4 [47.5, 95.4] 
100 
78.0 [54.5, 98.1] 
125 
83.1 [61.4, 99.6] 
150 
86.4 [66.6, 101] 
200 
90.4 [73.1, 102] 
300 
94.2 [80.1, 103] 
PI = Prediction Interval 
 
Figure 2 depicts the predicted decline in viral load versus C at Day 8 and boxplot 
summary of predicted C by proposed dose levels. 
Figure 2 
Simulated Predicted Decline in HIV-1 RNA versus Predicted C at 
Day 8 
Top panel – Dashed and solid blue lines are 5th, 95th and median of simulated data, respectively. Shaded area is the 
90% prediction interval of simulated data. Bottom panel – the middle bar inside the boxes represents the median; 
the ends of the boxes are the 25th and 75th percentiles; the whiskers are the 5th and 95th percentiles of simulated 
C. The red dashed line in both panels represents the 3xPBAEC90 (determined in-vitro based on virus with 
R361K/V362I/L363M substitutions). 
 


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Table 6 presents the model-predicted steady-state GSK3640254 PK parameters at the 
planned doses following QD administration with food. As expected, the predicted PK 
parameter values for the maximum proposed dose of 200 mg QD administered with food 
fall within the observed 95% CI of the geometric mean PK parameters from the PoC 
study 208132 (Table 3 in Section 2.2.4).  The associated inhibitory quotient (IQ) for each 
dose was calculated by dividing C median [5th – 95th percentiles] by the 3xPBAEC90 
(Table 6).  
The results show that all proposed doses are predicted to result in C values 
>3xPBAEC90 in more than 95% of the subjects (i.e. C 5th percentile for the 100 mg 
dose >0.11 g/mL) (Table 6). In addition, the planned doses provide a median IQ ranging 
from 4 – 8. Taking into account the variability in parameter estimates, the predicted IQ 
over the proposed doses ranges from 1.4 to 18.2.  By comparison, for GSK3532795, a 
previous generation MI, the median IQ in phase 2b (calculated as C/1xPBAEC90 based 
on in-vitro 370 virus) for the 180 mg QD dose (maximum tested dose) was 
approximately 1.5. Therefore, assuming a biologically plausible correlate between Day 8 
antiviral response and Week 24 efficacy, when GSK3640254 is combined with two 
potent NRTIs (ABC/3TC or FTC/TAF), the response rate at week 24 is likely to be 
similar or better than GSK3532795 180 mg QD (i.e. >82.4% for week 24 snapshot 
<40c/mL).  
Table 6 
Predicted Steady-State PK Parameters Median [90% PI] Following 
Once a Day Dosing of GSK3640254 with Food and Associated IQ 
Dose 
(mg) 
Median [5th – 95th Percentiles] 1 
Cmax (g/mL) 
AUC(0-24) (g.h/mL) 
C (g/mL) 
IQ (Fold Above 
3xPBAEC90)2 
100 
1.11 [0.652-1.9] 
15 [8.2-27] 
0.442 [0.153-0.999] 
4 [1.4 - 9.1] 
150 
1.67 [0.978-2.85] 
23 [12-41] 
0.663 [0.23-1.5] 
6 [2.1 - 13.6] 
200 
2.22 [1.3-3.8] 
30 [16-54] 
0.883 [0.307-2] 
8 [2.8 - 18.2] 
PI = Prediction Interval 
1All simulations included uncertainty and inter-subject variability in parameter estimates. 
2 3xPBAEC90 = 0.11 g/mL based on in-vitro virus containing R361K/V362I/L363M 
substitutions. 
 
Calculated Fold Coverage for Selected Doses 
Predicted GSK3640254 safety coverage based on NOAEL and LOAEL exposure in the 
non-clinical chronic toxicity studies in rat and dog for the at the planned doses given once 
daily with food  are presented in Table 7.  
Table 7 
Predicted Safety Cover Following  Once a Day Dosing of 
GSK3640254 with Food 
Dose (mg) 
Fold cover dog NOAEL:human 
AUC(0-24) 1 
Fold cover rat LOAEL:human 
AUC(0-24) 2 
Fold cover dog 
LOAEL:human AUC(0-24)3 
100 
0.56  
1.26  
3.1 
150 
0.36  
0.82  
2.0 
200 
0.28 
0.63  
1.6 


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1 Based on dog NOAELmean AUC of 8.37 from non-clinical chronic studies and the model-predicted median AUC 
(Table 6). 
2 Based on rat LOAEL mean AUC of 18.9 µg.h/mL  from non-clinical chronic studies and the model-predicted 
median AUC (Table 6).  
3 Based on dog LOAEL mean AUC of 46.4 µg.h/mL  from non-clinical chronic studies and the model-predicted 
median AUC (Table 6).  
 
At the highest planned dose of 200 mg QD, the model-based predicted exposure 
corresponds to 0.3-fold the NOAEL (AUC = 8.37 ug.hr/mL) in dogs, 0.63-fold the 
LOAEL in rats (AUC = 18.9 ug.hr/mL) and 1.6-fold the LOAEL in dogs (AUC = 46.6 
ug.hr/mL) from chronic toxicity studies (See Section 2.2.2) (Table 7). All microscopic 
findings in the stomach of rats and dogs and changes in serum gastrin were shown to be 
partially reversible following a 4-week recovery period. Potential effects in the stomach 
of humans during clinical trials are being investigated in a gastric safety substudy (See 
Section 1.3 and Section 8.6.1) with appropriate clinical monitoring (See Section 2.2, 
Section 4.1.5, and Section 8.6).   
With regard to potential for QT prolongation, as noted in Section 2.3, in the 
concentration-QTc analysis using the Multiple Ascending Dose data collected in the 
FTIH study 207187, a QTcF effect above 10 ms could be excluded up to GSK3640254 
mean plasma concentrations of approximately 2000 ng/mL, which corresponds to doses 
of approximately 200 mg (Table 3 and Table 6). The cardiovascular risk mitigation 
strategy for QT prolongation is described in Section 2.3.1. 
Evaluated and anticipated Drug Interactions Between GSK3640254 and 
coadministered ARVs 
In this Phase IIb study, investigators will choose either FTC/TAF or ABC/3TC fixed dose 
combination as the allowed NRTI backbone for use in combination with GSK3640254.  
DDI risk with FTC/TAF 
As emtricitabine and tenofovir are primarily eliminated by renal mechanisms with the 
majority of drug eliminated unchanged in the urine, a drug interaction with GSK3640254 
is not anticipated with these NRTIs. However, as unexpected drug interactions have been 
reported between tenofovir and other antiviral therapy agents, a one-way drug interaction 
clinical study was conducted to evaluate the potential impact of GSK3640254 on 
FTC/TAF (208134) [GlaxoSmithKline Document Number 2018383314_00]. Results 
from this study showed that GSK3640254 does not affect the steady-state plasma 
concentrations of TAF, tenofovir (TFV) or FTC. In addition, the PK of GSK3640254 in 
this study were similar to what has been observed previously .  
DDI risk with ABC/3TC 
ABC and 3TC are not significantly metabolised by CYP enzymes nor do they inhibit or 
induce this enzyme system. The primary pathways of ABC metabolism in human are by 
alcohol dehydrogenase (~30%) and by glucuronidation (~36%). These metabolites are 
excreted in the urine. Lamivudine is predominantly eliminated by active organic cationic 
secretion. Therefore, the likelihood of metabolic interactions between GSK3640254 with 
ABC or 3TC is low. 


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3TC and ABC demonstrate no or weak inhibition of the OATP1B1, OATP1B3, BCRP 
and Pgp or and toxin extrusion protein 2-K (MATE2-K). In addition, 3TC demonstrates 
no or weak inhibition of the drug transporters MATE1or OCT3 and ABC demonstrates 
minimal inhibition of organic cation transporter 1 (OCT1) and organic cation transporter 
2 (OCT2). 3TC and ABC are therefore not expected to affect the plasma concentrations 
of GSK3640254 in the event that it is a substrate of these transporters. In addition, 
although ABC is an inhibitor of MATE1 and 3TC is an inhibitor of OCT1 and OCT2 in 
vitro, they have low potential to affect the plasma concentrations of substrates of these 
transporters at therapeutic drug exposures (up to 600 mg for abacavir or 300 mg for 
lamivudine). 
In vitro, abacavir is not a substrate of OATP1B1, OATP1B3, OCT1, OCT2, OAT1, 
MATE1, MATE2-K, MRP2 or MRP4 therefore potential modulation of these 
transporters by GSK3640254 is not expected to affect ABC plasma concentrations.  
Although ABC and 3TC are substrates of BCRP and Pgp in vitro, clinical studies 
demonstrate no clinically significant changes in ABC pharmacokinetics when 
coadministered with lopinavir/ritonovir (Pgp and BCRP inhibitors) and inhibitors of these 
efflux transporters are unlikely to affect the disposition of 3TC due to its high 
bioavailability. 3TC is an in vitro substrate of MATE1, MATE2-K and OCT2. 
Trimethoprim (an inhibitor of these drug transporters) has been shown to increase 3TC 
3TC plasma concentrations however; the resulting increase was not clinically significant. 
3TC is a substrate of the hepatic uptake transporter OCT1. As hepatic elimination plays a 
minor role in the clearance of 3TC, drug interactions due to inhibition of OCT1 are 
unlikely to be of clinical significance.  
DDI risk with DTG 
A Phase 1, two-way drug interaction study with GSK3640254 and DTG showed no effect 
on plasma GSK3640254 PK. GSK3640254 200 mg QD increased plasma DTG AUC(0-
τ), Cmax and Cτ by 17%, 9%, and 24%, respectively. These increases were not 
considered clinically meaningful. 
In summary, based on the lack of observed or predicted clinically meaningful drug 
interactions, GSK3640254 can be administered with either NRTI backbone or DTG 
combinations without dose adjustments.  
Assessment of the Change in Formulation and Effect of Food 
The recently completed Phase 2a clinical trial (208132) utilized capsules; this Phase 2b 
will use tablets. Study 213567 was a relative bioavailability and food effect study 
performed to compare the exposures between the GSK3640254 tablet and capsule in the 
presence of moderate fat meal and to investigate the effect of food on the PK of the 
GSK3640254 tablet. As shown in Table 8, the tablet provided similar exposures to the 
capsule when both were given with food.  


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Table 8 
Assessment of Relative Bioavailability: Preliminary Statistical 
Comparison of Plasma GSK3640254 PK Parameters Based on 
Nominal Time (Study 213567) 
PK Parameter 
Ratio of GLS Means for Test vs. Reference [90%CI] (%Ref) 
AUC(0-) h*g/mL  
99.8 [92.6, 108] 
AUC(0-t) h*g/mL 
100 [93.2, 108] 
Cmaxg/mL 
109 [98.8, 121] 
1. 
Ref: Treatment A;  Test: Treatment B 
Treatment A: GSK3640254 200 mg (capsules) administered under moderate fat conditions. 
Treatment B: GSK3640254 200 mg (tablets) administered under moderate fat conditions. 
 
The summary of the statistical analysis for the assessment of food effect presented in 
Table 9 shows that GSK3640254 AUC(0-) and Cmax values following administration 
of the tablet with a moderate fat meal are 345% to 484% higher relative to administration 
in a fasted state, respectively. In addition, GSK3640254 AUC(0-) and Cmax following 
administration of the tablet with a high fat meal is 306% to 365% higher relative to 
administration in fasted state, respectively.  
Table 9 
Assessment of Food Effect: Preliminary Statistical Comparison of 
Plasma GSK3640254 PK Parameters Based on Nominal Time (Study 
213567) 
PK Parameter 
Test vs Ref 
Ratio of GLS Means for Test vs. Reference [90%CI] (%Ref) 
AUC(0-) h*g/mL  
C vs D 
345 [288, 413] 
E vs D 
306 [256, 366] 
AUC(0-t) h*g/mL 
C vs D 
378 [318, 449] 
E vs D 
335 [282, 399] 
Cmaxg/mL 
C vs D 
484 [391, 599] 
E vs D 
365 [295, 451] 
Treatment C: GSK3640254 200 mg (tablets) administered under moderate fat conditions (test). 
Treatment D: GSK3640254 200 mg (tablets) administered under fasted conditions (ref). 
Treatment E: GSK3640254 200 mg (tablets) administered under high fat conditions (test). 
In summary, the results from the RBA and food effect study indicate that no dose 
adjustments are required due to the change in formulation based on:  
• The similarity in PK parameters between the tablet used in this Phase 2b study 
and the capsule used in the Phase 2a in the presence of a moderate fat meal. 
• The dose predictions are based on modelling of the data from studies in which 
GSK3540254 was administered with food. 
In conclusion, the GSK3640254 dose range is anticipated to study a range of exposures 
which should provide therapeutic benefit (virologic suppression and antiviral activity) 
while being well tolerated (in combination with ABC/3TC or FTC/TAF and subsequently 
DTG). 


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4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
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. 
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the VH Investigational Product (IP) or other study 
treatment that may impact participant eligibility is provided in the current IB 
[GlaxoSmithKline Document Number 2018N379610_02] for GSK3640254, and in the 
current prescribing information for Epzicom (ABC/3TC) [Epzicom USPI, 2019], 
Descovy (FTC/TAF) [Descovy USPI, 2019 and Tivicay [Tivicay USPI, 2020]. 
The generation of geno/phenotype results from Monogram Biosciences (see Section 
8.6.2) can be affected by several factors (including but not limited to shipping delays and 
repeating of steps within the PCR process), resulting in reporting delays that can 
jeopardize the ability of a participant to be randomized within their Screening window.  
To mitigate this issue, the following actions may be taken: 
a. The 42-day Screening period may be extended to a maximum of 63 days 
while awaiting the Monogram results. See Section 5.5. 
b. There may be cases where local resistance test results may be used to 
determine eligibility. VH (Clinical Virologist) will review any local test 
results and the methodology used to determine if the results are suitable 
for use in this trial. The (sole) decision of VH will be final. See details in 
the SRM. 
c. Note: the Monogram Biosciences PSGT result will still be reported in 
usual fashion. In the unlikely event of a discordant result (local test 
genotypically susceptible and PSGT net assessment resistant), the 
randomized participant will be withdrawn from the study. 
Rescreen: Participants are allowed to rescreen for this study one time with the exception 
of clinically irreversible findings in Screening; examples include but are not limited to: 
presence of HLA-B*5701 allele, liver cirrhosis, CDC Stage 3 disease, drug 
allergy/sensitivity, significant psychiatric disorder, cardiac arrythmias, or established 
archived drug resistance. See Section 5.4. 
When a participant has to be rescreened, the Monogram results from the prior 208379 
Screening period may be used to determine eligibility (though the Monogram samples for 
the Rescreen should still be collected, results of which, too, should eventually be filed). 


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Retest: A single repeat test (retest) per laboratory analyte is allowed during a single 
Screening period to determine eligibility (with the exception of Screening 
genotype/phenotype, HLA testing or other, as determined by the medical monitor).  
Pre-procedure evaluations/assessments done/requested by the gastroenterologist prior to 
each of the EGDs should be done only once.  
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. 
Participants must be 18 years of age inclusive, at the time of signing the informed 
consent.   
 
Type of Participants and Disease Characteristics 
2. 
Treatment-naïve, defined as no ARVs (in combination or monotherapy) received 
after the diagnosis of HIV-1 infection (e.g., use of PreP meets inclusion); 
3. 
Documented HIV infection and Screening plasma HIV-1 RNA 1000 copies/mL; 
4. 
Screening CD4+ T-cell count 250 cells/mm3;  
5. 
Antiviral susceptibility to the NRTI backbone selected should be demonstrated 
Weight 
6. 
Body weight 50.0 kg (110 lbs.) for men and 45.0 kg (99 lbs) for women and 
body mass index (BMI) > 18.5 kg/m2.  Calculations will utilize sex assigned at 
birth. 
Sex 
7. 
Participants who are male at birth and participants who are female at birth  
*NOTE: There are no contraceptive requirements for participants who are male at 
birth. 
a. Participants who are female at birth 
Contraceptive use by participants who are female at birth should be consistent 
with local regulations regarding the methods of contraception for those 
participating in clinical studies. 
• A participant who is female at birth is eligible to participate if they are not 
pregnant or breastfeeding, and one of the following conditions applies: 
o Is a participant of non-childbearing potential (PONCBP) as defined in 
Section 10.4, Contraceptive and Barrier Guidance; 
OR 


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o Is a POCBP (as defined in Section 10.4) and using an acceptable 
contraceptive method as described in Section 10.4.2 during the study 
intervention period (at a minimum until after the last dose of study 
intervention). The investigator should evaluate the potential for 
contraceptive method failure (e.g., noncompliance, recently initiated 
in relationship to the first dose of study intervention.  
▪ If a hormonal method is selected, the participant is required to be 
clinically stable on it for at least one month prior to starting 
treatment in the study. 
• A POCBP must have a negative highly sensitive serum pregnancy test 42 
days before the first dose of study intervention. See Section 8.2.5 
Pregnancy Testing. 
• Additional requirements for pregnancy testing during and after study 
intervention are located in Section 8.2.5. 
• The Investigator is responsible for review of medical history, menstrual 
history, and recent sexual activity to decrease the risk for inclusion of a 
woman with an early undetected pregnancy. 
Informed Consent 
8. Capable of giving signed informed consent as described in Section 10.1.3 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
Other 
9. For participants enrolled in France: a participant will be eligible for inclusion in 
this study only if either affiliated to or a beneficiary of a social security category.  
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 
3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring systemic 
therapy; 
2. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, 
or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or 
penile intraepithelial neoplasia;  
Note: Other localized malignancies require agreement between the investigator 
and the ViiV Medical Monitor for inclusion. 
3. Presence of primary HIV-1 infection, evidenced by acute retroviral syndrome (e.g., 
fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented 
viremia without antibody production and/or evidence of recent (within 3 months) 
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4. Known history of liver cirrhosis with or without viral hepatitis co-infection;  
5. 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) 
6. History of ongoing or clinically relevant hepatitis within the previous 6 months; 
7. History of drug or other allergy that, in the opinion of the Investigator or Medical 
Monitor, contraindicates their participation;  
8. Any history of significant underlying psychiatric disorder, in the opinion of the 
Investigator or ViiV Medical Monitor, including but not limited to schizophrenia, 
bipolar disorder with or without psychotic symptoms, other psychotic disorders, or 
schizotypal (personality) disorder; or a clinical assessment of suicidality based on 
the responses on the eCSSRS; 
9. Any history of major depressive disorder with or without suicidal features, or 
anxiety disorders, that required medical intervention (pharmacologic or not) such as 
hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient 
treatment;   
Note: Participants with other conditions such as adjustment disorder or dysthymia 
that have required shorter term medical therapy (<6 months) without inpatient 
treatment and are currently well-controlled clinically or resolved may be 
considered for entry after discussion and agreement with the ViiV Medical 
Monitor. 
10. Any pre-existing physical or other psychiatric condition (including alcohol or drug 
abuse), which, in the opinion of the Investigator or ViiV Medical Monitor (with or 
without psychiatric evaluation), could interfere with the participant’s ability to 
comply with the dosing schedule and protocol evaluations or which might 
compromise the safety of the participant;  
11. A pre-existing condition, in the opinion of the Investigator or ViiV Medical Monitor, 
that could interfere with normal gastrointestinal anatomy or motility (e.g., 
gastroesophageal reflux disease [GERD], gastric ulcers, gastritis, inflammatory 
bowel disease), hepatic and/or renal function, or with the absorption, metabolism, 
and/or excretion of the study drugs or render the participant unable to take oral study 
treatment; 
12. Myocardial infarction in the past 3 months; 
13. Familial or personal history of long QT syndrome or sudden cardiac death; 
14. Medical history, current or historical, of significant cardiac arrhythmias or ECG 
findings which, in the opinion of the Investigator or ViiV Medical Monitor, will 
interfere with the safety of the participant;  
Note: Examples of ECG findings include symptomatic bradycardia, non-sustained 
or sustained atrial arrhythmias, non-sustained ventricular tachycardia (VT) or 
sustained VT, second degree atrioventricular block (AVB) Mobitz Type II, or 
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Prior/Concomitant Therapy 
15. Active Treatment for a viral infection other than HIV-1, such as Hepatitis B, with an 
agent that is active against HIV-1 (were known to be infected with HIV-1 after 
treatment for Hepatitis B was completed); 
16. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;  
17. Treatment with any of the following agents within 28 days of Screening: radiation 
therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant;  
18. Participants receiving any protocol-prohibited medication and who are unwilling or 
unable to switch to an alternate medication;   
19. Participants who are unwilling to stop any medications as required by the local lab 
test for H. pylori. 
20. Participants who require concomitant medications known to be associated with a 
prolonged QTc (see list from https://www.crediblemeds.org). 
 
Prior/Concurrent Clinical Study Experience 
21. Exposure to an experimental drug, human blood product, monoclonal antibody, or 
vaccine (which does not have emergency, conditional, or standard market 
authorization) within 28 days prior to the first dose of study treatment; 
Note: Consult with the Medical Monitor if clarification is needed. Treatment with 
a SARS-CoV-2 vaccine that has received emergency, conditional, or standard 
market authorization is allowed if the principal investigator (PI) determines that 
the benefit-risk profile for that individual study participant is favourable.  The use 
of other investigational COVID vaccines that have not received emergency, 
conditional, or standard market authorization and are still only used in clinical 
trials will not be allowed at this time.  
22. Current enrollment or past participation within the last 30 days before signing of 
consent in any other clinical study involving an investigational study intervention 
(including an investigational COVID vaccine) or any other type of medical research. 
Diagnostic assessments 
23. Any evidence of viral resistance based on the NRTI backbone selected  
24. Historical evidence (prior to study screening period) of the presence of resistance-
associated mutations gag A364V or A364A/V 
25. Creatinine Clearance <50 mL/min;  
26. ALT ≥ 3x ULN or ALT ≥ 2x ULN and total bilirubin ≥ 1.5x ULN (upper limit of 
normal) 
27. Evidence of Hepatitis B virus (HBV) infection based on the results of testing for 
Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), 
Hepatitis B surface antibody (anti-HBs) and reflex HBV DNA as follows: 


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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 on reflex testing 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. 
See SRM for additional details. 
28. Positive Hepatitis C antibody test result at Screening AND positive on reflex to 
Hepatitis C RNA; 
Note: Participants with positive Hepatitis C antibody due to prior resolved disease 
can be enrolled only if a confirmatory negative Hepatitis C RNA test is obtained  
29. Positive test results for Helicobacter pylori [Chey, 2017]; 
Note: Participants who test positive for H. pylori can be treated/eradicated and 
retested with the same Screening period. The repeat test for H. pylori must be done 
no sooner than 28 days after the last dose of antibiotic treatment for the infection 
[Chey, 2017]. 
30. Known or suspected active COVID-19 infection OR contact with an individual with 
known COVID-19, within 14 days of study enrollment (WHO definitions Section 
10.11.5.2.1). Note, this study does not require a negative molecular test for SARS-
CoV-2 for entry into the study.  
31. Untreated syphilis infection [positive rapid plasma reagin (RPR) at Screening] 
without documentation of treatment.   
Note: Patients with a known syphilis infection can be Screened for the study no 
sooner than 14 days after the last dose of treatment for the syphilis infection.  
Participants who are assessed to have syphilis by the Screening tests can be 
treated within the Screening period, though the start of study treatment can be no 
sooner than 30 days after the last dose of treatment for the syphilis infection.  
32. Presence of moderate-to-severe hepatic impairment (Class B or C) as determined by 
Child-Pugh classification (see Section 10.7);  
33. Any acute laboratory abnormality at Screening, which, in the opinion of the 
investigator or ViiV Medical Monitor, would preclude participation in the study of 
an investigational compound; 
34. Urine Drug Screen positive (showing presence of): Amphetamines, Barbiturates, 
Cocaine, MDMA, or Phencyclidine, or non-prescribed opiates, oxycodone, 
benzodiazepines, methadone, methamphetamines, or tricyclic antidepressants; 
Notes: 
If the urine drug screen shows the presence of opiates, oxycodone, 
benzodiazepines, methadone, methamphetamines, or tricyclic antidepressants that 
are prescribed, the participant can be considered for the trial at the discretion of 
the Investigator recognizing at the time of enrollment: no studies on relevant drug 
interaction or GSK3640254 absorption-distribution-metabolism-elimination 
(ADME) will have been completed.  


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A positive result for THC is not exclusionary, though the PI should assess usage 
and only refer for the treatment phase those participants who seem appropriate for 
the trial, i.e., whose use of marijuana would not interfere with the participant’s 
ability to comply with the required daily dosing schedule and protocol 
evaluations, or that might compromise the safety of the participant. 
35. Any clinically relevant Grade 4 laboratory abnormality at Screen, including results 
for creatine phosphokinase (CPK), and lipid abnormalities that lack a compelling 
explanation from the Investigator;        
Note:  Grade 4 CPK and lipid abnormalities that are explained by the Investigator, 
and with assent from the ViiV Medical Monitor, will not exclude the participant. 
36. Where participation in the study would result in donation of blood or blood products 
in excess of 500 mL within 28 days;  
37. Exposure to more than 4 new investigational drugs or vaccines (exclusive of a 
SARS-CoV-2  potential indication) within 12 months prior to the first dosing day;  
38. Treatment with radiation therapy or cytotoxic chemotherapeutic agents or any 
systemic immunosuppressive agent within 30 days of study drug administration or 
anticipated need for such treatment within the study;   
39. ECG Heart Rate <50 bpm or >100 bpm, or QTcF >450 msec; 
 
Notes: 
• A heart rate of <50 or >110 is exclusionary and cannot be rechecked to 
determine eligibility.  
• A heart rate from 101 - 110 bpm can be rechecked by a single repeat ECG or 
by vitals within 30 minutes to verify eligibility. 
• The QT interval is corrected for heart rate according to Fridericia’s formula 
(QTcF). It is either machine read or manually over-read by the Investigator. 
QTcF is used to determine eligibility and discontinuation for a participant in 
this study.  
• The Investigator’s or ViiV Medical Monitor’s over-read can supersede that of 
the machine at any time. 
40. FOR PORTUGAL ONLY: HIV-2 infection (either determined by prior testing, 
medical history, or obtained locally during the Screening window) 
Other Exclusions 
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 interventions. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Dose administration with GSK3640254 is required to be taken with a low-fat meal (may 
include but not limited to 400-500 calories, with 25% calories from fat) [FDA, 2019].   


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5.3.2. 
Alcohol, Tobacco and Marijuana 
• It is suggested that alcohol consumption should be limited throughout study 
participation to the following: An average weekly intake of <14 drinks for 
participants assigned as male at birth or <7 drinks for participants assigned as female 
at birth. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 
ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits. 
• Only clinically minor to moderate use (as determined by the PI/SI) of tobacco 
products will be allowed during study participation.  
• Participants should refrain from the use of marijuana. 
5.3.3. 
Activity 
Participants will abstain from strenuous exercise for 24 hours before each clinic visit to 
reduce the chances of seeing a high CPK result in the study lab results.  
See Section 10.9.5 for follow up assessments for elevated CPK. 
5.3.4. 
Counsel regarding safe sex practices 
All participants should be counselled on safer sexual practices including the use and 
benefit/risk of effective barrier methods and on the risk of HIV transmission to an 
uninfected partner. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, any/all eligibility criteria that have not been met, and 
any serious SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened an additional time if, in the opinion of the Investigator, a current 
clinical outlook of the participant seems favorable for study inclusion (and if the 
participant never received study medication in this trial).  Rescreened participants will be 
assigned a new participant number and will sign a new ICF(s).  
As noted in Section 5, clinically irreversible findings found during screening would result 
in the individual not being screened a second time; examples include but are not limited 
to: liver cirrhosis, CDC Stage 3 disease, drug allergy or sensitivity, significant psychiatric 
disorder, cardiac arrythmias, or established, archived drug resistance.   
5.5. 
Criteria for Temporarily Delaying Randomization 
The Screening period may be extended up to a maximum of 63 days for those 
participating in the optional Stomach Substudy for the purpose of accommodating any 


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scheduling issues for the procedure, or if more time is needed to obtain results needed to 
determine eligibility. 
5.5.1. 
Delaying Randomization for EGD Scheduling 
It is anticipated that the EGD procedure will not be able to be performed on the same day 
as the Day 1 clinic visit for the main study. It will need to be performed during the 
Screening period. The intent is to get a baseline assessment, regardless of the visit 
designation.  
The participant’s overall eligibility for the main study should be confirmed prior to the 
participant undergoing the EGD procedure during the Screening period. Ideally, the 
procedure should be scheduled as soon as possible for a date occurring during the 42-day 
Screening period after all lab results are expected to be available so that main study 
eligibility can be confirmed prior to proceeding with the EGD procedure.   
However, if the EGD cannot be scheduled within that 42-day timeframe, the EGD can be 
scheduled within an extended period of time, as long as the Day 1 start date for the main 
study can be accomplished on or before the maximum extension period of 63 days.  
5.5.2. 
Delaying Randomization – Other 
The Screening period may be extended beyond 42 days to a maximum of 63 days to 
account for additional time needed to determine eligibility. Examples include but are not 
limited to (subject to approval from the Medical Monitor): awaiting delayed Monogram 
results, allowing time for treatment for H. pylori and the subsequent retest, allowing time 
for the treatment of syphilis.   
5.5.3. 
Contemporary lab results  
If a Screening Period will be extended into the Day 43 – Day 63 timeframe, most 
Screening labs will need to be repeated to have a more current clinical picture of the 
participant.  
• Chemistry, hematology (preferably), HIV RNA, lymphocyte subsets should be 
repeated so that the results can be available to reassess eligibility by those results.  
New results override those done previously in the Screening period. At the time of 
Day 1, these results cannot be more than 42 days old. 
• HBV, HCV, HLA-B*5701 allele testing, geno/phenotype testing, lipids, RPR, 
PT/INR should not be repeated. 
• A repeat of the Urine Drug Screen is at the discretion of the Investigator. New 
results override those done previously in the Screening period. 


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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo, or medical device(s) intended to be 
administered to a study participant according to the study protocol. 
6.1. 
Study Intervention(s) Administered 
Randomised Phase 
Arm 1 
GSK3640254 100 mg 
+ ABC/3TC or 
FTC/TAF 
GSK3640254 100 mg 
+ ABC/3TC or 
FTC/TAF 
GSK3640254 100 mg + ABC/3TC or FTC/TAF 
Intervention 
Name 
GSK3640254 
Placebo to match 
GSK3640254 
ABC/3TC (The clinical label will state 
Abacavir/ Lamivudine, 600mg/300mg 
to match the SPC) 
FTC/TAF (The clinical label will 
state emtricitabine/ tenofovir 
alafenamide 200 mg / 25 mg to 
match the SPC) 
Type  
Drug 
Drug 
Drug 
Drug 
Dose Formulation 
Tablet 
Tablet 
Tablet 
Tablet 
Unit Dose 
Strength(s) 
100 mg  
0mg  
abacavir 600 mg / lamivudine 300 mg 
emtricitabine 200 mg / tenofovir 
alafenamide 25 mg 
Dosage Level(s) 
One tablet per day 
Two tablets per day 
One tablet per day 
One tablet per day 
Route of 
Administration 
Oral 
Oral 
Oral 
Oral 
Use 
Experimental 
Placebo 
Background 
Background 


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IMP and NIMP 
IMP 
IMP 
IMP where provided centrally; 
Otherwise dependent on local 
regulations. 
IMP where provided centrally; 
Otherwise dependent on local 
regulations. 
Sourcing 
Provided centrally by 
Sponsor 
Provided centrally by 
Sponsor 
Provided centrally by Sponsor or 
Locally sourced. 
Provided centrally by Sponsor or 
Locally sourced. 
Packaging and 
Labeling 
32 tablets per HDPE 
bottle, labelled per 
country requirement 
32 tablets per HDPE 
bottle, labelled per 
country requirement 
30 tablets per HDPE bottle, labelled 
per country requirement  
30 tablets per HDPE bottle, 
labelled per country requirement 
Arm 2 
GSK3640254 150 mg 
+ ABC/3TC or 
FTC/TAF 
GSK3640254 150 mg 
+ ABC/3TC or 
FTC/TAF 
GSK3640254 150 mg + ABC/3TC or FTC/TAF 
Intervention 
Name 
GSK3640254 
GSK3640254 
ABC/3TC (The clinical label will state 
Abacavir/ Lamivudine, 600mg/300mg 
to match the SPC) 
FTC/TAF (The clinical label will 
state emtricitabine/ tenofovir 
alafenamide 200 mg / 25 mg to 
match the SPC) 
Type  
Drug 
Drug 
Drug 
Drug 
Dose Formulation 
Tablet 
Tablet 
Tablet 
Tablet 
Unit Dose 
Strength(s) 
100 mg  
25 mg 
abacavir 600 mg / lamivudine 300 mg 
emtricitabine 200 mg / tenofovir 
alafenamide 25 mg 
Dosage Level(s) 
One tablet per day 
Two tablets per day 
One tablet per day 
One tablet per day 
Route of 
Administration 
Oral 
Oral 
Oral 
Oral 


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Use 
Experimental 
Experimental 
Background 
Background 
IMP and NIMP 
IMP 
IMP 
IMP where provided centrally; 
Otherwise dependent on local 
regulations. 
IMP where provided centrally; 
Otherwise dependent on local 
regulations. 
Sourcing 
Provided centrally by 
Sponsor 
Provided centrally by 
Sponsor 
Provided centrally by Sponsor or 
Locally sourced. 
Provided centrally by Sponsor or 
Locally sourced. 
Packaging and 
Labeling 
32 tablets per HDPE 
bottle, labelled per 
country requirement 
32 tablets per HDPE 
bottle, labelled per 
country requirement 
30 tablets per HDPE bottle, labelled 
per country requirement  
30 tablets per HDPE bottle, 
labelled per country requirement 
Arm 3 
GSK3640254 200 mg 
+ ABC/3TC or 
FTC/TAF 
GSK3640254 200 mg 
+ ABC/3TC or 
FTC/TAF 
GSK3640254 200 mg + ABC/3TC or FTC/TAF 
Intervention 
Name 
GSK3640254 
Placebo to match 
GSK3640254 
ABC/3TC (The clinical label will state 
Abacavir/ Lamivudine, 600mg/300mg 
to match the SPC) 
FTC/TAF (The clinical label will 
state emtricitabine/ tenofovir 
alafenamide 200 mg / 25 mg to 
match the SPC) 
Type  
Drug 
Drug 
Drug 
Drug 
Dose Formulation 
Tablet 
Tablet 
Tablet 
Tablet 
Unit Dose 
Strength(s) 
100 mg  
0mg  
abacavir 600 mg / lamivudine 300 mg 
emtricitabine 200 mg / tenofovir 
alafenamide 25 mg 
Dosage Level(s) 
2 tablets per day 
1 tablet per day 
One tablet per day 
One tablet per day 


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Route of 
Administration 
Oral 
Oral 
Oral 
Oral 
Use 
Experimental 
Placebo 
Background 
Background 
IMP and NIMP 
IMP 
IMP 
IMP where provided centrally; 
Otherwise dependent on local 
regulations.  
IMP where provided centrally; 
Otherwise dependent on local 
regulations. 
Sourcing 
Provided centrally by 
Sponsor 
Provided centrally by 
Sponsor 
Provided centrally by Sponsor or 
Locally sourced 
Provided centrally by Sponsor or 
Locally sourced. 
Packaging and 
Labeling 
32 tablets per HDPE 
bottle, labelled per 
country requirement 
32 tablets per HDPE 
bottle, labelled per 
country requirement 
30 tablets per HDPE bottle, labelled 
per country requirement  
30 tablets per HDPE bottle, 
labelled per country requirement 
Arm 4 / 
Reference Arm 
DTG + ABC/3TC or FTC/TAF 
DTG + ABC/3TC or FTC/TAF 
Intervention 
Name 
Tivicay (The clinical label will state 
Dolutegravir 50mg to match the SPC)  
ABC/3TC (The clinical label will state 
Abacavir/ Lamivudine, 600mg/300mg to 
match the SPC) 
FTC/TAF (The clinical label will state 
emtricitabine/ tenofovir alafenamide 200 
mg / 25 mg to match the SPC) 
Type  
Drug 
Drug 
Drug 
Dose Formulation 
Tablet 
Tablet 
Tablet 
Unit Dose 
Strength(s) 
Dolutegravir 50 mg 
abacavir 600 mg / lamivudine 300 mg 
emtricitabine 200 mg / tenofovir 
alafenamide 25 mg 
Dosage Level(s) 
One tablet per day 
One tablet per day 
One tablet per day 


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Route of 
Administration 
Oral 
Oral 
Oral 
Use 
Comparator 
Background 
Background 
IMP and NIMP 
IMP 
IMP where provided centrally; Otherwise 
dependent on local regulations. 
IMP where provided centrally; Otherwise 
dependent on local regulations. 
Sourcing 
Provided centrally by Sponsor 
Provided centrally by Sponsor or Locally 
sourced. 
Provided centrally by Sponsor or Locally 
sourced. 
Packaging and 
Labeling 
30 tablets per HDPE bottle, labelled 
per country requirement 
30 tablets per HDPE bottle, labelled per 
country requirement 
30 tablets per HDPE bottle, labelled per 
country requirement 
 


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6.2. 
Preparation/Handling/Storage/Accountability 
1. 
The Investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. 
Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff. 
3. 
The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
4. 
Further guidance and information for the final disposition of unused study 
intervention are provided in the SRM. 
• 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff.   
• 
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 and VH. 
• 
IP accountability will be evaluated using pill counts.  This assessment will be 
conducted during each clinic visit through study completion or early withdrawal. IP 
accountability records must be maintained throughout the course of the study. 
• 
Please refer to Appendix 11 in Section 10.11 for study management information 
during the COVID-19 pandemic. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This study will use an IVRS/IWRS. 
 
• All participants will be centrally randomized using an Interactive Voice/Web 
Response System (IVRS/IWRS).  Before the study is initiated, the telephone number 
and call-in directions for the IVRS and/or the log-in information & directions for the 
IWRS will be provided to each site 
• Study interventions will be dispensed at the study visits summarized in the SOA. 
• Returned study intervention should not be re-dispensed to any other participant. 
 
To minimize bias, the dose level of GSK3640254 in each of the treatment arms 
containing GSK3640254 will be blinded to the research participants and all study 
personnel during the study. The Sponsor personnel will also remain blinded until the 
database lock for the Week 24 analysis. 


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Controlled early access to unblinded PK and PKPD related data will be granted to the 
designated CPMS vendor contracted to perform the population PK model and any PK 
review necessary for planned or unplanned safety reviews. 
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
intervention assignment for any participant with an SAE. If the SAE requires that an 
expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
report, identifying the participant’s intervention assignment, may be sent to Investigators 
in accordance with local regulations and/or GSK and VH policy. 
The IVRS/IWRS will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
participant’s intervention assignment is warranted.  Participant safety must always be the 
first consideration in making such a determination.  If the investigator decides that 
unblinding is warranted, the investigator should make every effort to contact GSK prior 
to unblinding a participant’s intervention assignment unless this could delay emergency 
intervention of the participant.  If a participant’s intervention assignment is unblinded 
GSK must be notified within 24 hours after breaking the blind. The date and reason that 
the blind was broken must be recorded in the source documentation and case report form, 
as applicable. 
A participant will be withdrawn if the participant’s intervention code is unblinded by the 
Investigator or treating physician. The primary reason for the discontinuation (the event 
or condition which led to the unblinding) will be recorded expeditiously in the eCRF. 
6.4. 
Study Intervention Compliance 
• When participants are dosed at the site, the date and time of each dose administered in 
the clinic will be recorded in the source documents.  
• When participants self-administer study intervention(s) at home, compliance with 
study medications will be assessed by direct questioning and review of the diary card 
during the site visits and documented in the source documents and relevant form. 
Deviation(s) from the prescribed dosage regimen should be recorded. 
• A record of the number of study medication tablets dispensed to and taken by each 
participant must be maintained and reconciled with study intervention and 
compliance records.  
6.5. 
Dose Modification 
No dose modifications (to doses described in this protocol, or as modified by any IDMC 
recommendation [see Section 9.5.1]) are allowed in this protocol, including for a decline 
in Creatinine Clearance. 


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6.6. 
Continued Access to Study Intervention after the End of the 
Study 
The study (or a rollover study) is expected to close in the year 2027 at the time 
GSK3640254 would be expected to be commercially available and/or available in local 
access programs. 
6.7. 
Treatment of Overdose 
Any tablet intake exceeding the randomized daily number of tablets will be considered an 
overdose.  
Sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for AE/SAE and laboratory abnormalities until study 
intervention can no longer be detected systemically (at least 5 days). 
3. Obtain a plasma sample for PK analysis within 7 days from the date of the last dose 
of study intervention if requested by the Medical Monitor (determined on a case-by-
case basis). 
4. Document the quantity of the excess dose as well as the duration of the overdosing in 
the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
6.8. 
Concomitant Therapy 
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. Concomitant medications (prescription and non-
prescription) should be administered only as medically necessary during the study.   
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. 


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Because non-HIV vaccines (e.g. Influenza vaccine or SARS-CoV-2 vaccine) may cause a 
temporary increase in the level of HIV-1 plasma RNA, it is highly recommended that a 
vaccine, if necessary, be given during or immediately after a scheduled visit after all 
laboratory tests have been drawn when possible.  This approach will minimize the risk of 
non-specific increases in the level of plasma HIV-1 RNA at the next scheduled 
assessment if possible. 
DTG should be administered with the following considerations: 
• 
2 hours before or 6 hours after taking antacid or laxative products or sucralfate 
containing polyvalent cations (e.g. aluminium and magnesium) or calcium 
supplements.  Proton pump inhibitors and H2-antagonists may be used in place of 
antacids with no scheduling restrictions, though importantly, Proton Pump 
Inhibitors are prohibited therapy for any participant in any arm electing to 
participate in the Stomach substudy.  
• 
Concurrent administration with multivitamins is acceptable.  Iron supplements can 
be taken with study treatment provided that all are taken together with a meal. 
• 
Under fasted conditions, DTG should be given 2 hours prior to OR 6 hours after 
iron supplements. 
Metformin concentrations may be increased by DTG.  A dose adjustment of metformin 
should be considered when starting and stopping co-administration of DTG with 
metformin, to maintain glycemic control. 
Clinical monitoring is recommended for participants taking methadone, as methadone 
maintenance therapy may need to be adjusted in some participants. 
Non-protocol defined treatments or medical interventions (e.g., physical therapy, 
radiotherapy, surgical procedures) are permitted during the study for appropriate medical 
management of the participant.  
6.8.1. 
Prohibited Medications and Non-Drug Therapies 
6.8.1.1. 
Prohibited Medications: All Participants 
The following, general concomitant medications or therapies are not permitted at any 
time during the study: 
• 
HIV immunotherapeutic vaccines are not permitted at any time during the study.  
• 
Other experimental agents, antiretroviral drugs not otherwise specified in the 
protocol, cytotoxic chemotherapy, or radiation therapy may not be administered.  
• 
Systemically administered immunomodulators (such as interleukin and interferon 
agents) are prohibited (a list of examples is provided in the SRM) 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]. 


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• 
Proton Pump Inhibitors are prohibited therapy for any participant in any arm 
electing to participate in the Stomach substudy.  
6.8.1.2. 
Medications that need to be stopped in Screening 
The following medications need to be stopped at least 4 weeks prior to the first dose: 
• Carbamazepine 
• Oxcarbamazepine 
• Phenobarbital 
• Phenytoin 
• Rifampicin or rifapentine 
• St. John’s wort (Hypericum perforatum) 
• Any other strong CYP3A Inducers (e.g., dexamethasone, rifapentine, rifabutine, etc) 
• Fampridine 
The following medications need to be stopped at least 2 weeks prior to the first dose: 
• Dofetilide and pilsicainide. 
Any substrate of (OCT2), with a narrow therapeutic window should not be administered 
concurrently with DTG containing products.  
6.8.1.3. 
On Treatment Prohibited Medications: GSK3640254 Arms 
The following medications may significantly interact with GSK3640254 and are not 
permitted: 
• Strong CYP3A inhibitor (Clarithromycin, telithromycin, nefazodone, itraconazole, 
ketoconazole etc);  
• Strong CYP3A inducer (e.g. phenobarbital, dexamethasone, carbamazepine, 
phenytoin, rifampin, rifapentine, rifabutine, St John’s wort, etc); 
• Substrate of OATP1B3 (e.g. telmisartan, valsartan, olmesartan, rifampin, ezetimibe, 
statins such as atorvastatin, rosuvastatin, pitavastatin). 
For information on concurrent therapies and interactions suspected to be relevant to 
other antiretroviral therapy in the regimen, please consult the local prescribing 
information. 
6.8.1.4. 
On Treatment Prohibited Medications: When dosing with DTG in any 
arm 
This list applies to the Reference Arm, and to the GSK3640254 Arm once DTG is 
combined with the optimal dose in the open label Non-Randomised Phase. 


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• The following medications or their equivalents may cause decreased concentrations 
of DTG. Therefore, they may not be administered concurrently in participants on the 
DTG arm.  
• 
Carbamazepine 
• 
Oxcarbamazepine 
• 
Phenobarbital 
• 
Phenytoin 
• 
Rifampicin and rifapentine 
• 
St. John’s wort (Hypericum perforatum) 
• 
Fampridine 
• Dofetilide and pilsicainide are prohibited as DTG may inhibit their renal tubular 
secretion resulting in increased dofetilide/pilsicainide concentrations and potential for 
toxicity. Any substrate of the OCT2 with a narrow therapeutic window should not be 
administered concurrently with DTG containing products (see prescribing info). 
For information on concurrent therapies and interactions suspected to be relevant to 
other antiretroviral therapy in the regimen, please consult the local prescribing 
information. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Upon study discontinuation, cART should be started, as selected/prescribed/provided by 
their physician. 
7.1. 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention. If study intervention is permanently discontinued, the participant will 
perform an Early Withdrawal visit (see SOA, Section 1.3) and then be evaluated in 2-4 
weeks at a Final Follow-up Visit. See the SoA for data to be collected at the time of 
discontinuation of study intervention. 
Participants must be discontinued from the study for any of the following reasons: 
• 
Confirmed or Suspected Hypersensitivity Reaction; 
• 
Confirmed Virologic Failures as defined in Section 7.1.1; 
• 
Virologic Non-Responder at Week 24, defined as participants who have either: 
o 
HIV-1 RNA ≥200 c/mL at Week 24, or  
o 
HIV-1 RNA ≥50 c/mL on repeat testing of Week 24 results and prior to 
Week 28 (see Figure 1 in Section 4.1.2.2.1) 


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• 
If DTG resistance associated mutations (RAM) are detected in viral RNA at Week 
4 in participants in the GSK3640254 treatment arms, the participant may continue 
on study through the Week 48 secondary endpoint BUT may NOT switch over 
into the open label phase with GSK3640254 Optimal Dose + DTG due to the 
DTG RAM; 
• 
Participant requires substitution or dose modification of GSK3640254, ABC/3TC, 
FTC/TAF or DTG;  
• 
Switch of the dual NRTI background (ABC/3TC to FTC/TAF, or vice versa) 
occurring after the Week 2 visit AND the participant has a last on-treatment HIV-
1 RNA ≥50 c/mL; 
• 
Switch of the dual NRTI background (ABC/3TC to FTC/TAF, or vice versa) for a 
reason other than toxicity management; 
• 
Treatment emergent resistance to any component of the study medications. For 
participants receiving GSK3640254, the genotypic emergence of an A364V or 
A364A/V requires discontinuation.  
• 
For participants receiving GSK3640254, a PhenoSense Gag cFCIC50 > 50 (on-
treatment FCIC50/Day 1 FCIC50);  
• 
Liver toxicity where stopping criteria specified in Section 7.1.2 are met; 
• 
Allergic reaction or Rash criteria as described in Section 10.9.2.1 and Section 
10.9.2.2, respectively, are met and no compelling alternate cause is identified; 
• 
Renal toxicity is met and no compelling alternate cause is identified (an estimated 
GFR of <50mL/min on confirmed measurement as defined in Section 10.9.6); 
• 
Confirmed Proximal Renal Tubule Dysfunction ([PRTD] See Section 10.9.7); 
• 
Pregnancy (intrauterine), regardless of termination status of pregnancy (See 
Section 8.2.5); 
• 
Diagnosis of Hepatitis B or C viral infection; 
• 
Any clinically significant AE deemed to require discontinuation of the IP; 
• 
Moderate to severe (as clinically determined by the investigator) COVID-19 
infection (suspect, probable, or confirmed using the most recent version of the 
WHO case definition) 
• 
A Grade 4 or related Grade 3 AE: the Investigator will discontinue the participant 
from the study. If the AE, in the opinion of the investigator, may be representative 
of gastric toxicity (e.g. obstipation, diarrhea, dysphagia/odynophagia, GI 
bleeding, mucositis/stomatitis, or nausea), the Investigator may consider 
performing an evaluation/management plan incorporating elements in the GI 
Intolerability Evaluation and Management table (Section 8.2.7); 
• 
Any Grade 3 or higher Psychiatric AE. The Investigator will discontinue the 
participant from the study and arrange for emergency psychiatric 
evaluation/management; the panel for drugs of abuse will be tested. 


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• 
New onset suicidal ideation, as clinically diagnosed by the Investigator (in 
consultation with psychiatry, if needed). The Investigator will discontinue the 
participant from the study and arrange for urgent specialist psychiatric 
evaluation/management.   
• 
Any clinically relevant Grade 4 laboratory abnormalities (with the exception of an 
asymptomatic grade 4 cholesterol, triglyceride or CPK increase - in the absence of 
a clinically reasonable explanation);  
• 
Participants who require concomitant medications known to be associated with a 
prolonged QTc;  
• 
A triplicate set of on-treatment ECGs show the average QTcF >500 msec or 
increase from baseline QTc >60 msec (See Section 7.1.4);  
• 
If Stomach Substudy Individual Stopping Criteria are met (See Section 4.1.5.2). 
7.1.1. 
Protocol-Defined Virologic Failure  
Virologic failure must be confirmed by a repeat and consecutive plasma HIV-1 RNA 
measurement between two and four weeks after the initial suspected virologic failure 
sample.  
Participants should receive full dose of study treatments across all plasma sampling times 
used for determining virologic failure.  
For the purposes of clinical management in this study, protocol-defined virologic failure  
(PDVF) is defined as any of the following: 
Virologic Non-response  
• Decrease from Baseline (Day 1) in plasma HIV-1 RNA of ˂1.0 log10 c/mL unless 
plasma HIV-1 RNA is <200 c/mL by Week 12; 
• Confirmed plasma HIV-1 RNA levels ≥200 c/mL at or after Week 24 (See Figure 1 
and Table 4, Section 4.1.2.2.1);  
• Plasma HIV-1 RNA ≥50 c/mL on repeat testing of Week 24 results and prior to Week 
28 (see Figure 1 in Section 4.1.2.2.1). 
Virologic Rebound  
• Confirmed plasma HIV-1 RNA ≥200 c/mL after confirmed consecutive plasma 
HIV-1 RNA <50 c/mL (see Table 4 in Section 4.1.2.2.1). 
Participants who meet the definition of virologic failure must be immediately 
discontinued from the study.  


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7.1.1.1. 
Managing Suspected Virologic Failure/Endpoint Cases 
Inadequate adherence is a common cause for virologic failure and should be explored as a 
first step in management of study participants (e.g., at the first indication of inadequate 
virologic response or rebound).  
All cases that meet a criterion for suspected virologic failure must be confirmed by a 
second measurement performed at least 2 weeks but not more than 8 weeks (as 
specified below) apart from the date of the original sample, unless one of the 
extenuating circumstances outlined below applies.  
Only plasma HIV-1 RNA values determined by the central laboratory will be used to 
assess virologic failure. Please refer to Appendix 11 in Section 10.11 for study 
management information during the COVID-19 pandemic.  
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 therapy. 
The following guidelines should be followed for scheduling confirmatory plasma HIV-1 
RNA testing in an effort to avoid false-positive results:  
• 
Confirmatory testing should be scheduled 2 to <4 weeks following resolution of 
any intercurrent illness, during which time the participant should receive full dose 
of all IP.  
• 
Confirmatory testing should be scheduled 4 to ~6 weeks (but no more than 8 
weeks) following any immunization, during which time the participant should 
receive full dose(s) of all IP.  
• 
If therapy is interrupted due to 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.  
Sites should contact the study medical monitor to discuss individual participants, 
whenever necessary. 
7.1.1.2. 
Managing Confirmed Virologic Failure/Endpoint Cases 
A participant who meets confirmed virologic failure must be immediately discontinued 
from the study. Once a participant has been confirmed as meeting the protocol definition 
of confirmed virologic failure, a sample from the suspected virologic failure visit, and a 
sample from the Day 1 visit (if not sent previously), will be sent for genotypic and 
phenotypic resistance testing and the result made known to the Investigator when 
available.   
If the confirmed HIV-1 RNA level is ≥50 and <200 c/mL and the decision is taken to 
withdraw the participant, resistance testing will not be done and the participant should be 


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transitioned off study intervention immediately. For all other confirmed virologic failure 
cases where HIV-1 RNA ≥200 c/mL, resistance testing will be triggered. 
If a participant is withdrawn early from participation in the study, the Investigator must 
make every effort to perform the evaluations outlined in the Schedule of Activities 
(Section 1.3). These data will be recorded, as they comprise an essential evaluation that 
needs to be done before discharging any participant from the study. 
7.1.2. 
Liver Chemistry Stopping and Increased Monitoring Criteria 
Liver chemistry Stopping and Increased Monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology (in alignment with the FDA 
premarketing clinical liver safety guidance). Refer to Appendix 6 in Section 10.6. 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf 
Discontinuation of study intervention for abnormal liver tests is required when: 
• a participant meets one of the conditions outlined in the algorithm or 
• in the presence of abnormal liver chemistries not meeting protocol-specified 
stopping rules, the Investigator believes study intervention discontinuation is in 
the best interest of the participant. 
• Liver Safety Required Actions and Follow up Assessments Section can be found 
in Section 10.6. 
7.1.2.1. Study Intervention Restart or Rechallenge after liver stopping criteria met 
Study intervention restart or rechallenge after liver chemistry stopping criteria are met by 
any participant in this study is not allowed. 
7.1.3. 
Columbia-Suicide Severity Rating Scale 
Emergence of any positive (abnormal) response on the C-SSRS, confirmed by the 
Investigator, during the treatment phase of the study will be cause for immediate clinical 
assessment of suicidality (by the Investigator or a consulting psychiatrist). Emergence of 
new onset suicidal ideation or a Grade 3 or higher psychiatric AE will result in immediate 
discontinuation and urgent specialist psychiatric evaluation and management. 
7.1.4. 
QTc Stopping Criteria 
The same QTcF correction formula must be used for each participant to determine 
eligibility for and discontinuation from the study. This formula may not be changed or 
substituted once the participant has been enrolled. 
The Baseline QTcF should be based on averaged QTcF values of triplicate ECGs 
obtained over a brief recording period from the Day 1 pre-dose ECG (see Section 8.2.3). 


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If a clinically significant finding is identified (including, but not limited to changes from 
baseline in QT interval corrected using Fridericia’s formula [QTcF]) after enrollment, the 
Investigator or qualified designee will determine if the participant can continue in the 
study and if any change in participant management is needed. This review of the ECG 
printed at the time of collection must be documented. Any new clinically relevant finding 
should be reported as an AE. The Investigator’s or ViiV Medical Monitor’s over-read can 
supersede that of the machine at any time. If so, it must be noted in the chart. 
A randomized participant that develops an on-treatment single ECG QTcF >500 msec or 
an increase from baseline QTcF >60 msec should have two repeat unscheduled ECG’s 
within 10 minutes apart. Using these three ECGs, if the average QTcF shows either of the 
following, the participant will be withdrawn from the study (In addition, review of such 
an ECG with a Cardiologist is encouraged): 
• >500 msec, or 
• An increase from baseline QTcF >60 msec 
Finally, this participant should have 1) a complete, unscheduled chemistry panel, 2) an 
unscheduled GSK3640254 PK sample, and 3) repeated unscheduled ECGs until their 
QTc measurement returns to their original averaged QTcF value at Day 1 pre-dose.  
See the SoA (Section 1.3) for data to be collected at the time of intervention 
discontinuation and follow-up and for any further evaluations that need to be completed. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the study 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 compliance reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA. See SoA for data to be collected 
at the time of study discontinuation and follow-up and for any further evaluations 
that need to be completed. 
• The participant will be permanently discontinued both from the study intervention 
and from the study at that time. 
• If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
7.3. 
Lost to Follow Up 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 


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• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of Section 
10.1.9. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (See Section 1.3). 
• Please refer to Appendix 11 in Section 10.11 for study management information 
during the COVID-19 pandemic.  
• Protocol waivers or exemptions are not allowed.  
• Immediate safety concerns should be discussed with the Sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• Adherence to the study design requirements, including those specified in the SoA, 
is essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that 
potential participants meet all eligibility criteria. The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable.  
• Laboratory results that could unblind the study will not be reported to 
investigative sites or other blinded personnel  
• Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
8.1. 
Efficacy Assessments 
• Plasma for quantitative HIV-1 RNA will be generated at time points listed in the 
SOA (see Section 1.3). 
• An HIV-1 RNA PCR assay with a lower limit of detection (LLOD) of 40 c/mL 
will be used. However, the primary and secondary endpoints will define 
responders as HIV-1 RNA <50 c/mL. 


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• Details concerning the handling, labeling and shipping of these samples will be 
supplied separately. 
8.1.1. 
Lymphocyte Subsets by Flow Cytometry 
• Blood samples will be obtained from each participant for the analysis of 
lymphocyte subsets (CD4 and CD8) by flow cytometry at the timepoints listed in 
the SOA (Section 1.3).  
• Details concerning the handling, labeling and shipping of these samples will be 
supplied separately. 
8.1.2. 
Disease Progression 
• HIV-associated conditions will be recorded as per the SoA (Section 1.3).  
• CDC-classification will be assessed according to the 2014 CDC Revised 
Classification System for HIV Infection in Adults (See Section 10.10).  
8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.  
• A targeted physical examination will include, at a minimum, assessments of the 
skin, lungs, heart, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
• Investigators should pay special attention to any signs of rash. 
• Height and weight will also be measured and recorded.  Height will be captured 
only at Screening; Weight will be captured at each visit to accurately calculate 
Creatinine Clearance (CrCL) throughout the study. 
8.2.2. 
Vital Signs 
• 
Vital signs will be collected as indicated in the SOA (Section 1.3). 
• 
Vital signs will be measured in a semi-supine position after 5 minutes rest for the 
participant in a quiet setting without distractions (e.g., television, cell phones) 
and will include temperature, pulse rate (heart rate), respiratory rate, and systolic 
and diastolic blood pressure.  
o Blood pressure and pulse measurements will be done with a completely 
automated device. Manual techniques will be used only if an automated 
device is not available. 


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o Three readings of blood pressure and pulse will be taken. The first reading 
should be rejected. The second and third readings should be recorded in the 
eCRF where the average of the 2 readings will be calculated. 
8.2.3. 
Cardiac Monitoring with Electrocardiograms  
• 
Triplicate and Single 12-lead ECGs will be obtained as outlined in the SOA (see 
Section 1.3) using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTcF intervals. Refer to Section 7.1.4 for 
QTcF withdrawal criteria and additional QTcF readings that may be necessary. 
• 
At each time point at which triplicate ECG are required, 3 individual ECG 
tracings should be obtained as closely as possible in succession, but no more than 
2 minutes apart. The full set of triplicates should be completed in less than 4 
minutes. 
• 
Participant should remain still while the tracing is being recorded.  Site staff 
should review the tracing to look for movement artefact and redo the ECG, if 
necessary. 
• 
The high-quality ECG should be transmitted to the central vendor.  If there is an 
issue with electronic transmission (via analog or LAN), sites will upload the 
ECG tracing directly in the vendor portal. 
• 
The central vendor will not be providing over-reads on any of the ECGs. The 
Investigator (or designee) should review the Screening output to determine if any 
exclusion criteria have been met. Subsequent ECGs should be assessed by the 
Investigator (or designee) for any new issue or parameter results that meet QTc 
stopping criteria (See Section 7.1.4). In addition, review of such an ECG with a 
Cardiologist is encouraged.  
8.2.4. 
Clinical Safety Laboratory Assessments 
Refer to Appendix 2 in Section 10.2 for the list of clinical laboratory tests to be 
performed and to the SoA (Section 1.3) for the timing and frequency. All protocol 
required laboratory assessments must be performed by central laboratory services. Please 
refer to Appendix 11 in Section 10.11 for study management information during the 
COVID-19 pandemic. Laboratory assessments must be conducted in accordance with the 
Laboratory Manual, and SoA (Section 1.3).  Details for the preparation and shipment of 
samples will be provided by Q2 Solutions and are detailed in the laboratory manual.  
Reference ranges for all safety parameters will be provided to the site by Q2 Solutions. 
• 
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in participant management or 
are considered clinically significant by the investigator (e.g. SAE or AE or dose 
modification) the results must be recorded in the eCRF.  Please refer to 
Appendix 11 in Section 10.11 for study management information during the 
COVID-19 pandemic. 
• 
See Section 10.2 for the list of clinical laboratory tests to be performed and 
Section 1.3 for the timing and frequency.  


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• 
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.  
• 
Abnormal laboratory findings associated with the underlying disease are not 
considered clinically significant, unless judged by the investigator to be more 
severe than expected for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or medical monitor.  
• If such values do not return to normal/baseline within a period of time 
judged reasonable by the investigator, the etiology should be identified and 
the Sponsor notified. 
• 
All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3).  
• 
Refer to the SRM for processing and handling of samples to avoid duplicate 
and/or additional blood draws. 
• 
All study-required laboratory assessments will be performed by a central 
laboratory. 
• 
If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded in the eCRF.  Please refer to 
Appendix 11 in Section 10.11 for study management information during the 
COVID-19 pandemic. 
8.2.5. 
Pregnancy Testing 
• Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• Participants of childbearing potential must have a negative serum pregnancy test 
at Screening and a negative urine pregnancy test at Day 1 to be eligible for the 
start of administration of IP.  
o FOR CANADA ONLY: If the Screening Period goes beyond 30 days, a 
more recent serum test is required. See Footnote 9 to the SoA (Section 
1.3) for additional detail. 
• Pregnancy testing (urine and/or serum as required by local regulations) will be 
conducted at Screening, Day 1, and at monthly intervals during study intervention 
period, as outlined in the SOA (Section 1.3). 
8.2.6. 
Suicidal Ideation and Behaviour Risk Monitoring 
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1. Participants with HIV infection occasionally may present with symptoms of 
depression and/or other relevant psychiatric diagnoses that increase the risk for 
suicidality (suicidal ideation or behavior).  In addition, there have been some 
reports of depression, suicidal ideation and behavior (particularly in participants 
with a pre-existing history of depression or psychiatric illness) in some 
participants being treated with INIs, including DTG.  
2. GSK3640254 is not a CNS active drug nor is it being developed for a neurologic 
or psychiatric condition. However, the risk of suicidal ideation was identified with 
the previous generation MI GSK3532795 at supratherapeutic doses.  
Therefore, the use of the CSSRS is appropriate to monitor participants for potential risk 
of suicidality before and during treatment.   
Participants should be monitored appropriately and observed closely for suicidal ideation 
and behavior (SIB) or any other unusual changes in behavior. It is recommended that the 
investigator promptly referral participants for psychiatric evaluation and management 
who experience signs of SIB if encountered during the screening period.  
If randomized and on-treatment, participants presenting with new onset/treatment 
emergent depression (e.g. Grade 3-4) should be advised to contact the investigator 
immediately if symptoms of severe acute depression (including suicidal 
ideation/attempts) develop because discontinuation of study medication and urgent 
specialist psychiatric evaluation and management are required (as noted in Section 7.1.3). 
Independent of psychiatric symptoms, an on-treatment CSSRS will be performed at all 
study visits. Ultimately, in the event of a new onset suicidality as clinically diagnosed by 
the Investigator (in consultation with psychiatry, if needed), the participant will 
discontinue from the trial and the PI/SI will arrange for urgent specialist psychiatric 
evaluation and management.  
Assessment of treatment-emergent suicidality will be clinically diagnosed but monitored 
during this study using the Columbia Suicidality Severity Rating Scale (eC-SSRS). The 
definitions of behavioral suicidal events used in this scale are based on those used in the 
Columbia Suicide History Form [Posner, 2007].  Questions are asked on suicidal 
behavior, suicidal ideation, and intensity of ideation.  Screening visit questions will be in 
relation to lifetime experiences and current experiences (within the past 2 months); all 
subsequent questioning is in relation to the last assessment. 
Additionally, the investigator will collect information using the Possible Suicidality-
Related AE (PSRAE) eCRF form in addition to the AE (non-serious or SAE) eCRF form 
on any participant that experiences a possible suicidality-related AE 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 GSK/VH within 1 week of the investigator diagnosing a 
possible suicidality-related AE.  
In addition to new onset suicidality, emergent non-suicidal Psychiatric AEs will be  
evaluated and managed in the following manner: 


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Any Grade 1 or 2 Psychiatric AE: A Grade 1 or 2 Psychiatric AE may result in 
additional unscheduled visits (in-clinic or at home) as clinically indicated. This may 
include a more in-depth assessment of AE through interview, additional unscheduled 
clinical labs, and/or imaging. Psychiatric consultation may be required at the discretion of 
the PI/SI. Any pharmacotherapy should be discussed with the ViiV Medical Monitor.  
Any Grade 3 or 4 Psychiatric AE: As described in Section 7.1, a Grade 3 or 4 
Psychiatric AE will result in discontinuation from the trial and emergency psychiatric 
evaluation. A urine sample should be submitted for the Drugs of Abuse panel. 
8.2.7. 
GI Intolerability Evaluation & Monitoring Plan (with Stopping 
Criteria) 
Pre-clinical toxicology studies in rats and dogs have suggested a potential for GI related 
toxicity with GSK3640254. Prior clinical trials have not evaluated for the presence of 
gastric toxicity in humans. Thus, it is unclear if any of the GI AEs observed in any 
clinical trial were representative of, associated with, or resulted from gastric toxicity (if 
present). Thus, in a clinically conservative fashion, this section provides general guidance 
to the Investigator on the evaluation and management of primarily upper gastrointestinal 
symptoms (Table 10) irrespective of participation in the optional Stomach substudy. The 
Investigator may contact the VH Medical Monitor to discuss evaluation and management 
(including discontinuation of a participant) of any GI symptoms throughout the trial.


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Table 10 
GI Intolerability Evaluation and Management 
HISTORY  
For symptoms of all grades, a thorough history (and differentiation of acute and chronic manifestations) forms 
the foundation of proper evaluation and management. The following are potential manifestations of some GI 
clinical syndromes that may occur (possibly in combination) during the clinical trial.  
Abdominal Pain 
The Investigator should obtain information on chronology, location, intensity/character, aggravating and alleviating 
factors, and associated symptoms in the context of the participants relevant past medical history [Millham, 2016]. With 
chronic symptoms, factors suggestive of an organic process include: fever, night sweats, loss of appetite, weight loss, 
and nocturnal awakening [Yarze, 2016]. The historical and physical examination should be efficient and lead to an 
accurate diagnosis soon after presentation. 
Nausea and Vomiting 
The investigator should attempt to identify the etiology of these symptoms (and whether it is intraperitoneal, 
extraperitoneal, medication related, infection related, or due to a metabolic disorder [Hasler, 2012].  
Dyspepsia 
The Investigator should identify the presence of red flags (odynophagia, unexplained weight loss, recurrent vomiting, GI 
bleeding, jaundice, palpable mass or adenopathy, or family history of GI malignancy). Symptoms of dyspepsia could 
include early satiety, bloating, or belching. Additionally, atypical symptoms of dyspepsia could include: pharyngitis, 
asthma, bronchitis, hoarseness, chest pain, or abdominal pain.  
Diarrhea 
Similar to other GI symptoms, important historical assessment includes duration, onset, pattern, epidemiology (e.g. 
travel and diet), aggrevating or iatrogenic factors, alleviating factors, stool appearance, presence of other symptoms 
(e.g. abdominal pain), or weight loss. The differential can be narrowed if there are clear watery, inflammatory, or fatty 
manifestations [Schiller, 2016]. 
Other Clinical Syndromes 
Additional diagnostic criteria for other GI disorders potentially encountered in the clinical trial are available. [Stanghellini, 
2016 and Lacy, 2016] 


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PHYSICAL 
EXAMINATION 
Physical examination should complement elements obtained from the history [Hasler, 2012]. The exam elements 
may include: ausculatation for bowel sounds (up to 2 minutes if necessary) and palpation (including 
assessment for rebound, guarding, and muscular rigidity) [Millham, 2016]. Acutely, the investigator may assess 
for signs of intravascular volume depletion (e.g., orthostasis) and/or aspiration of vomitus as appropriate. 
Abdominal tenderness and guarding may indicate inflammation. The presence of fecal blood can indicate 
mucosal damage (e.g., from an ulcer). Complete evaluation of dyspepsia should include an oral examination 
(poor dentition or pharyngeal erythema) and lungs for wheezing.  
DIAGNOSTIC 
EVALUATION AND 
MANAGEMENT 
A major goal in the diagnostic evaluation of a participant with upper GI symptoms is to quickly arrive at a final 
diagnosis without exposing the participant to unnecessary (invasive) testing; Investigators should exercise 
good clinical judgment in this regard [Soll, 2009]. A major goal of therapy is directed at correcting the 
underlying identifiable medical or surgical abnormalities (e.g perforation or infarction) [Malagelada, 2016]. 
Consultation (eg, gastroenterologist) is recommended as clinically indicated. Emergent action should be taken 
as necessary: correction of hypovolemia or electrolyte abnormalities. 
Grade 1 symptoms 
Participants may be treated symptomatically. If participants develop dyspepsia alone, generally only limited and direct 
diagnostic testing should be performed. If the participant has dyspepsia, they should limit alcohol, caffeine, chocolate, 
tobacco, and eating directly before bedtime. Proton Pump Inhibitors are prohibited therapy for any participant in any arm 
electing to participate in the Stomach substudy. 
Grade 2 symptomsa 
Diagnostic testing may include but is not limited to the following (as clinically indicated): 
Serum chemistries (for evaluation of fluid and acid/base/metabolic status) and assessment of white blood cells (with 
differential) and hemoglobin if not recently performed. Amylase and Lipase may also be appropriate. 
Polymerase chain reaction (PCR) for viruses (e.g., Cytomegalovirus [CMV]) 


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Grade 3 symptomsa 
Diagnostic testing may include but is not limited to the following (as clinically indicated): 
• 
The testing outlined above in Grade 2 
• 
A barium swallow  
• 
CT scan to identify gastrointestinal inflammation  
• 
Upper endoscopy with biopsy as indicated (eg, mucosal injury or the presence of red flags). 
Generally, use of imaging should be appropriate and timely. Management should be targeted at addressing the 
underlying pathology. 
Grade 4 symptomsa  
Diagnostic testing may include but is not limited to the following (as clinically indicated): 
• 
The testing outlined above in Grade 2 and Grade 3 
• 
An acute abdominal series 
• 
Focused Assessment with Sonography in Trauma (FAST) Ultrasound 
Initial management can include correction of hemodynamic and electrolyte abnormalities as clinically indicated. After 
stabilization, management should be targeted at addressing the underlying pathology. 
a Grade 4 or related Grade 3 AE: The Investigator will discontinue the participant from the study (see Section 7.1). If the AE, in the opinion of the 
investigator, may be representative of gastric toxicity (e.g. obstipation, diarrhea, dysphagia/odynophagia, GI bleeding, mucositis/stomatitis, or nausea), 
the Investigator may consider performing an evaluation/management plan incorporating elements of the above GI Intolerability Evaluation and 
Management table. 
 


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8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of an AE or SAE can be found in Section 10.3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant discontinue the study (see Section 7).  
Please refer to Appendix 11 in Section 10.11 for study management information during 
the COVID-19 pandemic. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All SAEs will be collected from the signing of the informed consent form until the 
follow-up visit at the time points specified in the SoA (Section 1.3).   
• All AEs will be collected from the start of intervention until the follow-up visit at the 
time points specified in the SoA (Section 1.3). 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the eCRF not the AE section. 
• All SAEs will be recorded and reported to the sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Section 10.3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• Investigators are not obligated to actively seek information on AEs or SAEs after the 
conclusion of the study participation. 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 to be reasonably related to the study intervention or 
study participation, the investigator must promptly notify the Sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  


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8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is given in Section 
10.3. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the sponsor of a SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met.  
• The Sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study intervention under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
• An investigator who receives an investigator safety report describing a SAE or other 
specific safety information e.g., summary or listing of SAE) from the Sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
8.3.5. 
Pregnancy 
• 
Details of all pregnancies in participants will be collected after the start of study 
intervention and until 35 days after the last dose.  Details of pregnancies in partners 
of participants do not need to be collected in this study. 
• 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the participant 
pregnancy. 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. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• 
The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate 
and the information will be forwarded to GSK and VH.  
• 
GSK’s central safety department will forward this information to the Antiretroviral 
Pregnancy Registry. The international registry is jointly sponsored by 
manufacturers and licensees of antiretroviral products. Additional information and a 


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list of participating manufacturers/licensees are available from 
http://www.apregistry.com/. 
• 
Any post-study, pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.3.4. While the investigator is not obligated to actively seek this 
information in former study participant, he or she may learn of an SAE through 
spontaneous reporting. 
• Any participant who becomes pregnant while participating in the study will 
discontinue study intervention and be withdrawn from the study. 
8.3.6. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Section 10.3.3 and all deaths, whether or not 
they are considered SAEs, 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 eCRFs are presented as queries in response to reporting of certain CV MedDRA 
terms.  The CV information should be recorded in the specific cardiovascular section of 
the eCRF within one week of receipt of a CV Event data query prompting its completion.  
The Death eCRF 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.  
8.3.7. 
Disease-Related Events and/or Disease-Related Outcomes (HIV-
Associated Conditions) 
The events or outcomes listed in the CDC Classification System for HIV-1 Infections 
(Section 10.10) will be recorded on the HIV-Associated Conditions eCRF page if they 
occur.  However, these individual events or outcomes, as well as any sign, symptom, 
diagnosis, illness, and/or clinical laboratory abnormality that can be linked to any of these 
events or outcomes are not reported to GSK as AEs and SAEs even though such event or 
outcome may meet the definition of an AE or SAE, unless the following conditions 
apply: 
• 
The investigator determines that the event or outcome qualifies as an SAE under 
part ‘f’ of the SAE definition (Section 10.3.2), or 
• 
The event or outcome is in the investigator’s opinion of greater intensity, frequency 
or duration than expected for the individual participant, or 
• 
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 Disease Related Event on either the 
AE or SAE eCRF page (according to severity) in addition to the HIV Associated 


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Conditions eCRF page.  If categorized as an SAE, report promptly (Section 10.3.5) to 
GSK and VH. 
Additionally, the PI should designate on the eCRF whether or not the AE or SAE meets 
any aspect of being an AIDS defining condition. 
8.3.8. 
Adverse Event of Special Interest 
AEs of special interest (AESIs) include those related to GI intolerability/gastric toxicity, 
neuropsychiatric safety, QT prolongation and skin and subcutaneous tissue disorders. See 
Section 8.2.3, Section 8.2.6, Section 8.2.7 and Section 10.9.3 for further details. 
8.4. 
Pharmacokinetics 
Only participants who have been randomized to the treatment arms containing 
GSK3640254 will provide samples for PK analysis.  
Subjects will be expected to complete a dosing card with the date and time of IP 
administration of the last three doses prior to the scheduled clinic visits at which PK is 
collected (Weeks 4, 8, 12, 24, 36 and 48). These dates and times will be recorded in the 
eCRF. Additionally, dosing information on the clinic day, including whether or not the 
dose was administered with food, and the actual date and time of the PK samples must be 
recorded in the eCRF.  
 
The pre-dose samples must be collected within the window of 20-28 hours after the most 
recent dose taken, with the exception of the 24hr pre-dose collection (the final sample) at 
Week 2 which has a smaller window of 22-26 hours (see Table 11). 
 
Blood samples will be collected for measurement of plasma concentrations (including but 
not limited to GSK3640254) at the visits outlined in the SoA (Section 1.3) and as detailed 
in Table 11. 
• Samples may be collected at additional time points during the study if warranted 
and agreed upon between the investigator and Sponsor. The timing of sampling 
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. 
• Instructions for the collection and handling of biological samples will be provided 
by Sponsor. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• Genetic analyses will not be performed on these plasma samples.  
• Drug concentration information that may unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 


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Table 11 
Pharmacokinetic Sampling Schedule and Related Activities 
 
Time  
(Event) 
Window for blood draw 
Time  
(Relative to 
Dosing) 
Hour: Min 
Intensive PK 
Subgroup at 
Week 2 
(Day 11-14)  
Morning pre-dose work:  
20-28 hrs after the dose was taken the day 
prior: ECGs, vitals and full blood draw to 
include the pre-dose PK collectiona 
 
 
Eat Meal  
DOSEb: Administer study treatment and start the clock for subsequent blood 
draws. 
 
00:00 
1 hr PK blood drawc 
± 5 minutes 
01:00 
2 hr PK blood drawc and ECGd 
± 10 minutes 
02:00 
3 hr PK blood drawc 
± 10 minutes 
03:00 
3.5 hr PK blood drawc 
± 5 minutes 
03:30 
4 hr PK blood drawc and ECGd 
± 5 minutes 
04:00 
4.5 hr PK blood drawc 
± 5 minutes 
04:30 
5 hr PK blood drawc 
± 5 minutes 
05:00 
6 hr PK blood drawc and ECGd 
± 10 minutes 
06:00 
10 hr PK blood drawc 
± 1 hour 
10:00 
24 hr (morning pre-dose) PK blood draw 
± 2 hours 
24:00 
Eat Meal and administer study treatment.b 
Week 4 
20-28 hrs after the dose was taken the day 
prior:  Draw lab kit (including the pre-dose PK 
collection) except the post-dose PK tubea 
 
 
Eat meal. Administer doseb 
 
00:00 
1 PK sample 2-4hrs post-dosec 
 
02:00 – 04:00 


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Time  
(Event) 
Window for blood draw 
Time  
(Relative to 
Dosing) 
Hour: Min 
Week 8 
20-28 hrs after the dose was taken the day 
prior:  Draw lab kit (including the pre-dose PK 
collection)  except the post-dose PK tubea 
 
00:00 
Eat meal. Administer doseb 
 
00:00 
1 PK sample 4.5-8 hrs post-dosec 
 
04:30 – 08:00 
Week 12 
20-28 hrs after the dose was taken the day 
prior:  Draw lab kit (including the pre-dose PK 
collection)  except the post-dose PK tubea 
 
 
Eat meal. Administer doseb 
 
00:00 
ECG 2-6 hrs post dose 
 
02:00 - 06:00 
1 PK sample 8-12 hrs post-dosec  
 
08:00 – 12:00 
Weeks 24, 36, 
and 48 
20-28 hrs after the dose was taken the day 
prior:  Draw lab kit (including the pre-dose PK 
collection).a  There is no post-dose PK 
collection at these visits. 
 
 
Eat meal. Administer doseb 
 
00:00 
a) The pre-dose, full morning blood draw and ECG should be done in the standard required sequence of 
assessments: ECG – Vitals – Blood Draw (all within 15 minutes to ensure that the PK sample from the blood draw 
approximates that of the ECG).  
b) At visits with PK collections, aim to dose the participant near the same time that they have typically been dosing. 
Best Practice is to plan for approximately 30-45 minutes in which to get these pre-dose assessments and 
procedures done and the meal consumed by the participant. 
c) 
Each post-dose blood draw should be drawn relative to the time the dose was given; never base the interval for 
the next blood draw on the time of the previous blood draw  
d) For consideration at Week 2 Only: For the subsequent, small blood draws at 2, 4, and 6 hrs during the Intensive 
PK portion of the visit at Week 2, it is more important that the blood draw be done within the required window of 
time; attempting to acquire the ECG prior to the blood draw may interfere with that timing. Therefore, the ECG at 
2, 4 and 6 hrs can be performed after the blood draw at those time points. The goal is to perform the ECG 
procedure ±15 minutes of the time point (elapsed from time of dose). 
8.5. 
Genetics and/or Pharmacogenomics 
A 6 mL blood sample for deoxyribonucleic acid (DNA) isolation will be collected on 
Week 8 (or at any time later) from participants who have consented to participate in the 
genetics analysis (PGX) component of the study. Participation is optional. Participants 
who do not wish to take part in the genetic research may still participate in the main 
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I n t he e ve nt of D N A e xtr acti o n fail ure, a re pl ace m e nt ge netic bl o o d sa m ple ma y b e 
re q ueste d fr o m t he partici pa nt. Si g ne d i nf or me d c o nse nt will be re q uire d t o o btai n a 
re place me nt sa m ple u nless it was i ncl u de d i n t he ori gi nal c o ns e nt. 
See Secti o n 1 0. 5  f or inf or mati o n re gar di n g ge neti c researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt a n d destr ucti o n of t hes e sa m ples ca n be f o u n d i n t he la b orat or y 
ma n ual a n d t he S R M.  
8. 6.  
Bi o m ar k er s  
8. 6. 1.  
S er u m Bi o m ar k er s a n d  
wit h Bi o p s y i n t h e St o m a c h 
S u b st u d y  
As n ote d i n Secti o n 4. 1. 5 , a p pr o xi matel y 7 partici pa nts  i n eac h of t h e treat me nt ar ms will 
elect t o u n der g o e val uati o n s wit h 
wit h bi o ps y of t he greater a n d l esser c ur vat ur es of 
t he st o mac h a n d meas ure me nt of Ser u m Bi o mar kers t o e x pl ore t he cli nical ma nifestati o ns 
of gastric t o xicit y s ee n i n precli nical st u dies (see Secti o n 2. 2. 2 ). 
Pr ot o n P u m p I n hi bit ors are pr o hi bite d t hera p y f or a n y p artici pa nt i n a n y ar m electi n g t o 
partici pate i n t he St o mac h s u bst u d y.  
T hese partici p a nts  will u n der g o bi o mar ker assess me nts as f oll o ws:  
1.  Bl o o d c ollecti o n f or t h e meas ure me nt of Ser u m Bi o mar kers i ncl u di n g Gastri n a n d 
Pe psi n o ge n I a n d II (at mi ni m u m: Da y 1, Wee k 2 4, Wee k 4 8, a n d Wee k 9 6).  
•  A mi ni m u m of 1 2  h o urs of fasti n g is re q uire d pri or t o t hese c ollecti o ns.  
•  A ntaci ds or ot her me di cati o ns affecti n g st o mac h aci dit y or gastr oi ntesti nal 
m otilit y s h o ul d be disc o nti n ue d, if p ossi ble, f or at least 4 8 h o urs pri or t o 
c ollecti o n.  
•  Bi oti n c o ns u m pti o n (als o ter me d as vita mi n B 7 or B 8 , vita mi n H, or 
c oe nz y me R) s h o ul d be disc o nti n ue d f or at least 7 2 h o urs pri or t o t he 
c ollecti o n of a sa m ple . 
•  Es o p ha g o gastr o d u o de n os c o p y ( E G D)  
i. Pl a n ne d b i o psies i ncl u de tiss ue ta ke n fr o m disti nct l ocati o ns o n 
t he greater c ur vat ure (2 s peci me ns place d i n o ne s peci me n c u p)  
a n d fr o m i de ntifie d tr a nsiti o nal z o nes o n t he greater c ur vat ur e a n d 
lesser c ur vat ure (2 s peci me ns place d i n o ne s p eci me n c u p; see 
S R M f or details).  Pla n ne d Bi o psies will be ac q uir e d at Da y 1, 
Wee k 2 4 a n d Wee k 9 6, at a mi ni m u m.  
ii. U n pl a n ne d  b i o psies ma y be ta ke n, if necessar y, b ase d o n i ntra-
pr oce d ure fi n di n gs. At t he discreti o n of t he e n d osc o pist, tiss ue 
sa m ples ca n be t a ke n fr o m l ocati o ns ot her t ha n t h ose pla n ne d (see 
Pla n ne d Bi o psies a b o ve) t hat re pres e nt areas of cli nical i nterest .  
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U n pla n ne d Bi o psies ca n als o be ta ke n at ti me p oi nts ot her t ha n 
Da y 1, Wee k 2 4 a n d Wee k 9 6, if necessar y.   
2.  E x a mi nati o n of Bi o psies  
•  U n pl a n ne d  bi o ps y s a m ple s will be referre d t o a la b ca pa ble t o p erf or m 
i m me diate pr ocessi n g (st a n dar d pat h ol o g y stai ni n g) a n d dia g n osis. 
U n pla n ne d sa m ples ma y u n der g o s o me of t he hist ol o gical stai ni n g 
descri be d b el o w f or t he p la n ne d b i o psies ( See S R M f or s pecific details.) 
•  Pl a n ne d  b i o ps y sa m ples will u n der g o micr osc o pic e x a mi nati o n ( H/ E, 
P A S , a n d Alcia n Bl ue stai ns [p H 2. 5 ] hist oc he mical stai ns) b y t w o 
i n de pe n de nt p h ysicia ns. T he f oll o wi n g hist ol o gic para meters will be 
assesse d  (if prese nt): Pari etal cell l oss, Parietal cell necr osis, C hief cell 
c ha n ges, F o ve olar cell h y per plasia, I nfla m mati o n, S pas m ol ytic 
p ol y pe pti de -e x pressi n g meta plasia, I ntesti nal Meta plasia, a n d D ys plasia.  
N ote, stai ni n g f or H/ E will occ ur at t hree le vels f or eac h s a m ple; stai ni n g 
f or P A S a n d Alcia n Bl ue will occ ur at o ne le v el f or eac h s a m ple.  
Pl a n ne d  bi o ps y s a m ples will be pr ocesse d t hr o u g h paraffi n e m be d de d 
bl oc k  i n real ti me. H o we ver, micr ot o m y, stai ni n g a n d 
rea di n g/i nter pretati o n will occ ur i n batc h at a later date; t his will mai ntai n 
precisi o n.  Sa m pl es fr o m t he greater c ur vat ure will be e val uat e d, gra d e d, 
a n d d oc u me nte d se p aratel y fr o m t he s a m ples fr o m t he tra nsiti o nal z o nes 
o n t he greater a n d less er c ur vat ur es.  
Peer re vi e w will occ ur as f oll o ws: 1) a p h ysi cia n s cie ntist wit h s ur gical 
fell o ws hi p trai ni n g i n r es earc h wit h e x pertise i n E pit helial Bi ol o g y a n d 
Gastric Ca ncer will rea d sca n ne d sli des virt uall y (e. g. usi n g t he Leica 
A peri o A T 2 D X s yste m) a n d 2) a b oar d -certifie d p at h ol o gist will re vie w 
t he glass sli des. O v erall, o nl y o ne i nter pretati o n (reflecti n g a gree me nt 
bet wee n b ot h p h ysicia ns) will be pr o vi de d a n d d oc u me nte d f or t he greater 
c ur vat ur e s peci me n, a n d f or t he tra nsiti o nal z o nes s peci me ns o btai ne d 
fr o m t he greater a n d less er c ur vat ure.   T h ese fi n di n gs will pr o vi de t he 
basis f or i n di vi d ual partici pa nt - a n d st u d y-bas e d st o p pi n g criteria ( Secti o n 
4. 1. 5. 2  a n d Secti o n 4. 1. 5. 3 ). 
Base d u p o n t h e t otalit y of t hese res ults  t hr o u g h o ut t he st u d y, Im m u n o hist o -
c he mistr y (I H C) ma y b e e m pl o ye d i n t he f ut ure ( d uri n g or after t he st u d y) t o 
f urt her c h aracteriz e  gastric i nfla m mati o n, meta plasia or a b n or mal li nea ges 
(i ncl u di n g b ut n ot li mite d t o): MI S T 1, T F F 2, T F F 3, C D X 2, M U C 2, M U C 6, G S-
II, L E C TI N, U E A-1 L E C TI N, T G F -a, Ki-6 7, C D 1 6 3, C D 6 8 a n d  Pe psi n o ge n.  
T he fre q u e nc y of a d diti o nal  
m o nit ori n g wit h p l a n ne d b i o psies (e. g. Wee k 4 8, 
Wee k 1 4 4, etc .) will be b ase d u p o n e mer gi n g cli nical a n d scie ntific data s ol el y fr o m t his 
trial; f or e x a m ple, t he c o nsiste nc y a n d hist o pat h ol o gic c orrelati o n of Ser u m Bi o mar kers, 
t he s pecific hist o pat h ol o gic fi n di n gs (if a n y) o n bi o ps y, etc. Ser u m Bi o mar kers ( Gastri n, 
Pe psi n o ge n I a n d Pe psi n o ge n  II will als o be c ollecte d if/ w he n a d diti o nal 
wit h 
p l a n ne d b i o psies are perf or me d (e. g., Wee k 1 4 4).  
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Importantly, no formal statistical testing or analysis will be performed for either the GI 
Biomarkers, the histopathological findings from the greater and lesser curvatures of the 
stomach, or future IHC of the biopsy samples (should this occur). 
8.6.2. 
Viral Genotyping and Phenotyping Analyses 
Some of the plasma samples collected in this study will be used to test for the incidence 
of treatment emergent genotypic and phenotypic resistance to reverse transcriptase 
inhibitors, integrase inhibitors, protease inhibitors and the study drug, GSK3640254 
maturation inhibitor.   
• Samples collected from all participants at Screening will undergo resistance 
testing just after the samples are collected using the PhenoSense GT assay. As 
noted in Section 5, a local genotypic resistance assay may be acceptable to the 
VH study team. 
• Samples collected from participants in the GSK3640254 arms at Day 1 and Week 
4 will undergo resistance testing just after the samples are collected using the 
following 5 assays: PhenoSense GT, GeneSeq Integrase, PhenoSense Integrase, 
PhenoSense Gag assays for GSK3640254, and Gag genotype (using a Next 
Generation Sequencing platform). This will reveal any early development of 
resistance with GSK3640254.  Testing at this early stage for participants on the 
DTG reference arm is not necessary, as the resistance profile is already well-
described.  
• Development of PDVF in any participant will trigger shipment for resistance 
testing of the sample collected at the time point of interest for the same following 
5 assays: PhenoSense GT, GeneSeq Integrase, PhenoSense Integrase, PhenoSense 
Gag assays for GSK3640254, and Gag genotype (using a Next Generation 
Sequencing platform).     
The resistance assays will be performed at Monogram Biosciences. 
Details of the analyses to be performed will be specified in the SAP. 
8.6.3. 
Renal, Bone and Inflammation Biomarkers 
Blood and urine are being collected to perform renal, bone and inflammation biomarker 
assessments. 
Since the intention is to utilize these biomarkers for research purposes and the clinical 
significance of these results is uncertain, the Sponsor will not be reporting real time 
results of these assessments to the investigator except for Cystatin C (Day 1 only) and 
HbA1c. 
Renal biomarkers:  
• Cystatin C (blood) 
• Retinol Binding Protein (RBP, urine) 


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•  Beta -2 -Micr o gl o b uli n ( B 2 M, uri ne)   
•  Uri ne R B P/creati ni ne rati o  
•  Uri ne B 2 M/ creati ni ne rati o  
•  uri ne al b u mi n/creati ni ne rati o  
•  uri ne pr otei n/creat i ni ne rati o  
•  uri ne p h os p hate  
•  ser u m creati ni ne   
B o ne bi o mar kers ( bl o o d):  
•  b o ne -s pecifi c al kali ne p h os p hatase  
•  pr oc olla ge n t y pe 1 N -pr o pe pti de  
•  t y pe 1 c olla ge n cr oss-li n ke d C-tel o pe pti de 
•  oste ocalci n  
•  2 5 h y dr o x y -Vita mi n D  
I nfla m mat or y Bi o mar kers ( bl o o d):  
•  I nterle u ki n-6 (I L -6)  
•  Hi g h -s e nsiti vit y C reacti ve pr otei n ( hs-C R P)  
•  D -di mer  
•  S ol u ble C D 1 4 (s C D 1 4)  
•  S ol u ble C D 1 6 3 (s C D 1 6 3)  
H b A 1c a n d i ns uli n a n d gl uc ose f or
cal c ulati o n  
8. 7.  
I m m u n o g e ni cit y A s s e s s m e nt s 
N ot A p plica ble.  
8. 8.  
H e alt h E c o n o mi c s /M e di c al R e s o ur c e Utili z ati o n  
Healt h Ec o n o mics/ Me dic al Res o urce Utilizati o n a n d Healt h Ec o n o mics  para meters are 
n ot e val uate d i n t his st u d y.  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
St ati sti c al H y p ot h e s e s  
T he st u d y is desi g ne d t o i n vesti gate t he a nti viral acti vit y, safet y, a n d t olera bilit y of t hree 
d oses ( 1 0 0 m g, 1 5 0  m g, a n d 2 0 0  m g)  of G S K 3 6 4 0 2 5 4  gi ve n i n c o m bi nati o n wit h eit her 
A B C/ 3 T C or F T C F/ T A F  as c o m pare d t o  t he refere nce tr eat me nt ( defi ne d as eit her D T G 
+ A B C/ 3 T C or D T G + F T C/ T A F ), a n d t o select an o pti mal  G S K 3 6 4 0 2 5 4  d ose f or f urt her 
de vel o p me nt. Ba yesia n a nal yses will be c o n d ucte d t o e val uate t he pr o b a bilit y t hat t he 
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Week 24 response rate, defined as the proportion of participants with plasma HIV-1 RNA 
<50 c/mL as calculated by the FDA snapshot algorithm, of at least one dose of 
GSK3640254 has comparable efficacy to the reference treatment using a 10% margin. A 
positive efficacy decision will be made if any GSK3640254 dose has a high posterior 
probability (e.g., ≥0.85) of being within the 10% margin. 
Posterior distributions of response rates for each dose, d, of GSK3640254 and the 
reference treatment be calculated according to the following Bayesian model where θd is 
equal to the logit of the probability, p, of being a responder (plasma HIV-1 RNA <50 
c/mL) on arm d and follows a normal distribution with mean,
, and variance, 
. 
 
 
 
 
 
 
 
 
 
 
The decision to model the logit of θ as normal, rather than a traditional Beta-Binomial 
model, was made to align with the use of the FACTS (Fixed and Adaptive Clinical Trial 
Simulator) software. FACTS is the software of choice for evaluating operating 
characteristics of trials utilizing Bayesian analysis which incorporate adaptive decisions 
(i.e. early stopping, arm dropping, etc.) The effectiveness of the components of DTG + 
ABC/3TC as well as DTG + FTC/TAF has been assessed in numerous previous studies, 
including SPRING 1 [van Lunzen, 2012], SPRING 2 [Raffi, 2013], SINGLE [Walmsley, 
2013], and FLAMINGO [Clotet, 2014].  Historical data from these studies suggests that 
the Week 24 response rate for treatment naïve participants treated with either DTG +  
ABC/3TC or DTG + FTC/TAF is close to 92%.  It is assumed that there will be some 
differentiation in response rates among doses of GSK3640254. 
Bayesian analyses formally incorporate prior beliefs and information about population 
parameters. The assumptions made will help provide a more reliable estimate when the 
prior beliefs are combined with the observed data and the prior belief is reasonable. 
Therefore, the trial will utilize an informative Normal(2.61, 0.73242) distribution of the 
logit of response rate on the reference treatment arm. After inverse logit transformation 
this distribution has a mean at 0.916 and 2.5 and 97.5 percentiles at 0.765 and 0.982 
respectively. This distribution was chosen to mimic a Beta (23,2) distribution which has a 
mean at 0.92 and 2.5 and 97.5 percentiles at 0.789 and 0.990 respectively. Utilizing a 
Beta(23,2) prior to estimate the response rate on the reference treatment arm is similar to 
adding 23 responders and 2 non-responders to the reference treatment arm in the actual 
study. In the Bayesian framework these two choices of modelling the outcome (normal 


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logit or Beta-Binomial) should give exchangeable results. A non-informative Normal (0, 
52) prior distribution will be assumed for the logit of response rate for the GSK3640254 
arm.  
9.2. 
Sample Size Determination 
Approximately 300 participants will be screened to achieve approximately 150 randomly 
assigned to study intervention for an estimated total of 40 evaluable participants per 
GSK3640254 arm and 30 participants on the reference treatment arm.  Ideally, 28 
participants of the planned sample size of 150 will enrol in the optional Stomach 
substudy (as described in Section 4.1.5). However, additional participants may be 
enrolled to ensure adequate sample size of EGD evaluation criteria (See Section 4.1.5.1).  
The planned sample size of approximately 40 participants per active arm and 
approximately 30 participants assigned to the control arm is based on the primary 
efficacy endpoint of FDA Snapshot response rate at Week 24 (proportion of participants 
with plasma HIV-1 RNA <50 c/mL). Since the analysis will be conducted using Bayesian 
methodology, the sample size was determined using robust simulation rather than a 
closed form equation.  The determination of the proposed sample size was guided by two 
goals of the study: to minimize the probability that a dose with a truly poor response 
would be selected for further study, and maximize the probability accurately selecting the 
dose with the highest response rate when there is substantial dose differentiation across 
arms. Should efficacy be similar across dosing arms, other factors (i.e. safety, tolerability, 
resistance) will drive the dose selection process. The complete dose selection algorithm 
will be described in detail in the SAP for the study. 
Assuming a response rate of 92% on the reference treatment arm, a 2% separation 
between each dose of GSK3640254, and a response rate of 80% on the most efficacious 
dose, the probability of declaring success is approximately 0.167. Conversely, assuming a 
response rate of 90% on the most efficacious result, the probability of declaring success 
would be 0.861.  
Selected probabilities of making a positive efficacy decision (defined as at least one dose 
having a posterior probability of being within a 10% margin compared to the reference 
treatment of at least 0.85), assuming a 2% separation between each dose of GS3640254, 
are presented in Table 12. 
Table 12 
Simulated power under various realistic GSK3640254 response rates 
assuming 2% difference between each dose 
Response Rate of most efficacious 
dose of GSK3640254 
80% 
82% 
85% 
87% 
90% 
92% 
Probability of making a positive 
efficacy decision 
0.167 
0.265 
0.484 
0.634 
0.861 
0.944 
 
If there is large separation between the most and least efficacious dose, the trial’s 
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most efficacious dose (10% worse) will be identified as the maximally effective dose. For 
example, if the three GSK3640254 doses correspond to true response rates of 80%, 85%, 
and 90% then the probability that the trial will identify each dose as the maximally 
effective dose is 0.062, 0.219, and 0.719 respectively. These results indicate that the trial 
has very small chance (< 7%) to select the dose which is truly the least efficacious when 
there is definitive separation between doses.   
9.2.1. 
Sample Size Sensitivity 
To evaluate the study design’s sensitivity to sample size, simulations were also conducted 
using various numbers of participants on the active GSK3640254 doses and the same 
number of participants (size of 30) for the control arm. Increasing the number of 
participants enrolled to 50, or 60 participants per dose (compared to the proposed size of 
40 per dose) resulted in only modest increases in the probability of correctly making a 
positive efficacy decision at high response rates (> 90%) and minimal decreases in the 
probability of incorrectly making a positive efficacy decision at low response rates (< 
82%).  Figure 3 shows the comparison of decision-making curves for the various sample 
sizes explored.  
Figure 3 
Probability of Making a Positive Efficacy Decision at Various Sample 
Sizes Assuming 2% Difference in Response Rates Between Each 
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9.3. 
Analysis Sets 
For purposes of analysis, the following populations are defined: 
9.3.1. 
Intent-to-Treat Exposed Population (ITT-E) 
The ITT-E population consists of all randomized participants who received at least one 
dose of study intervention.  Participants will be analyzed according to the randomized 
treatment regardless of what treatment was actually received. Unless stated otherwise, the 
ITT-E population will be the primary population for efficacy analyses. 
9.3.2. 
Per Protocol Population (PP) 
This population will consist of participants in the ITT-E population with the exception of 
participants with significant protocol violations as defined in the SAP of this study. The 
PP population will be a secondary population for efficacy purposes. 
9.3.3. 
Pharmacokinetic Population 
The pharmacokinetic (PK) population will include all participants who receive 
GSK3640254, undergo intensive and/or limited/sparse PK sampling during the study, and 
provide evaluable GSK3640254 plasma concentration data, demographic and baseline 
characteristics, and/or information on concomitant medications. Participants in this 
population will be included in the Population PK analysis. A population PK analysis will 
be done under a separate Population-PK Reporting and Analysis Plan.  
See Section 6.3 for details of limited access to these data when the blind must be 
maintained. 
Details of the PK analyses and additional PK populations, if needed, will be provided in 
the SAP. 
9.3.4. 
Safety Population 
The Safety Population consists of all randomized participants who were exposed to 
study intervention with the exception of any participants with documented evidence of 
not having consumed any amount of study intervention. Participants will be analyzed 
according to the actual treatments received. The safety population will be the primary 
population for safety analyses.  
9.3.5. 
Screened Population 
Any participant who signs the ICF is considered to be Screened. 
9.3.6. 
Randomized Population 
Any participant who has been randomized (for this study, this means a randomization 
number was assigned), whether or not the participant ever took a dose of study 
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9. 4.  
St ati sti c al A n al y s e s  
T he statistical a nal ysis pla n will be fi nalize d pri or t o Data base Rel ease ( D B R ) a n d will 
i ncl u de a m ore te c h nical a n d detaile d des cri pti o n of t he statistical a nal yses. T his secti o n 
is a s u m mar y of t he pla n ne d statistical a nal yses of t he m ost i m p orta nt e n d p oi nts 
i ncl u di n g pri mar y a n d ke y sec o n dar y e n d p oi nts. 
9. 4. 1.  
Effi c a c y A n al y s e s  
E n d p oi nt  
St ati sti c al A n al ysi s M et h o d s  
Pri m ary  
T h e pri m ary efficacy st atistic al a nalysis will b e b ase d on t he pr op orti o n of 
p artici p a nt s i n th e I T T-E p op ul ati on wit h pl as m a HI V -1 R N A < 5 0 co pi es/ m L at 
W e ek 2 4  usi ng t he F D A S na ps hot alg orit h m. T he p ost erior distrib u ti o ns of th e 
diff er e nce i n pr o p orti o ns of p articip a nts wit h pl as m a HI V -1 R N A < 50 c o pi es/ m L 
o n e ac h G S K3 6 40 2 54 ar m c o m p ar e d wit h c o ntr ol ar m will b e pr o duc e d.  P oint 
esti m at es, B ay esia n cr edi ble i nt erv als , a nd fr eq u entist c o nfi de nc e int erv als will 
b e d eriv e d a n d dis pl aye d.  Se nsitivity a nalysis m ay b e p erf or me d to assess t he 
i m p act of t h e c h oic e of inf or m ativ e prior f or co ntr ol ar m. F ull d etails of th e 
pl a n ne d B ay esia n a n alys es will b e pr ovi d ed i n t h e a nalys is pl a n. 
S ec o nd ary  
S ec o nd ary statistic al an alyses will b e b as e d o n t he pr oporti o n of particip a nts i n 
t h e I T T-E p op ul ati on wit h plas m a HI V -1 R N A <5 0 co pi es/ m L  at W eeks  48 a n d 
9 6  usi n g t h e F D A S na psh ot al g orit h m. Full d et ails will b e pr ovid e d i n th e 
st atistic al an alysis pl an. 
 
9. 4. 2.  
S af et y A n al y s e s  
T he st u d y is desi g ne d t o select a d ose f or f urt her e val uati o n o n t he basis of t olera bilit y 
a n d vir ol o gic al efficac y i n c o nj u ncti o n wit h i m m u n ol o gical r es p o nse, safet y a n d 
p har mac o ki netic m eas ur es. Meas ures of safet y a n d t olera bilit y will be use d t o c o m pare  
t he d oses i n a pre-s pecifi e d ma n ner will be detaile d i n t he statistical a nal ysis pla n of t he 
st u d y. E x p os ure t o st u d y me dicati o n, meas ure d b y t he n u m ber of wee ks o n st u d y dr u g, 
will be s u m mariz e d b y tr eat me nt ar m. T he pr o p orti o n of partici pa nts re p orti n g a d v erse 
e ve nts ( A Es) will be ta b ulate d f or eac h tr eat me nt ar m. T he f oll o wi n g s u m m aries of A Es 
will be pr o vi de d:  
• I n ci de nce a n d se v erit y of All A Es;  
• I n ci de nce a n d se v erit y of treat me nt r elate d A Es;  
• I n ci de nce a n d se v erit y of A Es lea di n g t o wit h dra wal fr o m st u d y;  
• I n ci de nce of S A Es  
La b orat or y d ata, vital si g ns a n d E C G data (a bs ol ute val ues a n d c ha n ge fr o m baseli ne) 
will be s u m mariz e d b y visit a n d treat me nt gr o u p. M ore detaile d safet y a n al ys es will be 
descri be d i n t he statistical a nal ysis pla n a n d wi ll be perf or me d o n t he Safet y P o p ulati o n. 
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9.4.3. 
Health Outcomes Analyses 
The overall proportion of IP study medication taken relative to the planned amount will 
be estimated via pill counts and summarized by treatment arm for each IP.  
Data from C-SSRS assessments will be summarised by visit. 
9.4.4. 
Other Analyses 
PK, PK/PD, and biomarker exploratory analyses will be described in the SAP. The 
population PK analysis and pharmacodynamic analyses will be presented separately from 
the main clinical study report (CSR).  
Additionally, special statistical and data analysis considerations may be warranted in the 
event that the COVID-19 or related epidemics or natural disasters may affect the study 
and data integrity.  To the extent possible, these will be described in the main study SAP; 
alternatively, a separate SAP focusing on modified data handling rules (eg, changes to 
analysis populations, visit windows and endpoints) and analyses (eg, sensitivity analyses 
to assess impact of and account for missing data) may be prepared, taking in to account 
applicable regulatory guidance and industry best practices for handling such situations 
[FDA, 2020; EMA, 2020a; EMA, 2020b]. 
9.5. 
Interim Analysis 
At least four analyses will be performed throughout the course of the study in 
collaboration with an IDMC as described below: 
• An interim analysis will be conducted when data at a pre-specified early timepoint 
(prior to the Week 24 primary endpoint) is available for a pre-specified 
percentage of participants. This interim analysis will be conducted to determine if 
any of the GSK3640254 doses are suboptimal and: 1) should be discontinued 
from the study or 2) if the entire study should be stopped due to futility. Full 
details of this analysis are contained in the IDMC charter. 
• The primary analysis will be conducted to select an optimal dose when all 
participants have completed their Week 24 visit  
• An analysis will be conducted to confirm the dose selection when all participants 
have completed their Week 48 visit  
• A final confirmatory analysis will be conducted after the last participant reaches 
Week 96 to  characterise the long-term safety, tolerability and durability of 
antiviral response of all continued doses.  
Further data cuts and analyses may be conducted as necessary to support regulatory 
submissions and publications. No adjustment for multiplicity caused by repeated analysis 
on the primary endpoint will be made as the interim analysis will be secondary. Type I 
error rate will not be inflated for the treatment. 


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The ITT-E population will be the primary efficacy population and the safety population 
will be the primary safety population for any interim analysis. The actual dosage for 
participants randomized to a GSK3640254 arm will remain blinded to the sponsor until 
Week 24 database lock and will remain blinded to investigators and participants until the 
last participant completes their Week 48 visit.  
9.5.1. 
Independent Data Monitoring Committee 
This study will utilize an Independent Data Monitoring Committee (IDMC) to evaluate 
the efficacy, safety and tolerability of GSK3640254 at early time points in the study. The 
IDMC will be composed of at least 3 members with at least one member having a 
medical qualification and at least one member having statistical expertise. The IDMC 
will review at least one analysis before the primary Week 24 analysis. This review will be 
used to determine if a recommendation to the CMO and VSLC is warranted to modify 
study design or conduct including (but not limited to): 1) removing any sub-optimal 
doses of the GSK3640254 arm from the study or 2) discontinuing the study completely if 
all GSK3640254 doses are deemed sub-optimal.  
If the IDMC recommends discontinuation of one or more arms based on efficacy or 
safety reasons or both, VH governance board will make a determination to either 
transition subjects to other arms or to SOC to ensure positive benefit/risk of the study. 
In addition, there is an ongoing Phase 2b study in treatment-naïve participants 
investigating GSK3640254 + DTG (study 212483) that also includes an event triggered 
(by rate of AE or PDVF) IDMC. If this IDMC were to make a recommendation regarding 
the discontinuation of any arm in that study, VH governance would determine if/how to 
incorporate that decision into study 208379 (which may include an independent ad-hoc 
evaluation by the IDMC for study 208379). 
The IDMC charter will contain full details of all summaries and efficacy analyses that 
will be provided and will be finalized before the first participant is enrolled. To maintain 
the integrity of the clinical study, only selected staff may be unblinded at interim analyses 
before all participants have completed Week 24, as deemed necessary by the IDMC.  
 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• 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, IB, and other relevant documents (e.g., 
advertisements, patient-facing materials) 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.  
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation 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), European Medical 
Device Regulation 2017/745 for clinical device research (if applicable), 
and all other applicable local regulations. 


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10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to 
the participant or to their 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(s). 
GSK and VH (alone or working with others) may use participant’s coded study data and 
samples and other information to carry out this study; understand the results of this study; 
learn more about GSK3640254 or about the study disease; publish the results of these 
research efforts; work with government agencies or insurers to have the GSK3640254 
approved for medical use or approved for payment coverage.  
The ICF contains a separate section that addresses the use of participant data and 
remaining samples for optional further research. The investigator or authorised designee 
will inform each participant of the possibility of further research not related to the 
study/disease. Participant 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 
participant data and/or remaining leftover samples to be used for further research not 
related to the study/disease. Participants who decline further research will tick the 
corresponding “No” box. 


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10.1.4. 
Data Protection 
• Participant will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred.  
• The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent.  
• The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed by 
the sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.1.5. 
Committees Structure 
10.1.5.1. 
Safety Data Review by Safety Review Team and IDMC 
• Participant safety will be continuously monitored by the Sponsor’s internal safety 
review committee, which includes safety signal detection at any time during the 
study 
• In addition, an independent safety review by an IDMC for this study is planned 
prior to the Week 24 primary endpoint. (see Section 9.5.1) 
• Case unblinding may be performed for above reviews, if necessary. 
10.1.6. 
Dissemination of Clinical Study Data 
• Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of each of the clinical study reports.  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 or VH site or other mutually-agreeable location. 
• GSK and VH will also provide all investigators who participated in the study with 
a summary of the study results and will tell the investigators what treatment their 
participants received.  The investigator(s) is/are encouraged to share the summary 
results with the study participants, as appropriate. 
• Under the framework of the SHARE initiative, GSK and VH intend to make 
anonymized participant-level data from this trial available to external researchers 
for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by 
trial participants are used to maximum effect in the creation of knowledge and 
understanding. Requests for access may be made through 
www.clinicalstudydatarequest.com. 


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• GSK and VH will provide the investigator with the randomization codes for their 
site only after completion of the full statistical analysis. 
• The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK and/or VH Policy. 
• GSK and VH intend to make anonymized participant-level data from this trial 
available to external researchers for scientific analyses or to conduct further 
research that can help advance medical science or improve patient care. This 
helps ensure the data provided by trial participants are used to maximum effect in 
the creation of knowledge and understanding 
• A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF.  
• Guidance on completion of CRFs will be provided in the eCRF Completion 
Guidelines. 
• Quality tolerance limits (QTLs) will be pre-defined in the QTL report to identify 
systematic issues that can impact participant safety and/or reliability of study 
results. These pre-defined parameters will be monitored during and at the end of 
the study and all deviations from the QTLs and remedial actions taken will be 
summarized in the clinical study report. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• Monitoring details describing strategy including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Study Specific Monitoring Plan. 
• 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. 
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 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 


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Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the sponsor. 
No records may be transferred to another location or party without written 
notification to the sponsor. 
10.1.8. 
Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies 
must be explained. The investigator may need to request previous medical records 
or transfer records, depending on the study. Also, current medical records must be 
available. 
• Definition of what constitutes source data and its origin can be found in the 
Source Data Acknowledgment monitoring form. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF 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.  
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first participant Screening that is registered into the IVRS/IWRS is considered the 
first act of recruitment and will be the study start date. 
Study/Site Termination 
VH 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 VH. 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. 


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Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• Discontinuation of further study intervention development 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate or no recruitment of participants (evaluated after a reasonable amount 
of time) by the investigator 
• If the study is prematurely terminated or suspended, the sponsor shall promptly 
inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 
10.1.10. 
Publication Policy  
• The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.  
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 13 will be performed by the central laboratory with the 
exception of the test for H. pylori that will be done locally by either breath or stool.  
Please refer to Appendix 11 in Section 10.11 for study management information during 
the COVID-19 pandemic. 
Protocol-specific requirements for inclusion or exclusion of participant are detailed in 
Section 5 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
Table 13 
Protocol-Required Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1 
BUN 
Potassium 
Aspartate 
Aminotransferase 
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase 
(SGOT) 
Total and direct 
bilirubin 
Amylase, Lipase 
 
Creatinine 
Sodium, 
Bicarbonate, 
and Chloride 
Alanine 
Aminotransferase 
 (ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
Total Protein 
eGFR/Creatinine 
Clearance3 
 
Glucose (can be 
nonfasting; 
though fasting on 
days when 
fasting lipids are 
collected) 
Calcium, 
Magnesium, 
and 
Phosphate 
Creatinine 
Phosphokinase 
(CPK) 
Fasting Lipid 
Panel 
(Cholesterol, 
Triglycerides, 
High density 
lipoprotein 
[HDL], low 
density 
lipoprotein 
[LDL]) 
Alkaline 
phosphatase2 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
2 0 8 3 7 9  
 
1 3 1  
 
L a b or at or y 
A s s e ss m e nt s  
P ar a met er s  
S er u m 
Bi o m ark ers i n 
t h e St o m ach 
S u bstu dy  
•  F asti n g Gastri n, P e psi no gen I a n d P e psin o ge n II  
R e n al 
bi o m ark ers  
•  Cyst ati n -C ( bl o od), R eti nol Bi n di n g Pr otei n ( R B P, urin e); a n d 
B et a -2 -Micr o gl ob uli n ( B2 M, urin e), urin e R B P/cr eati ni ne r ati o, urine 
B 2 M/cr e ati nin e r atio 3 
B o n e 
bi o m ark ers  
•  B o n e -sp ecific alk ali ne p h osp h atas e, pr oc oll ag en ty pe 1 N -pr o p e pti d e, 
ty p e 1 c oll a ge n cross-li nk e d C-t el o p epti d e, oste ocalci n a n d 2 5 Hydr oxy -
Vit a mi n D 3 
I nfl a m m ati o n 
bi o m ark ers  
•  I nt erl e ukin-6 (I L -6), Hi gh -s ensitivity C r e activ e pr ot ein ( hs-C R P), D -di mer, 
S ol u bl e C D 1 4 (s C D 1 4), S olu bl e C D 16 3 (s C D 1 6 3) 3 
 
•  H b A 1c a n d ins uli n a n d gl ucos e for
c alc ul ati on 
R o uti n e 
Uri n alysis  
•  Al b u mi n  
•  S p ecific gr avity, p H,  gl uc ose, pr otei n, bl o o d, ket o n es, biliru bi n, nitrit e, 
l e uk ocyt e ester as e by di pstick 
•  Micr osc o pic ex a mi n atio n (if bl o o d or pr ot ei n is a b nor mal)  
Pr e g na ncy 
T esti n g  
•  Hi g hly s e nsitiv e ser u m hu m a n c h orio nic go na d otr o pi n (h C G) pr e gn a ncy 
t est ( as n e ed ed f or p articip ants  of c hil d be arin g p ote ntial)  
C CI


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
2 0 8 3 7 9  
 
1 3 2  
 
L a b or at or y 
A s s e ss m e nt s  
P ar a met er s  
Ot h er T ests  
•  F ollicl e -sti m ul ati n g h or mon e a n d estr adi ol  
•  Uri n e Dr u g Scr ee n (t o i ncl ud e at mi ni m u m: a m p het a min es, b ar bit ur at es, 
c oc ai n e, p he ncycli di ne, o piat es, oxyc o do ne, c an na bi noi ds, 
b e nzo di az e pi n es, m et h a don e, M D M A, m eth a m ph eta mi n es, a n d tricyclic 
a nti de pr es a nts)  
•  H L A -B* 5 70 1  Typi n g   
•  HI V -1 R N A  
•  C D 4 + a n d C D 8 + ly m p hocyte c o unts, C D 4 +/ C D 8 + c ell co u nt r ati o  
•  H e p atitis B:  he p atitis B vir us s urf ac e a ntig e n ( H Bs A g) , he p atitis B s urf ace 
a nti bo dy ( H Bs Ab), a nd h e patitis B c or e a nti b ody ( wit h refl ex to H B V D N A)  
•  H e p atitis C: h ep atitis C vir us a nti bo dy ( H C V Ab) wit h r efl ex t o H C V R N A, if 
p ositiv e  
•  S er u m al bu mi n  
•  P T/I N R  
•  r a pi d pl as m a r e agi n ( R P R)  
•  H. pyl ori  t est by br eat h or sto ol ( d on e at l ocal l a bs) 
 
N O T E S :  
1.  
D et ails of liv er c h e mistry st o p pi n g crit eri a a n d r e q uir e d acti o ns a n d f oll o w -u p ass ess m e nts aft er liv er st o p pi n g 
or m o nit ori n g ev e nt ar e giv e n i n S ecti o n 7. 1  a n d S ecti o n 1 0. 6 . 
2.  
If alk ali n e p h os p h at as e is el ev at e d, c o nsi d er fr acti o n ati n g. 
3.  
T h e i nt e nti o n is t o utiliz e t h es e bi o m ark er d at a f or r es e arc h p ur p oses; t h e s p o ns or will n ot b e r e p orti n g r e al-
ti m e r es ults of t h es e ass ess m e nts t o t h e i nv esti g at or, exc e pt f or Cyst ati n C ( D ay 1 o nly), 2 5 Hy dr oxy-Vit a mi n 
D, a n d  H b A 1c.  
M C V = m e a n c or p usc ul ar v ol u m e, M C H = m e a n c or p usc ul ar h a e m o gl o bi n, R B C = r e d bl o o d c ells, W B C = w hit e 
bl o o d c ells, B U N = Bl o o d ur e a nitr o g e n, P T/I N R = pr ot hr o m bi n ti m e/i nt er n ati o n al n or m aliz e d r ati o, H b A 1c = glyc at e d 
h a e m o gl o bi n,
I L-6 = i nt erl e uki n -6, hs -C R P = 
hi g h -s e nsitivity C r e activ e pr ot ei n, s C D = s ol u bl e C D.  
 
 
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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfill the definition of an AE 
or SAE.  
 


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Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
10.3.2. 
Definition of SAE 
An SAE is defined as any serious adverse event that, at any dose: 
a.   Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to 
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• This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• Possible Hy’s Law case: ALT≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as SAE 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, 
intensive treatment for allergic bronchospasm, blood dyscrasias, 
convulsions, or development of intervention dependency or intervention 
abuse. 
10.3.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 
 
 


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10.3.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the Sponsor E/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by VH/GSK. In this case, all participant identifiers, with the exception 
of the participant number, will be redacted on the copies of the medical records 
before submission to Sponsor. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study  using the DAIDS Grading Table, Version 2.1, March 2017 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf and assign it 
to 1 of the following categories:  
• 
Grade 1 (Mild) 
• 
Grade 2 (Moderate) 
• 
Grade 3 (Severe) 
• 
Grade 4 (Potentially Life Threatening) 
• 
Grade 5 (Death) 
Where a DAIDS toxicity scale is not available for a particular event or parameter, then 
the investigator will instead make an assessment of intensity using their clinical 
judgement based on the DAIDS scale.  
• 
NOTE: An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE. 
 
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 


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• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship 
cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to Sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to Sponsor. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as medically indicated or as 
requested by Sponsor to elucidate the nature and/or causality of the AE or SAE as 
fully as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Sponsor 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 Sponsor within 24 hours of 
receipt of the information. 
 
 
 


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10.3.5. 
Reporting of SAE to Sponsor 
SAE Reporting to Sponsor via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to Sponsor will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
The Investigator will capture the SAE Causality in the participant’s source notes 
in a timely manner and the investigator or an appropriately delegated team 
member will enter the causality into the eCRF.  Clinical research associates 
(CRAs) will monitor the subject source documentation to confirm that SAE 
causality is being documented by the Investigator in a timely manner. 
• 
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the Medical Monitor by telephone. 
• 
Contacts for SAE reporting can be found in Sponsor/Medical Monitor Contact 
Information page. 
 
SAE Reporting to Sponsor via Paper Data Collection Tool 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the Medical Monitor. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in Sponsor/Medical Monitor Contact 
Information page. 
 


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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions 
Participants of Childbearing Potential (POCBP) 
Participants who are female at birth in the following categories are considered POCBP 
(fertile): 
1. Following menarche 
2. From the time of menarche until becoming post-menopausal unless permanently 
sterile (see below) 
Notes: 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in participants who are female 
at birth not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, confirmation 
with more than one FSH measurement is required.  
o Participants who are female at birth on HRT and whose menopausal status is 
in doubt will be required to use one of the non-estrogen hormonal highly 
effective contraception methods if they wish to continue their HRT during the 
study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator 
discretion should be applied to determining study entry. 
 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 


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10.4.2. 
Contraception Guidance 
The list does not apply to participants of childbearing potential with same sex partners or 
for participants of childbearing potential who are and will continue to be abstinent from 
penile-vaginal intercourse on a long term and persistent basis, when this is their preferred 
and usual lifestyle.  Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception. 
Methods of contraception are categorized by their effectiveness and user dependency: 1) 
highly effective methods (failure rate of <1% per year when used consistently and 
correctly) that have a low user dependency, 2) highly effective methods that are user 
dependent, and 3) effective methods that are not highly effective (failure rate of ≥1% per 
year when used consistently and correctly, e.g., condoms, cervical cap, diaphragm, 
sponge).   
GSK3640254 and DTG are not genotoxic. 
There are no contraceptive requirements for participants who are male at birth based on 
data for GSK3640254 and the most recent data for DTG.  
GSK3640254 has an “unlikely” risk for teratogenicity/fetotoxicity and would allow the 
use of contraceptive methods both highly effective and effective.  However, DTG has a 
“possible” risk for teratogenicity/fetotoxicity and appropriate methods of contraception 
are thus limited to only those methods that are considered to be highly effective.  Because 
there is a DTG component in all 4 treatments arms over the course of the study, POCBP 
will need to adhere to the following highly effective methods of contraception: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
If a hormonal method is selected, the POCBP is required to be clinically stable on it for 
at least one month prior to starting treatment in the study. 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
• Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS)c 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the participant of childbearing potential and the absence of sperm 
has been confirmed. If not, an additional highly effective method of contraception should 
be used. Spermatogenesis cycle is approximately 90 days. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly. 
FOR CANADA ONLY: The partner of a participant who is a POCBP must use a condom with 
spermicide in combination with any of the methods listed below. 


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• Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• oral 
• intravaginal 
• transdermal 
• injectable 
• Progestogen-only hormone contraception associated with inhibition of ovulation 
• oral 
• injectable 
• 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 intervention. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
a. 
Contraceptive use by participants should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Male 
condom and female condom should not be used together (due to risk of failure from friction) 
 


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10.5. 
Appendix 5: Genetics 
USE/ANALYSIS OF DNA 
• 
Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and IRB/IEC allow, a blood sample will be collected for DNA 
analysis 
• 
DNA samples will be used for research related to GSK3640254 or HIV and related 
diseases. They may also be used to develop tests/assays including diagnostic tests) 
related to GSK3640254 or study interventions of this drug class, and HIV. Genetic 
research may consist of the analysis of one or more candidate genes or the analysis 
of genetic markers throughout the genome or analysis of the entire genome (as 
appropriate) 
• 
DNA samples will be analyzed if it is hypothesized that this may help further 
understand the clinical data.  
• 
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to GSK3640254 or study interventions of this class. The 
results of genetic analyses may be reported in the clinical study report or in a 
separate study summary. 
• 
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• 
The samples will be retained while research on GSK3640254 (or study 
interventions of this class) or HIV continues but no longer than 15 years after the 
last participant’s last visit or other period as per local requirements. 


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10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments 
Liver Chemistry Stopping Criteria - Liver Stopping Event 
If Baseline ALT ≤ 1.5x ULN 
ALT-absolute ALT ≥ 5X ULN  
ALT Increase 
NONE for this study. 
Bilirubin1, 2 
ALT  3xULN and bilirubin  2xULN (>35% direct bilirubin)  
Symptomatic3 ALT  3xULN with symptoms (new or worsening) believed to be related to liver 
injury or hypersensitivity 
If Baseline ALT > 1.5x ULN 
ALT-absolute ALT ≥ 5x ULN OR > 500 U/L (whichever occurs first) 
ALT Increase 
ALT ≥ 3x baseline but < 5x ULN persists for ≥ 2 weeks (with bilirubin <2x ULN 
and no signs or symptoms of acute hepatitis or hypersensitivity)  
Bilirubin1, 2 
ALT ≥ 3x baseline OR > 300 U/L (whichever occurs first) and bilirubin ≥ 2x 
ULN 
Cannot 
Monitor 
ALT ≥ 3x baseline but < 5x ULN and cannot  be monitored every 1-2 weeks 
Symptomatic3 ALT ≥ 3x baseline and symptoms (new or worsening) believed to be related to 
liver injury or hypersensitivity) 
Required Actions and Follow up Assessments following ANY Liver Stopping Event 
Actions 
Follow Up Assessments 
• Immediately discontinue study treatment. 
• Report the event to the medical monitor 
within 24 hours. 
• Complete the liver event CRF and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2. 
• Perform liver event follow up assessments.  
• Monitor the participant until liver chemistries 
resolve, stabilise, or return to within 
baseline (see MONITORING below). 
• Viral hepatitis serology, including: 
• 
Hepatitis A immunoglobulin M 
(IgM) antibody; 
• 
HBsAg and hepatitis B core 
antibody; 
• 
Hepatitis C RNA; 
• 
Hepatitis E IgM antibody. 
• Cytomegalovirus IgM antibody. 


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MONITORING: 
• Make every reasonable attempt to have 
participants return to clinic within 24 hours 
for repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver event follow up assessments 
at the central laboratory as described to the 
right.  
• A specialist or hepatology consultation is 
recommended. 
• Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline. 
 
• Epstein-Barr viral capsid antigen IgM 
antibody (or if unavailable, obtain 
heterophile antibody or monospot 
testing). 
• Syphilis screening. 
• Drugs of abuse screen, including alcohol. 
Record alcohol use on the liver event 
CRF 
• Serum acetaminophen adduct HPLC 
assay (quantifies potential 
acetaminophen contribution to liver injury 
in participants with definite or likely 
acetaminophen use in the preceding 
week [James, 2009]).  The site must 
contact the medical monitor when this 
test is required. NOTE: not required in 
China 
• Blood sample for pharmacokinetic (PK) 
analysis, obtained within 60 hours of last 
dose4. 
• Serum CPK and lactate dehydrogenase 
(LDH). 
• Fractionate bilirubin, if total bilirubin 
1.5xULN. 
• Obtain complete blood count with 
differential to assess eosinophilia. 
• Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG or gamma 
globulins). 
• Liver imaging (ultrasound, magnetic 
resonance, or computerised 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 liver injury, or 
hypersensitivity, fatigue, decreased 
appetite, nausea, vomiting, abdominal 
pain, jaundice, fever, or rash as relevant 
on the AE report form. 


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• Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications. 
• Record alcohol use on the liver event 
alcohol intake eCRF. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant if ALT  3xULN and bilirubin  2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. 
All events of ALT  3xULN and bilirubin  2xULN (>35% direct bilirubin) must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis); INR measurement is not required, and the threshold 
value stated will not apply to participants receiving anticoagulants 
3. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia).   
4. 
PK sample may not be required for participants known to be receiving non-ViiV comparator treatments.  Record 
the date/time of the PK blood sample draw and the date/time of the last dose of study treatment prior to blood 
sample draw on the CRF. 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 SRM.   
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event 
Criteria 
Actions 
ALT ≥3x baseline and <5x baseline 
and bilirubin <2x ULN without 
symptoms believed to be related to 
liver injury or hypersensitivity 
• Notify the medical monitor within 24 hours of 
learning of the abnormality to discuss participant 
safety.  
• Participant can continue study treatment   
• Participant must return every 2 weeks for repeat 
liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until resolution or stabilisation (ALT 
<5×ULN on 2 consecutive evaluations)  
• If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above. 
 
Asymptomatic Liver Enzyme Elevations 
For asymptomatic subjects who have ALT>3X ULN, following discussions with medical 
monitor, ALT and other specific lab tests can be repeated in an unscheduled visit. This 
may include liver panel tests included in study protocol, even though subject did not meet 
any liver monitoring or liver stopping criteria above. 


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10.7. 
Appendix 7: Child-Pugh Classification 
A participant is classified with mild hepatic impairment (Class A) if their overall sum of 
scores is 5-6 points, moderate hepatic impairment (Class B) if their overall sum of scores 
is 7-9 points, and severe hepatic impairment (Class C) if their overall sum of scores is 10-
15 based on the Child-Pugh system [Pugh, 1973] scoring described in the following table 
(Table 14).  For participants requiring anticoagulation therapy, discussion with the study 
medical monitor will be required. 
Table 14 
Child-Pugh System 
Finding  
Points Scored for Each Observed Finding  
 
1 
2 
3 
Encephalopathy Grade1  
None 
1 or 2 
3 or 4 
Ascites 
Absent 
Slight 
Moderate 
Serum bilirubin, SI units (μmol/L),  
Serum bilirubin, conventional units (mg/dL)  
<34 
<2 
34 to 52 
2 to 3 
>52 
>3 
Serum albumin, SI units (g/L)  
Serum albumin, conventional units (mg/dL)  
>35 
>3.5 
28 to 35 
2.8 to 3.5 
<28 
<2.8 
 Prothrombin Time (seconds prolonged) or 
INR  
<4 
<1.7 
4 to 6 
1.7 to 2.3 
>6 
>2.3 
1. 
Grade 0: normal consciousness, personality, neurological examination, electroencephalogram 
Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles per second waves 
Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves 
Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves 
Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cycles per second delta activity 
[Pugh, 1973; Lucey, 1997] 
 


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10.8. 
Appendix 8: Division of AIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events Corrected Version 
2.1, July 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. 
PARAMETER 
GRADE 
1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE- 
THREATENING 
Clinical adverse 
event  NOT 
identified 
elsewhere in 
the 
grading table 
Mild symptoms 
causing no or 
minimal 
interference 
with 
usual social & 
functional 
activities with 
intervention not 
indicated 
Moderate symptoms
causing greater 
than minimal 
interference with 
usual social & 
functional 
activities with 
intervention 
indicated 
Severe symptoms 
causing inability 
to perform usual 
social & 
functional 
activities 
with 
intervention 
or 
hospitalization 
indicated 
Potentially life-
threatening 
symptoms causing 
inability to perform 
basic self-care 
functions with 
intervention 
indicated to prevent 
permanent impairment, 
persistent disability, or 
death 
 
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, 
Corrected Version 2.1. [July 2017] is available from: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
 


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10.9. 
Appendix 9: Toxicity Management 
Adverse events that occur during the trial should be evaluated by the investigator and 
graded according to the DAIDS toxicity scales (see Section 10.8).  Additional 
information regarding detecting, documenting and reporting AEs and SAEs are available 
in Section 10.3.5. 
Grade 1 or Grade 2 Toxicity/Adverse Event 
Participants who develop a Grade 1 or Grade 2 AE or toxicity may continue study 
treatment 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. 
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 study treatment, dosing may continue after discussion with the medical 
monitor. 
Participants who develop a Grade 3 AE that the investigator considers related or possibly 
related to the study drugs should have study treatment discontinued. 
Should the same Grade 3 AE recur within 28 days in the same participant, study 
treatment should be permanently discontinued, and the participant withdrawn from study.  
Participants experiencing Grade 3 AEs requiring permanent discontinuation of study 
treatment should be followed weekly until resolution of the AE and have withdrawal 
study evaluations completed.  A Follow-up visit should be performed 4 weeks after the 
last dose of study drugs.  
Participants with asymptomatic Grade 3 laboratory abnormalities should be investigated 
for all potential non-drug related causes, and, following discussion with the medical 
monitor, may continue study drug if the investigator has compelling evidence that the 
toxicity is not related to study treatment. 
Exceptions are noted for lipid abnormalities (for example, isolated Grade 3 lipid 
abnormalities do not require withdrawal of IP) and rash in Section 10.9.7. 
Grade 4 Toxicity/Adverse Event 
Participants who develop a Grade 4 AE or toxicity should have study treatment 
discontinued.  However, for Grade 4 toxicities only (not AEs), if the investigator has 
compelling evidence that the toxicity is not causally related to the study drugs, dosing 
may continue after discussion with and assent from the medical monitor.  Participants 
should be rechecked each week until the toxicity returns to Grade 2. 


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Participants experiencing Grade 4 AEs requiring permanent discontinuation of study 
treatment should be followed weekly until resolution of the AE and encouraged to 
complete the withdrawal and follow-up study evaluations as noted above.  
Participants with asymptomatic Grade 4 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 study treatment.  Exceptions are noted for lipid abnormalities in 
Section 7.1.  An in-clinic Follow-Up visit will be conducted approximately 4 weeks after 
the last dose of study medication for participants with ongoing AEs, and SAEs regardless 
of attributability and also any laboratory abnormalities that are considered to be AEs or 
potentially harmful to the participant, at the last on-study visit. 
Specific Toxicities/Adverse Event Management 
General guidelines for the management of specific toxicities that are considered to be 
related or possibly related to study treatment are provided below.  
Participants who permanently discontinue study treatment for reasons of toxicity should 
be followed weekly until resolution of the AE and encouraged to complete the 
withdrawal and Follow-up study evaluations (see Section 1.3). 
10.9.1. 
Liver Chemistry Stopping and Follow-up Criteria 
Liver chemistry threshold stopping criteria have been designed to assure participant 
safety and to evaluate liver event aetiology during administration of study drug and the 
follow-up period. For a complete listing of stopping and follow-up criteria refer to 
Section 7.1.2 and Section 10.6. 
10.9.2. 
Hypersensitivity Reaction  
A well characterized and manageable drug-related HSR is the most important risk 
associated with ABC.  HSR has also been seen with DTG. 
10.9.2.1. 
Reporting of Hypersensitivity Reactions 
Subjects may continue study drug for Grade 1 or 2 allergic reactions at the discretion of 
the Investigator.  The subject 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.  
Subjects with Grade 3 allergic reactions that are considered to be possibly or probably 
related to the study drug should permanently discontinue study treatment and the subject 
should be withdrawn from the study.  Subjects should be treated as clinically appropriate 
and followed until resolution of the AE. 
Participants receiving ABC as part of their NRTI background regimen should be 
evaluated for the possibility of a clinically suspected ABC hypersensitivity reaction 
(HSR) and managed appropriately as outlined in the local prescribing information. 


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10.9.2.2. 
Abacavir Hypersensitivity Reaction (ABC HSR) 
Both ABC and DTG are associated with a risk for hypersensitivity reactions (HSR), and 
share some common features such as fever and/or rash with other symptoms indicating 
multi-organ involvement. Clinically it is not possible to determine whether a HSR with is 
caused by ABC or DTG in a combined regimen. HSRs have been observed more 
commonly with ABC, some of which have been life-threatening, and in rare cases fatal, 
when not managed appropriately. 
The risk for ABC HSR to occur is significantly increased for patients who test positive 
for the HLA-B*5701 allele. However, ABC HSRs have been reported at a lower 
frequency in patients who do not carry this allele.  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) [Mallal, 2008]. In clinical studies EPZ108859 (ARIES) and CNA109586 
(ASSERT), 0.8% (4/515) and 3.1% (6/192) of subjects who were HLA-B*5701 negative 
and who received ABC developed a clinically suspected ABC HSR, respectively [Post, 
2010; Squires, 2010].  
Investigators must ensure that subjects are fully informed regarding the risk of HSR prior 
to commencing ABC therapy.  Each Subject should also be reminded of the importance 
of reading the Alert Card accompanying their study medication, and keeping it with them 
at all times. 
The following should be adhered to in the management of Subjects presenting with 
signs and symptoms suggesting a possible hypersensitivity reaction: 
• 
In any Subject treated with DTG and/or ABC, the clinical diagnosis of suspected 
hypersensitivity reaction must remain the basis of clinical decision making. 
• 
DTG and/or ABC must be stopped without delay, even in the absence of the 
HLA-B*5701 allele, if a HSR is suspected. Delay in stopping treatment with 
after the onset of hypersensitivity may result in a life-threatening reaction. 
Clinical status including liver aminotransferases and bilirubin should be monitored.  
• 
Subjects who have experienced a hypersensitivity reaction should be instructed to 
dispose of their remaining tablets, in order to avoid restarting ABC. 
• 
After stopping treatment with DTG and/or ABC for reasons of a suspected 
HSR, DTG and/or ABC or any other medicinal product containing ABC or 
DTG must never be re-initiated. 
• 
Restarting ABC- containing products following a suspected ABC HSR can 
result in a prompt return of symptoms within hours and may include life-
threatening hypotension and death. 
Reporting of Hypersensitivity Reactions 
If a clinically suspected case of HSR to ABC meets one of the International Conference 
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addition to reporting the case as an SAE, the ABC HSR CRF should also be completed 
within one week of the onset of the hypersensitivity reaction. 
10.9.3. 
Rash & Skin Reactions 
10.9.3.1. 
Rash 
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 SJS, TEN and erythema multiforme, have 
been reported for DTG in clinical trials.  For further characterisation of HSR and rash 
observed with DTG-containing ART, please see the current version of the IB 
[GlaxoSmithKline Document Number RM2007/00683/13, September 2020]. 
Participants receiving ABC/3TC NRTI background regimen should be evaluated for the 
possibility of a clinically suspected ABC HSR and managed appropriately as outlined in 
the local prescribing information.  
Skin and Subcutaneous tissue disorders have also been reported across clinical trials with 
GSK3640254. 
Grade 1 Rash: 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. 
Grade 2 Rash: 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 any systemic signs, allergic symptoms, or if mucosal 
involvement develops. 
Grade 3 Rash: Participants should permanently discontinue study drug (and all other 
concurrent medication(s) suspected in the Investigators causality assessment) for an 
isolated Grade 3 rash, except where the aetiology has been definitively diagnosed as NOT 
attributable to study drug (see below).  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. 
Grade 4 Rash: Participants should permanently discontinue study drug (and all other 
concurrent medication(s) suspected in the Investigators causality assessment). 
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., 
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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, Section 10.8). 
10.9.3.2. 
Skin reactions without other symptoms that are typical of ABC HSR 
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 while 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., 
TRIUMEQ, ZIAGEN, TRIZIVIR, EPZICOM or KIVEXA). 
As many products other than abacavir also cause rash and/or serious skin reactions, all 
other medicinal products that the participant is receiving should also be reviewed and 
discontinued as appropriate. 
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.  
The index case of hypersensitivity with DTG involved a profuse, purpuric and coalescing 
leukocytoclastic vasculitis as well as clinically significant liver chemistry elevations.  
Other than this case, no other instances of serious skin reaction, including SJS, TEN and 
erythmea multiforme, have been reported for DTG in clinical trials. 
The following guidance is provided for clinical management of subjects who experience 
rash alone in the absence of accompanying diagnosis of ABC HSR, systemic or allergic 
symptoms or signs of mucosal or target lesions. 
Subjects with an isolated Grade 1 rash may continue IP and background ART at the 
Investigator’s discretion. The subject should be advised to contact the Investigator 
immediately if there is any systemic signs, allergic symptoms, or if mucosal involvement 
develops. 
Subjects may continue IP and background ART for an isolated Grade 2 rash. However, IP 
and background ART (and all other concurrent medication(s) suspected in the 


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Investigators causality assessment) should be permanently discontinued for any Grade ≥2 
rash that is associated with an increase in ALT (see Section 10.6). The subject should be 
advised to contact the physician immediately if rash fails to resolve (after more than two 
weeks), if there is any systemic signs, allergic symptoms, or if mucosal involvement 
develops. 
Subjects should permanently discontinue IP and background ART (and all other 
concurrent medication(s) suspected in the Investigators causality assessment) for an 
isolated Grade 3 or 4 rash, and the subject should be withdrawn from the study. Subjects 
should be treated as clinically appropriate and followed until resolution of the AE. 
The rash and any associated symptoms should be reported as adverse events (see Section  
10.3) and appropriate toxicity ratings should be used to grade the events (based on 
DAIDS toxicity gradings). 
If the etiology of the rash can be definitely diagnosed as being unrelated to IP and due to 
a specific medical event or a concomitant non-study medication, routine management 
should be performed and documentation of the diagnosis provided. 
10.9.4. 
Hypertriglyceridemia/Hypercholesterolemia 
Samples for lipid measurements must be obtained in a fasted state according to the 
Schedule of Activities (Section 1.3).  Participants who experience asymptomatic 
triglyceride or cholesterol elevations may continue to receive study drug. 
10.9.5. 
Creatine Phosphokinase (CPK) Elevation 
A Grade 3 or higher elevation in CPK should result in a repeat assessment within 2 to 4 
weeks to ensure the result is transient or due to exercise and will not require a change in 
study treatment.  A history regarding use of drugs known to cause increase of CPK (such 
as statins), physical activity or exercise preceding the CPK evaluation should be obtained.  
Grade 4 elevations in CPK should have a repeat assessment after the participant has 
abstained from exercise for >24 hours.  For persistent Grade 4 CPK elevations that are 
considered possibly or probably related to the study drugs, study treatment should be 
discontinued, and the participant withdrawn from the study. 
10.9.6. 
Decline in Renal Function 
Participants who experience an increase in serum creatinine from Baseline of 45 
micromoles/liter (μMol/L) (or 0.5 milligrams/deciliter [mg/dL]) should return for a 
confirmatory assessment within 2 to 4 weeks.  A urinalysis and urine albumin/creatinine 
and urine protein/creatinine ratios, serum cystatin C and an estimated GFR using the 
CKD-EPI cystatin C method [Inker, 2012] should also be done at this confirmatory visit 
(refer to the SRM for details on the collection and processing of these urine samples).  If 
the creatinine increase is confirmed, the investigator should contact the ViiV Medical 
Monitor to discuss additional follow-up and medical management. 
Participants who experience progression to an estimated GFR (using the CKD-EPI 
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2 weeks.  A urinalysis and urine albumin/creatinine and urine protein/creatinine ratios, 
serum cystatin C and an estimated GFR using the CKD-EPI cystatin C method [Inker, 
2012] should be done at this confirmatory visit (refer to the SRM for details on the 
collection and processing of these urine samples). 
If an estimated GFR of <50 mL/min is confirmed, then study medications should be 
discontinued and the participant withdrawn. 
10.9.7. 
Proximal Renal Tube Dysfunction 
PRTD is defined as: 
• 
Confirmed rise in serum creatinine of ≥0.5 mg/dL from Baseline AND serum 
phosphate <2.0 mg/dL; 
• 
Either of the above accompanied by any two of the following: 
o Glycosuria (≥250 mg/dL) in a non-diabetic; 
o Low serum potassium (<3 mEq/L); 
o 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 must be withdrawn from 
the study. 
10.9.8. 
Proteinuria 
Participants with an abnormal urine albumin/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 albumin/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. 
Refer to the SRM for details on the collection and processing of urine samples. 
 


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10.10. 
Appendix 10: 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 percentage 
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 
• 
Coccidioidomycosis, disseminated or extrapulmonary  


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• 
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. 


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10.11. 
Appendix 11: COVID-19 Pandemic and Clinical Trial 
Continuity 
The COVID-19 pandemic may impact the conduct of clinical studies. Significant 
logistical challenges may arise from quarantines, variable restrictions on site resource and 
operations, site closures, travel limitations and the inability of an individual participant to 
attend clinic visit, interruptions to the supply chain for the investigational product, or 
other considerations if site personnel or study participants become infected with COVID-
19. These challenges may lead to difficulties in meeting protocol-specified procedures, 
including dispensation of the investigational product to the participant or adhering to 
protocol-mandated visits and laboratory/diagnostic testing.   
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. 
This appendix outlines the measures which are approved for implementation within this 
clinical trial, to protect patient safety, welfare and rights, and to ensure data integrity and 
the integrity of the clinical trial, as a result of COVID-19 only. These measures may be 
implemented in accordance with any requirements and expectations set out by local 
Independent Review Boards/Independent Ethics Committees and National Competent 
Authorities, as necessary. 
This appendix does not apply for participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19.  
10.11.1. 
Changes to Study Visits and Study Procedures 
Every effort should be made to adhere to protocol-specified assessments for participants 
on study intervention, including follow up however when not possible, for the duration of 
these special circumstances, the following measures may be implemented for enrolled 
participants: 
• When site staff resources are limited due to COVID-19, abbreviated study visits 
may proceed without conducting all protocol-specified additional assessments 
(e.g. lab tests, questionnaires, etc.). If laboratory testing will be missed for more 
than one consecutive visit, medical monitor pre-notification is required, and all 
efforts should be made to find alternative approaches for lab testing.  
• Consider alternative travel options for participants, if possible.  
• When central laboratory testing is not possible at a particular visit, tests for 
management of participant safety, including HIV-1 RNA may be performed at an 
appropriately authorised/accredited local laboratory (or other relevant clinical 
facility), if this can be done within local restrictions on physical distancing. The 


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site should proactively inform the Sponsor about such instances. Local laboratory 
results done as per routine follow-up, including HIV-1 RNA, may be used to 
inform safety and patient management decisions.  Results should be retained in 
source records and added to the eCRF. 
o If labs are collected on site and cannot be processed (either via central lab 
shipping, or local labs), freeze (and maintain at correct temperature for 
later processing) those samples that are sent frozen. Please safely discard 
ambient samples per site standards. 
• When on-site visits are reduced, it is important that the investigator continue 
collecting relevant clinical information, including AEs/SAEs, from the participant 
through alternative means, e.g. by telephone contact or video app such a Skype, 
FaceTime, Zoom, etc., where allowed.  
o The assessment should include inquiries to determine if the participant has 
been impacted by COVID-19 (extent of travel restriction, have they been 
in contact with any known positive cases [See Section 10.11.5.2 for WHO 
definition of “contact” -  it is important to understand who among our 
participants could be at risk], assess for COVID-19 as part of the AE/SAE 
assessment (See Section 10.11.5.2), and inquire about any possibility that 
the participant has plans to be on an experimental agent for COVID-19 
See Section 10.11.4)  
o Other protocol assessments and procedures as specified in the Schedule of 
Activities should be completed where possible (e.g. answer questions, 
update concomitant medications, emphasize adherence, plan/schedule 
participants return for next scheduled visit). This information should be 
placed in source records and entered into the eCRF when next possible.  
o The CSSRS assessment is already planned to be done via telephone in this 
study, whether the subject is on site for an in-clinic visit or at home and 
doing a virtual visit.  When the participant is unable to be in the clinic for 
a required on-site visit, the eCSSRS is still able to be performed at home, 
preferably prior to virtual contact by the site. Plans for addressing any 
positive results and referring for care remain no matter from which 
location the eCSSRS is phoned in.  
• Missing protocol required data/visits due to COVID-19 should be noted in 
participant notes and recorded as a COVID-19 protocol deviation.  
• Where applicable country and local regulations and infrastructure for home 
healthcare allow, home healthcare may take place at a location other than the 
clinical trial site to perform study assessments, which may include collection of 
blood and urine samples, measurement of vital signs and weight, and performance 
of ECGs.  It is the responsibility of the investigator to inform GSK when this 
occurs and to document in source notes.  
• It may become necessary for the Sponsor to broadly incorporate the use of home 
healthcare staff to perform visits in the participant’s home. This possibility is also 
discussed in the ICF. 


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• There may be cases where the current PI of a site is indisposed for a period and 
may need to delegate parts of his/her duties temporarily, e.g. to a sub-investigator. 
Any such changes should be documented in the site’s source records. Any 
permanent changes in PI should be communicated to the sponsor. 
• There may also be circumstances where immediate actions are required by the 
sponsor and/or investigator, outside of what is contemplated in the protocol, in 
order to protect a study participant from immediate hazard. Any such measures 
will be carefully documented and conducted in accordance with the National 
Competent Authority (NCA)/IRB/IEC regulations. 
10.11.2. 
Changes to Informed Consent 
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval. 
Any updated informed consent form or other participant-facing materials should be 
provided to participants by e-mail, mail or courier before re-consent is obtained. Any 
consent obtained this way should be documented in source records and confirmed by way 
of normal consent procedure at the earliest opportunity when participants attend their 
next on-site study visit. 
The changes to the protocol, including COVID-19 related changes may be implemented 
before an ICF including COVID-19 related updates will be signed. 
10.11.3. 
Direct-To-Patient (DTP) Shipment of Study IP  
If a participant is unable to attend a study visit or to come to the site to pick-up 
investigational product (IP) due to site restrictions, or due to an inability to travel to the 
site (for personal precaution/sequestration, or government mandated travel restrictions, 
etc.), sites can consider DTP shipments of drug, from the site, to the participant, to ensure 
access to medicines.  All other options, including alternative travel options for 
participants, should be considered before reverting to DTP shipments. 
• If the study site is considering DTP shipment of 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 will 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 will be documented 
within the main ICF.   


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• DTP IP should be supplied only in a quantity that is sufficient to cover the interval 
to the next scheduled dispensation visit. There is a risk that accompanies 
dispensing more than a single 3-bottles set of blinded GSK3640254.  Please see 
the SRM for details about the limitations with dispensation. 
• GSK/VH suggest the use of Marken in most countries for DTP shipments.  
Otherwise, ensure local courier vendors, or vendors of hospital pharmacies, can 
ensure proper in-transit temperature monitoring, have enough shipper boxes and 
temperature loggers and can document storage conditions during IP 
transportation. 
• Where temperature monitoring is not available, oral protocol study treatments can 
be shipped at ambient temperatures with couriers that can provide shipper boxes 
capable of maintaining the shipment temperature storage requirements as 
described in the study guides. The risk of going outside of the excursion ranges 
listed in the study guide should be evaluated and documented. Proper 
documentation of the shipment should be maintained. In all cases IP 
accountability must be maintained, and all DTP dispensing documentation should 
be reflected in source records and dispensing logs per GCP. 
• Please refer to your CRA or local study manager for support with the DTP 
process, ensuring reference to current sponsor guidance and arrangement of a 
courier that can support shipment of IP directly to participants. 
• Remember that any courier deliveries can be affected by limitations of 
movements imposed by governments in relation to COVID-19.  
• Local courier vendors should be equipped to reduce risks of COVID-19 
contamination during transportation. 
10.11.4. 
COVID-19 Therapeutic 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. 
The protocol does not allow for concurrent enrolment in other interventional studies. 
10.11.5. 
COVID-19 Specific Data Capture 
10.11.5.1. Capturing COVID-19 Specific Protocol Deviations 
Please refer to the SRM for specific details on capturing protocol deviations as a result of 
COVID-19. 
10.11.5.2. Capturing COVID-19 Specific AEs and SAEs 
VH are monitoring the evolving situation with respect to COVID-19 carefully and the 
impact this may have on ongoing or planned clinical trials.  It is important for the study 
team to describe COVID-19 related adverse events/serious adverse events and their 
impact on study data and outcomes. Standardization of case definitions will facilitate 
future data analysis.  


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Please use the following guidance:  
1. 
AEs should continue to be evaluated as to whether they meet SAE criteria as 
defined in the protocol, and if so, submitted according to established SAE 
reporting requirements. SAEs and AEs should be submitted following usual study 
procedures and timelines.  
2. 
When an in-person clinic visit is not possible, please conduct a remote telehealth 
visit to assess for, and document any AEs/SAEs. 
3. 
Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released March 20, 2020, represents a time point for 
standardized collection. We recognize definitions are likely to continue to evolve; 
the most recent definitions should be consulted for each case (WHO). 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 in the 
setting of clinically defined mild COVID-19 infection.  
5. 
A new COVID-19 infection Case Report Form is included in the eCRF to collect 
additional details about the reported COVID-19 AE or SAE data. It is important 
that the correct information is collected from each participant reporting a COVID-
19 AE or SAE.  Therefore, please use the CRF templates to help you collect this 
information for all COVID-19 related AEs/SAEs. 
10.11.5.2.1. 
WHO Case Definition (December 16, 2020 Version):  
Please see the WHO Case Definition for Suspected, Probable or Confirmed case of 
SARS-CoV-2 infection: https://www.who.int/publications/i/item/WHO-2019-nCoV-
Surveillance_Case_Definition-2020.2 
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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10.12. 
Appendix 12: Country-specific requirements 
CANADA 
A country specific amendment for Canada, 208379/CAN-1, was previously published on 
18-SEP-2020 based on a requirement from Health Canada to include a requirement to 
perform a subsequent serum pregnancy test during Screening if the Screening period 
extends beyond 30 days – to be collected between Day -7 to Day -5 prior to Day 1. 
Text pertaining to this requirement was inserted in these sections: 
• Footnote 9 of the Schedule of Activities  
• Section 8.2.5, Pregnancy Testing 
Additionally, in both sections, additional text regarding both the urine and serum 
pregnancy testing during Screening and at Day 1 was added for clarity, per request from 
Health Canada.  (This clarifying text was also incorporated into Global Amendment 01.) 
 
PORTUGAL 
A country specific amendment for Portugal, 208379/POR-1, was previously published on 
18-SEP-2020 based on a requirement from their Central Ethics Committee to explicitly 
state that participants infected with HIV-2 would be excluded. 
A new Exclusion Criterion was added,  #41: HIV-2 infection (either determined by prior 
testing, medical history, or obtained locally during the Screening window) 
 
 
 
 


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10.13. 
Appendix 13: Abbreviations and Trademarks 
3TC 
Lamivudine 
ABC 
Abacavir 
ABC/3TC 
Epzicom 
ADME 
absorption-distribution-metabolism-elimination 
AE 
Adverse Event 
AESI 
AE of special interest 
AIDS 
Acquired Immunodeficiency Syndrome 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ART 
Anti-retroviral therapy 
ARV 
Anti-retroviral 
AUC(0-) 
Area under the curve (Area under the plasma drug concentration-time 
curve from pre-dose to the end of the dosing interval at steady state)  
AUC(0-24) 
Area under the plasma concentration time curve from zero to 24 
AVB  
Atrioventricular block 
β-HCG 
Human chorionic gonadotropin 
BDC 
Bile-Duct-Cannulated 
BMI 
Body mass index 
BMS 
Bristol-Myers Squibb 
bpm 
Beats per minute 
cART 
Combination anti-retroviral therapy 
c/mL 
Copies per millilitre 
C0 
Concentration, pre-dose 
C24 
Concentration, 24 hours post-dose 


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CAp24 
Capsid protein 24 
CD4 
Cluster of designation 4 
CD8 
Cluster of designation 8 
CDC 
Center for Disease Control and Prevention 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence interval 
CIB 
Clinical Investigator's Brochure  
CIOMS 
Council for International Organizations of Medical Sciences 
CMO 
Chief Medical Officer 
CMV 
Cytomegalovirus 
Cmax 
Maximum observed concentration  
CNS 
Central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials  
COVID-19 
Coronavirus Disease 2019 
CPK 
Creatine phosphokinase 
CrCl 
Creatinine Clearance 
CRF 
Case report form 
CSR 
Clinical study report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
Ct 
Concentration at end of dosing interval 
CV 
Cardiovascular 
CVb 
Between-participant coefficient of variation 
DAIDS 
Division of AIDS 
DBR 
Database Release 
DDI 
Drug-Drug Interaction 


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DNA 
Deoxyribonucleic acid 
DTG 
Dolutegravir 
EC90 
Effective concentration 
EGD 
Esophagogastroduodenoscopy 
ECG 
Electrocardiogram  
Emax 
Effect, at the maximum 
EMEA 
European Medicines Agency 
EW 
Early Withdrawal 
FACTS 
Fixed and Adaptive Clinical Trial Simulation 
FDA 
Food and Drug Administration  
FSH 
Follicle Stimulating Hormone 
FTIH 
First-time-in-human 
Gag 
Group-specific antigen 
GCP 
Good Clinical Practice 
GCSP 
Global Clinical Safety and Pharmacovigilance  
GERD 
Gastroesophageal reflux disease 
GI 
Gastrointestinal 
GSK 
GlaxoSmithKline  
h or hr 
hour 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B Virus 
HCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C Virus 
HCV Ab 
Hepatitis C antibody 
HDPE 
High-density polyethylene 


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HIPAA 
Health Insurance Portability and Accountability Act 
HIV-1 
Human immunodeficiency virus-1 
HRT 
Hormonal replacement therapy 
HSR 
Hypersensitivity Reaction 
ICF 
Informed consent form  
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee  
INI 
Integrase Inhibitor 
INR 
International normalized ration 
IQ 
Inhibitory quotient 
IRB 
Institutional Review Board  
INSTI 
Integrase Strand Transfer Inhibitor 
IP/IMP 
Investigational Product/Investigational Medicinal Product 
IRT 
Interactive Response Technology 
iSRC 
Internal Safety Review Committee 
ITT 
Intent to treat 
IUD 
Intrauterine Device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
IVRS/IWRS 
Interactive Voice/Web Response System 
kDa 
Kilodalton 
kg 
Kilogram 
lbs 
Pounds 
LDL 
Low density lipoprotein 
LOAEL 
Lowest observed adverse effect level 


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LLOD 
Lower limit of detection 
LOC 
Local Operating Company 
MAD 
Multiple ascending dose 
MedRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligrams 
MI 
Maturation inhibitors 
MOA 
Mechanisms of action 
MSDS 
Material Safety Data Sheet  
ms, msec 
Milliseconds 
NOAEL 
No-observed-adverse-effect-level 
NIMP 
Non-investigational Medicinal Product 
nM 
nanomolar 
NPO 
nil per os (Nothing by mouth) 
NRTI 
Nucleoside Reverse Transcriptase Inhibitor 
NNRTI 
Non- Nucleoside Reverse Transcriptase Inhibitor 
OCT1 
Organic cation transporter 1 
OCT2 
Organic cation transporter 2 
PBAEC90 
Protein binding adjusted concentration 
PBO 
Placebo 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic  
PDVF 
Protocol Defined Virologic Failure 
PI 
Principal Investigator  
PK 
Pharmacokinetic  
POC 
Proof of Concept 


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PRSAE 
Possible Suicidality-Related AE 
PGX 
Pharmacogenetics 
POCBP 
Participant of Childbearing Potential  
PONCBP 
Participant of Non-Childbearing Potential 
PP 
Per protocol 
PPI 
Proton pump inhibitor 
PPL 
Physician Product Lead 
PT/INR 
Prothrombin time/International normalized ratio 
QD 
Once daily 
QTc 
Corrected QT interval 
QTcF 
QT duration corrected for heart rate by Fridericia’s formula 
QTL 
Quality Tolerance Limit 
R 
Accumulation ratio 
RBC 
Red blood cells 
RNA 
Ribonucleic Acid 
RPR 
Rapid Plasma Reagin 
SAD 
Single ascending dose 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe Acute Respiratory Syndrome-Coronavirus-2 
SAS 
Statistical Analysis Software 
SD 
Standard deviation  
SGOT 
Serum Glutamic-Oxaloacetic Transaminase 
SGPT 
Serum Glutamic-Pyruvic Transaminase 
SI 
Sub-Investigator 


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SOA 
Schedule of activities 
SOC 
System Organ Class 
SP1 
Spacer peptide 1 
SRM 
Study Reference Manual  
SRT 
Safety Review Team 
SUSAR 
Suspected unexpected serious adverse reactions 
t1/2 
Apparent terminal phase half-life  
tlag 
Absorption lag time 
tmax 
Time of occurrence of Cmax  
TN 
Treatment naïve 
ULN 
Upper limit of normal  
VH 
ViiV Healthcare 
VLD 
Viral load drop 
VSLC 
ViiV Safety and Labelling Committee 
VT 
Ventricular Tachycardia 
WBC 
White blood cells 
Wk 
Week 
 
Trademarks of the ViiV Healthcare 
group of companies 
 
Trademarks not owned by the ViiV 
Healthcare group of companies 
EPZICOM 
 
DESCOVY 
TIVICAY 
 
GenoSure 
 
 
Leica Aperio AT2DX  
 
 
Monogram Biosciences 
 
 
PhenoSense 
 


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10.14. 
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 CAN-1 18-SEP-2020 
Overall Rationale for the Amendment:  
This is a country-specific amendment applicable only to Canada. 
To further protect the health and safety of participants who are women of childbearing 
potential, Health Canada requests to have another serum pregnancy test performed prior 
to Day 1 if the Screening period extends beyond 30 days.  In addition, it was requested to 
include some clarifying text around both the urine and serum pregnancy testing.  
Section # 
and Name 
Description of Change 
Brief Rationale 
1.3, Schedule 
of Activities, 
Footnote 9 
Inserted text to require a subsequent 
serum pregnancy test prior to Day 1 
(collected approximately on Day -7 to 
Day -5) if the Screening period goes 
beyond 30 days. 
This is specific only to Canada, per request. 
 
1.3, Schedule 
of Activities, 
Footnote 9 
 
8.2.5, 
Pregnancy 
Testing 
In both sections, inserted additional 
text regarding both the urine and 
serum pregnancy testing during 
Screening and at Day 1. 
These changes were requested for clarity. 
These will also be included in the next global 
amendment. 
Amendment POR-1 18-SEP-2020 
This amendment is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union because it neither significantly impacts the safety or physical/mental 
integrity of participants nor the scientific value of the study. 
Overall Rationale for the Amendment: 
The Central Ethics Committee requested that the protocol explicitly have an exclusion 
criterion for participants with concomitant HIV-2 infection. 
 


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Section # 
and Name 
Description of Change 
Brief Rationale 
5.2, Exclusion 
Criteria 
Inserted new exclusion criterion 
#41 to exclude participants with 
HIV-2 infection 
Portugal Only - CEC request 
 
Amendment 01: 25-SEP-2020 
This amendment is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union because it neither significantly impacts the safety or physical/mental 
integrity of participants nor the scientific value of the study. 
Overall Rationale for the Amendment:  
This is a global amendment. 
This amendment was created primarily to replace details of the internal Safety Review 
Committee to reflect the use instead of an Independent Data Monitoring Committee 
(IDMC).  The decision to switch was based on feedback received from several health 
authorities and ethics committees, with advice and approval by VH guidance committee.  
This amendment also includes corrections, clarifications and minor administrative errors.   
In addition, details from 2 prior country-specific amendments (Canada amendment CAN-
1 and Portugal amendment POR-1) were incorporated into this global amendment. 
This document now serves as the current global amendment for all countries. 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis, Objectives and 
Endpoints, Secondary Safety 
3, Objectives and Endpoints, 
Secondary Safety 
Replaced the term “antiviral 
efficacy” with the words “safety 
and tolerability” 
Error correction 
Synopsis, internal Safety Review 
Committee 
4.1, Overall Design 
9.5, Interim Analyses 
9.5.1, Internal Safety Review 
Committee 
10.1.5.1, Safety Data Review by 
Safety Review Team and iDMC 
Changed all references of an 
iSRC to IDMC. 
Provided detail on composition 
of IDMC and other clarifying 
text, as well as to make it clear 
that no employee of Sponsor 
will have access to the data 
being reviewed (only in Section 
9.5.1). 
Based on feedback from several 
health authorities and ethics 
committees, and with advice and 
approval by ViiV Safety and 
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Section # and Name 
Description of Change 
Brief Rationale 
1.3, Schedule of Activities 
ECG: Single reading POST 
dose was noted that the 
procedure is to be excluded 
from an EW visit 
 
Fasting Lipids: It was noted that 
the assessment is to be 
included at the Final visit or at 
an EW visit. 
 
Optional Renal, Bone and 
Inflammatory Biomarkers: 
Removed the word “optional” 
 
Inserted new footnote #15 to 
describe monthly dispensation 
of the blinded GSK3640254 
Error correction 
 
 
 
For clarity 
 
 
 
Error Correction 
 
 
To help minimize dose 
administration errors with 
GSK3640254  
1.3, Schedule of Activities, 
Footnote 9 
 
8.2.5, Pregnancy Testing 
Inserted additional text 
regarding both the urine and 
serum pregnancy testing during 
Screening and at Day 1 
 
Inserted a specific statement 
that pertains to Canada Only, 
requiring a subsequent serum 
pregnancy test during the 
Screening period if the 
Screening period extends 
beyond 30 days. 
For clarity 
 
 
 
To clarify country-specific 
requirements for Canada in the 
body of the protocol to align with 
Appendix 12 
4.1.2.3, Switch to Optimal Dose 
Provided detail about the factors 
that will be considered when 
assessing participant eligibility 
to continue into the Non-
Randomized Phase of the 
study. 
The detail was missing 
5.1, Inclusion Criteria, #6 
Inserted a NOTE to provide a 
statement that there are no 
contraceptive requirements for 
male study participants. 
For clarity. 
5.2, Exclusion Criteria #41 
Inserted MDMA and 
methamphetamines to the list of 
drugs that will be tested in the 
Error correction. 
 


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Section # and Name 
Description of Change 
Brief Rationale 
Drugs of Abuse panel. 
Inserted a specific Exclusion 
Criterion #41 that pertains to 
Portugal Only, requiring 
participants with HIV-2 infection 
to be excluded 
 
To clarify country-specific 
requirements for Portugal in the 
body of the protocol to align with 
Appendix 12 
6.1, Study Intervention(s) 
Administered 
For the Randomised Phase, 
Arm 2, indicated that the Use of 
GSK3640254 25mg tablets is 
Experimental, not Placebo 
Error Correction 
7.1.4, QTc Stopping Criteria 
8.2.3, Cardiac Monitoring with 
Electrocardiograms 
Inserted guidance for site to 
consult with a cardiologist if the 
ECG output shows QTc 
stopping criteria have been met 
To confirm participant should be 
discontinued 
8.3.5, Pregnancy 
Removed incorrect information 
from bullet 2, and removed 
bullet 4 – both containing 
incorrect information that 
directly conflicted with correct 
information in bullet 1.  
Reporting of partner 
pregnancies is not required. 
Error Correction 
8.6.1, Serum Biomarkers and 
EGD with Biopsy in the Stomach 
Substudy 
10.2, Appendix 2, Table 13, 
Protocol Required Safety 
Laboratory Tests 
Removed the measurement of 
gastric pH 
Assessment cannot be 
performed using EGD as planned 
9.1, Statistical Hypothesis 
Inserted a superscripted 2 at 
two values: 0.7324 and 5 
 
Inserted logit text 
To clarify that 0.7324  and 5 are 
the standard deviations not 
variances 
To clarify that the normal 
distribution represents the logit of 
response rate instead of the 
actual response rate 
9.2, Sample Size Determination 
Changed “non-inferiority margin” 
to “margin” 
To emphasize that this is not a 
formal powered non-inferiority 
study 
9.3.4, Safety Population 
Removed 3rd row of table, as 
the Safety Population is already 
described in the preceding text 
Removed redundancy 


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Section # and Name 
Description of Change 
Brief Rationale 
10.2, Appendix 2, Table 13, 
Protocol Required Safety 
Laboratory Tests 
Removed the word “Safety” 
from the table title as the table 
includes parameters for many 
purposes, not just safety. 
Removed Cystatin C from the 
standard clinical chemistry 
assessments; it is only done as 
part of the Biomarker 
assessments as outlined in a 
subsequent row. 
Added MDMA and 
methamphetamines to the Urine 
Drug Screen in “Other tests.” 
Error corrections. 
10.4.2, Contraceptive Guidance 
Inserted information that there 
are no contraceptive 
requirements for male study 
participants based on data for 
both GSK3640254 and the most 
recent data for DTG.  
Removed footnote c and its 
corresponding guidance on the 
use of male condoms 
For clarity, as the protocol did not 
previously include a specific 
statement that contraceptive 
measures were not required for 
male study participants. 
 
Error correction 
10.12, Appendix 12, Country-
specific requirements 
Added new sections to describe 
previous country specific 
amendments for Canada (CAN-
1) and Portugal (POR-1) that 
will now be incorporated into 
this global amendment. 
To provide clarity on past 
country-specific amendments 
(CAN-1 and POR-1) that have 
been published prior to this 
amendment and are 
consolidated into this global 
amendment 
10.13, Abbreviations and 
Trademarks 
Inserted new abbreviations used 
in this amendment 
For reader’s reference 
Section 10.14, Appendix 14: 
Protocol Amendment History  
Updated to incorporate changes 
from previous amendments 
To reflect current status of 
amendments 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore have not been 
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Amendment 1/SS-1 (244689): 11-DEC-2020 
Overall Rationale for the Amendment:  
This is a site-specific amendment applicable only to Site 244689 in South Africa. 
To further protect the health and safety of participants, the ethics committee at the 
University of Cape Town, Site 244689, requests to modify the existing Exclusion 
Criterion #13 to further exclude participants with a familial history of sudden cardiac 
death.  The EC believes that prolonged QT may be undiagnosed, especially in resource-
constrained settings, and knowledge of a familial or personal history of long QT 
syndrome may not be available. 
Section # 
and Name 
Description of Change 
Brief Rationale 
5.2, Exclusion 
Criteria, #13 
The existing exclusion criterion was 
modified to further exclude 
participants who have a familial 
history of sudden cardiac death. 
This is specific only to Site 244689 in South 
Africa, per EC request, 
 
 
Amendment 02: 09-APR-2021 
This amendment is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union because it neither significantly impacts the safety or physical/mental 
integrity of participants nor the scientific value of the study. 
Overall Rationale for the Amendment:  
This is a global amendment. 
This amendment was created primarily to make non-substantial changes generally related 
to inclusion/exclusion criteria and the screening period, esophagogastroduodenoscopy 
(EGD) biopsy-based stopping criteria for individual participants and the study overall. 
The other changes exist for further detail, clarity, and current information.  
Section # and Name 
Description of Change 
Brief Rationale 
1.1, Synopsis, Overall Design 
Inserted text to address the 
eradication of Helicobacter 
pylori  
For accuracy given that this 
protocol amendment will allow for 
eradicating and retesting of 
Helicobacter pylori within a single 
screening period. 
1.3, Schedule of Activities  
Screening 
 
Inserted detail that the 42-day 
Screening Period may be 
extended (delaying 
 
For consistency with the 
allowance for the Stomach 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
2 0 8 3 7 9  
 
1 7 6  
 
S e cti o n # a n d N a me  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
R a n d o miz ati on) t o a m axi m u m 
of 6 3 d ays in c ertai n 
circ u mst anc es 
S u bst u dy  
W e ek 2  
I ns ert e d D ay 1 1-14 wi n d o w f or 
t h e W e ek 2 visit 
F or cl arity  
El ectr oc ar di ogr a ms  ( E C Gs) 
 
I ncl u de d wi n d o ws of ± 1 5 
mi n ut es f or post -d os e E C Gs  
 
D et ail w as missi ng.  
O pti o nal St o m ac h Su bst udy                                               
 
Pr ovi d e d d et ail t h at t h e D ay 1 
n e e ds t o b e d o n e duri n g 
t h e Scr e e ni n g P eri o d, w hil e t he 
D ay 1 s ubst u dy Bi o m ark ers 
ar e dr a w n at th e D ay 1 visit.  
F or cl arity  
 
P h ar m ac oki n etic ( P K) –  S parse, 
P K -I nt e nsiv e 
 
Pr ovi d e d re mi nd ers th at t h ere 
ar e s e p arat e P K l a b kits f or 
W e ek 2 (I nt e nsiv e P K), an d 
W e eks 4, 8, 1 2, 2 4, 36 a n d 4 8 
( S p ars e P K).  At a ny visit 
w h er e P K is t o b e c oll ect e d, 
sit es will us e B O T H t h e r e gul ar 
l a b kit f or t he visit A N D t h e P K 
l a b kit f or t hat visit.  T h e P K l ab 
kit c ont ai ns a pre-d ose P K 
t u b e t h at sit es n e ed t o c ollect 
pr e -d os e al o n g wit h all of th e 
ot h er pr e -d os e la bs i n t h e 
r e g ul ar la b kit.    
T o e ns ure s ucc essf ul, pr o per P K 
c oll ecti on. 
F o ot n ot e # 6  
R e m ov e d text th at i ndicat es 
a ny p ositiv e r es p o ns e o n th e 
C S S R S w o ul d r es ult in 
excl usi on.  
T o all o w f or i ncre as ed cli nic al 
j u d g m ent i nto p atie nt eli gibility f or 
tri al ( n ote: C S S R S is still bei ng 
us e d d uri n g scr e eni n g)  
1. 3, Sc h ed ul e of Activities 
( Pr e g n a ncy T est, F o ot not e 9); 
2. 3. 1, Risk Ass ess m e nt  
4. 1. 2. 2. 2, Virt u al Visits;  
5. 1, I ncl usi o n Crit eri a ( # 6 –  ma d e 
# 7 by t his a m e n d m e nt);  
5. 3. 2, Alc o h ol, T o b acc o a n d 
M arij ua n a;  
8. 2. 5, Pr e g na ncy T esti n g;  
C h a n g e d all r ef ere nc es of 
W O C B P ( wo m e n of 
c hil db e ari ng p ot enti al) t o 
P O C B P ( p articip a nts of 
c hil db e ari ng p ot enti al) a n d 
c h a n g ed all r ef er e nc es of 
“ wo m e n/f e mal e” t o 
“ p articip a nts w h o ar e assi g n e d 
f e m al e at birth”; r ef er enc es t o 
m al es w er e c ha n g e d t o 
“ p articip a nts w h o ar e assi g n e d 
m al e at birt h”.  
T o ackn o wl e d ge g e n der div ersity 
a n d g e n der fl ui dity  
C CI


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Section # and Name 
Description of Change 
Brief Rationale 
8.3.5, Pregnancy; 
10.4 1, Appendix 4, Contraceptive 
and Barrier Guidance, Definitions 
10.4.2, Contraceptive Guidance 
2, Introduction, 3rd paragraph 
1.1, Synopsis 
Updated information about the 
GSK3640254 program 
To align with current information 
2.2.3, Key Clinical Data on 
GSK3640254 to date 
Updated information in 2nd, 4th 
and 5th bullets  
Removed 6th bullet 
To align with current results 
summaries 
2.2.4, Key Phase 2a (208132) 
Clinical Data on GSK3640254 
Removed the word 
“Preliminary” from the section 
title; 
Updated text with more current 
information; 
Updated Table 1 and Table 3 
with final data. 
Replaced Table 2 with final 
data. 
To align with current information 
2.3.1, Risk Assessment 
Updated most categories with 
current information. 
To align with current information 
4.1.1, Screening Period 
Indicated that the Screening 
Period may be extended up to 
a maximum of 63 in certain 
circumstances (no longer 
uniquely for stomach substudy 
participation). 
For consistency. 
4.1.2, Treatment Period 
 
Added timing information for 
the Week 2 Visit (to be 
performed Day 11-14) 
For clarity, and to be consistent 
with updates made in 4.1.2.1.1 
4.1.2.1.1, Optional Intensive PK 
Portion of Week 2 Visit – 
GSK3640254 Arms Only 
Updated the timing of Week 2 
visit from Day 9-14 to Day 11-
14. 
Day 11 is a more appropriate 
start of the window, considering 
the viral load interest at the visit. 
4.1.2.2.1, Virologic Management 
Figure 1 
Table 4, footnote d 
 
 
 
Changed instruction for Week 
24 Non-Responders – who 
must discontinue immediately 
from the study; 
 
 
For safety 
 
 
 


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Section # and Name 
Description of Change 
Brief Rationale 
Table 4 
Inserted bullets where needed 
For clarity and ease for the reader 
4.1.3,  Follow-up 
Inserted instructional text 
regarding required follow-up 
work on participants at the end 
of the study. 
Detail was missing 
4.1.4, Study Completion 
Moved text better suited for 
Section 4.1.3. 
For clarity 
4.1.5, Optional Stomach 
Substudy, (EGD with Biopsy and 
Serum Biomarkers) 
Provided detail that the Day 1 
EGD needs to be done during 
the Screening Period, while the 
Day 1 substudy Biomarkers 
are drawn at the Day 1 visit; 
 
Retracted statement that the 
GI Physician must be recorded 
as a co-Investigator /Sub-
Investigator and indicated that 
this should be the case only 
where locally allowed. 
For clarity 
 
 
 
 
 
To defer to local regulations 
4.1.5.2, Stomach Substudy 
Criteria for Stopping an Individual 
Participant 
 
Ensure participant safety 
4.1.5.3, Stomach Substudy 
Criteria for Stopping the Study 
To date, criteria for stopping an 
individual participant or the 
study overall based upon EGD 
findings (e.g. histopathology of 
the greater curvature and 
lesser curvature) were not in 
the protocol – but clearly 
stated as a topic for a future 
amendment. In this 
amendment, the criteria have 
been added 
Ensures participant safety. 
5, Study Population 
Provided mitigations for the 
Screening period when results 
are delayed.  
1: Screening period may be 
extended 
2: When Monogram 
Biosciences cannot report the 
PhenoSenseGT in a timely 
manner and a participant has 
to be rescreened, the 
To minimize delays in treating 
participants 


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Section # and Name 
Description of Change 
Brief Rationale 
Monogram test results from the 
initial Screening period may be 
used to determine eligibility in 
the subsequent Screening 
period. 
3: There may be cases where 
ViiV Healthcare (VH) will allow 
the use of local resistance labs 
to be used to determine 
eligibility only after review of 
the local lab test with VH 
responsible staff. 
Inserted clarifying text for 
Retesting in a single Screening 
period. 
5.1, Inclusion Criteria 
#4 
1.1, Synopsis 
 
Modified the CD4 count 
needed to meet eligibility from 
350 to 300 
Based upon early recruitment 
data through March 2021, the 
Sponsor is slightly lowering the 
CD4 T-cell count inclusion criteria 
to improve eligibility/recruitment 
without compromising safety. 
#5 
Inserted new Inclusion 
Criterion #5, requiring antiviral 
susceptibility to the selected 
Nucleoside Reverse 
Transcriptase Inhibitor (NRTI) 
backbone 
Inclusion criteria #5-#8 
subsequently shifted to 
become #6-#9 
To meet request made by Health 
Authority Review 
 
5.2, Exclusion Criteria  
#7 
 
Removed unnecessary text 
related to allergy or sensitivity 
to the study drugs or drugs in 
the same class as that 
information would not be 
known to those who are 
treatment-naive 
 
For accuracy 
# 8  
 
Provided the Investigator with 
the ability to make a full clinical 
assessment of the participant’s 
psychiatric fitness, in 
combination with output from 
the eCSSRS. 
To make this eligibility 
assessment more clinically 
appropriate 
 


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Section # and Name 
Description of Change 
Brief Rationale 
#13 
Inserted text to allow cardiac 
death to be assessed, because 
in some cases, there may not 
be any personal or familial 
historical record of prolonged 
QT  
To allow for a secondary way to 
assess personal or familial 
cardiac risk;  
This also aligns the global 
protocol with a site-specific 
request (2019N399207-04) 
#21, #22, #30 and #37 
Included current information 
relative to SARS CoV-2 
To align with the treatment 
options now available during the 
global pandemic 
#23 
Removed distinct mutations 
specific to study treatments in 
lieu of using the simple 
statement that resistance to 
the selected backbone would 
meet exclusion  
To meet request made by Health 
Authority Review 
 
#26 
Clarified that total bilirubin is 
the parameter to be assessed 
for bilirubin 
To align with the laboratory 
parameters as they are reported 
#27 
Indicated HBV DNA testing will 
be done on reflex 
To align with study central lab 
practices 
#29 
Indicated the parameters 
within which Helicobacter 
pylori can be eradicated, and 
retested within a single 
screening period 
To align with guidance [Chey, 
2017] 
#31 
Provided the parameters within 
which syphilis can be treated 
relative to Screening or Day 1. 
To align with internal VH 
guidance 
#36 
Reduced the length of time 
during which a max amount of 
blood or blood products can be 
donated 
To better align with protocol visit 
intervals 
#39 
Removed the criterion that 
excluded anyone with any 
positive response on the 
CSSRS 
To align with text now in 
Exclusion Criterion #8 
 
#40 (made #39 by this 
amendment) 
Corrected the lower bound for 
heart rate that may be 
rechecked - from 100 to 101 
For accuracy 
5.3.1, Meals and Dietary 
Included text guidance for 
content of a low-fat meal 
For ease of the reader 


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Section # and Name 
Description of Change 
Brief Rationale 
Restrictions 
(found in the FDA Draft 
Guidance [2017] already listed 
in References, Section 11). 
Removed restrictions with 
certain citrus fruits and juices 
and red wine. 
 
 
 
To align with decisions made 
within the program. 
5.5, Criteria for Temporarily 
Delaying Randomization; 
 
5.5.2, Delaying Randomization, 
Other; 
5.5.3, Contemporary lab result  
Described when and how 
randomization may be 
delayed/screening period may 
be extended. 
To align with new protocol 
strategies to improve 
eligibility/recruitment without 
compromising safety  
6.5, Dose Modifications 
Clarified information regarding 
dose modifications which are 
not allowed 
For accuracy 
6.8, Concomitant Therapy 
Provided an allowance for the 
possibility of the use of certain 
SAR CoV-2 vaccines 
To align with the treatment 
options now available during the 
global pandemic 
6.8.1.4, On Treatment Prohibited 
Medications: When dosing with 
DTG in any arm 
Indicated that any substrate of 
the OCT2 with a narrow 
therapeutic window should not 
be administered concurrently 
with DTG-containing products  
For accuracy. 
7.1.1,  Protocol –Defined Virologic 
Failure 
Removed information that is no 
longer applicable 
For accuracy 
7.1.1.2, Managing Confirmed 
Virologic Failure/Endpoint Cases 
Provided information that 
resistance testing will not be 
performed on samples with a 
HIV-1 RNA  too low for the 
resistance testing to be 
successful 
To eliminate unnecessary and 
futile testing  
 
8.2.3, Cardiac Monitoring with 
Electrocardiograms 
Corrected information for the 
actual practice of actions 
needed when electronic 
transmission methods for ECG 
have failed 
For accuracy 
8.2.6, Suicidal Ideation and 
Behaviour Risk Monitoring 
Removed text that would not 
actually be put into practice 
For accuracy 
8.3.5, Pregnancy 
Inserted information about the 
use of the Antiretroviral 
To align with VH practice of 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
2 0 8 3 7 9  
 
1 8 2  
 
S e cti o n # a n d N a me  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
Pr e g n a ncy R e gistry   
v ol u ntarily r e p orti n g pr eg n a ncies 
8. 3. 7, Dise as e -R el at e d Ev e nts 
a n d/ or Dis e as e -R el at e d 
O utc o m es ( HI V -Ass oci a t e d 
Co n diti o ns)  
M o difie d sectio n titl e  
Pr ovi d e d i nstructio n w h e n 
r ec or di ng A Es a nd S A Es t h at 
ar e AI D S -d efi ni ng c on ditio ns  
F or a p pr o pri at e n ess.  
T o ali gn wit h e C R F co m pl eti on 
r e q uir e me nts 
8. 3. 8, Advers e Ev e nts of S p eci al 
I nt er est 
I ns ert e d t his n e w s ecti on to 
a d dr ess t h e risks as h avi n g 
s p ecial int er est 
T o ali gn wit h co m p ou n d -r elat ed 
risks 
8. 4, P h ar m ac oki n etics, T a bl e 1 1  
M o difie d W e ek 2 visit 
ti m efr a m e  
A d d e d wi n d o ws f or t h e ti mi n g 
of p ost -dos e E C G t o t h e t a bl e 
f o ot n ot e 
F or accur acy  
8. 6. 1, Ser u m Bi o mark ers a n d 
wit h Bi o psy in t h e St o m ac h 
S u bst u dy  
Pr ovi d e d t ext to d escri be t h at 
m uc h det ail c a n n o w b e fo u n d 
i n t h e S R M. 
D efi n e d Pl an n e d vs, 
U n pl a n n e d bi o psi es  
F or cl arity  
8. 6. 2, Vir al G en oty pi n g an d 
P h e n oty pi n g A n alyses  
I ns ert e d t ext to i n dic ate t h at 
l oc al resist a nc e r esults m ay be 
c o nsid er e d to d et er mi n e 
eli gi bility.  
T o ali gn wit h n e w prot ocol 
str at e gies t o i m prov e 
eli gi bility/r ecr uit m e nt wit ho ut 
c o m pr o misi n g s af ety 
9. 5. 1, I n de p e n de nt Dat a 
M o nit ori n g C o m mitt ee  
 
1. 1, Sy n opsis  
Pr ovi d e d d et ail a b out acti o ns 
V H m ay t ake b as e d o n I D M C 
r ec o m m e n d ati o ns; 
Pr ovi d e d d et ail a b out s o m e 
eff ect t he a n alyses/ti mi ng i n a 
c o nc urre nt stu dy m ay h av e o n 
2 0 8 3 7 9.  
F or cl arity.  
1 0. 1. 7, Dat a Q u ality Ass ura nce, 
6 t h b ull et 
Pr ovi d e d i nf or m ati on t h at det ail 
c a n b e fo u n d i n t h e st u dy d ata 
m a n a g e m e nt pl a n  
F or i nf or mati o n o nly  
1 0. 2, A p p e ndix 2: Cli nic al 
L a b or at ory T ests  
C orr ect e d d et ail a b o ut R outi n e 
Uri n alysis  
I ns ert e d t esti n g f or Cr e ati nin e 
P h os p h oki n as e t o th e Cli nic al 
C h e mistry p a nel  
F or accur acy  
C CI


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Section # and Name 
Description of Change 
Brief Rationale 
10.3.4, Recording and Follow-Up 
of AE and SAE  
Simplified the definition of the 
Intensity grades. 
To simplify. 
10.4.2, Contraceptive Guidance 
Inserted a detail that is specific 
to Canada, as found in the 
Canada-specific amendment 
To bring alignment of prior 
amendments into this one 
document moving forward. 
10.6, Appendix 6: Liver Safety 
Required Actions and Follow-up 
Assessments 
Removed information 
regarding rechallenge or 
treatment restart. 
 
Included some additional 
follow up assessments to be 
performed. 
To clarify that study drug must be 
stopped immediately when ALT ≥ 
5X ULN and that restart is not 
permitted 
 
For accuracy. 
10.9, Appendix 9: Toxicity 
Management 
Removed text that described 
treatment interruptions, which 
are not allowed in this protocol. 
Inserted a detail that SAEs are 
to be followed into the post-
dosing follow-up period, 
regardless of attributability 
For accuracy 
 
 
For accuracy 
10.9.2.2, Abacavir 
Hypersensitivity Reaction 
Removed language that 
allowed a possible restart of 
DTG or ABC 
To mitigate treatment emergent 
resistance 
10.9.3.1, Rash 
10.9.3.2, Skin reactions without 
other symptoms that are typical of 
ABC HSR 
Modified actions to be taken 
with Grade 1 and/or Grade 2 
rash. 
For safety. 
10.11.4, COVID-19 Experimental 
Agents 
Defined the allowable 
vaccinations 
To be aligned with current  SARS 
CoV-2 pandemic guidance 
10.11.5.2.1, WHO Case Definition  Removed outdated text and 
provided hyperlink to updated 
WHO Case definitions 
Updates became available 
10.13, Appendix 13, Abbreviations 
and Trademarks 
Updated abbreviations, as 
needed, based on other 
amendment changes 
For accuracy 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore have not been 
summarized 
 


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Amendment 03: 10-MAY-2021 
This amendment is considered to be substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union because it significantly impacts the scientific value of the study. 
Overall Rationale for the Amendment: 
Study 208379 is undergoing this substantial amendment to reduce the sample size from 
approximately 210 participants to approximately 150 participants. This reduction of 60 
participants will occur equally among the 3 experimental arms. There is no change to the 
Dolutegravir (DTG) reference arm. Thus, the number of participants will be as follows 
(each arm in combination with open-label Nucleoside Reverse Transcriptase Inhibitor 
[NRTI] backbone as originally described):  
 
 
Arm 
Original Number of Participants  Amended Number of Participants  
GSK3640254 100 mg   
60  
40  
GSK3640254 150 mg   
60  
40  
GSK3640254 200 mg   
60  
40  
DTG  
30  
30  
Total 
210  
150  
  
The justification of this reduction in sample size is as follows:  
  
1) Since the trial began screening in November in 2020, approximately 89% of sites 
world-wide have been activated. The Sponsor anticipated screening would 
complete by 18 May 2021. However, at the time of this substantial amendment 
approximately 109 participants have been screened and approximately 22 have 
been randomized. The reasons for slower than anticipated recruitment are based 
upon the multi-factorial impact of the global Severe Acute Respiratory 
Coronavirus-2 (SARS-CoV-2) pandemic. Qualitative feedback from Investigators 
shows the incidence of known newly diagnosed Human immunodeficiency virus-
1 (HIV-1) infection has decreased. Moreover, physicians and newly infected 
patients have a strong desire to immediately start antiretroviral therapy so they are 
less likely to participate in this Phase 2b study which has a screening period of 
approximately 42 days.  
2) The Sponsor does not have formal statistical testing in this trial. Note, Section 9 
has been updated to describe modifications to the Statistical Considerations. The 
Sponsor finds the changes Type I error rate and Power to be clinically acceptable.  
3) A reduction in sample size does not limit the ability to make clinical inferences on 
the efficacy, safety/tolerability, and resistance of an optimal dose GSK3640254 
(for subsequent clinical development) – resulting in maintenance of clinical 
integrity and unchanged risk benefit ratio to study participants.  
4) Of the approximately 109 participants screened, a screening Phenosense GT result 
is available for 22 participants. Of the 22 participants, there is ample diversity in 
HIV-1 sub-type as follows: Sub-type B (13 participants), Sub-type C (2 


T M F -1 3 9 9 4 0 9 1  
C O N FI D E N TI A L  
 
 
2 0 8 3 7 9  
 
1 8 5  
 
partici pa nts), a n d 1 p artici pa nt i n eac h of t he f oll o wi n g S u b -t y pes: C o m ple x, A G, 
G, B/ G, F 1, A E, A 1. T h us, a s maller sa m pl e siz e w o ul d n ot li mit di versit y i n 
HI V -1 s u b -t y pe. Preser vi n g t he di versit y of HI V-1 s u b -t y pe still all o ws t he 
S p o ns or t o e val uate t he br oa d s pectr u m of efficac y of G S K 3 6 4 0 2 5 4 ( n ote: Ga g 
p ol y m or p his ms, var yi n g b y s u b -t y pe, i m pacte d pri or de vel o p me ntal Maturati o n 
I n hi bit ors).  
6)  T he S p o ns or will c o n d uct a ne w P hase 2 b st u d y ( S t u d y 2 1 2 4 8 3 a ntici pate d t o start 
i n J ul y 2 0 2 1) –  als o i n treat me nt naï ve a d ults –  i n vesti gati n g G S K 3 6 4 0 2 5 4 (at t he 
sa me 3 d oses) i n c o m bi n ati o n wit h D T G. T he e x peri me ntal sa m ple siz e i n t h ose 
ar ms will be 3 0 i n eac h ar m ( 9 0 t otal). C o m bi ne d, a r o b ust P hase  2 b data s et will 
still be ge nerate d e na bli n g a P has e 3 pr o gra m; s pecificall y, a p pr o xi matel y 1 2 0 
a n d 9 0 treat me nt naï v e a d ults, will be ra n d o mize d t o a n e x peri me ntal ar m 
c o ntai ni n g G S K 3 6 4 0 2 5 4 i n t his trial a n d St u d y 2 1 2 4 8 3, res pecti vel y.  
 
C CI


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Section # and Name 
Description of Change Brief Rationale 
Synopsis, Overall Design, Brief Summary, 
Number of Participants 
Section 4.1, Overall Design 
Section 4.1.1, Screening Period 
Section 4.1.5.1, Stomach Substudy 
Enrollment Considerations 
Section 9.2, Sample Size Determination 
Number of total 
participants in the study 
was reduced from 210 to 
150 
 
See the Overall Rationale 
for the Amendment 
described above. 
Synopsis, Number of Participants 
Section 1.2, Schema 
Section 4.1.2.1, Day 1 through Week 24 
Section 9.2 Sample Size Determination  
Section 9.2.1, Sample Size Sensitivity 
Number of participants in 
each of the GSK3640254 
treatment arms was 
reduced from 60 to 40 
See the Overall Rationale 
for the Amendment 
described above. 
Section 4.1.2, Treatment Period 
Corrected the protocol 
section number in 
paragraph 8 in reference 
to the Optional Intensive 
PK portion of the Week 2 
visit 
For accuracy 
Section 5.2, Exclusion Criteria, #21 (Note) 
and #31 (Note) 
More appropriate word 
choices were made 
For accuracy when 
translating the documents 
into other languages 
Section 6.6, Continued Access to Study 
Intervention after the End of the Study 
Corrected the GSK 
compound number 
For accuracy 
Section 9.2 Sample Size Determination 
(Table 12 and related text)  
 
Recalculations were done 
for Type l error and 
Power. 
Required due to the 
reduction in total number of 
participants and reduction in 
number of participants in 
each GSK3640254 arm. 
Section 9.2.1, Sample Size Sensitivity (and 
Figure 3) 
Updated due to change in 
sample size 
Required due to the 
reduction in total number of 
participants and reduction in 
number of participants in 
each GSK3640254 arm. 
 


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11. 
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