A Randomized, Double-Blind (Sponsor-Unblinded), Placebo-Controlled, Adaptive Study to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of VH3739937 in Treatment-Naïve Adults Living With HIV-1
Phase: PHASE2
Conditions: HIV Infections
Sponsor: ViiV Healthcare

CONFIDENTIAL 
ViiV Healthcare group of companies 
 
212580 
 
 
Protocol Amendment 1 Final 
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1 
 
Clinical Study Protocol 
Primary Study Intervention(s) 
VH3739937 
Other Study Intervention(s) 
N/A 
Study Identifier 
212580/Amendment 1 
EudraCT Number 
2021-003207-18 
EU CT Number  
2023-505780-37-00 
Approval Date 
06 Oct 2023 
Title 
A Randomized, Double-Blind (Sponsor-
Unblinded), Placebo-Controlled, Adaptive 
Study to Investigate the Antiviral Effect, 
Safety, Tolerability and Pharmacokinetics of 
VH3739937 in Treatment-Naïve Adults Living 
with HIV-1 (PROCLAIM) 
Compound Number/Name  
VH3739937 
Brief Title 
VH3739937 Proof-Of-Concept in Treatment-
Naïve Adults Living with HIV-1 
Sponsor 
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 
410 Blackwell Street 
Durham, NC 27701, USA 
Telephone: + 1 877 844 8872 
 
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 

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the Senior Vice President, Head of Research 
& Development. 
This study is sponsored by ViiV Healthcare.  
GSK is supporting ViiV Healthcare in the 
conduct of this study. 
Sponsor signatory 
Scott McCallister, MD 
Vice President & Head, R&D Physician Center 
of Excellence 
Medical monitor name and contact can be found in local study contact 
information document 
©2023 ViiV Healthcare and the GSK group of companies.  All rights reserved.  
Unauthorized copying or use of this information is prohibited. 
 

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Protocol Amendment 1 Investigator Agreement  
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments, with the terms of the clinical trial agreement and with any other study 
conduct procedures and/or study conduct documents provided by ViiV 
Healthcare/GSK. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of and will comply with GCP and all applicable regulatory 
requirements.  
• 
That I will comply with the terms of the site agreement. 
• 
To comply with local bio-safety legislation. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the ViiV Healthcare/GSK study intervention and other study-related duties and 
functions as described in the protocol. 
• 
To supervise any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site. 
• 
To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained on-site or 
elsewhere without the approval of ViiV Healthcare/GSK and the express physical 
and/or digital informed consent of the participant and/or the participant’s LAR. 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s).  
• 
To co-operate with representative(s) of ViiV Healthcare/GSK in the monitoring and 
data management processes of the study with respect to data entry and resolution of 
queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the study. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator(s)’ ownership interest 
in the sponsor or the study intervention(s), and more generally about their financial 
ties with the sponsor. ViiV Healthcare/GSK will use and disclose the information 
solely for the purpose of complying with regulatory requirements. 

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Hence, I: 
• 
Agree to supply ViiV Healthcare/GSK with any necessary information regarding 
ownership interest and financial ties (including those of my spouse and dependent 
children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
• 
Agree that ViiV Healthcare/GSK may disclose any information about such 
ownership interests and financial ties to regulatory authorities. 
• 
Agree to provide ViiV Healthcare/GSK with an updated Curriculum Vitae and all 
other documents required by regulatory agencies for this study. 

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Study identifier 
212580/Amendment 1 
 
EudraCT number 
2021-003207-18 
EU CT number 
2023-505780-37-00 
Approval date 
06 Oct 2023 
 
 
Title 
A Randomized, Double-Blind (Sponsor-Unblinded), 
Placebo-Controlled, Adaptive Study to Investigate 
the Antiviral Effect, Safety, Tolerability and 
Pharmacokinetics of VH3739937 in Treatment-
Naïve Adults Living with HIV-1 (PROCLAIM) 
Investigator name 
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 
 
 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 1 
06 Oct 2023 
Original Protocol 
01 June 2023 
Amendment 1 (06 Oct 2023) 
This amendment is considered non-substantial based on the criteria defined in EU 
Clinical Trial Regulation No 536/2014 of the European Parliament and the Council 
of the European Union because it neither significantly impacts the safety of participants 
nor the scientific value of the study. 
Overall rationale for the current Amendment:  
A request for clarification of inconsistencies in the participant discontinuation criteria 
described in Section 7.1 and Section 10.7 of the protocol was received from the FDA on 
18 September 2023. In addition, the format of the C-SSRS that will be used in the study 
has been corrected from participant-completed to clinician-administered (e.g. physician, 
physician assistant, or advanced practice nurse). This reflects a change in company policy 
to use the clinician-administered version for all studies.  
Additional minor clarifications, corrections and administrative changes have been made 
throughout. 
List of main changes in the protocol and their rationale: 
Section # 
and title 
Description of change 
Brief rationale  
Title page, 
Investigator 
signature 
page and 1.1 
Synopsis  
Added study acronym 
PROCLAIM 
To add the study acronym (PROCLAIM) 

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Section # 
and title 
Description of change 
Brief rationale  
7.1 
Discontinuati
on of study 
intervention 
Removed reference to renal 
toxicity management criteria in 
Appendix 7 
• Updated AE discontinuation 
criteria to align with 
language used in Section 
7.1.3 and Section 10.7.  
There are no specific renal toxicity 
management criteria detailed in Appendix 7, 
this text was included in error. Renal toxicity 
should be managed as any general 
toxicity/AE would be managed. 
Changes made at FDA request to clarify 
inconsistencies in AE discontinuation criteria. 
This section has been aligned to wording in 
Section 7.1.3 and Section 10.7, specifically 
that any Grade 4 AE would result in 
discontinuation, regardless of relatedness to 
study intervention. 
7.1.3 
Individual 
Participant 
Laboratory 
Abnormality 
and Adverse 
Event 
Stopping 
criteria 
Updated rash criteria to state 
any related Grade 3 or any 
Grade 4 rash would result in 
discontinuation. 
Changes made to clarify an inconsistency 
between Section 7.1.3 and rash toxicity 
management criteria described in Section 
10.7, as per FDA request. 
8.3.6 Suicidal 
ideation and 
behavior risk 
monitoring 
Revised C-SSRS description to 
the clinician-administered 
electronic C-SSRS, instead of 
the patient-completed eC-
SSRS.  
References to the eC-SSRS 
have been updated to C-SSRS 
throughout the protocol. 
Due to a change in company policy, all ViiV 
Healthcare/GSK studies will now use the 
clinician -administered version of the C-SSRS 
as standard. 
8.5 
Pharmacokin
etics 
The following updates were 
made to Table 7 and Table 8: 
• Increased the window for 
pre-dose procedures on 
Days 1-7 in Part 1A and 2A 
and on Day 1 in Part 1B 
and 2B to be -45 minutes 
before dosing. 
• Added meal window pre-
dose of -25 minutes on 
Days 1-7 in Part 1A and 2A, 
and on Day 1 in Part 1B 
and 2B. 
Section 5.3.1 requires participants eat a meal 
during the 25 minutes before dosing and to 
take their dose within 5 minutes of completing 
the meal. The window for pre-dose 
procedures has been updated to allow 
sufficient time for procedures to be completed 
before participants need to start their meal. 
Day 2 and Day 8 were split onto different rows 
as Day 8 does not include a meal and the 
window pre-dose procedures on that day 
remains -15 minutes. 
ECG updates were made for clarity and 
consistency with the SoA. 

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Section # 
and title 
Description of change 
Brief rationale  
• Added missing pre-dose 
ECGs 
8.8.1 Viral 
genotyping 
and 
phenotyping 
Added a statement that 
results of genotypic and 
phenotypic analyses will not 
be shared with investigators. 
The assays used to perform the genotypic 
and phenotypic analyses are not CE-marked 
for diagnostic use. As such, results of these 
analyses should not be used for diagnostic 
purposes and will not be shared with 
investigators.  
10.1.4 
Recruitment 
strategy 
Corrected the participant 
numbers to be screened (50 
participants) and enrolled 
(20 participants) in Part 2 
Updated for consistency with participant 
numbers for Part 2 given in Section 1.2 and 
Section 4.1. 
10.7 
Appendix 7 
Toxicity 
Management  
Revised text for 
discontinuation related to 
Grade 3 Toxicity/AE and for 
Grade 2 Rash. 
To correct inconsistencies between Section 
7.1.3 and rash toxicity management criteria 
described in Section 10.7, as per FDA 
request. 
 
 

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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY ........................................................................................ 21 
1.1. 
Synopsis ..................................................................................................... 21 
1.2. 
Schema ...................................................................................................... 22 
1.3. 
Schedule of Activities .................................................................................. 23 
2. 
INTRODUCTION .................................................................................................... 29 
2.1. 
Study rationale ............................................................................................ 29 
2.2. 
Background ................................................................................................ 29 
2.2.1. 
Key Clinical Safety and PK Data in Study 212548 ....................... 30 
2.3. 
Benefit/risk assessment .............................................................................. 31 
2.3.1. 
Risk assessment .......................................................................... 33 
2.3.2. 
Benefit assessment ..................................................................... 40 
2.3.3. 
Overall benefit-risk conclusion ..................................................... 40 
3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS .................................................... 41 
3.1. 
Objectives and Endpoints ........................................................................... 41 
3.2. 
Estimands ................................................................................................... 43 
4. 
STUDY DESIGN .................................................................................................... 45 
4.1. 
Overall design ............................................................................................. 45 
4.2. 
Scientific rationale for study design ............................................................. 47 
4.2.1. 
Participant input into design ......................................................... 48 
4.3. 
Justification for dose ................................................................................... 48 
4.4. 
End-of-study definition ................................................................................ 50 
5. 
STUDY POPULATION ........................................................................................... 50 
5.1. 
Inclusion criteria .......................................................................................... 51 
5.2. 
Exclusion criteria ......................................................................................... 52 
5.3. 
Lifestyle considerations ............................................................................... 55 
5.3.1. 
Meals and dietary restrictions ...................................................... 55 
5.3.2. 
Caffeine, alcohol, and tobacco ..................................................... 55 
5.3.3. 
Activity ......................................................................................... 56 
5.4. 
Screen failures ............................................................................................ 56 
5.5. 
Criteria for temporarily delaying 
enrollment/randomization/administration of study intervention .................... 56 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 57 
6.1. 
Study intervention(s) administered .............................................................. 57 
6.2. 
Preparation, handling, storage, and accountability ...................................... 58 
6.3. 
Assignment to study intervention ................................................................ 58 
6.4. 
Blinding ....................................................................................................... 59 
6.5. 
Study intervention compliance .................................................................... 60 
6.6. 
Dose modification ....................................................................................... 60 
6.7. 
Continued access to study intervention after the end of the study ............... 60 
6.8. 
Treatment of overdose ................................................................................ 61 
6.9. 
Prior and concomitant therapy .................................................................... 61 
6.9.1. 
Permitted Medications: ................................................................ 62 
6.9.2. 
Prohibited Medications and Non-Drug Therapies ......................... 62 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 63 
7.1. 
Discontinuation of study intervention ........................................................... 63 
7.1.1. 
Liver chemistry stopping criteria ................................................... 63 
7.1.2. 
QTc Stopping criteria ................................................................... 64 
7.1.3. 
Individual Participant Laboratory Abnormality and Adverse 
Event Stopping Criteria ................................................................ 65 
7.1.4. 
Temporary discontinuation ........................................................... 66 
7.1.5. 
Rechallenge ................................................................................. 66 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 66 
7.3. 
Lost to follow-up.......................................................................................... 67 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 68 
8.1. 
Administrative and general/baseline procedures ......................................... 69 
8.1.1. 
Collection of demographic data .................................................... 69 
8.1.2. 
Medical history ............................................................................. 69 
8.2. 
Efficacy assessments ................................................................................. 69 
8.2.1. 
HIV-1 RNA Sampling ................................................................... 69 
8.2.2. 
Lymphocyte Subsets by Flow Cytometry ..................................... 69 
8.2.3. 
Disease Progression .................................................................... 70 
8.3. 
Safety assessments .................................................................................... 70 
8.3.1. 
Physical examination ................................................................... 70 
8.3.2. 
Vital signs .................................................................................... 71 
8.3.3. 
Electrocardiograms ...................................................................... 71 
8.3.4. 
Clinical safety laboratory tests ..................................................... 72 
8.3.5. 
Pregnancy testing ........................................................................ 73 
8.3.6. 
Suicidal ideation and behavior risk monitoring ............................. 73 
8.3.7. 
Study stopping rules and safety monitoring .................................. 74 
8.3.8. 
GI Intolerability Evaluation and Monitoring Plan (with 
Stopping Criteria) ......................................................................... 75 
8.4. 
Adverse Events (AEs) serious adverse events (SAEs), and other 
safety reporting ........................................................................................... 77 
8.4.1. 
Time period and frequency for collecting AE and SAE 
information ................................................................................... 78 
8.4.2. 
Method of detecting AEs and SAEs ............................................. 78 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 78 
8.4.4. 
Regulatory reporting requirements for SAEs ................................ 78 
8.4.5. 
Pregnancy ................................................................................... 79 
8.4.6. 
Cardiovascular and death events ................................................. 79 
8.4.7. 
Disease-related events and/or disease-related outcomes 
not qualifying as AEs or SAEs ..................................................... 80 
8.4.8. 
Contact information for reporting SAEs ........................................ 81 
8.4.9. 
Participant card ............................................................................ 81 
8.5. 
Pharmacokinetics ....................................................................................... 81 
8.6. 
Pharmacodynamics .................................................................................... 85 
8.7. 
Genetics ..................................................................................................... 85 
8.8. 
Biomarkers ................................................................................................. 86 
8.8.1. 
Viral Genotyping and Phenotyping ............................................... 86 
8.8.2. 
HIV-1 Exploratory Analysis .......................................................... 86 
8.9. 
Immunogenicity assessments ..................................................................... 87 
8.10. 
Health economics or medical resource utilization and health 
economics .................................................................................................. 87 

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9. 
STATISTICAL CONSIDERATIONS ........................................................................ 87 
9.1. 
Statistical hypotheses ................................................................................. 87 
9.2. 
Analysis sets ............................................................................................... 87 
9.3. 
Statistical analyses ..................................................................................... 88 
9.3.1. 
General considerations ................................................................ 88 
9.3.2. 
Primary endpoint/estimand analysis ............................................. 89 
9.3.3. 
Secondary endpoint analyses ...................................................... 90 
9.3.4. 
Exploratory endpoint(s) analysis .................................................. 91 
9.4. 
Interim analyses .......................................................................................... 91 
9.5. 
Sample size determination .......................................................................... 92 
9.5.1. 
Sample Size Considerations ........................................................ 92 
9.5.2. 
Sample Size Sensitivity ................................................................ 93 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 94 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 94 
10.1.1. 
Regulatory and ethical considerations ......................................... 94 
10.1.2. 
Financial disclosure ..................................................................... 94 
10.1.3. 
Informed consent process ............................................................ 95 
10.1.4. 
Recruitment strategy .................................................................... 95 
10.1.5. 
Data protection ............................................................................ 96 
10.1.6. 
Committees structure ................................................................... 96 
10.1.7. 
Dissemination of Clinical Study Data ........................................... 97 
10.1.8. 
Data quality assurance ................................................................ 98 
10.1.9. 
Source documents ....................................................................... 98 
10.1.10. Study and site start and closure ................................................... 99 
10.1.11. Publication policy ....................................................................... 100 
10.2. 
Appendix 2: Clinical laboratory tests ......................................................... 100 
10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting .......................................... 102 
10.3.1. 
Definition of AE .......................................................................... 102 
10.3.2. 
Definition of SAE ........................................................................ 103 
10.3.3. 
Solicited events.......................................................................... 104 
10.3.4. 
Unsolicited AE ........................................................................... 104 
10.3.5. 
Definition of CV events .............................................................. 105 
10.3.6. 
Definition of TEAE ..................................................................... 105 
10.3.7. 
Recording, assessment and follow-up of AE, SAE, and 
pregnancies ............................................................................... 105 
10.4. 
Appendix 4: Contraceptive and barrier guidance ....................................... 109 
10.4.1. 
Definitions .................................................................................. 109 
10.4.2. 
Contraception guidance ............................................................. 110 
10.5. 
Appendix 5: Genetics ................................................................................ 110 
10.6. 
Appendix 6: Liver safety: suggested actions and follow-up 
assessments ............................................................................................. 110 
10.7. 
Appendix 7: Toxicity Management ............................................................ 113 
10.8. 
Appendix 8: Division of AIDS (DAIDS) table for grading the severity 
of adult and pediatric adverse events version 2.1, July 2017 .................... 115 
10.9. 
Appendix 9: CDC Classification for HIV infection (2014) ........................... 133 
11. REFERENCES ..................................................................................................... 136 
 

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LIST OF TABLES 
PAGE 
Table 1 
SoA ........................................................................................................ 23 
Table 2 
Objectives and Endpoints ....................................................................... 41 
Table 3 
Simulated PK trough concentration after the loading dose and 
the last dose for cohort 2, 3, 4 with Safety Cover ................................... 49 
Table 4 
Study Intervention(s) Administered......................................................... 57 
Table 5 
GI Intolerability Evaluation and Management ......................................... 75 
Table 6 
Contact information for reporting SAEs .................................................. 81 
Table 7 
Pharmacokinetic Sampling Schedule, Cardiac Monitoring with 
ECGs and Related Activities for QD cohorts (Parts 1A and 2A) ............. 82 
Table 8 
Pharmacokinetic Sampling Schedule, Cardiac Monitoring with 
ECGs and Related Activities for single dose cohorts (Parts 1B 
and 2B) .................................................................................................. 84 
Table 9 
Expected precision (measured by the 95% CI width) of the 
estimated mean of maximum VLD in log10 scale for various 
assumptions of observed data variability for N = 6 participants .............. 92 
Table 10 
Protocol-required safety laboratory tests .............................................. 100 
LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 22 
Figure 2 
Simulations of Plasma Concentrations of VH3739937 Achieved 
Following Dosing with 500mg as a Single Dose ..................................... 50 
Figure 3 
Expected precision (measured by the 95% CI width) of the 
estimated mean of maximum VLD in log10 scale for various 
assumptions on observed data variability and sample size .................... 93 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
µg/mL 
micrograms per milliliter 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AIDS 
Acquired Immunodeficiency Syndrome 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
anti-HBc 
Hepatitis B core antibody 
anti-HBs 
Hepatitis B surface antibody 
ART 
Antiretroviral Therapy 
ARV 
Antiretroviral 
AST 
Aspartate aminotransferase 
AUC(0-168) 
Area under the concentration-time curve from zero to 168h 
AUC(0-
24)/AUC(0-
24),ss 
Area under the concentration-time curve from zero to 24h/Area under 
the concentration-time curve from zero to 24h at steady state 
AUCinfinity 
Area under the plasma concentration-time curve from pre-dose to 
infinity 
AVB 
Atrioventricular block 
BMI 
Body mass index 
c/mL 
copies per milliliter 
C168 
Concentration at 168 h post dose 
C24/C24,ss 
Concentration at 24 h post dose following single dose/Concentration 
at 24 h post dose at steady state 
CA 
Competent authority 
cART 
Combination Antiretrovial Therapy 
CDC 
Centers for Disease Control 
CIOMS 
Council for International Organizations of Medical Sciences 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CL/F 
Apparent oral clearance 
Cmax/Cmax,ss Maximum observed concentration after single dose/Maximum 
observed concentration at steady state 
CMV 
Cytomegalovirus 
CNS 
Central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID 
Coronavirus disease 
CPK 
Creatinine phosphokinase 
CPMS 
Clinical Pharmacology Modeling and Simulation 

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CRA 
Clinical Research Associate 
CRF/eCRF 
Case report form/electronic case report form 
CSR 
Clinical study report 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CT 
Computerised tomography 
Ctrough 
Minimum concentration before next dose 
CV 
Cardiovascular 
DNA 
Deoxyribunucleic acid 
DRE 
Disease-related event 
DTG 
Dolutegravir 
EC90 
90% maximal effective concentration 
ECG 
Electrocardiogram 
ED 
Early discontinuation 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EoS 
End-of-study 
FAS 
Full analysis set 
FAST 
Focused Assessment with Sonography in Trauma 
FDA 
Food and Drug Administration, United States of America 
FSH 
Follicle stimulating hormone 
FSFV 
First subject first visit 
FTiH 
First-time in human 
g 
grams 
Gag 
Group-specific antigen 
GCP 
Good clinical practices 
GERD 
Gastroesophageal reflux disease 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
h or hr 
hour 
h*µg/mL 
microgram hours per milliliter 
HbsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HCVAb 
Hepatitis C antibody 
HDL 
High density lipoprotein cholesterol 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HRT 
Hormonal replacement therapy 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 

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ICMJE 
International Committee of Medical Journal Editors 
ICSR 
Individual case safety reports 
IDSL 
Integrated Data Standards Library 
IEC 
Independent ethics committee 
IMP 
Investigational medicinal product 
INSTI 
Integrase inhibitor 
INR 
International normalized ratio 
IQ 
Inhibitory quotient 
IRB 
Institutional review board 
IWRS 
Interactive web response system 
kDa 
Kilodalton 
kg 
Kilogram 
lbs 
pounds 
LDL 
Low denisty lipoprotein cholesterol 
LLOD 
Lower limit of detection 
LOAEL 
Lowest observed adverse effect level  
MAD 
Multiple Ascending Dose 
max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligrams 
mg/mL 
milligrams per milliliter 
MI 
Maturation inhibitor 
min 
Minimum 
mL 
milliliter 
MSDS 
Material Safety Data Sheet 
msec 
milliseconds 
NIMP 
Non-investigational medicinal product 
nM 
nanomolar 
NOAEL 
No observed adverse effect level 
NQ 
Non-quantifiable 
NSAIDS 
Non-steroidal anti-inlammatory drugs 
PBO 
Placebo 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PDAP 
Project data analysis plan 
PI 
Prediction interval 
PiB 
Powder in Bottle 
PII 
Personal identifiable information 
PK 
Pharmacokinetic 
PLWH 
People living with HIV 
POC 
Proof-of-Concept 

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POCBP 
Person of childbearing potential 
PONCBP 
Person of nonchildbearing potential 
PP 
Per protocol 
PR 
Protease 
PSRAE 
Possible Suicidality-Related AE 
QD 
Once daily 
QTc 
Corrected QT interval 
QTcF 
QT duration corrected for heart rate by Fridericia's formula 
QTL 
Quality tolerance limit 
QW 
Once weekly 
R 
Accumulation ratio 
RBA 
Relative Bioavailability 
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 
SD 
Standard deviation 
SIB 
Suicidal ideation behavior 
SoA 
Schedule of activities 
SOC 
Standard of Care 
SOP 
Standard operating procedure 
SRT 
Safety Review Team 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t1/2 
Terminal  half-life 
TEAE 
Treatment-emergent adverse event 
THC 
Tetrahydrocannabinol 
tmax 
Time to maximum observed concentration 
TMF/eTMF 
Trial Master File/electronic Trial Master File 
TN 
Treatment naïve 
ULN 
Upper limit of normal 
V/F 
Apparent volume of distribution 
VLD 
Viral load drop 
VT 
Ventricular tachycardia 
WBC 
White blood cell 
WHO 
World Health Organization 
 

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Term 
Definition 
Adverse Drug Reaction 
An adverse event where a causal relationship between a 
medicinal product and the adverse event is at least a 
reasonable possibility, i.e., the relationship cannot be 
ruled out. 
a. In the context of a clinical trial, an ADR can be 
serious or non-serious. Serious ADRs may be 
subject to expedited reporting if they are considered 
unexpected (see SUSAR definition). 
b. For marketed products, ADRs are subject to 
expedited reporting within the country where they 
are authorized 
Blinding: 
A procedure in which 1 or more parties to the study are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
study, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a SAE. 
In a double-blind study, the participant, the investigator 
and sponsor staff who are involved in the treatment or 
clinical evaluation of the participants and the review or 
analysis of data are all unaware of the intervention 
assignment. 
Caregiver 
A ‘caregiver’ is someone who  
− 
lives in the close surroundings of a participant 
and has a continuous caring role or 
− 
has substantial periods of contact with a 
participant and is engaged in their daily health 
care (e.g., a relative of the participant, a nurse 
who helps with daily activities in case of 
residence in a nursing home).  
In the context of a clinical study, a caregiver could 
include an individual appointed to oversee and support 
the participant's compliance with protocol-specified 
procedures. 
Co-administered 
(concomitant) products 
A product given to clinical trial participants as required 
in the protocol as part of their standard care for a 
condition which is not the indication for which the IMP 
is being tested and is therefore not part of the objective 
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Term 
Definition 
Comparator 
Any product used as a reference (including placebo, 
marketed product, ViiV Healthcare/GSK or non-ViiV 
Healthcare/GSK) for an investigational product being 
tested in a clinical trial. This is any product that is being 
used to assess the safety, efficacy, or other measurable 
value against the test product (IMP). 
CRA 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Eligible 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced 
Intervention number 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Investigational medicinal 
product 
A pharmaceutical form of an active substance or 
placebo being tested or used as a reference in a clinical 
trial, including products already with a marketing 
authorization but used or assembled (formulated or 
packaged) in a way different from the authorized form, 
or when used for an unauthorized indication, or when 
used to gain further information about the authorized 
form. 
Investigator 
A person responsible for the conduct of the clinical 
study at a study site. If a study is conducted by a team of 
individuals at a study site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate study-related duties and 
functions conducted at the study site to qualified 
individual or party to perform those study-related duties 
and functions 
Legally acceptable 
representative 
An individual, judicial or other body authorized under 
applicable law to consent on behalf of a prospective 
participant to the participant's participation in the 
clinical study. 

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Term 
Definition 
The terms legal representative or legally authorized 
representative are used in some settings. 
NIMP 
A NIMP is a medicinal product that is not classified as 
an IMP in a study, but may be taken by participants 
during the study, e.g., concomitant or rescue/escape 
medication used for preventive, diagnostic, or 
therapeutic reasons or medication given to ensure that 
adequate medical care is provided for the participant 
during a study. 
Participant number 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Participant 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject 
Placebo 
An inactive substance or treatment that looks the same 
as, and is given in the same way as, an active drug or 
intervention/treatment being studied. 
Primary Completion Date 
The date on which the last participant in a clinical study 
was examined or received an intervention to collect final 
data for the primary outcome measure. 
Whether the clinical study ended according to 
the protocol or was terminated does not affect this date. 
For clinical studies with more than one primary outcome 
measure with different completion dates, this term refers 
to the date on which data collection is completed for all 
the primary outcome measures.  
Randomization 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Source data 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical study necessary for the 
reconstruction and evaluation of the study. Source data 
are contained in source documents (original records or 
certified copies). 

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Term 
Definition 
Standard of Care 
Medicine(s) for a specific indication, or a component of 
the standard care for a particular medical indication, 
based on national and/or international consensus; there 
is no regulatory significance to this term. 
1. Products/regimens considered standard of care may 
differ country to country, depending on consensus in 
individual countries 
Study intervention 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Note: “Study intervention” and “study treatment” are 
used interchangeably unless otherwise specified. 
Study completion date 
The date on which the last participant in a clinical study 
was examined or received an intervention/treatment to 
collect final data for the primary outcome 
measures, secondary outcome measures, and AEs (that 
is, the last participant's last visit or LSLV). 
SUSAR 
Suspected Unexpected Serious Adverse Reaction; in a 
clinical trial, a serious adverse reaction that is 
considered unexpected, i.e., the nature or severity of 
which is not consistent with the reference safety 
information (e.g., the IB for an unapproved 
investigational medicinal product). All ADRs that are 
both serious and unexpected are subject to expedited 
reporting 
Virtual visit 
This term refers to study visits conducted using 
multimedia or technological platforms. 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
A Randomized, Double-Blind (Sponsor-Unblinded), Placebo-Controlled, Adaptive Study 
to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of 
VH3739937 in Treatment-Naïve Adults Living with HIV-1 (PROCLAIM) 
Brief Title: 
VH3739937 Proof-Of-Concept in Treatment-Naïve Adults Living with HIV-1 
(PROCLAIM) 
Rationale: Refer to Section 2.1. 
Objectives, Endpoints, and Estimands: Refer to Section 3. 
Overall Design: Refer to Section 4.1. 
Number of Participants: Refer to Section 9.5. 
Data Monitoring/Other Committee: Refer to Section 10.1.6. 
 

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1.2. 
Schema 
Figure 1 
Study design overview 
 
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1.3. 
Schedule of Activities 
Table 1 
SoA 
Procedure1 
Screening2  
(7-14 days 
before Day 
1) 
Study Intervention Period Days 1-7 
Post-Study Intervention Follow-
up 
Days 8-21 
Follow-
up/ED15 
Notes 
ED = early 
discontinuation/wit
hdrawal 
Day 1 
Day 2 
Days 3 and 4 
1 clinic visit and 1 
virtual3 
Days 5 and 6 
1 clinic visit and 1 
virtual3 
Day 7 Day 8 
Day 14 
(+/- 1 day) 
Day 21  
(+/- 1 day) 
Day 25 
(+/- 1 day) 
 
Clinic 
visit 1 
Clinic 
visit 2 
Clinic 
visit 3 
Virtual14 Clinic 
visit 4 
Virtual14 
Clinic 
visit 5 
Clinic 
visit 6 
Clinic visit 
7 
Clinic visit 
8 
Clinic visit 
9 
Outpatient Visit 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
 
Video/phone call 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.1.3 
for details 
Inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
Recheck clinical 
status before 1st dose 
of study medication. 
See Section 5.1 and 
Section 5.2 for 
Inclusion and 
Exclusion criteria 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.1.1 for 
more information 
Medical history 
(includes substance 
usage and Family 
history of premature 
CV disease) 
X 
 
 
 
 
 
 
 
 
 
 
 
Substances: Drugs 
and Alcohol 
 
Premature CV 
disease: female 
participant < 65 years 
or male participant < 

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Procedure1 
Screening2  
(7-14 days 
before Day 
1) 
Study Intervention Period Days 1-7 
Post-Study Intervention Follow-
up 
Days 8-21 
Follow-
up/ED15 
Notes 
ED = early 
discontinuation/wit
hdrawal 
Day 1 
Day 2 
Days 3 and 4 
1 clinic visit and 1 
virtual3 
Days 5 and 6 
1 clinic visit and 1 
virtual3 
Day 7 Day 8 
Day 14 
(+/- 1 day) 
Day 21  
(+/- 1 day) 
Day 25 
(+/- 1 day) 
 
Clinic 
visit 1 
Clinic 
visit 2 
Clinic 
visit 3 
Virtual14 Clinic 
visit 4 
Virtual14 
Clinic 
visit 5 
Clinic 
visit 6 
Clinic visit 
7 
Clinic visit 
8 
Clinic visit 
9 
55 years in first 
degree relatives only 
See Section 8.1.2 for 
more information 
Prior ART check to 
ensure naïve status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CDC classification 
X 
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.2 for 
more information  
HIV-associated 
conditions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.2 for 
more information  
Plasma for HIV-1 
genotype/phenotype4  
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
See Section 8.8 for 
more information  
HIV-1 RNA 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
See Section 8.2 for 
more information  
Physical examination 
including height and 
weight5 
X 
X 
 
 
 
 
 
 
X 
 
 
X 
See Section 8.3.1 for 
more information 
Vital signs 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
See Section 8.3.2 for 
more information 
C-SSRS 
Administration 
X 
 
 
 
 
 
 
 
X 
 
 
X 
See Section 8.3.6 for 
more information 
ECG: single reading X 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.3.3 for 
more information 

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Procedure1 
Screening2  
(7-14 days 
before Day 
1) 
Study Intervention Period Days 1-7 
Post-Study Intervention Follow-
up 
Days 8-21 
Follow-
up/ED15 
Notes 
ED = early 
discontinuation/wit
hdrawal 
Day 1 
Day 2 
Days 3 and 4 
1 clinic visit and 1 
virtual3 
Days 5 and 6 
1 clinic visit and 1 
virtual3 
Day 7 Day 8 
Day 14 
(+/- 1 day) 
Day 21  
(+/- 1 day) 
Day 25 
(+/- 1 day) 
 
Clinic 
visit 1 
Clinic 
visit 2 
Clinic 
visit 3 
Virtual14 Clinic 
visit 4 
Virtual14 
Clinic 
visit 5 
Clinic 
visit 6 
Clinic visit 
7 
Clinic visit 
8 
Clinic visit 
9 
ECG: single reading 
pre-dose13  
 
 
X 
X 
 
X 
 
X 
X 
 
 
X 
See Section 8.3.3 for 
more information 
ECG: triplicate 
reading pre-dose 
 
X 
 
 
 
 
 
 
 
 
 
 
See Section 8.3.3 for 
more information 
ECG: single reading 
post-dose at 5, 7, 8 
and 9 h 
 
X 
 
 
 
 
 
X6 
 
 
 
 
See Section 8.3.3 for 
more information 
Confirmation of 
PONCBP (female 
participants) 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.4.1.1 
for more information 
Hepatitis B and C 
serology 
X 
 
 
 
 
 
 
 
 
 
 
 
If test result available 
from within 3 months 
before first dose of 
study intervention, 
testing at screening 
is not required. 
See Section 8.3.4 for 
more information 
Hematology/Chemist
ry/Urine 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
See Section 8.3.4 for 
more information 
Fasting lipids and 
glucose (minimum 8 
h)7 
  
X 
 
 
 
 
 
 
X 
 
 
X 
See Section 8.3.4 for 
more information 
Lymphocyte T-cell 
subsets (CD4/CD8) 
X 
 
 
 
 
 
 
 
X 
 
 
 
See Section 8.3.4 for 
more information 

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Procedure1 
Screening2  
(7-14 days 
before Day 
1) 
Study Intervention Period Days 1-7 
Post-Study Intervention Follow-
up 
Days 8-21 
Follow-
up/ED15 
Notes 
ED = early 
discontinuation/wit
hdrawal 
Day 1 
Day 2 
Days 3 and 4 
1 clinic visit and 1 
virtual3 
Days 5 and 6 
1 clinic visit and 1 
virtual3 
Day 7 Day 8 
Day 14 
(+/- 1 day) 
Day 21  
(+/- 1 day) 
Day 25 
(+/- 1 day) 
 
Clinic 
visit 1 
Clinic 
visit 2 
Clinic 
visit 3 
Virtual14 Clinic 
visit 4 
Virtual14 
Clinic 
visit 5 
Clinic 
visit 6 
Clinic visit 
7 
Clinic visit 
8 
Clinic visit 
9 
Syphilis RPR 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.3.4 for 
more information 
Plasma for storage8 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
See Section 8.3.4 for 
more information 
IWRS (RAMOS NG) 
activity9 
X 
X 
X 
 
 
 
 
 
 
 
 
 
See Section 6.3 for 
more information 
Optional genetic 
sample 
 
X 
 
 
 
 
 
 
 
 
 
 
A separate genetics 
ICF is required 
Observed 
administration of 
study intervention 
 
X 
X10 
X10 
X10 
X10 
X10 
X10 
 
 
 
 
See Section 6.1 for 
more information 
Observed dosing 
with cART, and 
eCRF completion11 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
See Section 6.1 for 
more information 
AE review 
 
 
See Section 10.3.7 
for more information 
SAE review 
 
See Section 10.3.7 
for more information 
Concomitant 
medication review 
 
See Section 6.9 for 
more information 
Serial PK sampling12  
X 
 
 
 
 
  
X 
 
 
 
 
See Section 8.5 for 
more information 
Single pre-dose PK 
sample13 
 
 
X 
X 
 
X 
 
 X 
X 
X 
X 
X 
See Section 8.5 for 
more information 

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The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data review (e.g., to obtain data closer to the time of peak 
plasma concentrations) to ensure appropriate monitoring.  
The CA and IEC will be informed of any safety issues that constitute a substantial amendment and require alteration of the safety monitoring scheme or amendment of the ICF. The 
changes will be approved by the CA and the IEC before implementation. 
 
1. 
Order of procedures (pre-dose): C-SSRS – ECG – Vital Signs – Blood Draws to allow the blood draw to occur as close as possible to the nominal time (See Section 8.5 for 
further information regarding order of blood draw and ECG during Clinic Visits 1 and 5 [Study Days 1 and 7]).  
2. 
Participants will be randomized within approximately 7 to 14 days of the start of Screening but may be extended up to 28 days maximum. Screening laboratory assessments 
may be performed at the local laboratory in exceptional circumstances, if this more readily facilitates evaluation of the eligibility of potential study participants. The Investigator 
will review the local laboratory reports, confirm eligibility and document this in the eCRF. At the Screening site visit, the scheduled laboratory assessments should also be 
collected for analysis by the central laboratory.   
3. 
Participants who pass screening will be required to attend 9 in-clinic outpatient visits. Flexibility is offered for Clinic Visits 3 and 4 which may take place on either Study Day 3 
or Day 4 (Clinic Visit 3), or on Study Day 5 or Day 6 (Clinic Visit 4), with a virtual visit to be conducted on the non-clinic day. The visit schedule for each participant will be pre-
planned to be sure weekend, work schedules and clinic hours are appropriately considered. In particular, Clinic Visits 1 and 5 (Study Days 1 and 7) must be scheduled on 
days when participants and site staff will be able to complete serial PK sampling up to 12 h post-dose.  
4. 
Genotypic/Phenotypic testing will be conducted on Day 1 and Day 8 samples, with samples collected at other visits tested as appropriate. 
5. 
Complete Physical Exam performed at Screening and Clinic Visit 9. . At all other clinic visits perform a Brief Physical Exam including, at a minimum, assessments of the Skin, 
Heart, Lungs, and Abdomen (liver and spleen). Any abnormalities to be recorded as AEs. Height measured at Screening only, weight measured at all indicated visits.  
6. 
ECG reading at 5, 7, 8 and 9 h post-dose on Day 7 applies to Part 1A and optional QD cohorts in Part 2 only. 
7. 
Clinical chemistry includes a lipid panel (total cholesterol, HDL, LDL and triglycerides). Blood collection for Clinical Chemistry should be collected after a minimum of an 
8 hour fast on Days 1, 8 and 25 for fasting lipid assessment.  
8. 
Plasma samples for storage will be collected at each visit starting at Day 1, including unscheduled visits. These samples will be used when needed, such as when samples 
are lost or where quantity is insufficient for testing. In the event samples are not used by study completion, they will be utilized for additional research on antiretroviral 
resistance and/or HIV-1 disease biology/host immune response (excluding any human genetic testing). 
9. 
Log in to RAMOS NG at Screening to complete registration for participant ID assignment. Register any screen fails in RAMOS NG. Log in to RAMOS NG on Day 1 (Visit 1) 
and for Part 1A and optional QD cohorts in Part 2 on Day 2 (Visit 2) to dispense blinded study treatment.  Subsequently log-in to RAMOS NG for study treatment supply as 
needed. If a participant is discontinued from the study early, log in to RAMOS NG to record the discontinuation. 
10. 
 
 
11. Observed dosing with cART is required at Day 8. At subsequent study visits, observed dosing is optional, however, at visits from Day 8, the investigator must document 
whether all prescribed cART doses were taken, or to document any missing doses as appropriate.  
12. Serial Plasma VH3739937 PK samples will be collected on Days 1 and 7 
, as outlined in Table 7 and Table 8 in Section 8.5. In Part 2, 
QD cohorts will have the same PK sample schedule as Part 1A and single doses cohorts the same as Part 1B. 
13. For single dose cohorts in Part 1B and optional Part 2, timepoints listed as pre-dose in the SoA will be time-matched to the time of dosing on Day 1. 
14. HIV-associated conditions assessments, AE/SAE assessment, observed dosing with study intervention (Part 1A and optional Part 2A only), and concomitant medication 
review must be conducted with a participant during each day indicated. On the days when the participant does not come to the clinic (Study Day 3 or 4 and Day 5 or 6 as 
arranged with the participant), these assessments can be done via phone, preferably via a visual method (as locally permitted) of Skype, Facetime, WhatsApp, et. al. 
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15. Early discontinuation assessments to be performed if a participant withdraws early from study. Final follow-up visit will be approximately 18 days post last dose when it is 
estimated that the VH3739937 plasma concentrations are expected to be below the limit of quantification. 
 

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2. 
INTRODUCTION 
2.1. 
Study rationale 
The inhibition of maturation and release of HIV-1 is a novel target for drug development, 
distinct from viral protease, reverse transcriptase and integrase. There are no MIs 
approved for the treatment of HIV infection. VH3739937 is a MI that displays in vitro 
evidence of low nanomolar potency against multiple HIV-1 Gag polymorphisms and a 
broad spectrum covering multiple HIV-1 subtypes, supporting compound development.  
Study 212580 is a POC, randomized, double blind study to characterize antiviral activity, 
safety/tolerability, PK, and the relationship between PK and antiviral activity of 
VH3739937 administered orally 
 
, in HIV-1 infected treatment-naïve 
adults. The purpose of this study is to inform further clinical development of 
VH3739937. 
 
 
 
 
 
 
 
. This study will facilitate an understanding of the antiviral activity 
of VH3739937 
 and provide 
information on the safety profile, while limiting the exposure of HIV-1 infected 
participants to monotherapy with VH3739937 therefore reducing the likelihood of 
development of viral resistance.   
2.2. 
Background 
Infection with HIV-1 continues to be a serious health threat throughout the world, with 
approximately 1.2 million in the US and approximately 38.4 million infected individuals 
worldwide at the end of 2021 respectively, with approximately 1.5 million new HIV 
infections recorded in 2021 [UNAIDS, 2022]. Chronic exposure to cART has identified 
ARV-associated long-term toxicities (e.g., CNS or 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. There is still an on-going need for new ARV agents with improved 
safety and tolerability profiles with limited potential for drug-drug interactions for PLWH 
in particular as the population living with HIV ages. In this environment, medicines with 
novel mechanisms of action that can be used as part of the preferred cART regimen have 
an important role to play. However, any new oral ARV agent must be safe and effective, 
ideally provide a high barrier to resistance, have low toxicity, have minimal drug-drug 
interactions, and a desirable frequency of administration.  
Currently no HIV-1 MI has been approved by a regulatory authority for treatment of 
HIV-1 infection, although several early phase studies of other MIs (bevirimat, 
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GSK2838232, GSK3532795 and GSK3640254) have been conducted [Martin, 2008; 
Morales-Ramirez, 2018; DeJesus, 2020; Dicker, 2022; Spinner, 2022)]. The MI under 
evaluation, GSK3739937 (also known and hereinafter referred to as VH3739937), has the 
potential to meet the requirements for a new ARV agent. 
 
 
 
 
 
The clinical development of VH3739937 is on-going. Study 212548 was a FTiH study of 
oral formulation of VH3739937 investigating the safety, tolerability, and PK of single 
and repeated escalating doses in healthy participants. 
 
 
 
 
 Study 212548 has shown VH3739937 to be generally well-
tolerated in healthy participants and has demonstrated a PK profile suitable for 
progression to HIV-1 infected TN participants in this Phase 2a POC, 7-day monotherapy 
study 
  
Data from these studies will be utilized to support future clinical development of 
VH3739937. 
2.2.1. 
Key Clinical Safety and PK Data in Study 212548 
2.2.1.1. 
Safety 
In the FTiH study (212548) in healthy participants, VH3739937 PiB formulation 
following a moderate fat meal was observed to be safe and well tolerated. There were no 
Grade 3 or Grade 4 AEs, no SAEs or deaths, with the exception of 1 Grade 4 AE 
(transaminase elevation) in a participant randomised to receive PBO in Part 1 (SAD). 
Overall, the majority of AEs observed were Grade 1. No participant discontinued study 
due to an AE considered related to VH3739937 and no participant met a QTc study 
discontinuation criterion. Overall, the most commonly reported System Organ Classes for 
AEs were Gastrointestinal (abdominal pain, constipation and diarrhea) and General 
Disorders and Administration Site Conditions. The incidence of AEs considered related 
to the study drug was low and the majority of the study drug-related AEs were in the GI 
system-organ class. There were no clinically significant changes in clinical chemistry or 
hematology laboratory parameters, nor in vital signs, in participants who received 
VH3739937. There were no abnormal clinically significant arrhythmias or QTcF 
prolongations (values >500 msec) in the SAD, MAD and RBA / FE cohorts.  
A regression analysis of time-matched change from baseline in QTcF and VH3739937 
plasma concentration did not indicate a significant increase in change from baseline 
QTcF as concentration increases in either the SAD or MAD. A more robust 
cardiodynamic analysis is ongoing and is planned to be available prior to the start of this 
POC study; any clinically significant results will be sent to sites and ECs as a note to file. 
Full details are provided in the VH3739937 IB [GSK document No.: RPS-CLIN-
017061]. 
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2.2.1.2. 
Pharmacokinetics 
2.2.1.3. 
Summary 
In summary, Study 212548 has shown VH3739937 to be generally well-tolerated in 
healthy volunteer participants and has demonstrated a PK profile suitable for progression 
to HIV-1 infected TN participants in this Phase 2a POC 7-day, monotherapy study. 
 
 
 
 
 
2.3. 
Benefit/risk assessment 
Based upon pre-clinical studies and clinical studies of prior Mis (GSK3532795 and 
GSK3640254 – both terminated in Phase 2b after reaching their Week 24 primary 
endpoint) the potential risks are GI intolerability (e.g., abdominal pain and diarrhea), 
gastric toxicity (effects on parietal cells and chief cells), prolongation of QTc, skin and 
subcutaneous tissue disorders (maculopapular rash), neuropsychiatric safety, and 
treatment emergent virologic resistance. These are described in detail in the table below. 
To ensure the overall safety of participants (including the risks described above), this 
clinical study will include relatively healthy treatment-naïve adults living with HIV-1 
who will receive clinical, ECG, and laboratory evaluations during their participation. 
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More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of VH3739937 may be found in the IB [GSK document No.: 
RPS-CLIN-017061]. 
The Sponsor has assessed this study for any risks that may be posed to participants. The 
proposed risk assessment and management plan for the study has been developed in 
accordance with the tenets of FDA and the EMA guidance on strategies to identify and 
mitigate risks for clinical studies with IMPs [EMA, 2017]. 
 

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2.3.1. 
Risk assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (IP) [VH3739937] 
Cardiovascular (QT prolongation) 
Preclinical:  
• Weight of evidence from preclinical in vitro 
and in vivo cardiovascular studies suggests 
a low potential for QT prolongation in 
humans at exposures up to the highest 
predicted median maximum observed 
concentration (Cmax) of 
 µg/mL 
(
 µg/mL free) with no CV effects 
observed in a dog CV study at exposures of 
 µg/mL (
 µg/mL free). 
or in the 4-week dog study up to 
 µg/mL 
µg/mL free). 
Clinical:  
• In the 212548 FTiH study of VH3739937, no 
clinically significant elevations of QTcF were 
observed (nor did any patient meet QT 
stopping criteria).  
Clinical prior MI:  
• In a thorough QT study, supratherapeutic 
dose of GSK3640254 500 mg has shown to 
significantly prolong QTc interval 10.6 msec 
(clinically important threshold is 10 msec). 
• Protocol exclusion criteria based on ECG 
parameters and cardiac medical history 
(see Section 5.2). 
• ECGs and frequent clinical and vital sign 
evaluations will be collected during the 
study (see Section 1.3).  
• As noted in Section 7, if a clinically 
significant finding is identified (including but 
not limited to changes from baseline in 
QTcF) after enrolment, 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 minimum) as 
an AE.  
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
 
Gastrointestinal intolerability  
Preclinical:  
• Clinical signs indicative of gastrointestinal 
intolerability (sporadic vomiting and 
abnormal faeces) occurred mainly in dogs 
at ≥30 mg/kg/day. 
Clinical:  
• In the 212548 FTIH study, Gastrointestinal 
AEs:  diarrhea, constipation and abdominal 
pain were reported, the majority were 
considered grade 1. No GI event led to 
discontinuation. For further detail, please 
see IB [GSK document No.: RPS-CLIN-
017061]. 
Clinical prior MI:  
• GI events (abdominal pain, diarrhea and 
nausea) have been added as Adverse Drug 
Reactions to the non-EU Reference Safety 
Information of the GSK3640254 IB [GSK 
document No.: RPS-CLIN-045350]. 
Gastrointestinal intolerability is categorized 
as an identified risk for GSK3640254. 
• Protocol exclusion criterion based on pre-
existing GI pathology or baseline GI 
signs/symptoms 
• Study participants will undergo physical 
examinations, laboratory testing and  
continuous evaluation for adverse events. 
See stopping criteria based upon the 
incidence and intensity of treatment-
emergent AEs (Section 7.1.3). Additionally, 
a GI intolerability evaluation and monitoring 
plan is available to guide the investigator 
should GI AEs emerge (see Section 8.3.8). 
Gastric toxicity 
Preclinical:  
• Dose and duration-dependent microscopic 
changes (single-cell necrosis and 
decreased cellularity of parietal cells and/or 
• There is no specific clinical approach for 
evaluating gastric toxicity in Study 212580. 
However, based on nonclinical data, and 
the highest predicted clinical exposure in 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
chief cells), were observed in the glandular 
stomach of rats and dogs dosed with 
GSK3739937 from 7 days to 4 weeks 
duration. The stomach findings in the 
definitive 4-week studies were minimal to 
mild in nature and shown to be reversible in 
both rats and dogs with a NOAEL for rats of 
10 mg/kg/day and the LOAELs in rats and 
dogs, of 40 and 3 mg/kg/day, respectively 
(1.4X and 0.7X the highest median 
predicted clinical AUC0-24 
 in 
this clinical study, respectively). A NOAEL 
for microscopic changes in the stomach of 
dogs was not identified. 
Clinical prior MI: 
• GSK3640254 and GSK3532795: Toxicity 
findings of single-cell necrosis and 
decreased cellularity of parietal cells and/or 
chief cells in the stomach were present in 
preclinical species with GSK3640254 and 
GSK3532795. These findings were 
reversible. 
• GSK3640254: Phase 2b Study 208379 
included a gastric sub-study (n= 17). Gastric 
biopsies (2 in greater curvature and 2 in 
transitional zone) were taken at Day 1 and 
Week 24 and evaluated microscopically: 
Study 212580 at approximate parity to the 
LOAEL in rats and dogs, any changes to 
parietal or chief cells that may occur in the 
stomach of humans are expected to be 
minimal to mild, asymptomatic and 
reversible following up to 28 days of 
exposure.  
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Potential Risk of Clinical Significance 
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gastric biomarkers (gastrin, pepsinogen I 
and II) were obtained in all participants in 
the study (n = 17). At Week 24, there was 
no evidence of dose-dependent induction of 
gastric pathology by GSK3640254, findings 
were within normal limits including 
spontaneous mild reactive gastritis. There 
was no evidence of significant deleterious 
pathology including metaplasia or dysplasia. 
Serum gastrin levels were consistent with 
normal acid secretion from gastric parietal 
cells and there was no clear evidence of 
parietal cell loss following drug treatment 
 
Neurologic/psychiatric safety 
Preclinical:  
• CNS penetration data for GSK3532795 and 
GSK3640254 in rats demonstrate a similarly 
low brain distribution/penetration. CNS 
penetration studies with GSK3739937 have 
not yet been performed.  
Clinical:  
• In the FTIH and RBA study with VH3739937 
no psychiatric AEs have been reported. The 
most common nervous system disorder was 
headache. See VH3739937 IB for summary 
of nervous system AEs [GSK document 
No.: RPS-CLIN-017061 
• Protocol exclusion criterion based on any 
pre-existing psychiatric condition (including 
results of psychological assessment and the 
C-SSRS) for participants in the study. 
• Continuous evaluation for adverse events 
during their participation in the trial including 
direct AE inquiry. 
• Participants will have C-SSRS assessments 
regularly throughout the study. Ultimately, in 
the event of a new onset suicidality ideation 
or behavior, as determined by the 
investigator (in consultation with psychiatry, 
as needed), the participant will discontinue 
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Clinical prior MI:  
• Two psychiatric SAEs in previous MI 
GSK3532795 clinical program (acute 
psychosis, homicidal/suicidal ideation) at 
supratherapeutic doses were seen in 
healthy participants in TQT study. 
• Neuropsychiatric adverse events were 
reported infrequently in the GSK3640254 
program and were mostly grade 1; 
Psychiatric SAEs have been reported in the 
Phase 2b studies, none were considered 
related and all cases had either baseline 
psychiatric history (not disclosed during 
screening) or confounded factors which 
were the most likely cause of the event. For 
the Phase 2b study evaluating  
GSK3640254/DTG relative to DTG/3TC, the 
rates of nervous system AESI were 9-23% 
relative to 10%, respectively.  The 
psychiatric system AESI were 0-10% 
relative to 14%, respectively. 
• For the Phase 2b study evaluating 
GSK3640254 relative to DTG (both in 
combination with 2 NRTI), the rates of 
nervous system AESI were 9-17% relative 
to 8%, respectively. The psychiatric system 
arrange for urgent specialist psychiatric 
evaluation and management. 
• Guidance for the management of emergent 
psychiatric symptoms are available (see 
Section 8). 
• There are clinical stopping criteria based 
upon intensity of treatment-emergent 
psychiatric AEs (see Section 7). 
 
 
 

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AESI were 3-7% relative to 6%, 
respectively. 
Skin and subcutaneous tissue disorders  
Clinical:  
• In the 212548 FTIH study, no adverse 
events of rash considered by the 
investigator as attributable to VH3739937 
were reported.  
• In the FTIH and RBA study with 
GSK3739937, skin disorders AEs (primarily 
dermatitis due to ECG leads) were reported, 
the majority of which were mild (Grade 1) 
and not considered related to study 
medication.   
Clinical prior MI:  
• Across GSK3640254 clinical studies, AEs 
leading to discontinuation have included 
urticaria and maculopapular rash. 
• Rash has been added as Adverse Drug 
Reactions to the non-EU Reference Safety 
Information of the GSK3640254 IB [GSK 
document No.: RPS-CLIN-045350]. Skin 
and subcutaneous tissue disorders is 
categorised as an identified risk for 
GSK3640254. 
• Participants with a history of drug or other 
allergy that, in the opinion of the investigator 
or Medical Monitor, contraindicates their 
participation are excluded. 
• Study participants will undergo continuous 
evaluation for adverse events 
supplemented by physical examinations. 
• See clinical stopping criteria based upon the 
intensity of treatment-emergent skin and 
subcutaneous tissue disorder AEs and 
laboratory abnormalities (Section 7.1.3).  

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Potential Risk of Clinical Significance 
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HIV Resistance to VH3739937 
 
Clinical: 
• 
There is an intrinsic risk of resistance (genotypic 
changes or decreased phenotypic susceptibility) 
to any developmental ARV – particularly when 
given in monotherapy  
Clinical prior MI: 
• Data from the GSK3640254 Phase 2a POC 
study showed a decline in HIV-1 RNA and a 
variable PK/PD relationship. However, 4 of 
6 participants receiving GSK3640254 
 
 had treatment emergent 
genotypic changes associated with 
resistance to maturation inhibitors observed 
 However, no 
resistance to existing and commercially 
available classes of antiretroviral 
medications (e.g., reverse transcriptase, 
protease, integrase) was observed and 
there is no known cross-resistance between 
MIs and other classes of ARVs. Genotypic 
analysis of samples at Study Day 8 or 9 
revealed no treatment emergent resistance. 
• This Phase 2a study is limited to 7 days of 
monotherapy. Doses of VH3739937 in all 
active therapy Cohorts 2 to 4 were selected 
to ensure that from Day 1 throughout the 
dosing period, at least 95% of the study 
participants achieve plasma concentrations 
above 3-times the protein binding-adjusted 
EC90 (3xPBA-EC90) for a panel of HIV-1 to 
reduce the risk of emergent MI drug 
resistance. See IB [GSK document No.: 
RPS-CLIN-017061].  
• There are no commercially 
available/approved MIs nor is there 
evidence of cross-class resistance (e.g., as 
occurs for protease inhibitors). Therefore 
dosing with VH3739937 will not impact 
selection of effective ART at the completion 
of the study. 
• Study conduct will ensure strict adherence 
to criteria addressing concurrent 
medications 
Study Procedures  
Lead irritation from ECG leads  
• In the event of irritation from ECG leads, up 
to 2.5% topical hydrocortisone may be used 
at the discretion of the investigator 
• See Section 6.9 for further detail on 
permissible concomitant medications 
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2.3.2. 
Benefit assessment 
This study in HIV-1 infected, TN and otherwise healthy participants is a short-term 
monotherapy design. There is no expected longer-term anti-HIV benefit to administration 
of VH3739937 during this study; however, participants will transition to standard of care 
cART on study Day 8. Potential delays in initiating combination ART as a result of 
participating in this study are expected to be short and are not expected to have any 
clinically relevant impact upon study participant outcomes. 
2.3.3. 
Overall benefit-risk conclusion 
Given the preclinical and clinical profile to date, the overall risk to HIV-1 infected, TN 
and otherwise healthy participants at the proposed VH3739937 doses, for 7 days, is 
predicted to be low and manageable. Mean exposures at the highest dose to be studied are 
not projected to exceed mean LOAEL values obtained in 28-day toxicology studies, 
further reducing potential risk. 
Taking into account the measures taken to minimize risk to participants participating in 
this study, the potential risks identified in association with VH3739937 are justified by 
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3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS 
3.1. 
Objectives and Endpoints 
Table 2 
Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
 
• 
To evaluate the antiviral activity of 
VH3739937 in HIV-1 infected TN participants 
during 7 days of monotherapy  
• 
Maximum 
change 
from 
baseline 
(Day 1) in plasma HIV-1 RNA through 
Day 8 
Secondary 
 
• 
To assess the safety and tolerability of 
VH3739937 when administered as 
monotherapy over 7 days in HIV-1 infected 
TN participants 
• 
Incidence of SAEs, Deaths and AEs 
leading to Discontinuation through 
Day 8 
• 
To characterize the pharmacokinetics of 
VH3739937 in HIV-1 infected TN participants  
VH3739937 PK parameters : 
Following QD dosing: 
• Day 1: Cmax, tmax, C24 and 
AUC(0-24) 
• Day 7: Cmax,ss, tmax, C24,ss and 
AUC(0-24),ss 
Following single dose: Cmax, tmax, 
AUC(0-168) and C168  
Exploratory 
• 
To assess the safety and tolerability of 
VH3739937 when administered as 
monotherapy over time in HIV-1 infected TN 
participants 
• 
Incidence of AEs and severity of AEs 
through Day 25 
• 
Change from baseline and maximum 
toxicity grade increase from baseline 
for liver panel laboratory parameters 
(consisting of total and direct bilirubin, 
ALT, ALP and AST) 
• 
To assess the occurrence of Gag treatment 
emergent mutations or substitutions after 7 
days of monotherapy with VH3739937 
• 
Genotypic assessment to detect any 
change in the Gag gene sequence 
from Day 1 to Day 8 
• 
To assess the immunologic effects of 
VH3739937 when administered over 7 days 
in HIV-1 infected adults 
• 
Change from baseline in CD4+ T-cell 
count through Day 8  

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• 
To characterize the pharmacokinetics of 
VH3739937 in HIV-1 infected TN participants  
Additional VH3739937 PK parameters: 
• 
Following QD dosing (Day 7 only): 
CL/F, V/F and t1/2 will be determined if 
possible 
• 
Following single dose: AUC(0-24) and 
C24, In addition, AUCinfinity, CL/F, 
V/F and t1/2 will be determined where 
possible  
• 
To explore relationship(s) between plasma 
concentrations of VH3739937 and 
pharmacodynamic, efficacy and/or safety 
endpoints. 
 
• 
Appropriate VH3739937 PK 
parameters with pharmacodynamic, 
efficacy and/or safety endpoints (e.g., 
change in plasma HIV-1 RNA, CD4+ 
cell count etc) may be explored as 
deemed appropriate 
Note: Other exploratory objectives and endpoints may be specified in the SAP. 

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4. 
STUDY DESIGN 
4.1. 
Overall design 
This is a Phase 2a, POC, multi-center, randomized, double-blind (Sponsor-unblinded), 
placebo-controlled, adaptive clinical study to evaluate the antiviral effect, safety, 
tolerability, and PK/PD of orally administered VH3739937 over 7 days initially in 
approximately 20 TN HIV-1 infected adults who are termed “participants” in this study. 
Optionally approximately 20 further participants may be enrolled in Part 2. Please see 
Section 9 for statistical considerations and Section 9.5 for further detail on definition of 
screen failures and non-evaluable participants. 
All participants will be screened for eligibility preferably within approximately 7 to 
14 days before being randomized into a 7-day study intervention period. The screening 
period may be extended to 28 days to allow, at a minimum, receipt of all screening results 
and/or to accommodate scheduling. 
If participants prematurely discontinue the study for non-safety reasons, additional 
participants may be recruited with randomization and assignment to the same cohort (to 
ensure a minimum of 5 evaluable participants in each of cohorts 2 to 4 and optional 
cohorts 5, 6 and 7) at the discretion of the Sponsor in consultation with the Investigator. 
Participants will not be replaced if the reason for discontinuation is the original 
participant meeting stopping criteria (with the exception of moderate to severe 
COVID-19 infection). 
This study will be conducted in two parts. In the first part (Part 1), approximate 20 TN 
HIV-1 infected adults will be randomized to one of 4 cohorts as described in the table 
immediately below. Part 2 of the study is optional and will be adaptive; the dose(s) and 
frequency of administration of VH3739937 are to be determined based on a planned 
interim analysis by the Sponsor study team using available, unvalidated, preliminary 
clinical data from Part 1. If Part 2 is conducted, it will include up to 3 additional cohorts, 
where up to 6 participants would receive VH3739937 in each cohort; up to 2 further 
participants would also be enrolled into Cohort 1, to receive placebo. Part 2 QD cohorts 
(Part 2A) will follow the same schedule as those in Part 1A, and single dose cohorts (Part 
2B) will follow the same schedule as for Part 1B. If both QD and single dose cohorts are 
included in Part 2, an additional Cohort 1 participant will be enrolled into each of Parts 
2A and 2B. 
Part 
Cohort 
Number 
Number of 
Participants 
Intervention 
1A 
1 
1  
1 Placebo 
 
2 
6 
VH3739937 
 
 
3 
6 
VH3739937 
 
 
1B 
1 
1 
1 Placebo 
 
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Part 
Cohort 
Number 
Number of 
Participants 
Intervention 
4 
6 
VH3739937 
  
2A 
and/or 
B 
1 
Up to 2 
1Placebo 
 
 
5-7 
Up to 6 each Number of Cohorts, dose and dose frequency to be 
decided based on Part 1 Cohort data 
1 For placebo tablets please see Section 6.1 for further detail. 
 
 
In Part 1, 3 cohorts of approximately 6 participants will receive active doses of 
VH3739937 and one cohort of approximately 2 participants will receive placebo 
 
 Most 
participants will be randomized within approximately 14 days of the start of Screening; 
up to 28 days maximum will be allowed. Participants will receive SOC cART selected 
and prescribed by the Investigator starting on Day 8 after all study procedures and 
assessments have been performed. Participants will be followed for on study assessments 
until Day 25, 18 days after the last dose of study intervention. The SOC cART will be 
sourced as per local requirements. 
 
 
 
 
 
 
 
 
 
 
 Please see Section 4.3 for further detail 
on justification of the planned dose levels of VH3739937. 
Following Screening, the study requires a total of 9 in-clinic visits with flexibility of up 
to 2 virtual visits offered, one on either of Day 3 or Day 4 and one on either of Day 5 or 
Day 6. For all participants in Part 1, dose administration on Day 1 will occur at the study 
site. For participants in Part 1A only, an appropriate number of bottles will be dispensed 
on Day 2, with a supply sufficient to cover Days 2 to 7 of the treatment period. The 
bottles will contain 
 either the active (VH3739937) dose or placebo and will be 
dispensed in a manner ensuring the blinding of the participant and site staff. Participants 
will be provided with a dosing card with instructions on the number of 
 to take 
from each bottle per day. Participants will bring the bottles of study intervention to each 
clinic visit through to Day 7, so that administration of study intervention can be observed 
in the clinic after the study procedures have been performed.  
Part 2 may evaluate further 
 doses 
 
 
 
 
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Study treatments will be administered near the same time each morning, within a 2-hr 
window (e.g., 9 am +/- 2 hrs). 
On the days when participants in Part 1A (and optional Part 2A) self-administer the study 
treatment during a virtual visit, observed dosing with a site staff member may be 
achieved as locally permitted using various forms of video calling (when at all possible) 
such as FaceTime, Skype, WhatsApp. Virtual visits for Part 1B (and optional Part 2B) 
may be conducted by standard telephone call, as no observed dosing is required. 
The post-dosing of study intervention follow-up period will consist of 4 in-clinic visits on 
Days 8, 14, 21 and 25. On Day 8, participants will start cART selected and prescribed by 
the Investigator and sourced as per local requirements, immediately following the 
completion of Day 8 study assessments. PK and safety assessments will be taken 
approximately 24 h post last dose (Day 8) until the final Follow Up visit planned 
approximately 18 days post dose at Day 25, when it is estimated that VH3739937 plasma 
concentrations are expected to be below the limit of quantification. At this Day 25 visit, 
HIV-1 RNA, PK and safety (e.g., to follow any AEs to resolution), will be assessed as 
shown in the SoA (Section 1.3). 
Total duration of study participation is approximately 32 to 53 days based on the 
following: 
• 7 to 14 days, with a maximum of 28 days permitted for screening/qualification 
period 
• 7 days for treatment with the study intervention and assessment at all planned 
visits 
• 18 days for post-study intervention follow up visits including the final follow 
up visit. Participants will take cART throughout this period. 
4.2. 
Scientific rationale for study design 
This Phase 2a study of VH3739937 will be conducted in HIV-1 infected, TN participants 
to decrease the possibility of participants experiencing viral resistance to VH3739937. 
Dosing with VH3739937 will be limited to 7 days of monotherapy as an additional 
measure to decrease the probability of development of resistance to VH3739937. 
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 On Day 8, all participants 
will switch to combination antiretroviral therapy selected by the investigator and remain 
on study for evaluation based on the elimination of the majority of VH3739937 which is 
anticipated to be achieved approximately 18 days after the last dose of VH3739937. 
There are no commercially available/approved MIs nor is there evidence of cross-class 
resistance (e.g. as occurs for protease inhibitors) therefore dosing with VH3739937 will 
not interfere with selection of the cART regimen selected by the investigator on Day 8 
and any subsequent regimen following completion of the study. 
The justification for the use of a placebo control allows for blinded assessment of 
relationship to a treatment emergent adverse event. One placebo cohort of 2 participants 
will facilitate blinded assessment of safety and tolerability. Since Investigators and 
participants will be blinded, any safety event (AE, lab abnormality, ECG abnormality, 
etc) will be evaluated and managed in the same fashion. Further, there is no evidence that 
delaying initiation of cART by 7 days in a TN study participant will adversely impact the 
short and long term clinical outcomes following the initiation of cART [Egger, 2002]. 
4.2.1. 
Participant input into design 
This is the first study of VH3739937 in people living with HIV-1. Participants were not 
engaged in development of the study design which is consistent with other Proof of 
Concept Phase 2a studies of antiretroviral therapies. 
4.3. 
Justification for dose 
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4.4. 
End-of-study definition 
A participant is considered to have completed the study if the participant has completed 
all periods of the study including the last scheduled procedure shown in the SoA. 
The end of the study is defined as the date of the last visit of the last participant in the 
study. 
Part 2 of the study is optional. Completion of the study at the end of Part 1 will not be 
considered an early termination. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
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5.1. 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Participant must be 18 to 65 years of age inclusive at the time of signing the informed 
consent. 
Type of Participant and Disease Characteristics 
2. Participants who are overtly healthy (other than HIV infection) as determined by the 
Investigator or medically qualified designee based on a medical evaluation including 
medical history, physical examination, laboratory tests, and cardiac monitoring.    
3. Screening CD4+ T-cell count ≥200 cells/mm3  
4. Documented HIV infection and Screening plasma HIV-1 RNA ≥3000 (≥3.48log10) 
and <1,000,000 (<6.0log10) copies/mL. A single repeat of this test is allowed within 
a single Screening period to determine eligibility. 
5. Positive HIV antibody test 
6. Treatment-naïve: No ARVs (in combination or monotherapy) received after the 
diagnosis of HIV-1 infection.  
Weight 
7. Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and BMI 
for all participants within the range 18.5-35.0 kg/m2. 
Sex and Contraceptive/Barrier Requirements 
8. All participants in the study should be counseled on safer sexual practices including 
the use and benefit/risk of effective barrier methods (e.g., male condom) and on the 
risk of HIV transmission to an uninfected partner. 
*NOTE: There are no contraceptive requirements for participants who were male at 
birth. 
Participants Female at birth:  
A participant who was female at birth is eligible to participate if they are a PONCBP 
(see Appendix 4).  
 
Note: 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 
9. Capable of giving signed informed consent as described in Section 10.1, which 
includes compliance with the requirements and restrictions listed in the informed 
consent form and stated in this protocol. 
 

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Other Inclusions 
10. Participant must be willing and able to start cART as selected with the Investigator on 
Study Day 8 (except in the case of early termination, clinically relevant AE/SAE, lab 
abnormality, the withdrawal of consent, lost to follow-up, etc., where circumstances 
could dictate otherwise). 
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 during the study; 
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; or other localized malignancies require agreement between 
the investigator and the study medical monitor for inclusion of the participant prior to 
randomization. Treatment with radiation therapy or cytotoxic chemotherapeutic 
agents within 30 days of study drug administration or anticipated need for such 
treatment within the study; 
3. Any history of significant underlying psychiatric disorder, in the opinion of the 
Investigator or 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 C-SSRS. Participants’ history of suicidal behaviour and/or suicidal 
ideation should be considered when evaluating for suicide risk; 
4. 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 Medical Monitor. 
5. Any pre-existing physical or other psychiatric condition (including alcohol or drug 
abuse) which, in the opinion of the Investigator or Medical Monitor (with or without 
psychiatric evaluation), may interfere with the participant’s ability to comply with the 
dosing schedule and/or protocol evaluations or which may compromise the safety of 
the participant;  
6. Current or chronic history of liver disease or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones); 
7. Participants with primary HIV infection, evidenced by acute retroviral syndrome 
(e.g., fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) 

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documented viremia without antibody production and/or evidence of recent (within 
3 months) documented seroconversion; 
8. A pre-existing condition, in the opinion of the Investigator or Medical Monitor, that 
could interfere with normal gastrointestinal anatomy or motility (e.g., GERD, gastric 
ulcers, gastritis, inflammatory bowel disease), hepatic and/or renal function, that 
could interfere with the absorption, metabolism, and/or excretion of the study 
interventions or render the participant unable to take oral study treatment; 
9. Myocardial infarction, acute coronary syndrome, unstable angina, stroke, transient 
ischemic attack, or intermittent claudication in the past 3 months; 
10. Medical history of cardiac arrhythmias or cardiac disease or a family or personal 
history of long QT syndrome or sudden cardiac death. Any significant arrhythmia or 
ECG finding which, in the opinion of the Investigator or Medical Monitor, will 
interfere with the safety for the individual participant; 
• Examples of ECG findings include symptomatic bradycardia, non-sustained or 
sustained atrial arrhythmias, non-sustained VT or sustained VT, AVB Mobitz 
Type II, or third degree AVB. 
Prior/Concomitant Therapy 
11. Prior exposure to a MI 
12. Treatment with immunomodulating agents (such as systemic corticosteroids, 
interleukins, interferons) or any agent with known anti-HIV activity (such as 
hydroxyurea or foscarnet) within 30 days of study drug administration. If patients 
received ARV(s) for PrEP inadvertently after their diagnosis of HIV-1, they cannot 
screen for this trial until 5 half-lives have elapsed. 
13. Past or intended use of over-the-counter or prescription medication including herbal 
medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 
5 half-lives (whichever is longer) prior to dosing. Specific medications listed in 
Section 6.8 may be allowed; 
14. History of sensitivity to any of the study medications, or their components or drugs of 
their class, or a history of drug or other allergy that, in the opinion of the investigator 
or Medical Monitor, contraindicates their participation. Participants who require 
concomitant medications known to be associated with a prolonged QTc;  
15. Treatment with any of the following agents within 28 days of Screening: radiation 
therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant; 
16. Participants receiving any protocol-prohibited medication and who are unwilling or 
unable to switch to an alternate medication; 
Prior/Concurrent Clinical Study Experience 
17. The participant has received an investigational HIV vaccine (immunotherapeutic or 
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18. Exposure to an experimental drug or experimental vaccine within either 28 days, 5 
half-lives of the test agent, or twice the duration of the biological effect of the test 
agent, whichever is longer, prior to the first dose of study intervention; 
Diagnostic Assessments 
19. Untreated syphilis infection [positive RPR at screening] without documentation of 
treatment. Participants who have successfully completed treatment at least 7 days 
previously are eligible if recruitment is open; 
20. QTc >450 msec or QTc > 480 msec in participants with bundle branch block 
21. Exclusion criteria for screening ECG (a single repeat is allowed in some instances for 
eligibility determination):  
Heart Rate <50 or >100 bpm, or QTcF >450 msec; 
Notes:  
• A heart rate <50 or >110 bpm is exclusionary and cannot be rechecked to 
determine eligibility.  
• A heart rate from 101-110 bpm can be checked by a single repeat ECG or by 
vital signs within 30 minutes to verify eligibility. 
• The QTc is the QT interval 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 an 
individual participant in this study. The Investigator’s or Medical Monitor’s 
over-read can supercede that of the machine at any time. 
22. Presence of HBsAg or HBcAb at screening  
Note: Evidence of HBV infection based on the results of testing at Screening for 
HBsAg: 
• Patients who are negative for HBsAg should also be tested for anti-HBc, anti-
HBs and HBV DNA and excluded according to the following algorithm: 
o Participants negative for anti-HBs but positive for anti-HBc (negative 
HBsAg status) and positive for HBV DNA are excluded 
o 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. 
Note: HBV DNA testing will only be performed during screening and prior to 
randomisation for participants with positive anti-HBc and both negative HBsAg and 
anti-HBs (past and/or current evidence). 
23. 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 (central 
lab will automatically reflex to HCV RNA on positive HCVAb) 

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24. Any Grade 2-4 laboratory abnormality at Screening, with the exception of CPK and 
lipid abnormalities (e.g., total cholesterol, triglycerides, etc), ALT (described below) 
and eGFR, will exclude a participant from the study unless the investigator can 
provide a compelling explanation for the laboratory result(s) and has the assent of the 
sponsor.  A single repeat of any lab abnormality is allowed within a single Screening 
period to determine eligibility; 
25. ALT ≥ 1.5 x ULN or total bilirubin ≥1.5xULN. A single repeat of ALT and / or 
bilirubin is allowed within a single Screening period to determine eligibility; 
26. Any acute laboratory abnormality at screen which, in the opinion of the investigator, 
should preclude participation in the study of an investigational compound; 
27. eGFR of < 50 mL/min/1.73 m2 via CKD-EPI 2021 method; 
28. Any positive result for illicit drug use (e.g., cocaine, heroin) at Screening. A positive 
screen for marijuana / THC is not exclusionary, see Section 5.3.2 for guidance to be 
given to the participant. 
Other Exclusion Criteria 
29. Regular use of drugs of abuse 
30. Sensitivity to heparin or heparin-induced thrombocytopenia 
5.3. 
Lifestyle considerations 
5.3.1. 
Meals and dietary restrictions 
Participants will be required to fast for at least 8 h [overnight] prior to the morning check-
in at clinic visits on Days 1-8 and Day 25 in Part 1A (and optional Part 2A) and Days 1, 8 
and 25 in Part 1B (and optional Part 2B). Procedures will be performed in the following 
order: C-SSRS, ECG, Vital Signs and Blood Draws in a fasted state. On days when 
participants take the study intervention, each dose will be taken with approximately 
240 mL (8 ounce) water following ingestion of a moderate calorie and fat meal, to be 
completed within approximately 25 minutes just prior to dosing, with dose administration 
to occur within 5 minutes of completion of meal consumption. This includes the virtual 
visits where participants must have completed their meal within approximately 
25 minutes of their scheduled call with site staff, with dose administration to occur within 
5 minutes of completion of meal consumption. 
Refrain from consumption of red wine, Seville oranges, grapefruit, or grapefruit juice, 
pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices from 3 days before the 
start of study intervention until Day 8. 
5.3.2. 
Caffeine, alcohol, and tobacco 
During the study alcohol consumption will be limited 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. 

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No alcohol will be consumed on the in-clinic serial PK days (Day 1 and, if applicable, 
Day 7) until after the final assessment of the day and release from the clinic.  
Only clinically minor to moderate use (as determined by the Investigator) of tobacco 
products will be allowed during study participation, with extremely limited use on the in-
clinic serial PK days (Day 1 and, if applicable, Day 7). 
Participants should refrain from the use of marijuana during the treatment period. 
5.3.3. 
Activity 
Participants will abstain from strenuous exercise during Days 1 to 8. 
5.4. 
Screen failures 
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently randomized to study intervention. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure 
participants to meet the CONSORT publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure 
details, eligibility criteria, information from any previous trials with the same IP, and any 
SAE. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once if, in the opinion of the Investigator, the current clinical outlook 
of the participant is favorable for study inclusion.  
Rescreened participants should be assigned a new participant number for every 
screening/rescreening event. Previously assigned participant numbers are to be record in 
the participants’ CRF/eCRF. All screening procedures should be repeated at the 
rescreening visit. 
5.5. 
Criteria for temporarily delaying 
enrollment/randomization/administration of study 
intervention 
Not applicable 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
The definition of study intervention is provided in the table of definitions.  
6.1. 
Study intervention(s) administered 
Table 4 
Study Intervention(s) Administered 
Intervention Label 
 
 
Intervention on Label: 
VH3739937 
 
Placebo to match VH3739937 
  
Intervention Description 
 
 
Type  
Drug 
Drug 
Dose Formulation: 
 
 
Unit Dose Strength(s) 
 
N/A 
Dosage Level(s): 
Variable depending on dose 
Variable depending on dose 
Route of Administration  
Oral 
Oral 
Dosing instructions: 
 
Use 
Experimental 
Placebo  
IMP and NIMP 
IMP  
IMP 
Packaging and Labeling 
 
Blinded Study Intervention will 
be provided in high-density 
polyethylene (HDPE) bottles 
which contain a desiccant. 
Each bottle will be labelled as 
required per country 
requirement. 
Blinded Study Intervention will 
be provided in high-density 
polyethylene (HDPE) bottles 
which contain a desiccant.  
Each container will be labelled 
as required per country 
requirement. 
Sourcing / Manufacturer 
Provided centrally by the 
Sponsor 
Provided centrally by the 
Sponsor 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

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Current/Former Name(s) 
or 
Alias(es) 
GSK3739937 
Not Applicable 
6.2. 
Preparation, handling, storage, and accountability 
The investigator or designee must confirm appropriate conditions (e.g., temperature) have 
been maintained during transit for all study intervention received, and any discrepancies 
are reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention.  
All study intervention must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage conditions 
with access limited to the investigator and authorized site staff. 
The investigator, institution, the head of the medical institution (where applicable), or 
authorized site staff is responsible for study intervention accountability, reconciliation, 
and record maintenance (i.e., receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study interventions 
are provided in the pharmacy manual. 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff.  
A 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 ViiV Healthcare/GSK. 
6.3. 
Assignment to study intervention 
All participants will be centrally assigned to randomized study intervention according to 
a computer-generated randomization schedule provided by the Sponsor, using RAMOS 
NG. Before the study is initiated, the telephone number and call-in directions for 
RAMOS NG and/or the log-in information and directions for RAMOS NG will be 
provided to each site. 
Participants will ideally be randomized within 14 days of the start of Screening; up to 
28 days maximum may be allowed. In Part 1, 3 cohorts of approximately 6 participants 
will receive active doses of VH3739937 and 1 cohort of approximately 2 participants will 
receive placebo. As noted earlier, the dose(s)/frequency and exact arms/sample size for 
Part 2 are to be determined based upon a planned interim analysis of available 
preliminary unvalidated clinical data. 
Study intervention will be dispensed at the study visits as summarized in the SoA.  

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Returned study intervention should not be re-dispensed to the participants. 
6.4. 
Blinding 
Emergency unblinding RAMOS NG 
This is a double-blind study in which 
participants/care 
providers/investigators/outcomes assessors, 
etc. are blinded to study intervention. 
RAMOS NG will be programmed with 
blind-breaking instructions. In case of an 
emergency, the investigator has the sole 
responsibility for determining if unblinding 
of a participants’ 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 may, at the investigator’s 
discretion, contact ViiV Healthcare/GSK to 
discuss the situation prior to unblinding a 
participant’s intervention assignment unless 
this could delay emergency treatment for 
the participant. If a participant’s 
intervention assignment is unblinded, ViiV 
Healthcare/GSK must be notified within 
24 h of this occurrence. The date and 
reason for the unblinding must be recorded. 
If the investigator is unable to access 
RAMOS NG, they can contact the GSK 
helpdesk based on the information provided 
in the pharmacy manual.  
A physician other than the investigator 
(e.g., an emergency room physician) or 
participant/participant’s caregiver or family 
member may also request emergency 
access to the participant’s study 
intervention information as per participant 
card. 
This early phase study of relatively small size will not use an external DMC. The ongoing 
monitoring of blinded study data including clinical safety, efficacy and PK data will be 
overseen by an experienced central ViiV Healthcare/GSK study team. This central study 
team will have access to unblinded data if indicated and, if appropriate, will discuss data 
in a blinded fashion when interacting with site staff. As a general principle during study 

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conduct, members of the ViiV Healthcare/GSK study team and other ViiV 
Healthcare/GSK staff will remain blinded unless unblinding becomes necessary. 
A participant will be withdrawn if the participant’s intervention code is unblinded by the 
investigator or treating physician. The primary reason for discontinuation (the event or 
condition which led to the unblinding) will be recorded in the eCRF. 
ViiV Healthcare/GSK’s Global Safety 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 ViiV Healthcare/GSK policy. 
6.5. 
Study intervention compliance 
When the individual dose for a participant is prepared from a bulk supply, the preparation 
of the dose will be confirmed by a second member of the study site staff.  
When participants are dosed at the site, they will receive study intervention directly from 
the investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents. The dose of study 
intervention and study participant identification will be confirmed at the time of dosing 
by a second member of the study site staff other than the person administering the study 
intervention. 
When participants self-administer the study intervention at home, compliance with study 
intervention dosing will be assessed by observed dosing with a site staff member as 
locally permitted using various forms of video calling (when at all possible) such as 
FaceTime, Skype, WhatsApp. In addition, compliance with study intervention dosing will 
be confirmed by counting returned tablets during the site visits and documented in the 
source documents and relevant form. Deviation(s) from the prescribed dosing regimen 
should be recorded. 
A record of the quantity of VH3739937 
 and / or placebo dispensed to and 
administered by each participant must be maintained and reconciled with study 
intervention and compliance records. Intervention start and stop dates will also be 
recorded. 
6.6. 
Dose modification 
No dose modifications are permitted in this study. 
6.7. 
Continued access to study intervention after the end of the 
study 
Given the lack of longer-term clinical benefit (Section 2.3.2), ViiV Healthcare recognizes 
the balance between the need to conduct an early phase monotherapy clinical study (for 
the larger and long term unmet medical need) and the need for HIV-1 infected treatment 
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naïve patients to receive cART as soon as possible after diagnosis. To meet both needs, 
this study design is efficient in screening (shortest period: approximately 7 to 14 days) 
and the monotherapy treatment with VH3739937 (period: 7 days). On study Day 8, 
following the scheduled blood collection as per SoA, participants will commence cART 
selected and prescribed by the investigator and sourced as per local requirements. After 
this time, the investigator is responsible for ensuring that participants continue to receive 
cART, whether or not the Sponsor is providing reimbursement for post-study treatment. 
The Sponsor recognizes some HIV-1 infected adults may encounter barriers to accessing 
cART. Where it has been determined by the Investigator to be an acceptable option, 
participants receiving study treatment will have the option (but are not required) to 
receive reimbursement from the Sponsor for locally marketed ARVs (after the 
completion of dosing and through the study final follow-up visit) for up to a maximum of 
90 days. The selection of ARVs will be investigator-chosen based upon local standard of 
care. 
6.8. 
Treatment of overdose 
An overdose is any dose of study intervention given to a participant that exceeds the 
planned, randomized dose for an individual within a given dose group.  
In the event of an overdose, the investigator should: 
• 
Evaluate the participant to determine, in consultation with the Medical Monitor, if 
possible, whether study intervention should be interrupted or whether the dose 
should be reduced. 
• 
Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
VH3739937 can no longer be detected systemically (at least 18 days), as medically 
appropriate. 
• 
Obtain a plasma sample for PK analysis if requested by the medical monitor 
(determined on a case-by-case basis). 
• 
Document the quantity of the excess dose as well as the duration of the overdose. 
6.9. 
Prior and concomitant 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. 
Because vaccines may cause a temporary increase in the level of HIV-1 plasma RNA, it 
is highly recommended that a vaccine, if necessary, be given at least 14 days prior to 
Screening. Please discuss with medical monitor if planned to give during this time.  
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 
enrolment or receives during the study must be recorded along with: 
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• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.9.1. 
Permitted Medications: 
1. Acetaminophen/paracetamol at doses of ≤2 g/day or NSAIDs are permitted for use 
any time during the study and their use documented in the CRF.  
2. In the event of irritation from ECG leads, up to 2.5% topical hydrocortisone may be 
used at the discretion of the investigator. 
3. Any vaccine, including those available and approved for SARS-CoV-2 and other 
non-HIV vaccines should be administered at least 14 days prior to Screening. Please 
discuss with Medical Monitor if planned to give during the study period.  
4. Other concomitant medications may be considered on a case by case basis by the 
investigator in consultation with the medical monitor if required. 
Concomitant medications (prescription and non-prescription) should be administered 
only as medically necessary during the study. Participants must notify their Investigator 
of any current or proposed concomitant medication, whether prescribed or over-the 
counter because of the potential for interactions between such treatments and the study 
medications.  
6.9.2. 
Prohibited Medications and Non-Drug Therapies 
The following concomitant medications or therapies are not permitted at any time during 
the study: 
• 
HIV immunotherapeutic / immunomodulatory 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. This includes topical agents with substantial systemic 
exposure and systemic effects.  Use of topical imiquimod is permitted.    
• 
Chronic use of systemic (oral or parenteral) glucocortioids must be avoided due to 
immunosuppressive effect; however, short treatment courses (e.g., 14 days or less) 
of oral prednisone/ prednisolone/methylprednisolone are allowed. Topical, inhaled 
or intranasal use of glucocorticoids will be allowed. 
• 
Acetaminophen (paracetamol) cannot be used in patients with acute viral hepatitis 
[James, 2009]. 
• 
Participants must abstain from taking prescription or non-prescription drugs 
(including vitamins, recreational drugs, and dietary or herbal supplements) within 
7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives 

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(whichever is longer) before the start of study intervention until completion of the 
final visit on Day 25, unless, in the opinion of the investigator and sponsor, the 
medication will not interfere with the study. 
• 
Narrow therapeutic index drugs that are substrates of P-gp or CYP3A are not 
permitted during study. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or of the study as a whole are handled as part of 10.1. 
7.1. 
Discontinuation of study intervention 
‘Discontinuation’ of study intervention refers to any participant who has not received all 
planned doses of the 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 not remain in the study (i.e., continue with 
study visits). See the SoA (Section 1.3) for data to be collected at the time of early 
discontinuation of study intervention (ED Visit). If the participant agrees, participants 
who discontinue study intervention should return to complete a follow-up visit 
approximately 18 days after their final dose of study intervention. Any new clinically 
relevant finding should be reported as an AE.  
Participants must be discontinued from the study for any of the following reasons: 
• Liver toxicity where stopping criteria specified in Liver Chemistry Stopping 
Criteria (Section 7.1.1) are met and no compelling alternate cause is identified; 
• Cardiac Changes (e.g., QTc) (see Section 7.1.2) 
• Rash criteria as described in Section 10.7 are met and no compelling alternate 
cause is identified. 
• Grade 4 clinical AE (see Section 7.1.3 for further detail);  
Pregnancy (intrauterine), regardless of termination status of pregnancy (see 
Section 8.3.5). The primary reason for premature discontinuation of the study 
intervention will be documented in the eCRF based on the list below: 
7.1.1. 
Liver chemistry stopping criteria 
Discontinuation of study intervention for abnormal liver tests is required by the 
investigator 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 
if the investigator believes that it is in best interest of the participant. 

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Liver Chemistry Stopping Criteria Algorithm 
 
Refer to Section 10.6 for required Liver Safety Actions and Follow-up Assessments 
7.1.2. 
QTc Stopping criteria 
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 the study 
intervention 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 QTcF correction formula must be used for each individual participant to determine 
eligibility for and discontinuation from the study.   
The Baseline QTcF should be based on average QTcF values of triplicate 
electrocardiograms obtained over a brief (e.g., 5-10 minute) recording period from the 
Day 1 pre-dose ECG.   
The average of triplicate ECG readings is the preferred method for confirmation of 
stopping threshold. 
A randomized participant who develops an on-treatment QTcF >500 msec or an increase 
from baseline QTcF >60 msec should have two repeat unscheduled ECGs within 
10 minutes. Using these triplicate ECGs, if the average QTcF >500 msec or an increase 
from baseline QTcF >60 msec, the participant will be withdrawn from the study. Finally, 
this participant should have repeated unscheduled ECGs until their QTcF measurement 
returns to their original averaged QTcF value at Day 1 pre-dose. 
For participants with underlying bundle branch block, follow the discontinuation criteria 
listed below: 

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Baseline QTcF with Bundle Branch 
Block 
Discontinuation QTcF with Bundle 
Branch Block 
< 450 msec 
> 500 msec 
450 – 480 msec 
≥ 530 msec 
7.1.3. 
Individual Participant Laboratory Abnormality and Adverse Event 
Stopping Criteria 
Investigators should make every effort to have a discussion with the Medical Monitor 
before the next dose to help assess if the study intervention should be stopped. Individual 
participant laboratory abnormality and AE stopping criteria for the study, as follows: 
Adverse 
Event 
 
• Any clinically significant AE deemed to require discontinuation of 
the IP 
• Any related Grade 3 or any Grade 4 rash 
• Grade 2 rash with evidence of systemic involvement  
• Grade 2 or higher rash with concurrent fever, AST/ALT elevation or 
eosinophilia prior to the follow up phase will be withdrawn from 
study intervention 
• Grade 3 or higher allergic reaction 
• 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 
• 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 emergency specialist psychiatric evaluation/management  
• Any Grade 3 or higher AE related to study medication 
• Any Grade 4 AE or laboratory abnormalities (with the exception of 
an asymptomatic grade 4 cholesterol, triglyceride or CPK increase) 
• A participant meets the QTcF stopping criteria described in 
Section 7.1.2 
• 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) 
 

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7.1.4. 
Temporary discontinuation 
Withdrawal of study treatment, including any missed dose on Days 1 to 7 
, 
requires withdrawal from the study. See Section 7.2 for further detail. 
7.1.5. 
Rechallenge 
Study treatment restart or rechallenge after liver chemistry stopping criteria are met by 
any participant in this study is not allowed. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant may withdraw from the study at any time at the participant’s own request 
for any reason (or without providing any reason). 
A participant may be withdrawn at any time at the discretion of the investigator for 
safety, behavioral, or compliance reasons. 
Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
At the time of discontinuing from the study, if possible, an ED visit should be conducted 
together with a follow-up visit approximately 18 days after the last dose of study 
intervention, 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. 
A participant who is withdrawn from the study for any reason related to safety (listed in 
Section 7.1 or otherwise) will continue to be followed up to assess the outcome of the 
safety event that triggered discontinuation of study drug. If a participant is unable to 
return to the clinic for any reason, site staff are encouraged to contact the participant for 
assessment of AEs. 
The participant will be permanently discontinued from the study intervention and the 
study at that time. 
All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. 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, the participant may request destruction of any 
samples taken and not tested, and the investigator must document this in the site study 
records. 
The primary reason for participant discontinuation/ withdrawal from the study will be 
documented in the eCRF based on the list below: 
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Reasons 
Additional items/Sub-reasons 
AE 
Unsolicited AE 
Solicited AE 
Lost to follow-up 
Subject Relocated  
Subject was Incarcerated  
Other, specify 
Unknown 
Participant Reached 
Protocol-Defined Stopping 
Criteria 
 
Liver Event 
QTc 
Laboratory Abnormality 
Physician Decision 
Loss of ability to freely provide consent due to 
treatment of either a psychiatric or physical 
condition 
Pregnancy 
Protocol Deviation 
Repeat non-adherence of participant with 
protocol requirements or treatment 
Site Terminated by Sponsor 
Study Terminated by 
Sponsor 
Withdrawal by Participant 
Burden of Procedure  
Participant Relocated  
Pursue Alternative Treatment  
COVID-19 Pandemic  
Other 
Death 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.7.5). 
7.3. 
Lost to follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to 
return for scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 

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assigned visit schedule and ascertain whether 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, the participant will be considered 
to have withdrawn from the study.  
• 
Site personnel, or an independent third party, will attempt to collect the vital status of 
the participant within legal and ethical boundaries for all participants randomized, 
including those who did not get study intervention. Public sources may be searched 
for vital status information. If vital status of the participant is determined as 
deceased, this will be documented and the participant will not be considered lost to 
follow-up. Sponsor personnel will not be involved in any attempts to collect vital 
status information. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA (Section 1.3). 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. Subjects who have signed informed consent 
but are not eligible to proceed should be recorded in the eCRF with a status of 
‘screen failure’. 
• 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the timeframe defined in the SoA. 
• 
In the event of a significant study-continuity issue (e.g., caused by a pandemic), 
alternate strategies for participant visits, assessments, study intervention distribution 
and monitoring may be implemented by the sponsor or the investigator, as per local 
health authority/ethics requirements.   
• 
Safety/laboratory/analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded. 

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• 
The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will not exceed 
500 mL within 56 days. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
8.1. 
Administrative and general/baseline procedures 
8.1.1. 
Collection of demographic data 
Record demographic data such as date of birth (month and year), sex, race, and ethnicity 
in the participant’s eCRF.  
Collection of sex, race and ethnicity data is necessary to assess and monitor the diversity 
of the trial participants, and to determine if the trial participants are truly representative of 
the impacted population. 
8.1.2. 
Medical history 
Obtain the participant’s medical history by interviewing the participant and/or review of 
the participant’s medical records. Record any pre-existing conditions, signs and/or 
symptoms present prior to the first dose of study intervention in the eCRF. 
Any condition meeting the criteria of a SAE that occurs after signing the ICF but before 
the first dose of study intervention should be reported as described in Section 8.4. 
8.2. 
Efficacy assessments 
Planned timepoints for all efficacy assessments are provided in the SoA (Section 1.3). 
8.2.1. 
HIV-1 RNA Sampling 
Plasma for quantitative HIV-1 RNA will be generated at timepoints listed in the SoA 
(Section 1.3). 
An HIV-1 RNA PCR assay with a LLOD of 40 copies/mL or lower will be used.  
Details concerning the handling, labeling, and shipping of these samples will be provided 
in the laboratory manual. 
In order to maintain the blind, HIV-1 RNA results will not be provided to site staff. 
8.2.2. 
Lymphocyte Subsets by Flow Cytometry 
Blood samples will be obtained from each participant for the analysis of lymphocyte 
subsets 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 provided 
in the laboratory manual. 

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8.2.3. 
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 10.9). 
8.3. 
Safety assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical examination 
• 
A complete physical examination will include, at a minimum, assessments of the 
CV, respiratory, gastrointestinal, and neurological systems. A brief physical 
examination will include, at a minimum, assessments of the skin, lungs, CV system, 
and abdomen. 
• 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
• 
Height and weight will also be measured and recorded. Height will be captured at 
Screening only. Weight will be captured at each visit to accurately calculate BMI 
and eGFR. For guidance on weight measurement see Section 8.3.1.1. 
8.3.1.1. 
Weight measurement 
Adapted from WHO STEPS Surveillance Manual [WHO, 2017] 
Equipment 
To measure weight, you will need a weighing scale, (such as a SECA scale or the Tanita 
HS301 Solar Scale). Alternatively, a BMI scale measuring both height and weight (e.g., 
Growth Management Scale) can be used.  
Ensure the scale has been regularly calibrated according to the manufacturer instructions 
and that calibration documentations are filed and available to the study CRA as required. 
We recommend using the same scale across visits for individual study participants. 
We recommend having the same study staff performing the measurement across visits for 
individual study participants. 
We recommend that the time of day a participant’s weight is measured is consistent for 
every participant at the site within the study (e.g., If measured at 10 am at initial 
measurement, attempt to have the participant measured at 10 am at subsequent visits). 
Set up requirements 
Make sure the scales are placed on a firm, flat surface. Do not place the scales on: 
• carpet 

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• a sloping surface 
• a rough, uneven surface. 
Set up scales 
Follow the steps below before measuring the weight of a participant: 
1. Make sure the scale is on a firm, flat surface. 
2. Turn on the scale and wait until the display shows 0.0. 
Procedures 
Follow the steps below to measure the weight of a participant: 
1. Ask the participant to remove their footwear (shoes, slippers, sandals, etc). They 
should also take off any heavy belts and remove all objects out of their pockets 
(example: mobile phones, wallets, coins). 
2. Ask the participant to step onto scale with one foot on each side of the scale. 
3. Ask the participant to: 
• stand still 
• face forward 
• place arms on the side and 
• wait until asked to step off. 
4. Record the weight in kilograms to one decimal place in the eCRF. 
8.3.2. 
Vital signs 
Oral temperature, pulse rate, respiratory rate, and blood pressure will be recorded (before 
blood collection for laboratory tests). 
Blood pressure and pulse measurements will be assessed in semi-supine position with a 
completely automated device. Manual techniques will be used only if an automated 
device is not available. 
Blood pressure and pulse measurements will be preceded by at least 5 minutes of rest for 
the participant in a quiet setting without distractions (e.g., television, cell phones). 
3 consecutive blood pressure and pulse readings will be recorded at intervals of at least 
1 minute. The first reading should be rejected. The average of the second and third 
readings should be recorded. 
8.3.3. 
Electrocardiograms 
See Table 7 and Table 8 in Section 8.5. 
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 7.1.2 for QTcF withdrawal criteria and 
any additional QTcF readings that may be necessary. 

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At each timepoint at which triplicate ECGs 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. 
8.3.4. 
Clinical safety laboratory tests 
See Section 10.2 for the list of clinical laboratory tests to be performed in accordance 
with lab manual and the SoA (Section 1.3). 
The investigator must review the laboratory results, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory results 
must be retained with 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 or within 28 days after the last dose of study intervention should 
be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
o 
In the absence of a diagnosis, abnormal laboratory findings, assessments or 
other abnormal results the investigator considers clinically significant will 
be recorded as an AE or SAE, if they meet the definition of an AE or SAE 
(refer to Section 10.3.1 and Section 10.3.2).  
o 
If clinically significant 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. 
o 
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. 
Refer to the laboratory manual for appropriate 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, with the exception of Screening laboratory assessments which may be 
performed at the local laboratory in exceptional circumstances, if this more 
readily facilitates evaluation of the eligibility of candidate study participants. The 
Investigator will review the local laboratory reports, confirm eligibility and 
document this in the eCRF (see Section 10.2). At the Screening site visit, the 
scheduled laboratory assessments should also be collected for analysis by the 
central laboratory. NOTE: For eligible participants on Study Day 1, all laboratory 
assessments should be repeated and performed by the central laboratory as 
described in the SoA (See Section 1.3).  
• From Day 1 onwards, local laboratory results are only required in the event 
that the central laboratory results are not available in time for either a 
treatment and/or response evaluation to be performed. If a local sample is 

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required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either 
a treatment or a response evaluation or are considered clinically significant 
by the investigator (e.g., SAE or AE) the results must be entered in the eCRF. 
8.3.5. 
Pregnancy testing 
Participants who were female at birth are only eligible to participate if they are confirmed 
to be a PONCBP as defined in Section 10.4. 
8.3.6. 
Suicidal ideation and behavior risk monitoring 
VH3739937 is not a central nervous system active drug nor is it being developed for a 
neurologic or psychiatric condition. However, given the risk of suicidal ideation at 
supratherapeutic doses identified in one study with another MI, GSK3532795, all 
participants will undergo assessment for suicidality in this study. Any clinically 
diagnosed case of suicidality (using the C-SSRS as tool during Screening, on-treatment, 
and in follow-up) will result in exclusion from the trial or (if already randomized) 
immediate discontinuation from the study. Moreover, in these cases, the Investigator will 
arrange for urgent psychiatric evaluation and management. 
Participants with HIV infection occasionally may present with symptoms of depression 
and/or suicidality (suicidal ideation or behavior). In addition, there have been some 
reports of depression, suicidal ideation and behavior (particularly in patients with a 
pre-existing history of depression or psychiatric illness) in some patients being treated 
with other ARTs such as INSTIs, including DTG. Therefore, it is appropriate to monitor 
participants for suicidality before and during treatment. 
Participants being treated with VH3739937 should be monitored appropriately and 
observed closely for SIB or any other unusual changes in behavior, especially at the 
beginning and end of the course of intervention, or at the time of dose changes, either 
increases or decreases. Participants who experience signs of SIB should undergo a risk 
assessment. All factors contributing to SIB should be evaluated and consideration should 
be given to discontinuation of the study intervention. It is recommended that the 
investigator consider mental health consultation or referral for participants who 
experience signs of suicidal ideation or behavior. Participants presenting with new 
onset/treatment emergent depression should be advised to contact the investigator 
immediately if symptoms of severe acute depression (including suicidal 
ideation/attempts) develop, because medical intervention and discontinuation of the study 
medication may be required. 
When informed consent has been given, families and caregivers of participants being 
treated with VH3739937 should be alerted about the need to monitor participants for the 
emergence of unusual changes in behavior, as well as the emergence of SIB and to report 
such symptoms immediately to the study investigator. 
Baseline assessment of SIB and intervention-emergent suicidal ideation and behavior will 
be monitored during this study using the C-SSRS. The definitions of behavioral suicidal 
events used in this scale are based on those used in the Columbia Suicide History Form 

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[Posner, 2007]. Questions are asked on suicidal behavior, suicidal ideation, and intensity 
of ideation. Day 1 (Baseline) 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. The C-SSRS is to be administered by a clinician at the timepoints 
specified in the SoA (Section 1.3). The C-SSRS will be conducted electronically by 
computer/tablet connected to the internet. 
Additionally, the investigator will collect information using the 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 their medical and scientific judgment in deciding whether an event is possibly 
suicide-related. PSRAE forms should be completed and reported to GSK/ViiV 
Healthcare within 1 week of the investigator diagnosing a possible suicidality-related AE. 
As described in Section 7.1.3, new onset suicidal ideation of concern to the Investigator 
(see below) at any time will result in immediate discontinuation from the study and the 
Investigator will arrange for urgent specialist psychiatric evaluation and management. 
Emergent non-suicidal Psychiatric AE Evaluation and Management: 
• 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 Investigator. Any pharmacotherapy should be 
discussed with the Medical Monitor. 
• Any Grade 3 or 4 Psychiatric AE: As described in Section 7.1.3, a Grade 3 or 4 
Psychiatric AE will result in discontinuation from the study and emergency 
psychiatric evaluation (including potential hospitalization and pharmacotherapy 
as indicated). A urine sample should be submitted for the Drugs of Abuse panel.  
8.3.7. 
Study stopping rules and safety monitoring 
Participant safety will be continuously monitored by the Medical Monitor and designated 
Safety Lead (or delegate) throughout the study. Pertinent findings and conclusions are 
shared with the product’s SRT for review of the overall benefit-risk profile of the 
product. 
Once all participants in Part 1 (n=20) have completed Clinic Visit 6 (Study Day 8), all 
available preliminary unvalidated in-stream clinical data will be reviewed by the iDRC, 
for agreement on Part 2 (if opened) number of Cohorts (up to 3) and doses to be assessed. 
Enrollment will be paused during the review. If data from Part 1 is considered sufficient 
to meet the objectives and endpoints of the study, no further enrollment into the study 
will take place (See Section 9.4).  

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8.3.8. 
GI Intolerability Evaluation and Monitoring Plan (with Stopping 
Criteria) 
This section provides general guidance to the Investigator on the evaluation and 
management of primarily upper gastrointestinal symptoms (Table 5). The Investigator 
may contact the Medical Monitor to discuss evaluation and management (including 
discontinuation of a participant) of any GI symptoms throughout the trial. 
Table 5 
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, 2022].  
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), aggravating 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]. 

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Other Clinical 
Syndromes 
Additional diagnostic criteria for other GI disorders potentially 
encountered in the clinical trial are available. [Mearin, 2016; 
Stanghellini, 2016] 
PHYSICAL 
EXAMINATION 
Physical examination should complement elements obtained from 
the history [Hasler, 2022]. The exam elements may include: 
auscultation 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, 2008]. A major goal of therapy is directed at 
correcting the underlying identifiable medical or surgical 
abnormalities (e.g., perforation or infarction) [James, 2009; 
Malagelada, 2016]. Consultation (e.g., 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.  
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. 
PCR for viruses (e.g., 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 (e.g., 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 
• 
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 7.1.3). 
8.4. 
Adverse Events (AEs) serious adverse events (SAEs), and 
other safety reporting 
For definitions relating to safety information see Section 10.3 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording 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 study 
procedures, or that caused the participant to discontinue the study (see Section 7). This 
includes events reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). 
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. 

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8.4.1. 
Time period and frequency for collecting AE and SAE information 
All SAEs will be collected from the signing of the ICF until the final follow-up visit at 
the time points specified in the SoA.  
All AEs will be collected from the start of study intervention until the final follow-up 
visit at the timepoints specified in the SoA. 
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded as medical history/current medical conditions, not as 
AEs. 
All SAEs will be recorded and reported to the sponsor or designee immediately and under 
no circumstance should this exceed 24 h, as indicated in Section 10.3. The investigator 
will submit any updated SAE data to the sponsor within 24 h of it being available. 
A poststudy AE/SAE is defined as any event that occurs outside of the AE/SAE reporting 
period defined in Section 8.4.1. 
Investigators are not obligated to actively seek information on AEs or SAEs after 
conclusion of the study participation. However, if the investigator learns of any SAE, 
including a death, after a participant has been discharged from the study, the investigator 
must record it in the medical records. If the investigator considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor. 
8.4.2. 
Method of detecting AEs and SAEs  
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.4.3. 
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 resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is provided in 
Section 10.3.7.5. 
8.4.4. 
Regulatory reporting requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of 
a study intervention under clinical investigation are met. See Section 8.4.1 for reporting 
timeframes. 
For SAEs, the investigator must always provide an assessment of causality at the time of 
the initial report, as defined in the Section 10.3.7.6 

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An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
8.4.5. 
Pregnancy 
Female participants are only eligible to participate in the study if they are confirmed 
PONCBP as defined in Section 10.4). 
In the unlikely event that a female participant does become pregnant, instructions for 
pregnancy follow-up are given below. 
Female participants who become pregnant after the first study intervention dose must not 
receive subsequent doses of the study intervention but may continue other study 
procedures at the discretion of the investigator. 
Details of all pregnancies in female participants will be collected after the start of study 
intervention and until 28 days after the final dose. 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 h of learning of the female 
participant’s pregnancy. 
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 the sponsor within 24 h of the investigator becoming 
aware of it. 
Any poststudy pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 10.3. While the investigator is not obligated to actively seek this information in 
former study participants, they may learn of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention and be withdrawn from the study. 
8.4.6. 
Cardiovascular and death events 
For any CV events detailed in Section 10.3 and all deaths, whether or not they are 
considered SAEs, specific CV and Death sections of the eCRF will be required to be 
completed. These sections include questions regarding CV (including sudden cardiac 
death) and non-CV death.  

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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 CV 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. 
8.4.7. 
Disease-related events and/or disease-related outcomes not 
qualifying as AEs or SAEs 
The DREs listed in the CDC Classification System for HIV-1 Infections (Section 10.9) 
are common in participants living with HIV-1 and can be serious/life threatening: 
Because these events are typically associated with the disease under study, they will not 
be reported according to the standard process for reporting of SAEs even though the 
event may meet the definition of an SAE. These events will be recorded on the HIV-
associated conditions eCRF page if they occur, according to the timeframe defined in the 
CRF completion guidelines. These DREs will be monitored by a SRT on a routine basis. 
NOTE: However, if any of the following conditions applies, then the event must be 
recorded and reported as an AE/SAE (instead of a DRE): 
The event is, in the investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual participant. 
OR 
The investigator considers that there is a reasonable possibility that the event was related 
to study intervention. 
OR 
Death occurring for any reason during a study, including death due to a disease-related 
event, will always be reported promptly. 
OR 
Lymphomas and invasive cervical carcinomas are excluded from this exemption; they 
must be reported as SAEs even if they are considered to be HIV-related. 

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8.4.8. 
Contact information for reporting SAEs 
Table 6 
Contact information for reporting SAEs 
Contact for questions regarding SAEs, pregnancies or any other safety event that 
may meet a safety stopping criteria 
 
Contact the ViiV Healthcare medical monitor 
 
Contacts for reporting SAEs, AESIs and  pregnancies  
Available 24/24 h and 7/7 days 
uk.gsk-rd-gcsp-ctsm-admin@gsk.com  
 
8.4.9. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending physician that the 
participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator(s) or their back up. 
8.5. 
Pharmacokinetics 
• Blood samples of approximately 2 mL will be collected for measurement of blood 
concentrations of VH3739937 at the visits specified in the SoA (Section 1.3) and as 
detailed in Table 7.  
• A maximum of 10 samples may be collected at additional timepoints during the study 
if warranted and agreed upon between the investigator and the 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 
the sponsor. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• Samples will be used to evaluate the PK of VH3739937. Each blood sample will be 
processed and divided into 2 aliquots (1 each for PK and a backup). Samples 
collected for analyses of VH3739937 concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study. 
• Intervention concentration information that may unblind the study will not be 
reported to investigative sites or blinded personnel until the study has been unblinded, 
without first being anonymized. 

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• Once the plasma has been analyzed for VH3739937, any remaining plasma may be 
analyzed for other compound-related metabolites and the results reported under a 
separate protocol. 
• Intensive PK sampling (Day 1 and Day 7 
) begins with a 
pre-dose sample in the morning on the day of the visit. On Day 7, the pre-dose sample 
should be taken approximately 24 h after the dose of study intervention from the 
previous day (Day 6). 
• 
 
 
• It is critical to capture the exact date and time of each PK sample collection, even if 
drawn slightly off-schedule. If a sample collection time point is missed/late/not done 
within the specified window and the next collection time point has not yet been 
reached, collect the missed time point, and record the exact time of that collection, 
then get back on track for the next time point/on‑time collection. 
• Table 7 below lists the sampling schedule to be followed for the assessment of 
intensive PK 
  
• 
 
 
• Further details of PK blood collection and sample processing will be provided in the 
central laboratory manual. 
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8.6. 
Pharmacodynamics 
See Section 9.3.3. 
8.7. 
Genetics 
A 6 mL blood sample for DNA isolation will be collected from participants who have 
consented to participate in the genetic analysis component of the study. Participation is 
optional. Participants who do not wish to participate in the genetic research may still 
participate in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent. 
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See Section 10.5 for information regarding genetic research. Details on processes for 
collection and shipment and destruction of these samples can be found in laboratory 
manual. 
8.8. 
Biomarkers 
8.8.1. 
Viral Genotyping and Phenotyping 
Whole venous blood samples will be collected from each participant to provide plasma 
for viral genotype and phenotype analysis. Samples will be collected according to the 
schedule described in the SoA (Section 1.3) and as detailed in the laboratory manual.   
Whole venous blood samples will be collected from each participant to provide “plasma 
for storage samples” according to the schedule described in the SoA (Section 1.3; for 
potential additional viral genotypic and phenotypic analyses) and as detailed in the 
laboratory manual.  
Details concerning the handling, labeling and shipping of these samples will be supplied 
separately. Genotypic and phenotypic analyses may be carried out by Monogram 
Biosciences. 
The genotypic and phenotypic analyses will be performed by using Gag/PR assays, in 
which PCR amplification is used to generate HIV PCR amplicons including the Gag and 
the PR regions. Phenotypic analyses of the Gag/PR region will include susceptibility to 
VH3739937. Analysis will be done on samples collected on study Day 1 and Day 8 
initially with other timepoints analyzed if indicated as data emerge for viral load 
response. 
The results of any genotypic and phenotypic analyses are for research purposes only and 
will not be shared with investigators. 
GSK/ViiV Healthcare may store samples for up to 15 years after the end of the study to 
achieve study objectives or other period as per local requirements. Additionally, with 
participants consent, samples may be used for further research by GSK/ ViiV Healthcare 
or others such as universities or other companies to contribute to the understanding of 
HIV-1 Infections or related conditions, the development of related or new treatments or 
research methods. For further detail, please see Section 10.5.  
8.8.2. 
HIV-1 Exploratory Analysis 
Additional exploratory analyses for HIV-1 treatment emergent changes during the course 
of monotherapy may include viral genotyping and/or phenotyping on a representative 
subset of Baseline samples or virologic analysis on stored plasma samples from other 
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8.9. 
Immunogenicity assessments 
Not applicable 
8.10. 
Health economics or medical resource utilization and health 
economics 
Medical resource utilization and health economics parameters are not evaluated in this 
study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
The primary objective of this study is outlined in Section 3 and will be addressed using 
an estimation approach (descriptive statistics) with no hypothesis testing. The primary 
treatment effect to be estimated is the maximum change from Baseline in plasma HIV-1 
RNA over 7 days of VH3739937 treatment. 
9.2. 
Analysis sets 
Analysis Set 
Definition  
Analyses Evaluated 
Screened  
• All participants who are screened for 
eligibility 
• Study Population 
Randomized  
• All participants who are randomly assigned 
to study treatment (i.e., VH3739937 or 
placebo) in the study 
• Study Population 
Safety 
• All randomized participants who take at 
least 1 partial or full dose of study 
treatment  
• Participants will be analysed according to 
the treatment they actually received 
• Safety 
Full Analysis Set 
(FAS) 
• All randomized participants who received 
at least one full dose of study treatment 
• Data will be reported according to the 
randomized study intervention 
• Efficacy 
Per-Protocol 
(PP) 
• All participants in the full analysis set for 
whom there were no major protocol 
deviations that impact the primary 
analyses 
• Data will be reported according to the 
treatment actually received 
• Specific details of major protocol 
deviations that would exclude participants 
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Analysis Set 
Definition  
Analyses Evaluated 
from the PP analysis set are provided in 
Section 9.3.1.1 
Pharmacokinetic 
(PK) 
• All participants in the Safety analysis set 
who had at least 1 PK assessment (NQ 
values will be considered as non-missing 
values) 
• Data will be reported according to the 
actual study treatment 
• PK 
Analysis populations may be added, removed, or modified. Full details will be available 
in the final SAP. 
9.3. 
Statistical analyses 
The SAP will be finalized prior to database lock and it will include a more technical and 
detailed description of the statistical analyses described in this section. This section is a 
summary of the planned statistical analyses of the most important endpoints including 
primary and key secondary endpoints. 
9.3.1. 
General considerations 
Data will be summarized by dose for VH3739937 and placebo, unless otherwise 
specified. 
Data will be summarized either by visit or for the study intervention period and overall 
(i.e., study intervention period plus cART period) separately, as appropriate for each 
endpoint.  
For all endpoints, except for ECG, the baseline value will be the latest pre-dose 
assessment with a non-missing value, including those from unscheduled visits. Day 1 
pre-dose ECGs will be performed in triplicate and the average of pre-dose triplicate 
measurements will be used as baseline. 
Continuous and categorical variables will be summarized using the following descriptive 
statistics, unless otherwise specified: 
• Continuous data: n (number of participants used for the summary), arithmetic 
mean, SD, median, interquartile range, minimum and maximum. For PK data, 
geometric mean, SD of log-transformed data and geometric %CVb may also be 
used. 
• Categorical data: number and percentage of participants 
9.3.1.1. 
Protocol Deviations leading to exclusion from PP analysis set 
The SAP will describe the important protocol deviations leading to exclusion from the 
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9.3.2. 
Primary endpoint/estimand analysis 
Plasma HIV-1 RNA values will be used for the primary efficacy analysis. Change from 
Baseline will be calculated for each participant at each assessment time point during the 
study intervention period in the original and log10 scales. Maximum change from 
baseline during the study intervention period will be calculated for each participant from 
the set of available change from Baseline values at each assessment time point in the 
original and log10 scales. The log10 transformation is used to allow for direct 
comparisons with data from other compounds publicly available in the same scale, and 
hence aid in interpretation. 
9.3.2.1. 
Definition of endpoint(s)/estimands 
See Section 3 for definition of primary endpoint and estimand. 
9.3.2.2. 
Main Analytical Approach 
The primary efficacy analysis will be based on the FAS.  
Maximum change from baseline in plasma HIV-1 RNA during study intervention period 
will be summarized by treatment (i.e., VH3739937) and dose level, and collectively for 
placebo, in original and log10 scales.  
In addition, change from Baseline in plasma HIV-1 RNA at each assessment time point 
during study intervention period will be summarized by treatment, i.e., VH3739937 dose 
level, and collectively for placebo, in original and log10 scales. 
Descriptive statistics will be provided as described in Section 9.3.1. 
Handling of missing data and Intercurrent Events leading to exclusion of data 
Any missing HIV-1 RNA data (e.g., due to missed visits in the clinic, lost to follow-up or 
for any other reason) will not be imputed and will remain missing. Whatever HIV-1 RNA 
data are available for a participant during study intervention and prior to starting cART 
will be used to calculate maximum plasma HIV-1 RNA. 
Participants who withdraw from study prior to the end of study intervention period, 
preventing assessment of primary endpoint, no imputation will be performed for missed 
assessments after their study withdrawal. 
9.3.2.3. 
Supplementary/supportive analysis/analyses 
A supplementary analysis will be conducted to summarize maximum change from 
Baseline and change from Baseline by visit in plasma HIV-1 RNA based on the PP 
Analysis set. 
Additional analyses may be conducted, including borrowing historical or contemporary 
placebo control data.  Details of any of these analyses will be included in PDAP. 

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9.3.3. 
Secondary endpoint analyses 
See Section 3 for definition of secondary endpoints and estimands. 
9.3.3.1. 
Safety Analysis 
All safety analyses will be performed on Safety Analysis set. Safety data will be 
presented in tabular format and summarized descriptively according to GSK’s IDSL. No 
formal statistical analysis of the safety data will be conducted. 
9.3.3.1.1. Analysis Method 
The number and proportion of participants with AEs will be tabulated overall and by 
severity grade, by treatment and dose level. The number and proportion of participants 
with AEs leading to discontinuation of VH3739937 or placebo will also be tabulated. In 
AE tabulations, each participant’s AE will be counted once under the maximum severity. 
AEs will be tabulated using latest version of MedDRA preferred terms. AEs will be 
tabulated for the study intervention period and overall (i.e., study intervention period plus 
SOC period) separately.  
For liver panel laboratory parameters, summary statistics (e.g., mean, median, std etc.) of 
change from Baseline values by visit will be presented by treatment and dose level. 
Number and percentage of participants with maximum toxicity grade increase from 
Baseline for liver panel parameters will be presented by treatment and dose level; this 
will be done separately for the study intervention period and overall (i.e., study 
intervention period plus SOC period). 
Handling of missing data and Intercurrent Events leading to exclusion of data 
All available safety data will be considered in summaries of AEs and liver panel 
laboratory parameters within the respective period (e.g., study intervention or 
intervention plus SOC) regardless of whether study treatment was discontinued. 
No imputation will be performed for missed assessments while participants are on study 
or after study withdrawal. 
9.3.3.2. 
Pharmacokinetic Analyses 
All pharmacokinetic analyses will be performed on the Pharmacokinetic analysis set. 
9.3.3.2.1. Analysis Method 
Plasma VH3739937 concentration-time data will be analyzed by non-compartmental 
methods with WinNonlin 8.1 or higher, Phoenix (Pharsight Corporation) or comparable 
software to derive the PK parameters. This analysis will be based on actual sampling 
times recorded during the study. The various PK parameters will be inferred as data 
permits. Individual plasma PK parameters for each participant will be determined, 
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Plasma concentrations will be presented in graphical form and will be summarized 
descriptively by treatment (i.e., VH3739937) and dose level. PK parameters will be 
summarized descriptively by treatment (i.e., VH3739937) and dose level. Descriptive 
summaries will be used as described in Section 9.3.1. 
The data from this study may be combined with the data from other studies for a 
population PK analysis, which may be reported separately. 
Handling of missing data and Intercurrent Events leading to exclusion of data 
VH3739937 plasma concentrations and PK parameters derived after discontinuation of 
VH3739937 will be excluded from descriptive summaries.  
More information on the handling of PK concentrations after partial/missed VH3739937 
doses when summarizing trough (pre-dose) concentrations by visit will be provided in the 
SAP.  
No imputation will be performed for missed plasma concentrations and PK parameters 
while on study or after study withdrawal. 
9.3.4. 
Exploratory endpoint(s) analysis 
Details on the analyses of exploratory endpoints and other analyses will be included in 
the SAP.  
9.4. 
Interim analyses 
An informal interim analysis will be conducted using available preliminary unvalidated 
in-stream unblinded clinical data once all participants (to include a minimum of 
5 participants per active arm and 2 placebo participant) from Part 1 have, at a minimum, 
completed their Day 8 visit. GSK/ViiV Healthcare CPMS (and associates) may be 
provided individual participant level plasma drug concentration and viral load 
information at one or more time points prior to all participants in Part 1 having completed 
their Day 8 visit, to refine the population PK model and develop a PK/PD model that will 
be used to explore the exposure-response relationship between PK and viral load to 
determine whether additional doses need to be evaluated in optional Part 2 of the study.  
The interim analyses will evaluate the PK and PD (antiviral activity) of each respective 
VH3739937 dose and inform if additional optional dosing arm(s) for VH3739937 will be 
evaluated in Part 2. Depending on the Part 1 results, a higher dose, lower dose, or a dose 
between the 2 QD doses evaluated in Part 1 may be evaluated in Part 2, 
 
. It is also possible that Part 2 will not be 
conducted if the doses evaluated in Part 1 adequately describe the exposure response of 
VH3739937. The interim results will also inform future clinical development of 
VH3739937. 
The interim results are not intended for public dissemination. Criteria for data quality for 
data used in the interim analyses will be described in the study data management plan. 
Throughout the conduct of the study ViiV Healthcare/GSK (and associates) will be 
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blinded to the assignment for individual participants except for key roles necessary to 
prepare for and conduct the interim analyses. These roles will minimally include the 
clinical lead physician/medical monitor, safety physician/scientist, team lead, statistician, 
programmer, clinical pharmacologist(s), modeller(s) and clinical virologist who will have 
access to unblinded data. Moreover, unblinded data may be shared with GSK/ViiV 
Healthcare Medical Governance Committees (at their request and consistent with internal 
SOPs).  
After the interim analysis, a final EoS analysis will be conducted after the completion of 
the study (i.e., when all participants complete the Day 25 visit, discontinue or are 
withdrawn) and final datasets authorization. At the EoS analysis all primary, secondary 
and exploratory endpoints will be evaluated with the exception of viral resistance and any 
exposure-responses analyses, which will be evaluated at a later stage and reported 
separately. 
Additional interim analyses may be performed during the course of the study to inform 
internal decision-making activities. No changes to the conduct of the study will be 
implemented as a result of these analyses. 
9.5. 
Sample size determination 
The sample size is based on feasibility and no formal calculation of power or sample size 
has been performed.  
9.5.1. 
Sample Size Considerations 
Based on data from the short-term monotherapy study of the BMS-955176/GSK3532795 
proof of concept study (AI468002), the GSK2838232 proof of concept study, and the 
GSK3640254 proof of concept study (208132), the distribution of maximum change from 
baseline VLD values on the log scale can be assumed to be normal.  
Assuming normality, the sample size of N=6 participants per intervention cohort allows 
estimation of the mean maximum VLD in log10 scale with precision shown on Table 9 
shows the expected precision of the estimated mean maximum VLD in log10 scale 
measured by the 95% CI width for various observed data variability assumptions as 
reflected by the sample SD. 
Table 9 
Expected precision (measured by the 95% CI width) of the estimated 
mean of maximum VLD in log10 scale for various assumptions of 
observed data variability for N = 6 participants 
 
Sample SD 
Precision 
(95% CI Upper Limit) 
0.40 
0.84 
0.50 
1.05 
0.65 
1.36 
0.80 
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9.5.2. 
Sample Size Sensitivity 
To evaluate study’s sensitivity to sample size we calculated the expected precision of the 
estimated mean of maximum VLD in log10 scale for a treatment intervention for various 
sample sizes. Figure 3 shows the expected precision, measured by the 95% CI width, of 
the estimated mean maximum VLD in log10 scale for various sample sizes for a 
treatment intervention and various assumptions on the observed data variability (reflected 
by the sample SD). 
Figure 3 
Expected precision (measured by the 95% CI width) of the estimated 
mean of maximum VLD in log10 scale for various assumptions on 
observed data variability and sample size 
 
Figure 3 shows how the expected precision of the estimated mean of the maximum log10 
VLD changes with an increase in the sample size for various observed data variabilities 
(measured by the sample standard deviation) within an active arm. Figure 3 indicates a 
smaller gain in the expected precision for increases of sample size beyond N=6 relative to 
gain in the expected precision up to N=6. For example, for observed data variability 
SD=0.65, increasing the sample size from N=4 participants to N=6 the precision of the 
estimated mean increases by 34%, whereas increasing the sample size from N=6 to N=8 
the precision increases only by 20%. Of note, a much higher sample size is needed to 
achieve significant gains in precision, especially for smaller observed data variability. For 
example, for observed data variability SD=0.65, to get a ~40% more precise estimate of 
the mean maximum VLD a sample size of N=12 participants is needed. So, a sample size 
of N=6 participants per intervention cohort was considered appropriate for the study. 

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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 the following: 
o 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS international ethical guidelines 
o 
Applicable ICH GCP guidelines 
o 
Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated.  
• Substantial amendments to the protocol (or non-substantial amendments where local 
regulations require) will require IRB/IEC 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, as applicable: 
o 
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/IEC 
o 
Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures 
o 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 

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10.1.3. 
Informed consent process 
• The investigator or the investigator’s representative will explain the nature of the 
study, including the risks and benefits, to the participants and answer all questions 
regarding the study. 
• Potential participants must be informed that their participation is voluntary. They will 
be required to physically or digitally sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, HIPAA 
requirements, privacy and data protection requirements, where applicable, and the 
IRB/IEC or study center. 
• The medical record must include a statement that physical or digital informed consent 
was obtained before the participant was enrolled in the study and the date the physical 
or digital consent was obtained. The authorized person obtaining the informed 
consent must also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
• A physical or digital copy of the ICF(s) must be provided to the participant. 
• Participants who are rescreened are required to sign a new ICF. 
• ViiV Healthcare / GSK (alone or working with others) may use participants’ coded 
study data and samples and other information to carry out this study; understand the 
results of this study; learn more about VH3739937 or about the study disease; publish 
the results of these research efforts; work with government agencies or insurers to 
have VH3739937 approved for medical use or approved for payment coverage. 
• The ICF will contain a separate section that addresses the use of participant data and 
remaining samples for optional further research either related to the study or for other 
research not related to the study/disease. The investigator or authorized designee will 
inform each participant of the possibility of further research not related to the 
study/disease. Participants will be told that they are free to refuse to participate and 
may withdraw their consent at any time and for any reason during the storage period. 
A separate signature will be required to document a participant's agreement to allow 
any participant data and/or remaining leftover samples to be used for further research 
related to the study and for further research not related to the study/disease. 
Participants who decline further research related to the study and/or not related to the 
study/disease will tick the corresponding “No” boxes. 
• In case of unexpected pregnancy, participant must be informed that PII such as date 
of birth, sex of the baby will be collected as part of safety follow-up. Consent for the 
baby may be obtained from the participant.  
10.1.4. 
Recruitment strategy 
Approximately 50 participants will be screened globally, with the expectation of 
approximately 20 being enrolled into Part 1 of the study. Should Part 2 be required, 
approximately a further 50 participants will be screened, with the expectation of 
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has been evaluated to determine the most suitable countries and sites to recruit the study 
population. Considerations have also been given to diversity targets and local availability 
of SOC treatment for participants from Day 8 onwards. 
Recruitment will be monitored by GSK/ViiV Healthcare LOCs using real time 
monitoring of screening and enrolment information.  
Recruitment will primarily be performed by the Investigators from their existing patient 
population. 
If a study site considers it may be beneficial, IRB/IEC approved advertisements may be 
placed in public areas of the study site i.e., waiting rooms in order to increase awareness 
of the study. 
10.1.5. 
Data protection 
• Participants will be assigned a unique identifier by the investigator. 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. 
• GSK/ViiV Healthcare will ensure protection of the personal data of the investigator 
and site staff which is collected within the framework of and for the purpose of the 
study. 
• The participant must be informed that their 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, that their data will be used as described in 
the informed consent. 
• The participant must be informed that their 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. 
• The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure or 
access. GSK/ViiV Healthcare and/or trusted third parties working on behalf of 
GSK/ViiV Healthcare and/or institutions working with GSK/ViiV Healthcare for the 
purposes of this study are contractually bound to protect participant coded data. GSK 
will protect participant coded data and will only share it as described in the ICF. 
10.1.6. 
Committees structure 
A SRT is in place for each GSK/ViiV Healthcare product. It comprises of a global cross-
functional team responsible for the ongoing assessment of benefit-risk for a product. The 

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SRT contribute to the continual assessment of incoming new efficacy and safety 
information.  
• All safety data collected will be summarized and reviewed by GSK/ViiV Healthcare 
SRT for agreement of next steps. 
• The SRT is an internal ViiV Healthcare/GSK requirement put in place to ensure 
holistic evaluation of the safety profile of an investigational product with systematic, 
periodic and documented reviews of available safety data, with the appropriate 
communication and escalation of new findings that have the potential to impact 
patient safety. 
• In particular, data will be reviewed by the sponsor for identification of the following 
events that would potentially contribute to a requirement to pause/stop the study.  
o Any deaths, regardless of causality 
o Adverse events and laboratory abnormalities as cited in Section 7.3 
'Discontinuation of Study Intervention' 
• Case unblinding may be performed for above reviews if this is considered necessary.  
In addition, data from Part 1 will be reviewed by the Sponsor’s internal safety review or 
other committee in order to determine whether initiation of enrollment into Part 2 of the 
study is required to address the primary objective of the study. Data will be reviewed 
once all participants in Part 1 have completed Day 8/Clinic Visit 6 and will include all 
available safety and virology data, together with PK data up to Day 8. 
10.1.7. 
Dissemination of Clinical Study Data 
• The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or ViiV Healthcare Clinical Study Register in 
compliance with applicable regulations/ViiV Healthcare policy. ViiV Healthcare will 
aim to register protocols summaries prior to study start and target results summaries 
submission within 12 months of primary/ study completion date. Where external 
regulations require earlier disclosure, ViiV Healthcare will follow those timelines.  
• Where required by regulation, summaries will also be posted on applicable national 
or regional clinical study registers. 
• Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. ViiV Healthcare will also provide the 
investigator with the full summary of the study results, including a summary of trial 
results understandable to laypersons. The investigator is encouraged to share the plain 
language summary with the study participants, as appropriate. The full study report 
will be made available upon request, after decision on marketing authorization by 
regulatory authorities.   
• ViiV Healthcare will provide the investigator with the randomization codes and 
participant-level line listings for their site only after completion of the full statistical 
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• ViiV Healthcare intends to make anonymized participant-level data from this study 
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 study participants are used to maximum effect in the creation of 
knowledge and understanding. 
10.1.8. 
Data quality assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRFs 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 eCRFs will be provided in eCRF completion guidelines. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents. 
• QTLs will be predefined in the QTL plan or equivalent document to identify 
systematic issues that can impact participant right, safety and/or reliability of study 
results. These predefined parameters will be monitored during the study, and 
important deviations from the QTLs and remedial actions taken will be summarized 
in the CSR. 
• 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, 
involvement of central reading mechanism) methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, remote, or on-site monitoring) are provided in the monitoring plan or 
equivalent document. 
• The sponsor or designee is responsible for the data management of this study, 
including quality checking of the data. 
• The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• 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 CSR/ 
equivalent summary unless local regulations or institutional policies require a 
different 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.  
10.1.9. 
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 
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• Data reported on the eCRF 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. 
• The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• The sponsor or designee will perform monitoring 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. 
10.1.10. 
Study and site start and closure 
Start of study and first act of recruitment 
The start of study and the first act of recruitment are defined as FSFV (first ICF signature 
date) at a country-level. 
Study/Site Termination 
GSK/ViiV Healthcare or designee reserves the right to close the study site or terminate 
the study at any time for any reason at the sole discretion of GSK/ViiV Healthcare. Study 
sites will be closed upon study completion. A study site is considered closed when all 
required documents and study supplies have been collected and a study-site closure visit 
has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
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 (evaluated after a reasonable amount of time) of 
participants by the investigator 
• Total number of participants included earlier than expected 

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If the study is prematurely terminated or temporarily 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 
temporary 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. 
10.1.11. 
Publication policy 
The results of this study may be published in peer reviewed scientific literature and/or 
presented at scientific meetings. The sponsor will comply with the requirements for 
publication of study results in accordance with standard editorial and ethical practice and 
as per the sponsor’s internal policy. Authorship will be determined by mutual agreement 
and in line with ICMJE authorship requirements. 
10.2. 
Appendix 2: Clinical laboratory tests 
• The tests detailed in Table 10 will be performed by the central laboratory. 
• Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration and/or 
response evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time. Additionally, if the local laboratory 
results are used to make either a study intervention decision or response evaluation, 
the results must be recorded in the eCRF. 
• Protocol-specific requirements for inclusion or exclusion of participants 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. 
• Investigators must document their review of each laboratory safety report. 
Table 10 
Protocol-required safety laboratory tests  
Hematology 
Platelet count  
Automated WBC differential: 
RBC count 
Neutrophils 
WBC count (absolute)  
Lymphocytes 
Hemoglobin 
Monocytes 
Hematocrit 
Eosinophils 
MCV 
Basophils 
Clinical Chemistrye 
BUN 
Potassium 
AST  
Total and direct bilirubin 
Creatinine 
Chloride 
ALT  
Albumin  
Glucosea 
Cystatin C 
Alkaline phosphatase 
Creatine phosphokinase 
Sodium 
Lipase 
Phosphate 
eGFRb 
Calcium 
GGT 
Protein 
Lipid profilea (Total 
cholesterol, HDL, LDL, 
Triglycerides) 

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Routine Urinalysis 
Specific Gravity 
pH 
Glucose 
Protein 
Blood 
Ketones 
Bilirubin 
Urobilinogen 
Nitrite 
Leukocyte 
esterase by 
dipstick 
 
 
Microscopic examination if blood or protein is abnormal 
Other Tests 
Plasma HIV-1 RNA 
CD4+ and CD8+ cell count 
Serology: HIV antibody, HbsAg, anti-HBc, anti-HBs and HBV DNA (by PCR) if indicated, and 
hepatitis C antibody, with reflex to HCV RNA (by PCR) if positive (Screening)d 
Syphilis RPR 
Urine drug screen (to include at a minimum amphetamines, barbiturates, cocaine, opiates, 
marijuana, heroin, cannabinoids and benzodiazepines, buprenorphine, fentanyl, methadone) 
Follicle stimulating hormone (FSH) and estradiol (only for instances when postmenopausal 
status is questionable) 
a) Glucose and lipid profile can be non-fasting except on Days 1, 8 and 25, as indicated in Section 1.3.  
b) Glomerular filtration rate (eGFR) will be estimated by the central laboratory using the refitted, race-neutral 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R) method [Delgado, 2022]. In addition, GFR 
will be estimated by the central laboratory using the refitted, race-neutral CKD-EPI-cystatin C [Delgado, 2022] 
at Day 1 and when indicated by renal toxicity criteria. 
c) 
For fasting lipids assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments. 
d) HBV DNA will only be performed for participants with a positive anti-HBc and negative HbsAg and negative 
anti-HBs (past and/or current evidence). 
e) Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1.1 and Section 10.6. In addition, the laboratory may perform 
Hepatitis E IgM and Cytomeglavirus IGM if required in the event of a liver event. All events of ALT 3 × upper 
limit of normal (ULN) and total bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and INR >1.5, if INR 
measured, which may indicate severe liver injury (possible Hy’s law), must be reported to GSK/ViiV Healthcare 
in an expedited manner (excluding studies of hepatic impairment or cirrhosis). 
f) 
Laboratory tests for eligibility may be performed by local laboratory in exceptional circumstances, however, 
central laboratory samples must also be collected at the screening visit. The results of each test used for 
eligibility must be entered in the eCRF. 
The addresses of the clinical laboratories in charge of human biological sample testing 
are provided in a separate document (‘List of clinical laboratories used for human 
biological sample analysis’) and stored in TMF at the time of the protocol finalization. 

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10.3. 
Appendix 3: AEs and SAEs: 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 condition 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. 
• Events that occur as a result of protocol-mandated procedures (i.e. invasive 
procedures, modification of participant’s previous therapeutic regimen). 
• "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 that 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, admission for routine examination.). 
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. Pre-existing diseases will be 
recorded in the medical history section of the eCRF. 
Hospitalization for elective treatment of a pre-existing condition (known or diagnosed 
before signing the informed consent) that did not worsen from baseline. 
DRE typically associated with the disease under study. These events will be recorded 
in the participant’s eCRF and will be monitored by the SRT on a routine basis. 
However, if 1 or both of the following conditions apply, then the event should be 
reported promptly to GSK as an SAE (see Section 8.4.8): 
The event is, in the investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual participant, or 
The investigator considers that there is a reasonable possibility that the event was 
related to the administration of the study intervention 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets 
one or more of the criteria listed: 
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 

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An SAE is defined as any untoward medical occurrence that, at any dose, meets 
one or more of the criteria listed: 
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 conduct 
normal life functions. 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) that may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant 
f. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) 
g. Other situations: 
Possible Hy’s Law case: ALT ≥ 3x ULN AND total bilirubin ≥ 2x ULN (>35% direct 
bilirubin) or 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. 
Solicited events  
Definition of solicited event 
There are no solicited AEs in this study  
10.3.4. 
Unsolicited AE  
Definition of unsolicited AE 
An unsolicited AE is an AE that was not solicited using a participant diary and that is 
communicated by a participant who has signed the informed consent. Unsolicited AEs 
include serious and nonserious AEs. 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare provider). 

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Definition of unsolicited AE 
The participants will be instructed to contact the site as soon as possible to report 
medically attended event(s), as well as any events that, though not medically attended, 
are of participant concern. Detailed information about reported unsolicited AEs will be 
collected by qualified site personnel and documented in the participant’s records. 
Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during an interview with the participants and by review of 
available medical records at the next visit. 
10.3.5. 
Definition of CV events  
CV definition: 
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs: 
Myocardial infarction/unstable angina 
Congestive heart failure 
Arrhythmias 
Valvulopathy 
Pulmonary hypertension 
Cerebrovascular events/stroke and transient ischemic attack 
Peripheral arterial thromboembolism 
Deep venous thrombosis/pulmonary embolism 
Revascularization 
10.3.6. 
Definition of TEAE 
TEAE Definition: 
A TEAE is an event that emerges during treatment, having been absent pre-treatment 
or worsens relative to the pre-treatment state. 
10.3.7. 
Recording, assessment and follow-up of AE, SAE, and 
pregnancies  
10.3.7.1. 
AE and SAE recording 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
The investigator will then record all relevant AE/SAE information. 

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It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the Sponsor in lieu of completion of the eCRF/required form. 
There may be instances when copies of medical records for certain cases are requested by 
the Sponsor. In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to the 
Sponsor. 
The investigator will attempt to 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. 
10.3.7.2. 
Assessment of intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to one of the following categories according to the DAIDS 
toxicity scales (refer to Section 10.8). 
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 one of the severity 
categories described in the functional DAIDS table shown in Section 10.8. 
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE. 
Note: Grade 4 DAIDS toxicity grades for laboratory parameters that are asymptomatic 
would not necessarily be considered SAEs, a clinical correlation would be necessary. 
10.3.7.3. 
Assessment of causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. 
A reasonable possibility of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
For causality assessment, the investigator will also consult the IB and/or product 
information, for marketed products. 
The investigator must review and provide an assessment of causality for each AE/SAE 
and document this in the medical notes There may be situations in which an SAE has 
occurred and the investigator has minimal information to include in the initial report to 
the 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 
the Sponsor. 

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The investigator may change their 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. 
10.3.7.4. 
Assessment of outcomes 
The investigator will assess the outcome of all serious and nonserious unsolicited AEs 
recorded during the study as: 
Recovered/resolved 
Recovering/resolving 
Not recovered/not resolved 
Recovered with sequelae/resolved with sequelae 
Fatal (SAEs only). 
10.3.7.5. 
Follow-up of AEs, SAEs, pregnancies or any other events of interest  
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor 
to elucidate the nature 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 the Sponsor with a copy of any postmortem findings 
including histopathology. 
New or updated information will be recorded in the originally submitted documents. 
The investigator will submit any updated SAE data to the Sponsor within 24 h of receipt 
of the information. 
After the initial AE/SAEpregnancy or any other event of interest, the investigator is 
required to proactively follow each participant at subsequent visits/contacts. All SAEs (as 
defined in the Section 10.3.2), will be followed until the event is resolved, stabilized, 
otherwise explained, or the participant is lost to follow-up. 
Other nonserious AEs must be followed until the last study visit or until the participant is 
lost to follow-up. 
Follow-up during the study 
AEs documented at a previous visit/contact and defined as not recovered/not resolved or 
recovering/resolving will be reviewed at subsequent visits/contacts until the last study visit. 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available postmortem findings, including 
histopathology. 

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Follow-up of pregnancies 
Pregnant participants will be followed to determine the outcome of the pregnancy. At the 
end of the pregnancy, whether full-term or premature, information on the status of the 
mother and child will be forwarded to GSK using the paper or electronic pregnancy 
follow-up report and the AE Report if applicable. Generally, the follow-up period does 
not need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, the investigator must report any SAE occurring as a result of a poststudy 
pregnancy that is considered by the investigator to be reasonably related to the study 
intervention, to GSK as described in the Section 10.3.7.7. 
10.3.7.6. 
Updating of SAE and pregnancy information after removal of write 
access to the participant’s eCRF 
When additional SAE or pregnancy information is received after write access to the 
participant’s eCRF is removed, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be sent to the Study contact for reporting SAEs (refer to Section 
8.4.3). 
10.3.7.7. 
Reporting of SAEs and pregnancies  
SAE Reporting to the Sponsor via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to the 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) to report the event within 24 h. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken offline 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 offline, then the site can report this information on a paper SAE 
form (see next section) or to the medical monitor by telephone. 
• If the site during the course of the study or poststudy becomes aware of any 
serious, nonserious AEs, pregnancy exposure, related to any ViiV 
Healthcare/GSK non-IMP they will report these events to ViiV Healthcare/GSK 
or to the concerned competent authority via the national spontaneous reporting 
system.  These will be classified as spontaneous ICSRs. 

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• Contacts for SAE reporting can be found in Section 8.4.8. 
SAE Reporting to the Sponsor via Paper Data Collection Tool 
• Email/facsimile transmission of the SAE paper data collection tool is the 
preferred method to transmit this information to the Sponsor. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting 
timeframes. 
• Contacts for SAE reporting can be found in Section 8.4.8. 
10.4. 
Appendix 4: Contraceptive and barrier guidance 
10.4.1. 
Definitions 
10.4.1.1. 
 Person of Nonchildbearing Potential (PONCBP) 
Participants who were female at birth and are in the following categories are considered 
PONCBP: 
• Premenarchal: Tanner stage 1 (prepubertal) 
Permanently sterile due to one of the following procedures: 
a. Documented hysterectomy 
b. Documented bilateral salpingectomy 
c. 
Documented bilateral oophorectomy 
For permanently sterile individuals 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. If reproductive 
status is questionable, additional evaluation should be considered. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
• Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
A high FSH level in the postmenopausal range may be used to confirm a postmenopausal 
state in women not using hormonal contraception or HRT. However, in the absence of 
12 months of amenorrhea, confirmation with more than one FSH measurement is 
required. 
Females on HRT and whose menopausal status is in doubt must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment. 

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10.4.2. 
Contraception guidance 
Not applicable 
10.5. 
Appendix 5: Genetics 
Use/Analysis of DNA 
• 
Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and 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 from consenting participants. 
• 
DNA samples will be used for research related to VH3739937 or HIV-1 infection 
and related diseases. They may also be used to develop tests/assays, including 
diagnostic tests related to VH3739937 or interventions of this drug class and HIV-1 
infection. 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). 
• 
Additional analyses of DNA samples may be conducted 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 VH3739937 or study interventions of this class to 
understand the study disease or related conditions. 
• 
The results of genetic analyses may be reported in the CSR 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 VH3739937 or study interventions of 
this class or indication continues but no longer than 15 years or other period as per 
local requirements. 
10.6. 
Appendix 6: Liver safety: suggested actions and follow-up 
assessments 
Phase 2 Liver chemistry stopping and increased monitoring criteria have been 
designed to assure participant safety and evaluate liver event etiology  
Phase 2 Liver Chemistry Stopping Criteria and Required Follow-Up Assessments  
Liver Chemistry Stopping Criteria  
ALT-absolute 
ALT 3xULN 

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 Bilirubin1, 2 
ALT 3xULN and total bilirubin 2xULN (>35% direct bilirubin) 
INR2 
ALT 3xULN and INR>1.5 
Required Actions, Monitoring and Follow-up Assessments  
Actions 
Follow-Up Assessments 
• Immediately discontinue study 
intervention  
• Report the event to GSK within 24 h 
• Complete the liver event form and 
complete an SAE data collection tool if 
the event also meets the criteria for an 
SAE2 
• Perform follow-up assessments as 
described in the Follow-Up Assessment 
column.  
• Monitor the participant until liver 
chemistries resolve, stabilize, or return 
to within baseline (see MONITORING 
below) 
MONITORING: 
If ALT 3xULN AND total bilirubin 2xULN 
or INR >1.5:  
• Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total 
bilirubin and INR) and perform liver 
event follow-up assessments within 24 h 
• Monitor participant twice weekly until 
liver chemistries resolve, stabilize or 
return to within baseline  
• A specialist or hepatology consultation 
is recommended 
For all other stopping criteria (total bilirubin 
<2xULN and INR 1.5):  
• Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total 
bilirubin and INR) and perform liver 
event follow-up assessments within 24-
72 h  
• Viral hepatitis serology4 
• Obtain INR and recheck with each liver 
chemistry assessment until the 
aminotransferases values show downward 
trend 
• Obtain blood sample for PK analysis, 
obtained within 60 h after last dose5 
• Obtain serum creatine phosphokinase 
(CPK), lactate dehydrogenase (LDH), ), 
gamma-glutamyltransferase [GGT], 
glutamate dehydrogenase [GLDH], and 
serum albumin. 
• Fractionate bilirubin, if total 
bilirubin2xULN 
• Obtain complete blood count with 
differential to assess eosinophilia 
• Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the liver event form 
• Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, recreational drugs, and other 
over-the-counter medications. 
• Record alcohol use on the liver event 
alcohol intake form. 
If ALT 3xULN AND total bilirubin 2xULN or 
INR >1.5 obtain the following in addition to the 
assessments listed above:  
• Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins. 
• Serum acetaminophen adduct assay 
should be conducted (where available) to 

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• Monitor participant weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
 
 
RESTART/RECHALLENGE 
• Do not restart/rechallenge participant 
with study intervention since not allowed 
per protocol; continue participant in the 
study for any protocol-specified follow-
up assessments. 
assess potential acetaminophen 
contribution to liver injury unless 
acetaminophen use very unlikely in the 
preceding week (e.g., where the 
participant has been resident in the clinical 
unit throughout).  
• Liver imaging (ultrasound, magnetic 
resonance, or computed tomography) to 
evaluate liver disease; complete Liver 
Imaging form. 
• Liver biopsy may be considered and 
discussed with local specialist if available: 
o In participants when serology raises 
the possibility of autoimmune hepatitis 
(AIH) 
o In participants when suspected DILI 
progresses or fails to resolve on 
withdrawal of study intervention 
o In participants with acute or chronic 
atypical presentation 
• If liver biopsy conducted complete liver 
biopsy form 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin 
fractionation is not immediately available, discontinue study intervention for subject if ALT 
≥3xULN and total 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 total bilirubin ≥2xULN (>35% direct bilirubin) or ALT 
≥3xULN and INR>1.5, which may indicate severe liver injury (possible ‘Hy’s Law’), must 
be reported as an SAE (excluding studies of hepatic impairment or cirrhosis); the INR 
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. Includes: hepatitis A Immunoglobulin M (IgM) antibody; HbsAg and HBcAb ; hepatitis 
CRNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if 
unavailable, obtain heterophile antibody or monospot testing); hepatitis E IgM antibody  
5. Record the date/time of the PK blood sample draw and the date/time of the last dose of study 
intervention prior to pk 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 laboratory 
manual 

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10.7. 
Appendix 7: Toxicity Management 
Adverse events that occur during the study 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. 
Study drug may  be interrupted at the discretion of the investigator and according to the 
severity of the AE.  
No toxicity-related dose reductions of study drugs will be allowed. Guidance is provided 
below on subject management and study drug interruptions based on the severity of the 
AE for specific toxicities. All changes in study drug must be accurately recorded in the 
participant’s eCRF.  
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 or toxicity that the investigator considers related 
to the study drugs should have study treatment permanently discontinued and be 
rechecked each week (at minimum) until the resolution of the AE .  
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. 
Grade 4 Toxicity/Adverse Event 
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. 
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). 

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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 7.1.1 and Section 10.6. 
Hypertriglyceridemia/Hypercholesterolemia 
Samples for lipid measurements must be obtained in a fasted state according to the SoA 
(see Section 1.3). Participants who experience asymptomatic triglyceride or cholesterol 
elevations may continue to receive study drug.  
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 subject has 
abstained from exercise for >24 h. For persistent Grade 4 CPK elevations that are 
considered possibly or probably related to the study drugs, study treatment should be 
discontinued and the subject withdrawn from the study 
RASH 
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 with evidence of 
systemic involvement (e.g. concurrent fever, an increase in AST/ALT or eosinophilia). 
The participant should be advised to contact the physician immediately if rash fails to 
resolve (after more than two weeks), if there is any worsening of the rash, if any systemic 
signs or allergic symptoms develop, or if mucosal involvement develops (which would 
indicate a Grade 3 rash, at minimum). 
Grade 3 or 4 rash  
Participants should permanently discontinue study drug (and all other concurrent 
medication(s) suspected in the Investigators causality assessment) for a related Grade 3 
or any Grade 4 rash. 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. 

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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). 
10.8. 
Appendix 8: Division of AIDS (DAIDS) table for grading the 
severity of adult and pediatric adverse events 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 utilized 
for AE reporting. A grading (severity) scale is provided for each AE term. The 
investigator will make an assessment of intensity for each AE and SAE reported during 
the study. For more information, please refer to the DAIDS grading table Version 2.1, 
July 2017 at (https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf). 
The Investigator may contact the ViiV Healthcare Medical Monitor with questions on 
estimating the severity grade for parameters not identified in the original table. 
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 
ESTIMATING SEVERITY GRADE 
Clinical adverse 
event NOT identified 
elsewhere in this 
DAIDS AE Grading 
Table  
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Symptoms 
causing inability 
to perform basic 
self-care 
functions OR 
Medical or 
operative 
intervention 
indicated to 
prevent 
permanent 
impairment, 
persistent 
disability, or 
death  

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
SYSTEMIC 
Acute systemic 
allergic reaction  
Localized 
urticaria 
(wheals) with 
no medical 
intervention 
indicated 
Localized urticaria 
with medical 
intervention 
indicated OR Mild 
angioedema with 
no medical 
intervention 
indicated 
Generalized 
urticaria OR 
Angioedema with 
medical 
intervention 
indicated OR 
Symptomatic mild 
bronchospasm 
Acute 
anaphylaxis OR 
Life-threatening 
bronchospasm 
OR laryngeal 
edema 
Chills 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities  
Symptoms causing 
inability to perform 
usual social & 
functional activities 
NA 
Fatigue 
Malaise 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Incapacitating 
fatigue/ malaise 
symptoms 
causing inability 
to perform basic 
self-care 
functions 
Fever (nonaxillary) 
37.7 – 38.6C 
38.7 – 39.3C 
39.4 – 40.5C 
>40.5C  
Pain (indicate body 
site) 
DO NOT use for pain 
due to injection (See 
Injection Site 
Reactions: Injection 
site pain) 
See also Headache, 
Arthralgia, and 
Myalgia 
Pain causing no 
or minimal 
interference 
with usual 
social & 
functional 
activities 
Pain causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Pain causing 
inability to perform 
usual social & 
functional activities 
Disabling pain 
causing inability 
to perform basic 
self-care 
functions OR 
Hospitalization 
(other than 
emergency room 
visit) indicated 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Unintentional weight 
loss 
NA 
5 – 9% loss in 
body weight from 
baseline 
10 – 19% loss in 
body weight from 
baseline 
20% loss in 
body weight from 
baseline OR  
Aggressive 
intervention 
indicated [e.g., 
tube feeding or 
total parenteral 
nutrition (TPN)] 
INFECTION 
Infection (any other 
than HIV infection) 
Localized, no 
systemic 
antimicrobial 
treatment 
indicated AND 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Systemic 
antimicrobial 
treatment indicated 
OR Symptoms 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Systemic 
antimicrobial 
treatment indicated 
AND Symptoms 
causing inability to 
perform usual 
social & functional 
activities OR 
Operative 
intervention (other 
than simple 
incision and 
drainage) indicated 
Life-threatening 
consequences 
(e.g., septic 
shock) 
INJECTION SITE REACTIONS 
Injection site pain 
(pain without 
touching) 
Or 
Tenderness (pain 
when area is 
touched)  
Pain/tendernes
s causing no or 
minimal 
limitation of use 
of limb 
Pain/tenderness 
limiting use of limb 
OR 
Pain/tenderness 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
 
Pain/tenderness 
causing inability to 
perform usual 
social & functional 
activities 
 
Pain/tenderness 
causing inability 
to perform basic 
self-care function 
OR 
Hospitalization 
(other than 
emergency room 
visit) indicated for 
management of 
pain/tenderness 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Injection site reaction (localized) 
Adult > 15 years 
 
Erythema OR 
Induration 
of 5x5 cm – 
9x9 cm (or 
25 cm2 – 
81 cm2) 
Erythema OR 
Induration OR 
Edema  
>9 cm any 
diameter 
(or >81 cm2) 
Ulceration OR 
Secondary 
infection OR 
Phlebitis OR 
Sterile abscess 
OR Drainage 
Necrosis 
(involving dermis 
and deeper 
tissue) 
 
Pediatric  15 years 
Erythema OR 
Induration OR 
Edema present 
but 2.5 cm 
diameter 
Erythema OR 
Induration OR 
Edema >2.5 cm 
diameter but <50% 
surface area of the 
extremity segment 
(e.g., upper 
arm/thigh) 
Erythema OR 
Induration OR 
Edema involving  
50% surface area 
of the extremity 
segment (e.g., 
upper arm/thigh) 
OR Ulceration OR 
Secondary 
infection OR 
Phlebitis OR 
Sterile abscess 
OR Drainage 
Necrosis 
(involving dermis 
and deeper 
tissue) 
Pruritis associated 
with injection  
See also Skin: 
Pruritis (itching - no 
skin lesions) 
Itching localized 
to injection site 
AND Relieved 
spontaneously 
or with <48 h 
treatment  
Itching beyond the 
injection site but 
not generalized 
OR Itching 
localized to 
injection site 
requiring 48 h 
treatment  
Generalized 
itching causing 
inability to perform 
usual social & 
functional activities 
NA 
SKIN – DERMATOLOGICAL 
Alopecia 
Thinning 
detectable by 
study 
participant (or 
by caregiver for 
young children 
and disabled 
adults) 
Thinning or patchy 
hair loss 
detectable by 
health care 
provider 
Complete hair loss 
NA 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Cutaneous reaction – 
rash 
Localized 
macular rash  
Diffuse macular, 
maculopapular, or 
morbilliform rash 
OR Target lesions  
Diffuse macular, 
maculopapular, or 
morbilliform rash 
with vesicles or 
limited number of 
bullae OR 
Superficial 
ulcerations of 
mucous 
membrane limited 
to one site 
Extensive or 
generalized 
bullous lesions 
OR Stevens-
Johnson 
syndrome OR 
Ulceration of 
mucous 
membrane 
involving two or 
more distinct 
mucosal sites OR 
Toxic epidermal 
necrolysis (TEN) 
Hyperpigmentation 
Slight or 
localized 
Marked or 
generalized 
NA 
NA 
Hypopigmentation 
Slight or 
localized  
Marked or 
generalized 
NA 
NA 
Pruritis (itching – no 
skin lesions)  
(See also Injection 
Site Reactions: 
Pruritis associated 
with injection) 
Itching causing 
no or minimal 
interference 
with usual 
social & 
functional 
activities 
Itching causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Itching causing 
inability to perform 
usual social & 
functional activities  
NA 
 
CARDIOVASCULAR 
Cardiac arrhythmia 
(general) 
(By ECG or physical 
exam) 
Asymptomatic 
AND No 
intervention 
indicated 
Asymptomatic 
AND Non-urgent 
medical 
intervention 
indicated 
Symptomatic, non-
life-threatening 
AND Non-urgent 
medical 
intervention 
indicated  
Life-threatening 
arrhythmia OR 
Urgent 
intervention 
indicated 
Cardiac-
ischemia/infarction 
NA 
NA 
Symptomatic 
ischemia (stable 
angina) OR 
Testing consistent 
with ischemia  
Unstable angina 
OR Acute 
myocardial 
infarction 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Hemorrhage 
(significant acute 
blood loss) 
NA 
Symptomatic AND 
No transfusion 
indicated 
Symptomatic AND 
Transfusion of  2 
units packed RBCs 
(for children 
10 cc/kg) 
indicated  
Life-threatening 
hypotension OR 
Transfusion of 
>2 units packed 
RBCs (for 
children > 
10 cc/kg) 
indicated 
Hypertension 
Adult > 17 years 
(with repeat testing at 
same visit) 
140 – 
159 mmHg 
systolic 
OR 
90 – 99 mmHg 
diastolic 
160 – 179 mmHg 
systolic 
OR 
100 – 109 mmHg 
diastolic 
≥180 mmHg 
systolic 
OR 
≥110 mmHg 
diastolic 
 
Life-threatening 
consequences 
(e.g., malignant 
hypertension) OR 
Hospitalization 
indicated (other 
than emergency 
room visit) 
Correction: in Grade 2 to 160 - 179 from >160-179 (systolic) and to 100 -109 from >100-109 (diastolic) 
and  
in Grade 3 to  180 from >180 (systolic) and to  110  from >110 (diastolic). 
Pediatric  
17 years 
(with repeat testing at 
same visit) 
 
NA 
91st – 94th 
percentile adjusted 
for age, height, 
and gender 
(systolic and/or 
diastolic) 
≥95th percentile 
adjusted for age, 
height, and gender 
(systolic and/or 
diastolic) 
Life-threatening 
consequences 
(e.g., malignant 
hypertension) OR 
Hospitalization 
indicated (other 
than emergency 
room visit) 
Hypotension 
NA 
Symptomatic, 
corrected with oral 
fluid replacement 
Symptomatic, IV 
fluids indicated 
Shock requiring 
use of 
vasopressors or 
mechanical 
assistance to 
maintain blood 
pressure 
Pericardial effusion 
Asymptomatic, 
small effusion 
requiring no 
intervention 
 
Asymptomatic, 
moderate or larger 
effusion requiring 
no intervention 
 
Effusion with non-
life threatening 
physiologic 
consequences OR 
Effusion with non-
urgent intervention 
indicated 
Life-threatening 
consequences 
(e.g., tamponade) 
OR Urgent 
intervention 
indicated 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Prolonged PR interval 
Adult > 16 years 
PR interval  
0.21 – 0.25 sec 
PR interval 
>0.25 sec 
Type II 2nd degree 
AV block OR 
Ventricular pause 
>3.0 sec 
Complete AV 
block  
Pediatric ≤16 years 
1st degree AV 
block 
(PR >normal for 
age and rate) 
Type I 2nd degree 
AV block  
Type II 2nd degree 
AV block  
Complete AV 
block 
Prolonged QTc 
Adult >16 years 
 
Asymptomatic, 
QTc interval 
0.45 – 0.47 sec 
OR Increase 
interval <0.03 
sec above 
baseline 
Asymptomatic, 
QTc interval 0.48 – 
0.49 sec OR 
Increase in interval 
0.03 – 0.05 sec 
above baseline 
Asymptomatic, 
QTc interval  
0.50 sec OR 
Increase in interval  
 0.06 sec above 
baseline 
Life-threatening 
consequences, 
e.g., Torsade de 
pointes or other 
associated 
serious 
ventricular 
dysrhythmia 
Pediatric ≤16 years 
Asymptomatic, 
QTc interval 
0.450 –  
0.464 sec  
Asymptomatic, 
QTc interval 0.465 
–  
0.479 sec  
Asymptomatic, 
QTc interval 
0.480 sec  
Life-threatening 
consequences, 
e.g.  Torsade de 
pointes or other 
associated 
serious 
ventricular 
dysrhythmia 
Thrombosis/embolis
m 
NA 
Deep vein 
thrombosis AND 
No intervention 
indicated (e.g., 
anticoagulation, 
lysis filter, invasive 
procedure)  
Deep vein 
thrombosis AND 
Intervention 
indicated (e.g., 
anticoagulation, 
lysis filter, invasive 
procedure)  
Embolic event 
(e.g., pulmonary 
embolism, life-
threatening 
thrombus)  
Vasovagal episode 
(associated with a 
procedure of any 
kind) 
Present without 
loss of 
consciousness  
Present with 
transient loss of 
consciousness 
NA  
NA 
Ventricular 
dysfunction 
(congestive heart 
failure) 
NA 
Asymptomatic 
diagnostic finding 
AND intervention 
indicated 
New onset with 
symptoms OR 
Worsening 
symptomatic 
congestive heart 
failure 
Life-threatening 
congestive heart 
failure 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
GASTROINTESTINAL 
Anorexia 
Loss of appetite 
without 
decreased oral 
intake 
Loss of appetite 
associated with 
decreased oral 
intake without 
significant weight 
loss 
Loss of appetite 
associated with 
significant weight 
loss 
Life-threatening 
consequences 
OR Aggressive 
intervention 
indicated [e.g., 
tube feeding or 
total parenteral 
nutrition (TPN)] 
Comment: Please note that, while the grading scale provided for Unintentional Weight Loss may be 
used as a guideline when grading anorexia, this is not a requirement and should not be used as a 
substitute for clinical judgment.  
Ascites 
Asymptomatic 
Symptomatic AND 
Intervention 
indicated (e.g., 
diuretics or 
therapeutic 
paracentesis) 
Symptomatic 
despite 
intervention 
Life-threatening 
consequences 
Cholecystitis 
NA 
Symptomatic AND 
Medical 
intervention 
indicated 
 
Radiologic, 
endoscopic, or 
operative 
intervention 
indicated 
Life-threatening 
consequences 
(e.g., sepsis or 
perforation)  
Constipation  
NA 
Persistent 
constipation 
requiring regular 
use of dietary 
modifications, 
laxatives, or 
enemas  
Obstipation with 
manual evacuation 
indicated 
Life-threatening 
consequences 
(e.g., obstruction) 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Diarrhea 
Adult and Pediatric 
1 year 
Transient or 
intermittent 
episodes of 
unformed stools 
OR Increase of 
≤ 3 stools over 
baseline per 24-
hour period 
Persistent 
episodes of 
unformed to 
watery stools OR 
Increase of 4 – 6 
stools over 
baseline per 24-
hour period 
Bloody diarrhea 
OR Increase of ≥ 7 
stools per 24-hour 
period OR IV fluid 
replacement 
indicated 
Life-threatening 
consequences 
(e.g., hypotensive 
shock) 
Pediatric <1 year 
Liquid stools 
(more unformed 
than usual) but 
usual number of 
stools 
Liquid stools with 
increased number 
of stools OR Mild 
dehydration 
Liquid stools with 
moderate 
dehydration 
Liquid stools 
resulting in 
severe 
dehydration with 
aggressive 
rehydration 
indicated OR 
Hypotensive 
shock 
Dysphagia-
Odynophagia  
Symptomatic 
but able to eat 
usual diet 
Symptoms causing 
altered dietary 
intake without 
medical 
intervention 
indicated 
Symptoms causing 
severely altered 
dietary intake with 
medical 
intervention 
indicated 
Life-threatening 
reduction in oral 
intake 
Mucositis/stomatitis  
(clinical exam) 
Indicate site (e.g., 
larynx, oral) 
See Genitourinary for 
Vulvovaginitis  
See also Dysphagia-
Odynophagia and 
Proctitis 
Erythema of the 
mucosa 
Patchy 
pseudomembrane
s or ulcerations  
Confluent 
pseudomembrane
s or ulcerations 
OR Mucosal 
bleeding with 
minor trauma 
Tissue necrosis 
OR Diffuse 
spontaneous 
mucosal bleeding 
OR Life-
threatening 
consequences 
(e.g., aspiration, 
choking) 
Nausea  
Transient (<24 
h) or 
intermittent 
nausea with no 
or minimal 
interference 
with oral intake 
Persistent nausea 
resulting in 
decreased oral 
intake for 24 – 48 
h 
Persistent nausea 
resulting in 
minimal oral intake 
for >48 h OR 
Aggressive 
rehydration 
indicated (e.g., IV 
fluids) 
Life-threatening 
consequences 
(e.g., hypotensive 
shock) 

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Pancreatitis 
NA 
Symptomatic AND 
Hospitalization not 
indicated (other 
than emergency 
room visit) 
Symptomatic AND 
Hospitalization 
indicated (other 
than emergency 
room visit) 
Life-threatening 
consequences 
(e.g., circulatory 
failure, 
hemorrhage, 
sepsis) 
Proctitis (functional- 
symptomatic) 
Also see 
Mucositis/stomatitis  
for clinical exam 
 
 
Rectal 
discomfort AND 
No intervention 
indicated 
 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
OR Medical 
intervention 
indicated  
Symptoms causing 
inability to perform 
usual social & 
functional activities 
OR Operative 
intervention 
indicated  
Life-threatening 
consequences 
(e.g., perforation) 
 
Vomiting 
Transient or 
intermittent 
vomiting with no 
or minimal 
interference 
with oral intake 
Frequent episodes 
of vomiting with no 
or mild dehydration 
Persistent vomiting 
resulting in 
orthostatic 
hypotension OR 
Aggressive 
rehydration 
indicated (e.g., IV 
fluids) 
Life-threatening 
consequences 
(e.g., hypotensive 
shock) 
NEUROLOGIC 
Alteration in 
personality-behavior 
or in mood (e.g., 
agitation, anxiety, 
depression, mania, 
psychosis) 
Alteration 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities  
Alteration causing 
greater than 
minimal 
interference with 
usual social & 
functional activities  
Alteration causing 
inability to perform 
usual social & 
functional activities  
Behavior 
potentially 
harmful to self or 
others (e.g., 
suicidal and 
homicidal 
ideation or 
attempt, acute 
psychosis) OR 
Causing inability 
to perform basic 
self-care 
functions  

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PARAMETER 
 
GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Altered Mental Status  
For Dementia, see 
Cognitive and 
behavioral/attentional 
disturbance 
(including dementia 
and attention deficit 
disorder) 
Changes 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Mild lethargy or 
somnolence 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Confusion, 
memory 
impairment, 
lethargy, or 
somnolence 
causing inability to 
perform usual 
social & functional 
activities 
Delirium OR 
obtundation, OR 
coma 
Ataxia  
Asymptomatic 
ataxia 
detectable on 
exam OR 
Minimal ataxia 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptomatic 
ataxia causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptomatic 
ataxia causing 
inability to perform 
usual social & 
functional activities  
Disabling ataxia 
causing inability 
to perform basic 
self-care 
functions 
Cognitive and 
behavioral/attentional 
disturbance 
(including dementia 
and attention deficit 
disorder)  
Disability 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities OR 
Specialized 
resources not 
indicated 
Disability causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
OR Specialized 
resources on part-
time basis 
indicated 
Disability causing 
inability to perform 
usual social & 
functional activities 
OR Specialized 
resources on a full-
time basis 
indicated 
Disability causing 
inability to 
perform basic 
self-care 
functions OR 
Institutionalizatio
n indicated 
CNS ischemia 
(acute) 
NA 
NA 
Transient ischemic 
attack 
Cerebral vascular 
accident (CVA, 
stroke) with 
neurological 
deficit  

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Developmental delay 
– Pediatric 16 
years 
Mild 
developmental 
delay, either 
motor or 
cognitive, as 
determined by 
comparison 
with a 
developmental 
screening tool 
appropriate for 
the setting  
Moderate 
developmental 
delay, either motor 
or cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting  
Severe 
developmental 
delay, either motor 
or cognitive, as 
determined by 
comparison with a 
developmental 
screening tool 
appropriate for the 
setting  
Developmental 
regression, either 
motor or 
cognitive, as 
determined by 
comparison with 
a developmental 
screening tool 
appropriate for 
the setting 
Headache  
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
Symptoms 
causing inability 
to perform basic 
self-care 
functions OR 
Hospitalization 
indicated (other 
than emergency 
room visit) OR 
Headache with 
significant 
impairment of 
alertness or other 
neurologic 
function  
Insomnia 
NA 
Difficulty sleeping 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Difficulty sleeping 
causing inability to 
perform usual 
social & functional 
activities 
Disabling 
insomnia causing 
inability to 
perform basic 
self-care 
functions 
Neuromuscular 
weakness  
(including myopathy 
& neuropathy) 
Asymptomatic 
with decreased 
strength on 
exam OR 
Minimal muscle 
weakness 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Muscle weakness 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Muscle weakness 
causing inability to 
perform usual 
social & functional 
activities  
Disabling muscle 
weakness 
causing inability 
to perform basic 
self-care 
functions OR 
Respiratory 
muscle weakness 
impairing 
ventilation 

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Neurosensory 
alteration (including 
paresthesia and 
painful neuropathy) 
Asymptomatic 
with sensory 
alteration on 
exam or 
minimal 
paresthesia 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities  
Sensory alteration 
or paresthesia 
causing greater 
than minimal 
interference with 
usual social & 
functional activities  
Sensory alteration 
or paresthesia 
causing inability to 
perform usual 
social & functional 
activities 
Disabling sensory 
alteration or 
paresthesia 
causing inability 
to perform basic 
self-care 
functions 
 
Seizure: (new onset) 
– Adult ≥18 years 
See also Seizure: 
(known pre-existing 
seizure disorder) 
NA 
1 seizure  
2 – 4 seizures  
Seizures of any 
kind which are 
prolonged, 
repetitive (e.g., 
status 
epilepticus), or 
difficult to control 
(e.g., refractory 
epilepsy) 
Seizure: (known pre-
existing seizure 
disorder)  
– Adult ≥18 years 
For worsening of 
existing epilepsy the 
grades should be 
based on an increase 
from previous level of 
control to any of 
these levels 
NA 
Increased 
frequency of pre-
existing seizures 
(non-repetitive) 
without change in 
seizure character 
OR Infrequent 
break-through 
seizures while on 
stable medication 
in a previously 
controlled seizure 
disorder 
Change in seizure 
character from 
baseline either in 
duration or quality 
(e.g., severity or 
focality)  
Seizures of any 
kind which are 
prolonged, 
repetitive (e.g., 
status 
epilepticus), or 
difficult to control 
(e.g., refractory 
epilepsy) 
Seizure  
– Pediatric <18 
years 
Seizure, 
generalized 
onset with or 
without 
secondary 
generalization, 
lasting <5 
minutes with 
<24 h post ictal 
state 
Seizure, 
generalized onset 
with or without 
secondary 
generalization, 
lasting 5 – 20 
minutes with  
<24 h post ictal 
state 
Seizure, 
generalized onset 
with or without 
secondary 
generalization, 
lasting  
>20 minutes  
Seizure, 
generalized onset 
with or without 
secondary 
generalization, 
requiring 
intubation and 
sedation 

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Syncope (not 
associated with a 
procedure) 
NA 
Present 
NA 
NA 
Vertigo 
Vertigo causing 
no or minimal 
interference 
with usual 
social & 
functional 
activities 
Vertigo causing 
greater than 
minimal 
interference with 
usual social & 
functional activities  
Vertigo causing 
inability to perform 
usual social & 
functional activities 
Disabling vertigo 
causing inability 
to perform basic 
self-care 
functions 

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
RESPIRATORY 
Bronchospasm 
(acute) 
FEV1 or peak 
flow reduced to  
70 – 80% 
FEV1 or peak flow  
50 – 69% 
FEV1 or peak flow  
25 – 49%  
Cyanosis OR 
FEV1 or peak 
flow <25% OR 
Intubation 
Dyspnea or respiratory distress 
Adult ≥14 years 
Dyspnea on 
exertion with no 
or minimal 
interference 
with usual 
social & 
functional 
activities  
Dyspnea on exertion 
causing greater than 
minimal interference with 
usual social & functional 
activities  
Dyspnea at rest 
causing inability 
to perform usual 
social & 
functional 
activities  
Respiratory 
failure with 
ventilatory 
support 
indicated 
Pediatric <14 years 
Wheezing OR 
minimal 
increase in 
respiratory rate 
for age 
Nasal flaring OR Intercostal 
retractions OR Pulse 
oximetry 90 – 95% 
Dyspnea at rest 
causing inability 
to perform usual 
social & 
functional 
activities OR 
Pulse oximetry 
<90% 
Respiratory 
failure with 
ventilatory 
support 
indicated 
MUSCULOSKELETAL 
Arthralgia 
See also Arthritis 
Joint pain 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Joint pain causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Joint pain causing 
inability to perform 
usual social & 
functional activities 
Disabling joint 
pain causing 
inability to 
perform basic 
self-care 
functions 
Arthritis 
See also Arthralgia 
Stiffness or joint 
swelling 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Stiffness or joint 
swelling causing 
greater than 
minimal 
interference with 
usual social & 
functional activities 
Stiffness or joint 
swelling causing 
inability to perform 
usual social & 
functional activities 
Disabling joint 
stiffness or 
swelling causing 
inability to 
perform basic 
self-care 
functions  

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Bone Mineral Loss 
Adult ≥21 years 
BMD t-score  
-2.5 to -1.0  
BMD t-score <-2.5 
Pathological 
fracture (including 
loss of vertebral 
height) 
Pathologic 
fracture causing 
life-threatening 
consequences  
Pediatric <21 years 
BMD z-score  
-2.5 to -1.0 
BMD z-score <-2.5 
Pathological 
fracture (including 
loss of vertebral 
height) 
Pathologic 
fracture causing 
life-threatening 
consequences  
Myalgia 
(non-injection site) 
Muscle pain 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Muscle pain 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Muscle pain 
causing inability to 
perform usual 
social & functional 
activities 
Disabling muscle 
pain causing 
inability to 
perform basic 
self-care 
functions 
Osteonecrosis 
NA 
Asymptomatic with 
radiographic 
findings AND No 
operative 
intervention 
indicated 
Symptomatic bone 
pain with 
radiographic 
findings OR 
Operative 
intervention 
indicated 
Disabling bone 
pain with 
radiographic 
findings causing 
inability to 
perform basic 
self-care 
functions 
GENITOURINARY 
Cervicitis  
(symptoms) 
(For use in studies 
evaluating topical 
study agents)  
For other cervicitis 
see Infection: 
Infection (any other 
than HIV infection)  
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities  
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities  
Symptoms causing 
inability to perform 
usual social & 
functional activities  
 
Symptoms 
causing inability 
to perform basic 
self-care 
functions  

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Cervicitis  
(clinical exam) 
(For use in studies 
evaluating topical 
study agents)  
For other cervicitis 
see Infection: 
Infection (any other 
than HIV infection)  
Minimal cervical 
abnormalities 
on examination 
(erythema, 
mucopurulent 
discharge, or 
friability) OR 
Epithelial 
disruption  
<25% of total 
surface 
Moderate cervical 
abnormalities on 
examination 
(erythema, 
mucopurulent 
discharge, or 
friability) OR 
Epithelial 
disruption of 25 – 
49% total surface 
Severe cervical 
abnormalities on 
examination 
(erythema, 
mucopurulent 
discharge, or 
friability) OR 
Epithelial 
disruption  
50 – 75% total 
surface 
Epithelial 
disruption  
>75% total 
surface 
Inter-menstrual 
bleeding (IMB) 
Spotting 
observed by 
participant OR 
Minimal blood 
observed during 
clinical or 
colposcopic 
examination 
Inter-menstrual 
bleeding not 
greater in duration 
or amount than 
usual menstrual 
cycle 
Inter-menstrual 
bleeding greater in 
duration or amount 
than usual 
menstrual cycle 
Hemorrhage with 
life-threatening 
hypotension OR 
Operative 
intervention 
indicated 
Urinary tract 
obstruction (e.g., 
stone) 
NA 
Signs or symptoms 
of urinary tract 
obstruction without 
hydronephrosis or 
renal dysfunction 
Signs or symptoms 
of urinary tract 
obstruction with 
hydronephrosis or 
renal dysfunction 
Obstruction 
causing life-
threatening 
consequences 
Vulvovaginitis  
(symptoms) 
(Use in studies 
evaluating topical 
study agents)  
For other 
vulvovaginitis see 
Infection: Infection 
(any other than HIV 
infection) 
Symptoms 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities  
Symptoms causing 
greater than 
minimal 
interference with 
usual social & 
functional activities  
Symptoms causing 
inability to perform 
usual social & 
functional activities  
 
Symptoms 
causing inability 
to perform basic 
self-care 
functions  

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Vulvovaginitis  
(clinical exam) 
(Use in studies 
evaluating topical 
study agents)  
For other 
vulvovaginitis see 
Infection: Infection 
(any other than HIV 
infection) 
Minimal vaginal 
abnormalities 
on examination 
OR Epithelial 
disruption  
<25% of total 
surface 
Moderate vaginal 
abnormalities on 
examination OR 
Epithelial 
disruption of 25 - 
49% total surface 
Severe vaginal 
abnormalities on 
examination OR 
Epithelial 
disruption  
50 - 75% total 
surface 
Vaginal 
perforation OR 
Epithelial 
disruption 
>75% total 
surface 
OCULAR/VISUAL 
Uveitis 
Asymptomatic 
but detectable 
on exam 
Symptomatic 
anterior uveitis OR 
Medical 
intervention 
indicated 
Posterior or pan-
uveitis OR 
Operative 
intervention 
indicated 
Disabling visual 
loss in affected 
eye(s)  
Visual changes (from 
baseline) 
Visual changes 
causing no or 
minimal 
interference 
with usual 
social & 
functional 
activities 
Visual changes 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
Visual changes 
causing inability to 
perform usual 
social & functional 
activities 
Disabling visual 
loss in affected 
eye(s) 
ENDOCRINE/METABOLIC 
Abnormal fat 
accumulation 
(e.g., back of neck, 
breasts, abdomen) 
Detectable by 
study 
participant (or 
by caregiver for 
young children 
and disabled 
adults) 
Detectable on 
physical exam by 
health care 
provider 
Disfiguring OR 
Obvious changes 
on casual visual 
inspection 
NA 
Diabetes mellitus 
NA 
New onset without 
need to initiate 
medication OR 
Modification of 
current 
medications to 
regain glucose 
control 
New onset with 
initiation of 
medication 
indicated OR 
Diabetes 
uncontrolled 
despite treatment 
modification 
Life-threatening 
consequences 
(e.g., 
ketoacidosis, 
hyperosmolar 
non-ketotic 
coma)  

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GRADE 1 
MILD 
GRADE 2 
MODERATE 
GRADE 3 
SEVERE 
GRADE 4 
POTENTIALLY 
LIFE-
THREATENING 
Gynecomastia 
Detectable by 
study 
participant or 
caregiver (for 
young children 
and disabled 
adults) 
Detectable on 
physical exam by 
health care 
provider 
Disfiguring OR 
Obvious on casual 
visual inspection 
NA 
Hyperthyroidism  
Asymptomatic 
 
Symptomatic 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
OR Thyroid 
suppression 
therapy indicated 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
OR Uncontrolled 
despite treatment 
modification  
Life-threatening 
consequences 
(e.g., thyroid 
storm) 
Hypothyroidism 
Asymptomatic 
Symptomatic 
causing greater 
than minimal 
interference with 
usual social & 
functional activities 
OR Thyroid 
replacement 
therapy indicated 
Symptoms causing 
inability to perform 
usual social & 
functional activities 
OR Uncontrolled 
despite treatment 
modification  
Life-threatening 
consequences 
(e.g., myxedema 
coma) 
Lipoatrophy 
(e.g., fat loss from the 
face, extremities, 
buttocks) 
Detectable by 
study 
participant (or 
by caregiver for 
young children 
and disabled 
adults) 
Detectable on 
physical exam by 
health care 
provider 
Disfiguring OR 
Obvious on casual 
visual inspection 
NA 
10.9. 
Appendix 9: CDC Classification for HIV 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. 

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• 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  
• 
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)  

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• 
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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11. 
REFERENCES 
CDC. 2014. “Revised Surveillance Case Definition for HIV Infection.” Morbidity and 
Mortality Weekly Report 63(3): 1–13. 
DeJesus, Edwin et al. 2020. “A Phase IIa Study Evaluating Safety, Pharmacokinetics, and 
Antiviral Activity of GSK2838232, a Novel, Second-Generation Maturation Inhibitor, in 
Participants With Human Immunodeficiency Virus Type 1 Infection.” Clinical infectious 
diseases : an official publication of the Infectious Diseases Society of America 71(5): 
1255–62. 
Delgado, Cynthia et al. 2022. “A Unifying Approach for GFR Estimation: 
Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in 
Diagnosing Kidney Disease.” American journal of kidney diseases : the official journal of 
the National Kidney Foundation 79(2): 268-288.e1. 
Dicker, Ira et al. 2022. “GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an 
Optimized Virology Profile.” Antimicrobial agents and chemotherapy 66(1): e0187621. 
Egger, Matthias et al. 2002. “Prognosis of HIV-1-Infected Patients Starting Highly 
Active Antiretroviral Therapy: A Collaborative Analysis of Prospective Studies.” Lancet 
(London, England) 360(9327): 119–29. 
EMA. 2017. “Guideline on Strategies to Identify and Mitigate Risks for First-in-Human 
and Early Clinical Trials with Investigational Medicinal Products.” : 1–22. 
https://www.ema.europa.eu/en/strategies-identify-mitigate-risks-first-human-early-
clinical-trials-investigational-medicinal#current-effective-version-section. 
GSK document No.: RPS-CLIN-017061. GSK3739937 (VH3739937) Investigator’s 
Brochure Version 01. December 2021. 
GSK document No.: RPS-CLIN-045350. GSK3640254 Clinical. Investigator’s Brochure 
Version 05. November 2022. 
Hasler, William L. 2022. “Nausea, Vomiting, and Indigestion.” In Harrison’s Principles 
of Internal Medicine, 21e, eds. Joseph Loscalzo et al. New York, NY: McGraw-Hill 
Education. 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784. 
Malagelada, Juan R, and C Malagelada. 2016. “Nausea and Vomiting.” In Sleisenger and 
Fordtran’s Gastrointestinal and Liver Disease, Elsevier. 
Martin, David E, Karl Salzwedel, and Graham P Allaway. 2008. “Bevirimat: A Novel 
Maturation Inhibitor for the Treatment of HIV-1 Infection.” Antiviral chemistry & 
chemotherapy 19(3): 107–13. 

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Mearin, Fermín et al. 2016. “Bowel Disorders.” Gastroenterology. 
Millham, FH. 2016. “Acute Abdominal Pain.” In Sleisenger and Fordtran’s 
Gastrointestinal and Liver Disease, Elsevier. 
Morales-Ramirez, Javier et al. 2018. “Safety, Efficacy, and Dose Response of the 
Maturation Inhibitor GSK3532795 (Formerly Known as BMS-955176) plus 
Tenofovir/Emtricitabine Once Daily in Treatment-Naive HIV-1-Infected Adults: Week 
24 Primary Analysis from a Randomized Phase IIb Trial.” PloS one 13(10): e0205368. 
Posner, Kelly et al. 2007. “Columbia Classification Algorithm of Suicide Assessment (C-
CASA): Classification  of Suicidal Events in the FDA’s Pediatric Suicidal Risk Analysis 
of Antidepressants.” The American journal of psychiatry 164(7): 1035–43. 
Schiller, LR, and J Sellin. 2016. “Diarrhea.” In Sleisenger and Fordtran’s 
Gastrointestinal and Liver Disease,. 
Soll, Andrew H, and David Y Graham. 2008. “Peptic Ulcer Disease.” In Textbook of 
Gastroenterology, John Wiley & Sons, Ltd, 936–81. 
Spinner, Christoph D et al. 2022. “Phase IIa Proof-of-Concept Evaluation of the Antiviral 
Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation 
Inhibitor GSK3640254.” Clinical infectious diseases : an official publication of the 
Infectious Diseases Society of America 75(5): 786–94. 
Stanghellini, Vincenzo et al. 2016. “Gastroduodenal Disorders.” Gastroenterology 
150(6): 1380–92. 
UNAIDS. 2022. “Global HIV & AIDS Statistics: 2022 Fact Sheet. UNAIDS. 2022.” 
Unaids. https://www.unaids.org/en/resources/fact-sheet. 
World Health Organization (WHO). 2017. STEPS Surveillance Manual. The WHO 
STEPwise Approach to Noncommunicable Disease Risk Factor Surveillance. 
Yarze, JC, and LS Friedman. 2016. “Chronic Abdominal Pain.” In Sleisenger and 
Fordtran’s Gastrointestinal and Liver Disease, Elsevier. 
 

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