A Phase 2a Multicentre, Randomized, Open-Label, Two-Part Adaptive Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A, an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in Antiretroviral-naïve HIV-1-Infected Adults
Phase: PHASE2
Conditions: HIV Infections
Sponsor: ViiV Healthcare

Protocol 
Study ID: 207959 
Official Title of Study: A Phase 2a Multicentre, Randomized, Open-Label, Two-Part 
Adaptive Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of 
GSK3810109A, an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in 
Antiretroviral-naïve HIV-1-Infected Adults 
NCT Number-NCT04871113
Approval Date of Document: 26-Jul-2021 

TMF-13894674  
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ViiV Healthcare group of companies 
 
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TITLE PAGE 
Protocol Title: A Phase 2a Multicentre, Randomized, Open-Label, Two-Part Adaptive 
Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A, 
an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in Antiretroviral-
naïve HIV-1-Infected Adults 
Protocol Number: 207959/ Amendment 04 
Compound Number: 
GSK3810109A 
Study Phase: Phase 2a 
Short Title: GSK3810109A Proof Of Concept in Viremic HIV-1 Infected Adults 
BANNER: Broadly-neutralizing Antibody N6LS in ART-Naives to Evaluate virologic 
Response 
Sponsor Name and Legal Registered Address (excluding US): 
ViiV Healthcare UK Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
US IND Sponsor Name and Legal Registered Address: 
ViiV Healthcare Company 
Five Moore Drive 
P.O. 13398 
Research Triangle Park, NC 27709-3398, USA 
Telephone: + 1 919 438 2100 
In some countries, local law requires that the Clinical Trial sponsor is a local 
company legal entity. In these instances, the appropriate company to be identified as 
Sponsor must be agreed with the global ViiV Healthcare clinical team and signed off 
by the Vice President, Global Research and Medical Strategy 
This study is sponsored by ViiV Healthcare. GlaxoSmithKline is supporting ViiV 
Healthcare in the conduct of this study. 
Copyright 2021 ViiV Healthcare group of companies. All rights reserved. Unauthorised 
copying or use of this information is prohibited. 

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Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual  
Regulatory Agency Identifying Number(s): 
US IND: 148241 
Approval Date: XX-XXX-2021 
 

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SPONSOR SIGNATORY: 
Protocol Title: A Phase 2a Multicentre, Randomized, Open-Label, Two-Part Adaptive 
Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A, 
an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in Antiretroviral-
naïve HIV-1-Infected Adults 
Protocol Number: 207959/ Amendment 04 
Compound Number: 
GSK3810109A 
 
 
 
 
 
Max Lataillade, DO, MPH 
VP, Head of Global Research Strategy 
ViiV Healthcare 
 
Date 
 
The signed page is a separate document. 
 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 4 
XX-XXX-2021 
TMF-13894674 
Amendment 3 
11-MAR-2021 
TMF-11879657 
Amendment 2 
05-NOV-2020 
2018N378492_02 
Amendment 1 
01-SEP-2020 
2018N378492_01 
Original Protocol 
14-JUL-2020 
2018N378492_00 
 
Amendment 4: XX-XXX-2021 
Overall Rationale for Amendment 4: Inclusion criteria have been edited for clarity and 
to reduce the CD4+ eligibility threshold. Group 1 (high dose) sample size required for the 
interim analysis has been updated from 10 to approximately 10 evaluable participants to 
clarify that the interim analysis may proceed with a lower number, as supported by the 
sample size sensitivity analysis included in the protocol. 

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Section # 
and Name 
Description of Change 
Brief Rationale 
4.2 Scientific 
Rationale for 
Study Design  
 
207959 is designed as an open-
label study; an open label trial 
design affords the availability of 
real time safety data following 
antibody infusions. Based upon 
the small sample size 
(approximately 10 participants for 
all Groups in Part 1 and Part 2) 
and the open-label trial design, 
safety and tolerability will be 
assessed in-stream (via a Safety 
Review Team) as well as at 
defined analysis timepoints (via 
the Safety and Dose Evaluation 
Committee). Enrollment in Part 1 
will continue until approximately 
10 evaluable participants are 
confirmed in Group 1. 
 
Group 1 sample size updated to 
“approximately 10” for consistency with 
other dosing groups. 
5.2 Inclusion 
Criteria 
Participants must have 
documented HIV-1 infection at 
the Screening Visit: 
• Plasma HIV-1 RNA 
5000 c/mL. 
NOTE: A single repeat test is 
allowed to determine 
eligibility. An HIV-1 RNA 
result 5000 c/mL will serve as 
confirmation of HIV-1 
infection. 
 
Screening CD4+ T-cell count  
250 cells/mm3: 
 
NOTE: A single repeat test is 
allowed to determine 
eligibility. 
 
Changes made to clarify eligibility criteria, 
and change the entry threshold for 
screening CD4+ cell count. 

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Section # 
and Name 
Description of Change 
Brief Rationale 
8.0 Study 
Assessments 
and 
Procedures 
 Part 1 of the study will 
evaluate two doses of 
GSK3810109A administered 
by IV infusion on Day 1 in the 
2 groups. Enrollment in Part 1 
will continue until 
approximately 10 evaluable 
participants are confirmed in 
Group 1 to support the Go / No 
Go criteria (see Section 4.4 and 
Section 9.5). Participants will 
be randomized equally (1:1) 
between Group 1 and 2. 
 Group 1 sample size updated to 
“approximately 10” for consistency with 
other dosing groups. 
9.2 Sample 
Size 
Determination 
 The sample size of 
approximately 10 evaluable 
participants for Group 1 was 
chosen to allow for an accurate 
estimate of the primary 
treatment effect of the highest 
dose. A sample size of 
approximately 10 for the 
remaining groups was chosen 
primarily based on feasibility 
in order to explore 
approximately 4 additional 
groups at varying dose 
concentrations and modes of 
delivery (IV and 
subcutaneous). The required 
sample size of approximately 
10 for Group 1 is to be able to 
account for the possibility of 
some participants being non-
sensitive to GSK3810109A, 
and to accurately estimate the 
primary treatment effect 
among the sensitive-only 
subgroup. 
 Group 1 sample size updated to 
“approximately 10” for consistency with 
other dosing groups. 
 
 

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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE .................................... 4 
1. 
PROTOCOL SUMMARY ...................................................................................... 11 
1.1. 
Synopsis .................................................................................................. 11 
1.2. 
Schema .................................................................................................... 13 
1.3. 
Schedule of Activities (SoA) ...................................................................... 14 
1.3.1. 
Screening Schedule of Activities ................................................. 15 
1.3.2. 
Monotherapy Phase Schedule of Activities ................................. 17 
1.3.3. 
Standard of Care Follow-Up Phase Schedule of Activities ........... 21 
2. 
INTRODUCTION ................................................................................................. 23 
2.1. 
Study Rationale ........................................................................................ 23 
2.2. 
Background .............................................................................................. 24 
2.3. 
Benefit/Risk Assessment .......................................................................... 25 
2.3.1. 
Risk Assessment........................................................................ 26 
2.3.2. 
Benefit Assessment ................................................................... 35 
2.3.3. 
Overall Benefit: Risk Conclusion ................................................. 35 
3. 
OBJECTIVES AND ENDPOINTS ......................................................................... 35 
4. 
STUDY DESIGN .................................................................................................. 37 
4.1. 
Overall Design .......................................................................................... 37 
4.1.1. 
Screening Phase........................................................................ 37 
4.1.2. 
Randomized Monotherapy Phase ............................................... 37 
4.1.3. 
Standard of Care Follow-Up Phase............................................. 38 
4.2. 
Scientific Rationale for Study Design ......................................................... 38 
4.3. 
Justification for Dose ................................................................................ 41 
4.4. 
Interim Go / No Go Criteria and Dose Selection for Part 2.......................... 42 
4.5. 
End of Study Definition ............................................................................. 43 
5. 
STUDY POPULATION ......................................................................................... 43 
5.1. 
Inclusion Criteria ....................................................................................... 43 
5.2. 
Exclusion Criteria...................................................................................... 45 
5.3. 
Lifestyle Considerations ............................................................................ 48 
5.3.1. 
Meals and Dietary Restrictions ................................................... 48 
5.3.2. 
Caffeine and Alcohol .................................................................. 48 
5.3.3. 
Activity ....................................................................................... 48 
5.4. 
Screen Failures ........................................................................................ 48 
6. 
STUDY INTERVENTION ..................................................................................... 48 
6.1. 
Study Intervention(s) Administered............................................................ 49 
6.2. 
Handling, Storage and Accountability of GSK3810109A ............................ 49 
6.3. 
Pharmacy Procedures .............................................................................. 50 
6.4. 
Preparation of Study Product Administration ............................................. 51 
6.5. 
Administration of GSK3810109A ............................................................... 53 
6.6. 
Measures to Minimize Bias: Randomization .............................................. 53 
6.7. 
Study Intervention Compliance.................................................................. 54 
6.8. 
Concomitant Therapy................................................................................ 54 
6.8.1. 
Prohibited Medications and Non-Drug Therapies ........................ 55 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
8  
 
6. 9.  
D o s e M o dific ati o n  ..................................................................................... 5 5  
6. 1 0.  I nt er v e nti o n i n F oll o w-U p P eri o d: C o m bi n ati o n Or al A R T St a n d ar d 
of C ar e P h as e  .......................................................................................... 5 5  
6. 1 1.  I nt er v e nti o n aft er t h e E n d of t h e St u d y ...................................................... 5 6  
7.  DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ................................................................... 5 6  
7. 1.  
Di s c o nti n u ati o n of St u d y I nt e r v e nti o n ........................................................ 5 6  
7. 1. 1.  
Q T c St o p pi n g Crit eri a  ................................................................. 5 7  
7. 1. 2.  
Vir ol o gi c F ail ur e  ......................................................................... 5 7  
7. 1. 3.  
D efi niti o n of Pr ot o c ol -D efi n e d Vir ol o gi c F ail ur e ............................ 5 8  
7. 1. 4.  
M a n a gi n g Vir ol o gi c F ail ur e  ......................................................... 5 9  
7. 2.  
Li v er C h e mi str y St o p pi n g Crit eri a  .............................................................. 6 0  
7. 2. 1.  
T e m p or ar y Di s c o nti n u ati o n  ......................................................... 6 1  
7. 3.  
P arti ci p a nt Di s c o nti n u ati o n/ Wit h dr a w al fr o m t h e St u d y  .............................. 6 2  
7. 4.  
L o st t o F oll o w U p  ...................................................................................... 6 2  
8.  S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  .................................................... 6 3  
8. 1.  
Effi c ac y A s s es s m e nt s  ............................................................................... 6 6  
8. 1. 1.  
Pl as m a HI V -1 R N A  .................................................................... 6 6  
8. 1. 2.  
L y m p h o c yt e S u b s et s  .................................................................. 6 6  
8. 1. 3.  
P h ar m ac o ki n eti c s ....................................................................... 6 6  
8. 2.  
S af et y A s s e s s m e nt s  ................................................................................. 6 7  
8. 2. 1.  
P h y si c al E x a mi n ati o n s  ............................................................... 6 7  
8. 2. 2.  
Vit al Si g n s .................................................................................. 6 7  
8. 2. 3.  
C D C HI V -1 Cl as sifi c ati o n a n d HI V A s s o ci at e d C o n diti o n s  ........... 6 7  
8. 2. 4.  
El e ctr o c ar di o gr a m s  .................................................................... 6 8  
8. 2. 5.  
Cli ni c al S af et y L a b or at or y A s s e s s m e nt s  ..................................... 6 8  
8. 2. 6.  
I m m u n o g e ni cit y A s s e ss m e nt s .................................................... 6 8  
8. 2. 7.  
S ui ci d al I d e ati o n a n d B e h avi or Ris k M o nit ori n g  ........................... 6 9  
8. 3.  
A d v er s e E v e nt s a n d S eri o us A d v er s e E v e nt s  ............................................ 7 0  
8. 3. 1.  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n................................................................................. 7 0  
8. 3. 2.  
M et h o d of D et e cti n g A E s a n d S A E s ............................................ 7 0  
8. 3. 3.  
F oll o w -u p of A E s a n d S A E s ........................................................ 7 1  
8. 3. 4.  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s ............................. 7 1  
8. 3. 5.  
Pr e g n a n c y  ................................................................................. 7 1  
8. 3. 6.  
C ar di o v as c ul ar a n d D e at h E v e nt s ............................................... 7 2  
8. 3. 7.  
Di s e as e -R el at e d E v e nt s a n d/ or Di s e as e -R el at e d 
O ut c o m e s N ot Q u alif yi n g as S A E s .............................................. 7 2  
8. 3. 8.  
S p e cifi c T o xi citi e s/ A d v er s e E v e nt M a n a g e m e nt  .......................... 7 2  
8. 3. 8. 1.  
I nj e cti o n/ I nf u si o n Sit e R e acti o ns (I S R s) .................... 7 2  
8. 3. 8. 2.  
S e v er e I m m u n e R e acti o n s  ........................................ 7 3  
8. 4.  
Tr e at m e nt of O v er d o s e  ............................................................................. 7 4  
8. 5.  
P h ar m ac o ki n eti c s  ..................................................................................... 7 4  
8. 6.  
G e n eti c s  ................................................................................................... 7 4  
8. 8.  
Vir al G e n ot y pi n g a n d P h e n ot y pi n g  ............................................................ 7 6  
C CI
C CI

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
9  
 
6  
7  
7  
7  
9.  S T A TI S TI C A L C O N SI D E R A TI O N S  ...................................................................... 7 7  
9. 1.  
St ati sti c al H y p ot h e s e s ............................................................................... 7 7  
9. 2.  
S a m pl e Si z e D et er mi n ati o n ....................................................................... 7 7  
9. 3.  
P o p ul ati o n s f or A n al y s e s ........................................................................... 7 9  
9. 4.  
St ati sti c al A n al y s e s  ................................................................................... 8 0  
9. 4. 1.  
Effi c ac y A n al y s e s  ....................................................................... 8 0  
9. 4. 2.  
S af et y A n al y s e s  ......................................................................... 8 1  
9. 4. 2. 1.  
Im m u n o g e ni cit y A n al y s e s  .......................................... 8 1  
9. 4. 2. 2.  
P h ar m ac o ki n eti c A n al y s e s ......................................... 8 1  
9. 4. 3.  
Ot h er A n al y s e s  .......................................................................... 8 1  
9. 5.  
I nt eri m A n al y s e s ....................................................................................... 8 1  
1 0.  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S ............................................................................................. 8 4  
1 0. 1.  A p p e n di x 1: R e g ul at or y, Et hi c al, a n d St u d y O v er si g ht 
C o n si d er ati o n s  ......................................................................................... 8 4  
1 0. 1. 1.  R e g ul at or y a n d Et hi c al C o n si d er ati o n  ......................................... 8 4  
1 0. 1. 2.  Fi n a n ci al Di s cl o s ur e  ................................................................... 8 4  
1 0. 1. 3.  I nf or m e d C o n s e nt Pr oc e s s ......................................................... 8 5  
1 0. 1. 4.  D at a Pr ot e cti o n  .......................................................................... 8 5  
1 0. 1. 5.  P u bli c ati o n P oli c y  ....................................................................... 8 5  
1 0. 1. 6 . Di s s e mi n ati o n of Cli ni c al St u d y D at a  .......................................... 8 6  
1 0. 1. 7.  D at a Q u alit y A s s ur a n c e  .............................................................. 8 6  
1 0. 1. 8.  S o ur c e D o c u m e nt s ..................................................................... 8 7  
1 0. 1. 9.  St u d y a n d Sit e Cl o s ur e ............................................................... 8 7  
1 0 . 1. 1 0. Pr o vi si o n of St u d y R e s ult s t o I n v e sti g at or s, P o sti n g of 
I nf or m ati o n o n P u bli cl y A v ail a bl e Cli ni c al Tri al s R e gi st er s 
a n d P u bli c ati o n  .......................................................................... 8 8  
1 0. 2.  A p p e n di x 2: Cli ni c al L a b or at or y T e st s  ....................................................... 8 9  
1 0. 3.  A p p e n di x 3: A d v er s e E v e nt s: D efi niti o n s a n d Pr o c e d ur e s f or 
R e c or di n g, E v al u ati n g, F oll o w -u p, a n d R e p orti n g  ...................................... 9 1  
1 0. 3. 1.  D efi niti o n of A E  .......................................................................... 9 1  
1 0. 3. 2.  D efi niti o n of S A E  ........................................................................ 9 2  
1 0. 3. 3.  D efi niti o n of C ar di o v as c ul ar E v e nt s  ............................................ 9 3  
1 0. 3. 4.  R e c or di n g a n d F oll o w -U p of A E a n d S A E  ................................... 9 4  
1 0. 3. 5.  R e p orti n g of S A E t o G S K  ........................................................... 9 6  
1 0 . 4. A p p e n di x 4: T o xi cit y M a n a g e m e nt ............................................................. 9 8  
1 0. 5.  A p p e n di x 5: C o ntr ac e pti v e G ui d a n c e a n d C oll e cti o n of Pr e g n a n c y 
I nf or m ati o n ............................................................................................. 1 0 0  
1 0. 5. 1.  D efi niti o n s:  ............................................................................... 1 0 0  
1 0. 5. 2.  C o ntr ac e pti o n G ui d a n c e:  .......................................................... 1 0 1  
1 0. 5. 3.  C oll e cti o n of Pr e g n a n c y I nf or m ati o n:  ........................................ 1 0 2  
1 0. 6.  A p p e n di x 6: G e n eti c s .............................................................................. 1 0 4  
1 0. 7.  A p p e n di x 7: Li v er S af et y: R e q uir e d A cti o n s a n d F oll o w -u p 
A s s e s s m e nt s  .......................................................................................... 1 0 5  
1 0. 8.  A p p e n di x 8: C D C Cl as sifi c ati o n f or HI V -1 I nf e cti o n ( 2 0 1 4)  ....................... 1 0 8  
1 0. 9.  A p p e n di x 9: C hil d -P u g h Cl as sific ati o n  ..................................................... 1 1 0  
C CI

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10.10. Appendix 10: COVID-19 Pandemic and Clinical Trial Continuity............... 111 
10.10.1. Changes to Study Visits and Study Procedures ........................ 111 
10.10.2. Changes to Informed Consent .................................................. 112 
10.10.3. COVID-19 Vaccines ................................................................. 112 
10.10.4. COVID-19 Experimental Agents ............................................... 112 
10.10.5. COVID-19 Specific Data Capture.............................................. 113 
10.10.5.1. Capturing COVID-19 Specific Protocol 
Deviations ............................................................... 113 
10.10.5.2. Capturing COVID-19 Specific AEs and SAEs........... 113 
10.11. Appendix 11: Abbreviations and Trademarks........................................... 116 
10.12. Appendix 12: Protocol Amendment History.............................................. 120 
11. REFERENCES .................................................................................................. 125 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 2a Multicentre, Randomized, Open-Label, Two-Part Adaptive 
Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A, 
an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in Antiretroviral-
naïve HIV-1-Infected Adults 
Short Title: GSK3810109A Proof Of Concept in Viremic HIV-1 Infected Adults 
Rationale: This Phase 2a proof of concept (PoC) trial will be the first study of 
GSK3810109A (N6LS) in HIV-infected participants and will evaluate the efficacy, 
safety, tolerability, and pharmacokinetics of the broadly neutralizing HIV antibody 
GSK3810109A in treatment naïve viremic adults after a single dose administered as 
infusion or SC injection. Data from this study will be utilized to select doses and routes 
of administration for further studies of GSK3810109A in combination with other ART in 
Phase 2b and beyond. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
To evaluate the antiviral activity following a 
single dose of GSK3810109A in treatment-
naïve HIV-1 infected participants 
Plasma HIV-1 RNA maximum change from 
Baseline during the monotherapy phase  
• 
To assess safety parameters following 
a single dose infusion or SC injection 
with GSK3810109A in treatment-naïve 
HIV-1 participants 
Adverse events, Grade 2-4 ALT/ AST, 
treatment-emergent ECG abnormalities and 
Grade 2-4 injection site reactions 
Secondary 
• 
To characterize the pharmacokinetics 
of GSK3810109A in treatment-naïve 
HIV-1 infected participants following a 
single IV or SC administration 
GSK3810109A PK parameters following 
single dose administration e.g.: AUC (0-t), 
Cmax, Tmax, Ct 
• 
To explore the potency of 
GSK3810109A 
Relationship between GSK3810109A 
exposure and change in plasma HIV-1 RNA 
over time. 
• 
To assess the immunologic changes 
following a single IV or SC dose of 
GSK3810109A 
Absolute values and change in T cell counts 
from baseline over time  
• 
To assess whether anti-drug antibodies 
develop following a single dose of 
GSK3810109A 
Incidence of and titre in serum of anti 
GSK3810109A antibodies over time 

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Objectives 
Endpoints 
Safety 
• 
Safety and tolerability of GSK3810109A 
following a single dose infusion or SC 
injection with GSK3810109A in 
treatment-naïve HIV-1 participants 
Clinical laboratory parameters, ECGs, vital 
signs, and injection site reactions over time. 
 
Overall Design: Protocol 207959 is a two-part, randomized, open label adaptive design 
study to characterize the antiviral activity, safety/tolerability, PK and 
PK/Pharmacodynamics (PD, HIV-1 RNA decline) of GSK3810109A administered both 
intravenously (IV) and subcutaneously (SC) in HIV-1 infected, treatment-naïve adults. 
The study design includes a screening phase, a randomized monotherapy phase and a 
standard of care follow-up phase. The two parts of the randomized phase will each 
include a single dose monotherapy evaluation period after which all participants will 
enter a long-term follow-up period during which participants will initiate an appropriate 
integrase-based standard of care treatment regimen. 
Disclosure Statement: This is an open-label, sequential, treatment, two-part, parallel 
group treatment study with up to 6 arms. 
Number of Participants: Approximately 85 participants will be screened to achieve up 
to 60 randomly assigned to study intervention and 50 evaluable participants for an 
estimated total of 10 evaluable participants per intervention group. 
Intervention Groups and Duration: The study is designed in two parts, with Part 1 
comprised of two parallel, randomized IV dosing groups followed by an interim review 
where pre-defined Go/No Go criteria will be assessed. Part 2 will follow a positive 
review of the Go/No Go criteria and will be comprised of up to 4 parallel, randomized 
dosing groups, with the potential for both IV and SC dosing. 
Both Part 1 and Part 2 will employ a response-guided approach to the monotherapy 
period followed by a 48-week standard of care follow-up period. The duration of the 
study is up to 28 days for screening, up to 84 days for the monotherapy period and 48 
weeks for the SOC follow-up period for a total maximum duration of approximately 15 
months. 
Data Monitoring Committee: A Safety and Dose Evaluation Committee (SDEC) will 
be used to ensure data integrity in dose selection decisions by performing clinical data 
review and appropriate quality control of data prior to making dose selection decisions 
for this study. The Committee will review emerging data and make recommendations per 
the Go/No Go criteria included in this protocol, recommend study changes, including 
dose for Part 2, and review safety parameters during the course of the study. A No Go 
decision by the SDEC will apply to all subsequent dosing groups. The details and 
composition of the Safety and Dose Evaluation Committee will be included in a Charter, 
to be completed prior to commencement of enrollment in study 207959. 

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1.2. 
Schema 
 
 

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1.3. 
Schedule of Activities (SoA) 
Please note the following information regarding this adaptive study design: 
• The timing and number of planned study assessments, including HIV-1 RNA, safety, 
pharmacokinetic, pharmacodynamic/biomarker assessments may be altered during the 
course of the study based on newly available data (e.g., to obtain data to adequately 
characterize the viral load decline and return to baseline value). Please see Table 3 for 
allowable visit windows for study visits noted within the SOA. 
• Any changes in the timing or addition/deletion of time points for any planned study 
assessments as the result of emerging pharmacokinetic/pharmacodynamic data from 
this study must be documented and approved by relevant study team members and 
then archived in the sponsor and site study files but will not constitute a protocol 
amendment.   
• The Regulatory Agencies and ethics committee (EC) will be informed of any safety 
issues that constitute a substantial amendment and require alteration of the safety 
monitoring scheme or amendment of the informed consent form (ICF). The changes 
will be approved by the Regulatory Agencies and the EC before implementation. 
 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
2 0 7 9 5 9  
1 5  
1. 3. 1.  
S cr e e ni n g S c h e d ul e of A cti viti e s  
Pr o c e d ure  
Scre e ni n g  
N ot e s: Particip a nts sh o uld b e r a n d o mize d ( R an d o mizatio n t o occur o n D ay 1) wit hin 2 8 d ays fr o m t h e Scr e e nin g Visit. 
Scr e e nin g m ay b e ext e n d e d u p t o o n e a d ditio n al w e ek if la b r esults ar e p e n din g (r a n d o mizatio n or scr e e n f ailur e m ust 
occur wit hin 3 5 d ays f ollo win g  t h e Scr e e nin g Visit). Se e also Sectio n 8  f or d escriptio ns of assess m e nts 
Cli ni c al A s s e s s me nt s  
Writt e n I nf or m e d C o nse nt  
X  
Eligibility Verificatio n (I nclusio n a n d 
Exclusio n Crit eria)  
X  
D e m o gr a p hy  
X  
Sex at birt h a n d curr e nt g e n d er will b e collect e d.  
M e dical/ M e dicatio n Hist ory  
X  
HI V risk f act ors m ay b e collect e d at a lat er st u dy visit  
Sy m pt o m Dir ect e d Physical Exa m a n d 
M e dical Assess m e nt  
X  
Weig ht, H eig ht a n d B MI  
X  
Particip a nts sh o uld r e m ove sh o es a n d w eig h o n t h e sa m e scale at e ach visit if p ossible.  
Vit al sig ns, inclu din g t e m p er at ure  
X  
blo o d pr essur e, h e art r at e a n d b o dy t e m p erat ur e  
1 2 -le a d E C G
X  
Triplicat e E C Gs as p er Sectio n 8. 2. 4  
Prior P E P/ P R E P T h er apy  
X  
Se e I nclusio n Crit erio n # 4  
C D C Classificatio n f or HI V -1 I nf ectio n  
X  
Se e Ap p e n dix 8 : C D C Classificatio n f or HI V-1 I nf ectio n ( 2 0 14) 
HI V Associat e d C o n ditio ns  
X  
L a b orat ory A s s es s me nts  
Qu a ntit ative plas m a HI V -1 R N A  
X  
HI V Ge n otyp e/ Ph e n otyp e (R T/ P R O /I NI) 
X  
Ly m p h ocyt e Su bset  
X  
C D 4/ C D 8 Absolut e valu es a n d %  
Clinical C h e mistry  
X  
H e m at olo gy  
X  
F astin g L a bs  
X  
Glucose, C h olest er ol ( T ot al, H D L a n d L D L) a n d Triglycerides  
H e p atitis B a n d C Scr e e nin g  
X  
Pr e g n a ncy t est ( P O C B P o nly)  
S  
S =ser u m t estin g, Se e Sectio n 8. 3. 5  
R a pid Plas m a R e a gin ( R P R)  
X  
Urin alysis  
X  
P T/ P T T/I N R  
X  
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Procedure 
Screening 
Notes: Participants should be randomized (Randomization to occur on Day 1) within 28 days from the Screening Visit. 
Screening may be extended up to one additional week if lab results are pending (randomization or screen failure must 
occur within 35 days following the Screening Visit). See also Section 8 for descriptions of assessments 
COVID-19 testing 
X 
 
Other Assessments 
SAE review 
X 
 

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1.3.2. 
Monotherapy Phase Schedule of Activities 
Procedure 
Monotherapy Phase (Part 1/ Part 2)1 
ED 
Follow-up4 
Notes 
See also Section 8 for descriptions of 
assessments  
E.D = early discontinuation/withdrawal 
Day 1  
Day 3 - Day 212 
Every 
7 days 
(up to 
Day 
84)2 
SOC 
Initiation3 
 
Pre-
Dose 
Infusion/ 
Injection 
In 
clinic 
follow-
up5 
24h 
3 
6 
9 
11 
14 
17 
21 
 
 
 
Clinical Assessments 
Entry Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 prior to dosing 
Vital signs 
X 
X6 
X6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood pressure, heart rate and body 
temperature will be collected at all timepoints;  
SpO2 and respiratory rate will be monitored 
for 4 hours following dosing.  
Body weight and height should be recorded at 
Day 1 Pre-Dose and used for dose 
calculation, if required. Body weight and 
height is not required at other visits during the 
Monotherapy Phase. 
12-lead ECG 
X 
 
X8 
 
 
 
 
 
 
 
 
 
X 
X 
 
Triplicate ECGs as per Section 8.2.4 
CDC 
Classification 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV Associated 
Conditions 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Concomitant 
Medications 
X 
X7 
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
IP 
(GSK3810109A) 
Administration 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infusion should be performed over 
approximately 30 minutes; for SC injections, 
please refer to Section 6.4. 
AE/SAE Review 
X 
X7 
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
1 8  
 
Pr oce d ur e  
M o n ot h er a py Ph ase ( Part 1/ Part 2) 1 
E D  
F ollo w -u p 4 
N ot es  
Se e also Sectio n 8  f or d escriptio ns of 
assess m e nts  
E. D = e arly disco ntin u atio n/ wit h dra w al  
D ay 1   
D ay 3 - D ay 2 1 2 
Every 
7 d ays 
( u p t o 
D ay 
8 4) 2 
S O C 
I nitiatio n3 
 
Pr e -
D ose  
I nf usio n/ 
I njectio n 
I n 
clinic 
f ollo w-
u p 5 
2 4 h  
3  
6  
9  
1 1  
1 4  
1 7  
2 1  
 
 
 
I S R Assess m e nt 
 
X 7 
X 8 
X  
X  
X  
 
 
 
 
 
 
 
 
 
Diary car d t o b e distrib ut e d t o su bjects at D ay 
1 (se e Sectio n 8. 3. 8. 1 ) 
Acce pt a bility of 
Tr e at m e nt  
 
X 7 
 
 
 
 
 
 
 
 
 
 
X  
X  
 
T o b e a d minist er e d b ef or e a ny ot h er 
assess m e nts.  
L a b or at ory Assess m e nts  
Qu a ntit ative 
plas m a HI V -1 
R N A  
X  
X 7 
X 8 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
P K T estin g  
X  
X 7 
X 8 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
G S K3 8 1 0 1 0 9 A a ntib o dy co nce ntratio ns in 
Ser u m. Each ser u m sa m ple will b e collect e d 
e q u ally int o 2 aliq u ots wit h o n e aliq u ot as a 
b acku p t o b e st or e d at sit es a n d ship p e d lat er.  
Ant i-dr u g 
a ntib o dy ( A D A)  
X  
 
 
 
 
 
 
 
 
 
 
X 9 
X  
X  
 
 
Wh o le Blo o d 
( P B M C) 
X  
 
 
 
 
 
 
 
 
 
 
 
X  
X  
 
 
Ly m p h ocyt e 
Su bset  
X  
X 7 
X 8 
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
 
 
Saf ety L a bs 
X  
X 7 
X 8 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Clinical ch e mistry, H e m at olo gy  
C CI
C CI

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
1 9  
 
Pr oce d ur e  
M o n ot h er a py Ph ase ( Part 1/ Part 2) 1 
E D  
F ollo w -u p 4 
N ot es  
Se e also Sectio n 8  f or d escriptio ns of 
assess m e nts  
E. D = e arly disco ntin u atio n/ wit h dra w al  
D ay 1   
D ay 3 - D ay 2 1 2 
Every 
7 d ays 
( u p t o 
D ay 
8 4) 2 
S O C 
I nitiatio n3 
 
Pr e -
D ose  
I nf usio n/ 
I njectio n 
I n 
clinic 
f ollo w-
u p 5 
2 4 h  
3  
6  
9  
1 1  
1 4  
1 7  
2 1  
 
 
 
F as tin g L a bs 
X  
 
 
 
 
 
 
 
 
 
 
 
X  
X  
 
Glucose, C h olest er ol ( T ot al, H D L a n d L D L) 
a n d Triglycerid es  
Pr e g n a ncy t est 1 1 
U/ S  
 
 
S  
S  
S  
S  
S  
S  
S  
S  
S  
S  
S  
S  
 
Uri n alysis 
X  
 
 
 
 
 
 
 
 
 
 
 
X  
X  
 
 
C O VI D -1 9 
1 2
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. T h e Sc h e d ule of Acti vities will b e t h e sa m e f or Part 1 a n d Part 2 of t h e st u d y, alt h o u g h d oses a n d r o ut es of a d mi nistrati o n m a y b e different. I n b ot h Part 1 a n d 
Part 2, p artici pa nts will re m ai n i n cli nic fr o m Pre -D ose f or 4 h o ur s f or vit al si g ns e v al uati o n, re gar dless of ra n d o miz e d tre at ment a ssi g n me nt. A n i nt eri m a nal ysis 
a n d sit e c o m m u nic ati o n will pre c e d e c o m me nc e me nt of Part 2.  
2. T h e mi ni m u m d urati o n of t he m o n ot hera p y p hase is Da y 1 1. T h e m o n ot h era p y p h ase will b e e xt e n ded wit h st u d y visits c o n d ucte d a s list e d t hr o u g h Da y 2 1, a n d 
t h e n e v er y 7 d a ys u p t o Da y 8 4 i n p artici p a nts wit h d ata d e m o nstrati n g t hat viral re b o u n d h as n ot o c curre d. I n n o c ase will t h e m o n ot hera p y p hase e xt en d b e y o n d 
Da y 8 4.  
3. A n S O C I nitiati o n visit m ust b e c o n d ucte d i n all p artici pa nts  a n d will b e t h e la st visit i n t h e m o n ot hera p y p hase. If t h e S O C I nitiati o n visit c oi n ci d es wit h a 
pla n n ed st u d y visit (e. g. Da y 1 1), t h e S O C I nitiati o n will pre v ail, t h e S O C I nitiati o n sc h ed ule of a cti vities m ust b e f oll o we d a n d t he visit re c or d ed a s t h e S O C 
I nitiati o n visit i n t h e e C R F. T h e first d ose of oral S O C c o m bi n ati o n A R T s h o ul d b e gi v e n d uri n g t his visit , aft er all ot h er assess me nts a n d e val uati o ns ha v e b e e n 
c o m plete d. T h e  S O C F oll o w -U p Sc h e d ule of Acti vities will b e f oll o we d f or s u bse q u ent st u d y visits. T h e S O C I nitiati o n  visit m a y b e c o n d u ct ed a s a n 
u nsc h e d ule d visit if res ults b e c o me a vaila ble i n dic ati n g t hat t h e p artici pa nt h as met t he m o n ot hera p y e n d p oi nt crit eria.  
4. A n i n -cli nic F oll o w-u p Visit / p h o n e c all will b e c o n d ucte d o nl y f or p artici pa n ts wit h t h e f oll o wi n g c o n diti o ns at t he la st o n-st u d y visit: All o n g oi n g S A Es a n d 
n o n -seri o us A Es of s p e cial i nt erest (a s d efi n ed i n Se cti o n 8. 3. 8 ), re gar dless of attri b uta bilit y. H o we ver, t h e i n v esti gat or, i n c o ns ultati o n wit h t h e me dic al m o nit or, 
s h o ul d f oll o w-u p wit h t h e partici pa nt u ntil t h e e v e nt is res ol v e d, st a biliz e d, ot her wise e x plai n ed, or t h e p artici pa nt is l ost t o f oll o w -u p. T h e n e ed f or a n i n -cli nic 
f ollo w -u p visit vs. a p h o ne c all will b e d et er mi n ed b y t h e I n vesti gat or b ase d o n t h e cli nic al st at us of t h e p artici pa nt . 
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5. An in-clinic follow-up period is required for all study participants. The in-clinic follow-up period will last for 4 hours from the start of the infusion/ injection(s) 
and will include frequent vital signs monitoring as well as other clinical and laboratory evaluations.  
6. Vital signs of blood pressure, heart rate, body temperature, respiratory rate and SpO2 will be measured every 15 minutes during GSK3810109 infusion, including 
at the conclusion of the infusion. For subcutaneous dosing, vital signs will be measured at the conclusion of SC dosing. In a ll dosing groups, vital signs will be 
measured at least every 30 minutes from the start of infusion/ injection for 2 hours, then every hour for another two hours. All vital signs should be recorded in 
the medical record and findings deemed clinically-significant by the Investigator must be reported as Adverse Events (Section 8.3). 
7. Evaluations/blood draws to be conducted following the infusion/ injection. 
8. Evaluations/blood draws to be conducted during the in-clinic follow-up period at 3 hours from start of infusion/ injection. 
9. ADA samples will be collected at the Day 28, Day 56 and Day 84 study visits, if conducted, at the same time as the PK samples are collected. 
10. Storage samples will be used as replacement samples if they are lost or arrive at the laboratory unevaluable or for additional evaluations as required. 
11. At the Day 1 Visit (before start of study treatment), a urine (U) test must be used to confirm pregnancy status prior to administration of study treatment. 
Additionally, a serum sample will be sent for pregnancy testing at the same time. Pregnancy testing will be conducted on POCBP only on serum (S) samples. 
12. COVID-19 testing will be PCR or antigen at Day 1 (pre-dose). COVID-19 PCR or antigen testing will be optional at all study visits should infection be 
suspected. 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
2 1  
 
1. 3. 3.  
St a n d ar d of C ar e F oll o w -U p P h a s e S c h e d ul e of A cti viti e s  
Pr o c e d ure  
S o C Oral F oll o w U p P h as e  
(We e k s  fr o m E n d of Part 1/ Part 2) 
E. D.  
F oll o w -u p a 
E. D = e arly disco ntin u atio n/ wit h dra w al  
+1 we e k  
+4 we e k s  
+8 we e k s  
+1 6 we e k s  +2 4 we e k s  
+3 2 we e k s  
+4 8 we e k s  
N ot e s  
Cli ni c al a n d Ot her A s se s s m ents  
Vit al sig ns  
X  
X  
X  
X  
X  
X  
X  
X  
 
blo o d pr essur e, h e art r at e a n d b o dy 
t e m p er at ur e 
Bo dy Weig ht/ B MI  
 
 
 
 
X  
 
X  
X  
 
 
HI V Associat e d 
C o n ditio ns  
 
X  
X  
X  
X  
X  
X  
X  
 
 
Acce pt a bility of 
Tr e at m e nt  
 
 
 
 
X  
 
X  
X  
 
T o b e a d minist er e d b ef or e a ny ot h er 
assess m e nts.  
A E /S A E R evie w  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
C o nco mit a nt 
M e dicatio ns  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
L a b orat ory A ss e s s me nt s  
Qu a ntit ative plas m a 
HI V -1 R N A  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
P K T estin g  
X  
X  
X  
X  
X  
X  
X  
X  
 
G S K3 8 1 0 1 0 9 A a ntib o dy co nce ntration 
in ser u m. Each ser u m sa m ple will b e 
collect e d e q u ally int o 2 aliq u ots wit h 
o n e aliq u ot as a b acku p t o b e st or e d 
at sit es a n d ship p e d lat er.  
A D A sa m ple  
 
X  
X  
X  
X  
X  
X  
X  
 
 
C CI
C CI

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
2 2  
 
Pr o c e d ure  
S o C Oral F oll o w U p P h as e  
(We e k s  fr o m E n d of Part 1/ Part 2) 
E. D.  
F oll o w -u p a 
E. D = e arly disco ntin u atio n/ wit h dra w al  
+1 we e k  
+4 we e k s  
+8 we e k s  
+1 6 we e k s  +2 4 we e k s  
+3 2 we e k s  
+4 8 we e k s  
N ot e s  
Ly m p h ocyt e Su bset  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
Saf ety L a bs  
X  
X  
X  
X  
X  
X  
X  
X  
 
Clinical ch e mistry a n d h e m at olo gy  
F astin g L a bs  
 
 
 
 
X  
 
X  
X  
 
Glucose, C h olest er ol ( T ot al, H D L a n d 
L D L) a n d Triglycerid es  
Pr e g n a ncy t est   
S  
S  
S  
S  
S  
S  
S  
S  
 
S =ser u m  
Urin alysis  
 
 
 
 
X  
 
X  
X  
 
 
C O VI D -1 9 t estin g c 
 
 
 
 
 
 
 
 
 
 
a.  An in -clinic F ollo w -u p Visit / p h o n e call will b e co n d uct e d o nly f or p articip a nts wit h t h e f ollo win g co n ditio ns at t h e last o n -st u dy visit: All o n g oin g S A Es a n d n o n -serio us A Es of 
sp ecial int er est ( as d efin e d in Sectio n 8. 3. 8 ), r e g ar dless of attrib ut a bility.  H o w ever, t h e investig at or, in co nsult atio n wit h t h e m e dical m o nit or, sh o uld f ollo w -u p wit h t h e 
p articip a nt u ntil t h e eve nt is r esolve d, st a bilize d, ot h er wise e xplain e d, or t h e p articip a nt is lost t o f ollo w -u p.  
b.  T h ese sa m ples will b e use d f or vir al g e n o/ p h e n o ( R T/ P R O/I N ) in eve nt of vir olo gic f ailur e, as r e place m e nt sa m ples if t h ey ar e lost or arrive at t h e la b or at ory u n evalu a ble or 
f or a d ditio n al evalu atio ns as re q uir e d.  
c. C O VI D -1 9 P C R or a ntig en  t estin g will b e o ptio n al at all st u dy visits sh o uld inf ectio n b e susp ect e d. 
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2. 
INTRODUCTION 
Despite significant progress in the treatment and prevention of HIV infection, it has 
remained a significant public health problem since the virus was discovered in 1983. 
While current treatment and prevention options are effective, none of the current 
therapeutic or prophylactic regimens can completely prevent or cure an infection or 
induce a full recovery of the host immune system. Therefore, novel agents and strategies 
continue to be investigated. 
Broadly neutralizing antibodies (bNAb) reactive to viral proteins expressed by circulating 
virus hold the promise as effective therapeutic or prophylactic agents against HIV. 
Several broadly neutralizing human monoclonal antibodies have been isolated and are in 
various stages of development for treatment and prevention of HIV infection. These 
include antibodies with specificities to the CD4 binding site (VRC01 [Bar, 2016], 
VRC07-523LS [Kwon, 2012], 3BNC117 [Scheid, 2011]), the high mannose patch (10-
1074 [Mouquet, 2012], PGT121 [Walker, 2011]), the V2 apex (PG9 [Walker, 2009] 
[McLellan, 2011], PDGM 1400 [Walker, 2011], CAP256.25 [Doria-Rose, 2015]) and the 
membrane-proximal external region (10E8 [Kwon, 2016]). 
N6 is a broadly neutralizing HIV antibody that has shown high potency against various 
HIV isolates, including strains that are resistant to other antibodies. N6 was isolated from 
a patient with a 21-year known history of HIV-1 infection that was controlled in the 
absence of HAART [Huang, 2016] and is in the class of bNAbs that targets the CD4-
binding site of the HIV envelope protein by occluding the binding site for the cellular 
receptor CD4. 
In order to improve the pharmacokinetics of N6, two amino acid substitutions 
(methionine to leucine and an asparagine to serine) were introduced within the C-
terminus of the heavy chain region of N6 via site-directed mutagenesis to increase its 
binding affinity for the neonatal Fc-receptor. Incorporation of the LS mutations did not 
affect the neutralization breadth or potency of N6LS compared to N6 [Huang, 2016]. 
Based on preclinical and clinical studies of other bNAbs with and without the LS 
mutation [Rudicell, 2014; Ko, 2014; Gaudinski, 2018], the LS modification is expected to 
result in enhanced recirculation and longer plasma half-life of N6LS relative to the wild-
type antibody (N6). N6LS (GSK3810109A) is being developed for the treatment of HIV-
1 infection in adults in combination with other agents. 
2.1. 
Study Rationale 
This Phase 2a proof of concept (PoC) trial will be the first study of GSK3810109A 
(N6LS) in HIV-infected participants and will evaluate the efficacy, safety, tolerability, 
and pharmacokinetics of the broadly neutralizing HIV antibody GSK3810109A in 
treatment naïve viremic adults after a single dose administered as infusion or SC 
injection. Data from this study will be utilized to select doses and routes of administration 
for further studies of GSK3810109A in combination with other ART in Phase 2b and 
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2.2. 
Background 
GSK3810109A belongs to a class of broadly neutralizing HIV antibodies (bNAb). These 
antibodies target the CD4-binding site of the HIV envelope protein. A detailed 
description of the chemistry, pharmacology, and data from the first time in human (FTIH) 
study (Protocol VRC609) is provided in the GSK3810109A Investigators Brochure. 
Protocol VRC609, the FTIH study of GSK3810109A in healthy individuals assessed the 
safety, tolerability and pharmacokinetics of this antibody. The FTIH study was an open-
label, single and repeat dose administration of N6LS given across 6 dose groups of either 
a single IV infusion at 5, 20, or 40 mg/kg dose levels (N=3 for each group), a single SC 
injection at the 5 mg/kg dose level (N=3), in 3 administrations 12 weeks apart by SC 
injection at the 5 mg/kg dose level (N= 5) or in 3 administrations 12 weeks apart by IV 
infusion at the 20 mg/kg dose level (N=5). Enrolment was completed with 22 participants 
enrolled and all participants have completed dosing. 
GSK3810109A was generally well tolerated, with no SAEs, dose-limiting toxicities or 
deaths reported. Treatment-emergent laboratory abnormalities have been few and mostly 
Grade 1. Data from the FTIH study was utilized to support future clinical development of 
GSK3810109A and determined the starting doses to be used in Part 1 of 207959. 
The current study, 207959, is designed based on the known data from GSK3810109A 
along with experiences from other CD4-binding site bNAbs VRC01 [Lynch, 2015] and 
3BNC117 [Caskey, 2015] as well as the modified versions of VRC01LS and VRC07-
523LS which are designed for extended serum half-life by increased binding affinity to 
the neonatal Fc receptor, which are similar to GSK3810109A [Gaudinski, 2018] 
[Gaudinski, 2019]. 
These other bNAbs were administered at similar doses, frequency and routes as 
GSK3810109A in the FTIH VRC609 study and have been generally well-tolerated with 
no deaths or serious adverse events assessed as related to the investigational drug. The 
predominant local reactogenicity complaint has been mild pain/tenderness, although 
reports of mild injection site pruritus, redness and swelling have occurred at modestly 
higher frequencies with the SC administration. Malaise, muscle pain and headache have 
been the most frequently reported events noted in the 3 days post product administration. 
These events have been mild in severity and transient. Although infrequent, infusion 
reactions comprised of chills, rigors, myalgia, and headache have been reported after IV 
infusions at product doses of 10 to 40 mg/kg. These reactions have been transient, 
resolving within 24-hours of onset, without sequelae, and have generally been treated 
with over-the-counter analgesics and antipyretics. 
This Phase 2a proof of concept (PoC) trial will be the first study of GSK3810109A in 
HIV-infected participants and will evaluate the efficacy, safety, tolerability, and 
pharmacokinetics of the bNAb GSK3810109A in antiretroviral-naïve, viremic adults 
following a single dose infusion or single dose subcutaneous injection. 

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2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of GSK3810109A may be found in the 
GSK3810109A Investigator’s Brochure. 
In the first time in human study (Protocol VRC609), no SAEs or deaths were reported 
and no withdrawals were due to drug-related AEs. All reported AEs were either Grade 1 
or 2. Furthermore, there was no evidence of a dose or administration route relationship 
with regard to AEs. 
The safety concerns identified for N6LS from non-clinical toxicology studies and limited 
clinical data from the VRC Phase 1 clinical trial include: local/systemic reactogenicity, 
liver chemistry elevations, neutropenia, serious/severe immune reactions and 
immunogenicity. The main safety concern in this single dose study in HIV-infected 
treatment-naïve participants are local and systemic reactogenicity. These reactions are to 
be expected due to the route of administration and in the Phase 1 study were transient, 
without sequelae, and treated with over the counter analgesics and antipyretics. With the 
implementation of appropriate risk mitigation strategies, all safety concerns are 
considered manageable (see Section 2.3.1). 
To ensure the overall safety of participants this clinical trial will include participants who 
will receive clinical, laboratory, and safety assessments prior to and during their 
participation in the trial. Furthermore, a Safety and Dose Evaluation Committee (SDEC) 
will review emerging data and make recommendations per the Go/No Go criteria 
included in this protocol, recommend study changes, including doses and routes of 
administration for Part 2, and review safety parameters during the course of the study. 
 

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2.3.1. 
Risk Assessment 
The following table outlines the risk assessment and mitigation strategy for this protocol. Additionally, all participants will be closely 
monitored over the 11 days (minimum monotherapy duration) following the administration of a single dose of GSK3810109A. During the 
Standard of Care follow-up phase, all participants will be placed on an oral integrase-based combination ART with frequent monitoring at 
approx. 1, 2, 4, 6, 8, and 12 months after the monotherapy phase. 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (IP) GSK3810109A 
Serious/severe immune 
reactions 
(Anaphylaxis and 
Cytokine release 
syndrome [CRS]) 
Non-clinical 
No serious/severe immune reactions noted in the non-
clinical rat study 
  
Clinical 
Administration of mAbs may cause immune reactions 
such as acute anaphylaxis, serum sickness and the 
generation of antibodies. However, these reactions are 
rare and more often associated with mAbs targeted to 
human proteins or with the use of murine monoclonal 
antibodies which would have a risk of human anti-
mouse antibodies.  
 
CRS reactions most commonly occur within the first 
few hours of beginning the infusion and are more 
Anaphylaxis is a life-threatening reaction with respiratory, cardiovascular, 
cutaneous, or gastrointestinal manifestations.  
  
Vital signs will be monitored during the infusion and prompt treatment of 
anaphylaxis is critical, with subcutaneous or intramuscular epinephrine and 
intravenous fluids. Adjunctive measures include airway protection, 
antihistamines, steroids, and beta agonists. Some symptoms may be treated 
by slowing or stopping the infusion. Supportive treatment may also be 
indicated for some signs and symptoms. 
  
Patients with anaphylaxis should be closely monitored for the possibility of 
recurrent symptoms after initial resolution. 
  

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
common with the first mAb infusion received. This is 
because cytokine release is associated with lysis of 
cells targeted by the mAb and the burden of target 
cells is greatest at the time of the first mAb. 
  
GSK3810109A is expected to have a low risk for 
serious/severe immune reactions as it is directed 
against a viral antigen and is human in origin. No 
serious/severe immune reactions have been 
previously observed with GSK3810109A. 
Urinary and serum histamine levels and plasma tryptase levels drawn after 
onset of symptoms may assist in diagnosis 
  
In stream study pause criteria (participant level): 
Acute Allergic reaction or cytokine release syndrome (DAIDS criteria Grade 
3-4) reasonably attributable to dosing with GSK3810109A, in the opinion of 
the Investigator and Sponsor 
Local reactogenicity 
(injection site reactions) 
Non-clinical 
The repeat dose IV and SC administration of 
GSK3810109A at 40 and 400 mg/kg (IV) and 5 and 50 
mg/kg (SC) in male and female Sprague-Dawley rats 
produced test article-related effects in injection site 
irritation (slight erythema observed with low incidence, 
reversible, considered not toxicologically relevant). 
  
Clinical 
All reported instances of local reactogenicity 
(pain/tenderness, swelling, redness, bruising, pruritus) 
were mild (Grade 1) except for one moderate (Grade 
2) instance each of swelling and redness. All local 
Exclusion criteria as described in Section 5.2 will prohibit participants with an 
underlying skin disease or disorder (i.e. infection, inflammation, dermatitis, 
eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that would 
interfere with assessment of injection sites. 
 
Participants will be closely monitored for local/systemic reactions.  
  
Administration advice to minimize risk of poor administration technique giving 
rise to injection site reactions. Advice on care, monitoring, natural course, and 
treatment of ISRs given in study documentation 
  

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
reactogenicity events were reported as recovered 
within 5 days of onset.  
  
The most frequently reported event was Grade 1 
pain/tenderness at the injection site in the SC groups 
(6/8, 75%). Overall, there was more reactogenicity in 
the SC groups (16 reactions over 18 administrations) 
versus the IV groups (1 reaction over 24 
administrations) 
  
  
Advice to participants on care of injection site on day/days immediately post 
administration, use of analgesia, compresses where appropriate 
  
AEs Participants will be closely monitored for ISRs particularly for signs of 
pain, tenderness, infections, erythema, swelling, induration, or nodules 
(granulomas or cysts) throughout the study.  
  
Complications of ISRs such as infections (abscess, cellulitis) and collections 
of fluid requiring drainage will be monitored.  
  
Significant ISRs will be photographed and referred to a dermatologist for 
specialist advice and possible biopsy. 
  
In stream study pause criteria (participant level): 
Any Grade 4 AE assessed as related to GSK3810109A by the Investigator 
Or 
Any Serious Adverse Event (SAE), regardless of its severity, that is 
considered be clinically significant and reasonably attributable to dosing with 
GSK3810109A, in the opinion of the Investigator or Sponsor. 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
  
In stream study pause criteria (cohort level):  
If ≥30% of participants within a dose group have a Grade 3 or higher AE 
trend or laboratory abnormality trend (with the exception of asymptomatic 
Grade 3 or higher cholesterol, triglyceride) once half of study participants 
have been dosed. 
Systemic reactogenicity 
Non-clinical 
 In the repeat dose study in Sprague Dawley rats of 3-
weeks duration, two females given 40 mg/kg/IV 
showed hypoactivity and prostrate posture on Day 21 
immediately and/or 2-4 hours post dose with recovery 
within 24 hours, consistent with an infusion related 
reaction. 
 
  
Clinical 
All reported instances of systemic reactogenicity 
(malaise, myalgia, headache, nausea, chills) were mild 
(Grade 1) and were reported as recovered within 1 day 
of onset.  
  
Participants will be closely monitored for local/systemic reactions.  
  
IV access will be placed in an arm vein in an aseptic manner. GSK3810109A 
will be administered with approximately 100 mL of normal saline IV over 1 
hour minutes. Infusions lasting longer than 1 hour are allowed.  If the 
participant experiences side effects during the infusion, the rate of infusion 
may be slowed or stopped to alleviate the symptoms.  
  
Vital signs will be monitored during infusions. 
  
In stream study pause criteria (participant level): 
Any Grade 4 AE assessed as related to GSK3810109A by the Investigator 
Or 

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Potential Risk of 
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The most frequently reported event was Grade 1 
headache in 1/8 (13%) participant in the SC groups 
and 4/14 (27%) participants in the IV groups. 
  
Overall, there was more systemic reactogenicity in the 
IV groups (7 reactions over 24 administrations) versus 
the SC groups (4 reactions over 18 administrations). 
  
  
Any Serious Adverse Event (SAE), regardless of its severity, that is 
considered be clinically significant and reasonably attributable to dosing with 
GSK3810109A, in the opinion of the Investigator or Sponsor. 
  
In stream study pause criteria (cohort level):   
If ≥30% of participants within a dose group have a Grade 3 or higher AE 
trend or laboratory abnormality trend (with the exception of asymptomatic 
Grade 3 or higher cholesterol, triglyceride) once half of study participants 
have been dosed. 
 
Gastrointestinal 
disorders 
(Diarrhea) 
Non-clinical 
N/A 
 
Clinical 
In the phase 1 study, three participants experienced 
diarrhea (Grade 1 - Grade 3) considered related by the 
Investigator. Time to onset was 1 to 6 days from last 
dose and all recovered within 2 days. One additional 
participant with Grade 1 diarrhea was not considered 
related (time to onset was 19 days post dose). 
Careful monitoring of adverse GI events will occur throughout the study. 
Serious/severe events will be managed appropriately and will be 
followed to resolution as per standard ViiV Medical Monitoring 
practices. 
 
In stream study pause criteria (participant level): 
Any Grade 4 AE assessed as related to GSK3810109A by the Investigator 
Or 

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Potential Risk of 
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Summary of Data/Rationale for Risk 
Mitigation Strategy 
Any Serious Adverse Event (SAE), regardless of its severity, that is 
considered be clinically significant and reasonably attributable to dosing with 
GSK3810109A, in the opinion of the Investigator or Sponsor. 
 In stream study pause criteria (cohort level):   
If ≥30% of participants within a dose group have a Grade 3 or higher AE 
trend or laboratory abnormality trend (with the exception of asymptomatic 
Grade 3 or higher cholesterol, triglyceride) once half of study participants 
have been dosed. 
Liver chemistry 
elevations  
Non-clinical 
The repeat dose IV and SC administration of 
GSK3810109A at 40 and 400 mg/kg (IV) and 5 and 50 
mg/kg (SC) in Sprague-Dawley rats produced test 
article-related effects in clinical chemistry with up to 
1.5-fold increase in aspartate aminotransferase (AST), 
alanine aminotransferase (ALT) and/or alkaline 
phosphatase (ALP), correlating with the 
histopathologic findings in the liver, within high-end of 
normal ranges and considered not to have reached a 
level of toxicity. 
 
 
 
Exclusion criterion for Phase 2a: participants with liver impairment based 
on screening liver chemistry: 
 
Participants with ALT>1.5 ULN or total bilirubin >1.5 ULN are excluded. 
 
Liver transaminases (ALT and AST) will be monitored throughout this study 
(refer to SoA, Section 1.3) and the liver chemistry stopping criteria will be 
adopted as described in Section 7.3 of this protocol.  
 
In stream study pause criteria (participant level):  
Phase 2a liver chemistry stopping criteria:  

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Clinical 
A total of 3 (14%) participants experienced liver 
enzyme elevations: 2 ALT elevation; 1 AST elevation. 
All Grade 1 or 2) and transient. 
 
 
• ALT≥3xULN 
• If ALT≥3xULN AND bilirubin 2xULN (>35% direct bilirubin), i.e. Hy’s case, 
report event as SAE. 
In stream study pause criteria (cohort level):    
If ≥30% of participants within a dose group have a Grade 3 or higher AE 
trend or laboratory abnormality trend (with the exception of asymptomatic 
Grade 3 or higher cholesterol, triglyceride) once half of study participants 
have been dosed. 
Neutropenia 
Non-clinical 
The repeat dose IV and SC administration of 
GSK3810109A at 40 and 400 mg/kg (IV) and 5 and 
50 mg/kg (SC) in Sprague-Dawley rats produced test 
article-related effects in monocytes up to 2.6-fold 
increase, reticulocytes up to 3.7-fold increase and 
eosinophils up to 72.7% decrease, all reversible, 
correlated with non-adverse histopathology findings in 
axillary lymph nodes, spleen and bone marrow and/or 
organ weight findings in spleen. 
  
 
Close monitoring of blood counts in participants initiating therapy will be 
conducted throughout this study (refer to SoA, Section 1.3). 
 
In stream study pause criteria (participant level): any Grade 4 AE 
assessed as related to GSK3810109A by the Investigator. 
Or 
Any Serious Adverse Event (SAE), regardless of its severity, that is 
considered be clinically significant and reasonably attributable to dosing with 
GSK3810109A, in the opinion of the Investigator or Sponsor. 
  

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Clinical 
A Grade 2 neutropenia in 1/22 participant was 
considered possibly related by the Investigator in the 
Phase 1 study. Baseline neutrophil count was 3.15 x 
103 cells/L. Neutropenia (0.75 x 103 cells/L) started 
23 days post dose (single IV dose (20 mg/kg) and 
returned to 3.11 x 103 cells/L (within normal range) 
13 days later at the next specimen collection. No 
intercurrent illness or confounding concomitant 
medication was reported. 
  
In stream study pause criteria (cohort level):    
If ≥30% of participants within a dose group have a Grade 3 or higher AE 
trend or laboratory abnormality trend (with the exception of asymptomatic 
Grade 3 or higher cholesterol, triglyceride) once half of study participants 
have been dosed. 
 
Immunogenicity 
Non-clinical 
GSK3810109A exhibited lower serum concentrations 
after repeat administration via both routes in the dose 
ranges studied suggesting the formation of anti-drug 
antibodies which was more prominent in the SC dose 
groups but also apparent in the 40 mg/kg IV dose 
group. Following repeated administration of 400 mg/kg 
IV during the main study there was faster clearance in 
some animals by Day 56. In addition, two females 
given 40 mg/kg/IV showed hypoactivity and prostrate 
posture on Day 21 immediately and/or 2-4 hours post 
dose with recovery within 24 hours, consistent with an 
infusion related reaction. The toxicities observed are 
therefore considered possibly to be a result of the 
formation and subsequent clearance of anti-drug 
The emergence of ADAs will be actively monitored using a validated ADA 
assay (screening, confirmation, and titration). 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
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antibodies (ADAs), although this cannot be confirmed 
since immunogenicity analysis was not conducted. 
  
Clinical 
Animal studies are generally not predictive of 
immunogenicity and sequelae related to 
immunogenicity in humans. ADAs were detected in 
2/22 (9%) of GSK3810109A-treated subjects at any 
time after dosing, however, exhibited no neutralizing 
activity. There were no discernible effects of 
immunogenicity on the safety and PK profiles from the 
Phase 1 study. 

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2.3.2. 
Benefit Assessment 
This study in treatment naïve, HIV-1 infected participants includes a single dose 
monotherapy phase in both Part 1 and Part 2 which includes frequent site visits and close 
monitoring for new signs and symptoms following a single dose infusion or single dose 
SC injection. The monotherapy period uses a response-guided approach so that 
participants will initiate combination antiretroviral therapy (cART) as soon as possible 
following necessary evaluations to fully characterize the potency and duration of 
virologic effect of GSK3810109A. While no direct benefits should be expected for study 
participants in this part of the study, the information learned may help others living with 
HIV, and help advance new long-acting treatments for people living with HIV. 
A Go/No-Go decision (see Section 9.5) to progress to Part 2 will be based on the 
virologic response from the 40 mg/kg IV dose group and the safety data from both dose 
groups in Part 1. The Safety and Dose Evaluation Committee (SDEC) will review 
emerging data from the two dose groups in Part 1 in order to select appropriate doses and 
routes of administration for Part 2. 
During the standard of care follow-up period all participants will initiate an integrase-
based oral combination therapy to treat their HIV and be monitored for an additional 48 
weeks. Oral HIV treatment with fixed-dose dolutegravir + lamivudine will be provided 
through the study for use during the follow-up period. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Given the non-clinical and clinical profile to date, data from other bNAb studies, the 
frequent visit schedule, and the proposed dose levels in the single dose monotherapy 
phase, the overall risk to treatment-naïve HIV-1 infected participants in this study is 
predicted to be low and manageable. 
Additionally, the doses administered in this study will not exceed those in the FTIH study 
(VRC609), see Section 2.2 for additional information on this study. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To evaluate the antiviral activity following a 
single dose of GSK3810109A in treatment-
naïve HIV-1 infected participants 
Plasma HIV-1 RNA maximum change from 
Baseline during the monotherapy phase  
• 
To assess safety parameters following 
a single dose infusion or SC injection 
with GSK3810109A in treatment-naïve 
HIV-1 participants 
Adverse events, Grade 2-4 ALT/ AST, 
treatment-emergent ECG abnormalities and 
Grade 2-4 injection site reactions 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
3 6  
 
O bje ctiv e s  
E n d p oi nts  
Se c o n d ar y  
•  
T o ch aracterize th e p h ar macoki n etics 
of G S K3 8 1 0 1 0 9 A i n tre at me nt -n aïve 
HI V -1 i nfecte d p artici p a nts foll o wi n g a 
si n gl e I V or S C a d mi nistrati o n  
•  
G S K3 8 1 0 1 0 9 A P K p ara meters 
foll o wi n g si n gl e d ose a d mi nistrati o n 
e.g.: A U C (0 -t), C max, T max, Ct 
•  
T o expl ore th e p ote ncy of 
G S K3 8 1 0 1 0 9 A  
R el ati o nshi p b et w e e n G S K3 8 1 0 1 0 9 A 
exp osure a n d ch a n g e i n pl as ma HI V -1 R N A 
over ti me. 
•  
T o assess th e i m mu n ol o gic ch a n g es 
foll o wi n g a si n gl e I V or S C d ose of 
G S K3 8 1 0 1 0 9 A  
Absol ute val u es a n d ch a n g e i n T cell co u nts 
fro m b aseli n e over ti me  
•  
T o assess w h eth er a nti -dru g a nti b o di es 
d evel o p foll o wi n g a si n gl e d ose of 
G S K3 8 1 0 1 0 9 A  
Inci d e nce of a n d titre i n seru m of a nti 
G S K3 8 1 0 1 0 9 A a nti b o di es over ti me  
Safety  
•  
Safety a n d tol era bility of G S K3 8 1 0 1 0 9 A 
foll o wi n g a si n gl e d ose i nfusi o n or S C 
i nj ecti o n with G S K3 8 1 0 1 0 9 A i n 
tre at me nt-n aïve HI V -1 p artici p a nts  
Cli nical l a b oratory p ara meters, E C Gs, vital 
si g ns, a n d i nj ecti o n site re acti o ns over ti me. 
Ex pl or at or y  
C CI

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
3 7  
 
O bje ctiv e s  
E n d p oi nts  
 
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
Pr ot o c ol 2 0 7 9 5 9 is a t w o -p art, ra n d o mize d, o p e n la b el a d a pti v e d esi g n st u d y t o 
c h ara cteriz e t h e a nti viral a cti vit y, s afet y/t olera bilit y, P K a n d P K/ P h ar m a c o d y n a mics ( P D, 
HI V -1 R N A d e cli n e) of G S K 3 8 1 0 1 0 9 A a d mi nistere d b ot h i ntra ve n o usl y (I V) a n d 
s u b c uta n e o usl y ( S C) i n HI V-1 i nf e cte d, tre at m e nt -n aï v e a d ults. T h e st u d y d esi g n i n clu des 
a s cre e ni n g p h as e, a ra n d o mize d m o n ot h era p y p h as e a n d a sta n d ar d of c are f oll o w -u p 
p h as e. T h e t w o p arts of t h e ra n d o miz e d p h as e will e a c h i n cl u de a si n gle d os e 
m o n ot h era p y e v al uat i o n p eri o d after w hic h all p artici p a nts will e nter a l o n g-ter m f oll o w-
u p p eri o d d uri n g w hic h p artici p a nts will i nitiate a n a p pr o priate i nte gras e -b ase d sta n dar d 
of c are tre at m e nt re gi m e n.  
4. 1. 1.  
S cr e e ni n g P h a s e  
I nf or m e d c o ns e nt m ust b e o btai ne d pri or t o a n y st u d y pr oc e d ures, i n cl u di n g a n y 
Scre e ni n g ass ess m e nt.  
Partici p a nts will c o m plete a s cre e ni n g p eri o d of u p t o 2 8 d a ys. Scre e ni n g m a y b e 
e xte n d e d u p t o o n e a d diti o n al w e e k if la b res ults are p e n di n g (ra n d o miz ati o n or s cre e n 
f ail ure m ust o c c ur wit hi n 3 5 d a ys f oll o wi n g t h e Scre e ni n g Visit). A si n gle re p e at of a 
pr o c e d ure/la b p ara m eter is all o w e d t o d eter mi n e eli gi bilit y ( u nless ot h er wis e s p ecifie d). 
Partici p a nts m a y b e re -s cre e n e d o n c e w hic h re q uires a n e w p artici pa nt n u m b er. 
Partici p a nts w h o are ra n d o miz e d i nt o t h e trial a n d s u bs e q u e ntl y wit h dra w n fr o m t h e 
st u d y, f or a n y re as o n, m a y n ot b e re -s cree n e d. Partici p a nts m a y b e ra n d o miz e d o n D a y 1 
as s o o n as all eli gi bilit y re q uire m e nts h a v e b e e n c o nfir m e d at t h e site.  
4. 1. 2.  
R a n d o mi z e d M o n ot h er a p y  P h a s e  
T h e ra n d o miz e d p h as e will  o c c ur i n Part 1 a n d, if pre -d efi ne d G o/ N o G o criteria are m et, 
Part 2.  
Part 1 will i n cl u d e 2 d os e gr o u ps a d mi nistere d as a si n gle I V i nf usi o n of eit h er 4 0 m g/ k g 
or 2 8 0 m g flat d os e (re pres e nti n g a p pr o xi m atel y 4 m g/ k g f or a n a v era ge 7 0  k g 
i n di vi d u al). Ra n do miz ati o n will b e b ala n c e d ( 1: 1) i nt o t h e t w o d os e gr o u ps i n Part 1.  
Part 2 is a ntici p ate d t o i n cl u d e 3 d os e gr o u ps ( b ut m a y i n cl u d e u p t o f o ur d os e gr o u ps 
d e p e n d e nt u p o n d ata ge n erate d fr o m Part 1) a d mi nistere d as a si n gle I V i nf usi o n or S C 
i nje cti o n (t h e S C d os e m a y re q uire m ulti ple i nje cti o ns gi v e n at o n e ti m e). Ra n d o miz ati o n 
will b e b ala n c e d i nt o e a c h of t h e d os e gr o u ps s ele cte d f or Part 2.  
C CI

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An interim analysis will be conducted from data obtained during the Part 1 monotherapy 
period (Groups 1 and 2) and available data from ongoing SOC, in which virologic 
response, safety and PK will be evaluated. The interim analysis will be conducted 
according to criteria defined in Section 4.4 and Section 9.5. Further groups will then be 
studied in Part 2 across a range of up to 4 additional dose levels. Final doses and 
administration routes in Part 2 will be determined following evaluation of data from Part 
1. 
An SDEC will review data from Part 1 and determine study progression based upon the 
pre-defined Go/No Go criteria. The SDEC will also determine dosing in Part 2. In Part 2, 
GSK3810109A will be administered either intravenously or subcutaneously. 
4.1.3. 
Standard of Care Follow-Up Phase 
Following the monotherapy period, a standard of care integrase-based treatment regimen 
will be initiated and maintained for the duration of the long-term follow-up period. 
Virologic response, safety and PK will continue to be assessed during the follow-up 
period. Assessments of tolerability, acceptability and markers of immune function will 
also be collected throughout the study. 
A SOC Initiation visit will be conducted in all participants at the conclusion of the 
monotherapy period. The SOC is stipulated to be an integrase inhibitor-based cART 
regimen, and must be initiated the day of the SOC Initiation visit. A regimen of 
dolutegravir + lamivudine will be provided through the study if deemed appropriate by 
the investigator and consistent with local guidelines. Alternative integrase inhibitor-based 
cART regimens may be permissible for use during the SOC follow-up phase after 
consultation and agreement with the medical monitor. Alternative SOC regimens will not 
be provided through the study and must be procured locally. A plan for SOC therapy 
should be considered at the time participants are screened to assure that an appropriate 
SOC regimen is selected and available prior to randomization into the monotherapy phase 
of the study. Reimbursement for alternative SOC regimens may be available, where 
agreed in advance with the medical monitor. 
4.2. 
Scientific Rationale for Study Design 
Previous studies with bNAbs have found that HIV-1 RNA nadir was achieved after 7-10 
days of dosing (VRC01 – day 9 [Lynch, 2015], 3BNC117 – day 7 [Caskey, 2015], 10-
1074 – day 10.3 [Caskey, 2017]). 
Study 207959 is a Phase 2a, open label, single dose study evaluating up to 6 IV or SC 
dose levels of GSK3810109A, including a maximum 40 mg/kg dose. A Go/No Go 
decision to progress to Part 2 will be based on the virologic response from the 40 mg/kg 
infusion dose group of Part 1, see Section 4.4 and Section 9.5 for additional information.  
Study 207959 will include a monotherapy period following a single dose to determine 
antiviral activity and characterize viral dynamics. Emerging data from the two IV dose 
levels in Part 1 will be utilized to select appropriate doses and administration routes for 
Part 2. If SDEC review determines that criteria to continue are met, additional 

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participants will be enrolled in Part 2 and receive GSK3810109A 40 mg/kg given as a 
single dose infusion or SC injection. 
Study 207959 is designed to evaluate safety, PK and virologic endpoints when 
GSK3810109A is administered both via IV infusion and by SC injection. The inclusion 
of both routes of administration in this study is an efficient design to enable rapid 
progression to Phase 2b in either or both routes of administration. Further, subsequent 
studies of GSK3810109A are envisioned to be conducted in a stably suppressed HIV-
infected patient population. Therefore, the inclusion of both IV and SC administration in 
the current study enables evaluation of these endpoints by both routes of administration, 
including exploratory immunologic endpoints, in an ART-naïve, HIV-infected 
population. 
207959 is designed as an open-label study; an open label trial design affords the 
availability of real time safety data following antibody infusions. Based upon the small 
sample size (approximately 10 participants for all Groups in Part 1 and Part 2) and the 
open-label trial design, safety and tolerability will be assessed in-stream (via a Safety 
Review Team) as well as at defined analysis timepoints (via the Safety and Dose 
Evaluation Committee). Enrollment in Part 1 will continue until approximately 10 
evaluable participants are confirmed in Group 1. If participants prematurely discontinue 
during Part 1 or Part 2 additional replacement participants may be enrolled at the 
discretion of the Sponsor. These replacement participants will be assigned to the same 
dose as the corresponding participant who prematurely discontinued from the study. 
Consistent with other proof of concept studies of CD4 binding site bNAbs, no placebo 
arm is included in this study [Bar, 2016; Gaudinski, 2019]. The FTIH (VRC609) has 
provided supportive data on the safety and tolerability of GSK3810109A at similar 
exposures to those planned in this study, supporting progression without the need for a 
control group for safety comparisons. A placebo control group would not be expected to 
improve interpretation of the PK or virologic endpoints, which are laboratory-derived. 
Furthermore, current clinical practice recommends immediate initiation of combination 
antiretroviral therapy (cART) at the time of diagnosis; inclusion of a placebo group 
would delay the initiation of cART in those participants without expected scientific 
benefit. 
The monotherapy period in Part 1 and Part 2 is designed to balance a minimum duration 
to observe viral activity (viral nadir) of GSK3810109A with the need to initiate standard 
of care therapy as soon as possible. A minimum monotherapy period has been established 
to observe virologic response in all participants, even where modest or non-response may 
occur. In this study with frequent follow-up visits, a minimum monotherapy period of 11 
days will yield at least 4 assessments to evaluate viral dynamics of GSK3810109A prior 
to initiation of SOC cART, with a high likelihood to observe viral nadir based on data 
from other CD4 binding site bNAbs. 
A response-guided algorithm will be used to determine initiation of SOC cART in 
participants with a more robust virologic response. In those participants, the monotherapy 
period will be extended until virologic rebound is achieved, up to Day 84. A response-
guided extension of the monotherapy period allows for a more complete characterization 

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of the viral nadir, thus aiding in final dose, dose frequency and administration route 
selection. 
Participants should continue in the monotherapy period until meeting one of the 
following monotherapy endpoint criteria, which are assessed at each study visit beginning 
at Day 11: 
1. Virologic non-response. Virologic non-response will be confirmed if, at Day 11, viral 
nadir decline is <0.5log10. Viral nadir is defined as the lowest observed post-Dose 
HIV-1 result and viral nadir decline is calculated from the Day 1 (Pre-Dose) HIV-1 
RNA result. 
2. Virologic rebound. Virologic rebound will be confirmed if either of the following 
have occurred at or after Day 11: 
• HIV-1 RNA rebound of 1.0log10 increase from nadir.  
• HIV-1 RNA rebound to <0.5log10 from Baseline. This criteria will be met 
where there is a rebound from nadir that is less than 1.0log10 , but within 0.5 
log10 of the Day 1 (Pre-Dose) study visit. 
3. Missing/delayed data from previous visits. HIV-1 RNA results are generally expected 
to be returned within 48-72 hours from the central lab, however, a delay can impede 
the ability to determine a study participant’s status to continue in monotherapy or 
initiate SOC cART. This is especially important during the first 21 days of the 
monotherapy period where study visits are frequent and results from the immediately 
preceding visit may not be available. In cases where HIV-1 RNA results are not yet 
available, monotherapy endpoint status is generally to be determined from available 
results at the time of study visits, but must be reviewed and agreed with the study 
medical monitor prior to initiation of SOC cART. 
4. Day 84. In no instance will the monotherapy period go beyond Day 84, even if 
virologic rebound criteria have not been met. The SOC Initiation visit must be 
conducted in all participants no later than Day 84. 
A standard of care cART regimen will be initiated in all study participants at end of the 
monotherapy period in Parts 1 and 2 in order to both limit the potential development of 
resistance or reduced susceptibility to GSK3810109A as well as to meet the desire to 
initiate cART as soon as possible in these antiretroviral-naive HIV-infected participants. 
An integrase-based regimen is further stipulated in this study due to the very rapid viral 
suppression typically seen with this class of antiretroviral agents, thus achieving these 
two objectives as quickly as possible following the monotherapy period in Parts 1 and 2. 
Participants who receive GSK3810109A will continue to be followed for safety purposes 
according to the study schedule of activities. Participants will not be discontinued or 
replaced in the study for initiating or changing ART during the SOC follow-up period 
(including substitution of a non-integrase-based regimen, if deemed appropriate by the 
principal investigator) and will continue to be followed for safety purposes according to 
the study schedule of evaluations. ART regimen changes will be documented in the 

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participant’s record. Oral dolutegravir + lamivudine (Dovato™) will be provided in the 
study for use during the SOC follow-up period, if appropriate and consistent with local 
Guidelines. 
Initiation of an integrase-based ART is expected to occur immediately after participants 
complete the monotherapy study evaluations. Participants who remain viremic on 
antiretroviral therapies (ARTs) will be encouraged to talk to their primary care provider 
about their ARV regimen, per local guidelines (Department of Human and Health 
Services (DHHS) guidelines [DHHS, 2019] in the US). 
4.3. 
Justification for Dose 
The dose range for investigation in this study is defined by PK data from healthy 
volunteers (Study VRC609) and preclinical potency data. Based on in vitro experiments, 
the estimated 90th percentile of GSK3810109A potency (IC90) is ~ 10 µg/mL. The 
observed preliminary exposures at day 14 at the clinical doses studied and the overages 
compared to the IC90 values in FTIH study (Study VRC609) are listed in Table 1. The 
recommended starting doses of 280 mg and 40 mg/kg in Part 1 of the current study reflect 
the dose range of approximately 5 – 40 mg/kg doses studied in the FTIH study and 
thereby provides systemic GSK3810109A exposures at day 14 that are approximately 1X 
and 32X fold above the IC90 respectively. Additionally, the dose range to be evaluated is 
selected to allow adequate characterization of the exposure-response relationship between 
GSK3810109A exposures and viral load changes. 
Table 1 
Observed preliminary exposures at Day 14 from Study VRC609 
Dose (mg/kg) 
Concentration on day 14 
(Mean (SD) µg/mL) 
IC90 Overage 
5 mg/kg SC 
16.9 (3.9) 
>1.5X 
5 mg/kg IV 
21.6 (2) 
>2X 
20 mg/kg IV 
171.8 (52.5) 
>17X 
40 mg/kg IV 
326.6 (71.7) 
>32X 
Preliminary PK data from Study 609 VRC (n=3 for each of these dose groups) 
In addition, there are other bNAbs that are administered at similar doses, frequency and 
routes as GSK3810109A in the FTIH VRC609 study and have been generally well-
tolerated with no deaths or serious adverse events assessed as related to the 
investigational product. 
Part 1, Group 1 (high dose group) will evaluate an IV infusion of GSK3810109A 
(40 mg/kg) that has been previously tested in the prior Phase 1 study (VRC609, Section 
2.2). This dose is targeted to achieve the maximum anticipated reduction of HIV-1 RNA 
and was well-tolerated with a single IV administration in the FTIH VRC609 study. This 
is the highest dose to be tested in this study.  
Part 1, Group 2 will assess GSK3810109A administered at a lower flat dose (280 mg) IV 
infusion. The doses in Part 1 are selected to allow full characterization of single-dose 
antiviral activity and to select optimal doses for the subsequent study groups in Part 2. 

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For more information on data from the FTIH study with GSK3810109A and clinical data 
from other bNAbs see Section 2.2. 
Doses in Part 2 of this study may be modified based on the data from Part 1, see Section 
6.9 for more information. 
4.4. 
Interim Go / No Go Criteria and Dose Selection for Part 2 
In this study, a <0.5 log10 decrease will serve as the no effect threshold for antiviral 
effect. This is in line with the variation of <0.5 log10 HIV-1 RNA observed in serial viral 
load measurements from chronic HIV-1 infected patients, serves as an intra-person 
control, and would obviate the need for a placebo arm. [Holodniy, 1994; Lima, 2017].  
The efficacy Go or No-Go criteria will use a log10 nadir viral load decline (∆) at the 
highest IV dose (Part 1, Group 1) to predict population average nadir viral load decline. 
A minimum value (MV) for viral load decline was set at ∆= 1 log10. The target value 
(TV) viral load decline was based on historical bNAb POC data and was set at ∆ = 
1.3 log10 if all participants are considered and ∆ = 1.4 log10 if only viral load responders 
are considered. The specific criteria for the interim decision criteria are detailed in 
Section 9.5. 
Emerging viral load data at the two dose levels in Part 1 i.e. the log10 nadir viral load 
decline (∆) and the viral kinetics i.e. time to reach viral nadir and rebound, as well as key 
safety elements, will be utilized to select appropriate doses for Part 2 of the study. The 
doses will be selected to allow adequate characterization of the exposure-response 
relationship between GSK3810109A and viral load decline. 
At the Part 1 interim analysis stage, safety Go / No-Go criteria are pre-defined as: 
No Go: 
• If ≥35% of treated participants in Part 1 receiving GSK3810109A have a 
clinically significant Grade 3 or higher AE trend or laboratory abnormality trend 
(with the exception of asymptomatic Grade 3 or higher cholesterol, triglyceride) 
determined by the SDEC 
Go:  
• The above safety ‘no go’ criteria is not met. 
The safety interim analysis will be based on all available safety data from the 
monotherapy phase of Part 1 participants at the time of the interim efficacy data cut-off. 
>65% of Part 1 participants must complete monotherapy without a clinically significant 
Grade 3 or lab abnormality trend before the study can proceed with Part 2 (Go decision). 
Additional ongoing safety data from Part 1 participants through the monotherapy phase 
completion will be added to the interim safety analysis until a definitive decision (Go or 
No Go) can be reached. 

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If a No Go decision is reached, the study will be stopped and no additional cohorts will 
be recruited. 
4.5. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all 
assessments in the Monotherapy Phase and the SOC follow-up phase shown in the SoA. 
The end of the study is defined as the date of the last visit of the last participant in the 
SOC follow-up phase of the study or last scheduled procedure shown in the SoA for the 
last participant in the trial. 
The SoA can be found in Section 1.3. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
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 must have documented HIV-1 infection at the Screening Visit: 
o Plasma HIV-1 RNA 5000 c/mL. 
NOTE: A single repeat test is allowed to determine eligibility. An HIV-1 RNA 
result 5000 c/mL will serve as confirmation of HIV-1 infection. 
3. Screening CD4+ T-cell count  250 cells/mm3: 
NOTE: A single repeat test is allowed to determine eligibility. 
4. Antiretroviral naïve: No ARTs (in combination or monotherapy) received after the 
diagnosis of HIV-1 infection:   
Participants who received HIV post-exposure prophylaxis (PEP) or pre-exposure 
prophylaxis (PrEP) in the past are allowed as long as the last PEP/PrEP dose was 
>6 months from HIV diagnosis or there is documented HIV seronegativity at least 2 
months after the last prophylactic dose and prior to the date of HIV diagnosis. The 
study site must have viewable documentation of the seronegative test available and 
placed into the study source documents. 

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Weight 
5. Body weight 50 kg to 115 kg  
Sex 
6. Male and/or female 
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
All participants participating in the study should be counselled 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. 
a. Participants who are female at birth are eligible to participate if at least one of the 
following conditions applies: 
• Not Pregnant or breastfeeding and at least one of the following conditions applies: 
o Is not a participant of childbearing potential (POCBP).  
OR 
o Is a POCBP and using an acceptable contraceptive method as described in 
Section 10.5.2 during the intervention period (at a minimum until after the 
last dose of study intervention). The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose 
of study intervention. 
• A POCBP must have a negative highly sensitive (see Section 10.5.2) pregnancy 
test (urine or serum as required by local regulations) on Day 1, prior to the first 
dose of study intervention. 
• 
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), 
a serum pregnancy test is required.  In such cases, the participant must be 
excluded from participation if the serum pregnancy result is positive.  
• 
Additional requirements for pregnancy testing during and after study 
intervention are located in Section 1.3. 
• 
All participants in the study should be counselled 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.  
• 
The investigator is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a POCBP with an 
early undetected pregnancy. 
Contraception Guidance and Collection of Pregnancy Information can be found in 
Section 10.5. 

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QTc 
7. QTc Interval 450 msec. 
Informed Consent 
8. Capable of giving signed informed consent as described in Section 10.1.3 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Participants with primary HIV infection, evidenced by acute retroviral syndrome 
(e.g., fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) 
documented viremia without antibody production and/or evidence of recent (within 3 
months) documented seroconversion. 
2. Participants who are pregnant, breastfeeding, plan to become pregnant or breastfeed 
during the study. 
3. The participant has an underlying skin disease or disorder (i.e. infection, 
inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, 
urticaria) that would interfere with assessment of injection sites. 
4. Known history of cirrhosis with or without viral hepatitis co-infection. 
5. History of clinically relevant hepatitis within last 6 months. 
6. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at 
screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-
HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV DNA as follows: 
• Participants positive for HBsAg are excluded. 
• Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg 
status) and positive for HBV DNA are excluded. 
Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and 
negative for HBV DNA are not excluded. 
Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti-
HBs (past and/or current evidence) are immune to HBV and are not excluded. 
7. Patients with Hepatitis C co-infection. 
8. Untreated syphilis infection (positive rapid plasma reagin (RPR) at screening) without 
documentation of treatment. Participants who are one month post completed 
treatment are eligible if recruitment is open. 
• Rescreening is allowed after treatment. 

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9. Prior receipt of licensed or investigational monoclonal antibody. 
10. 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. 
11. Known or suspected moderate or severe hepatic impairment (Class C as determined 
by Child-Pugh Classification, Section 10.9) coagulopathy, hypoalbuminaemia, 
oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary 
abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). 
12. Clinically significant cardiovascular disease, as defined by history/evidence of 
congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery 
bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty 
(PTCA) or any clinically significant cardiac disease at the discretion of the 
investigator. 
13. 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; other localized malignancies require agreement between the 
investigator and the study medical monitor for inclusion of the participant prior to 
randomization. 
14. Any pre-existing physical or mental condition which, in the opinion of the 
investigator, may interfere with the participant’s ability to comply with the dosing 
schedule and/or protocol evaluations, or which may compromise the safety of the 
participant; 
15. Participants with substance abuse disorders or social restraints that the investigator 
considers to be possible deterrents to successful completion of the study. 
16. Participants who in the investigator’s judgment, pose a significant suicidality risk. 
Participants’ history of suicidal behavior and/or suicidal ideation should be 
considered when evaluating for suicide risk. 
17. 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. 
18. Any condition which, in the opinion of the investigator, may interfere with the 
absorption, distribution, metabolism or excretion of the study drugs, combination 
ART or render the participant unable to take oral medication. 
19. Participants with a positive COVID-19 test at Screening. Participants with known 
COVID-19 positive contacts within the past 14 days, or with symptoms suggestive of 
active COVID-19 (fever, cough, myalgias, shortness of breath, loss of taste or smell), 
should be excluded. Participants who remain symptom-free for at least 14 days after a 
COVID-19 exposure are allowed. 
Prior/Concomitant Therapy 
20. Has received any HIV-1 immunotherapeutic vaccine or prophylactic vaccine. 

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21. Treatment with any of the following agents within 28 days of screening: 
• radiation therapy; 
• cytotoxic chemotherapeutic agents; 
• any systemic immune suppressant; 
22. 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 IP. 
23. Participants receiving any prohibited medication and who are unwilling or unable to 
switch to an alternate medication. 
Prior/Concurrent Clinical Study Experience 
24. Participant enrolled in a prior or concurrent clinical study that includes a drug 
intervention within the last 30 days. 
Diagnostic assessments 
25. Any acute laboratory abnormality at Screening, which, in the opinion of the 
investigator, would preclude the participant’s inclusion in the study of an 
investigational compound. 
26. Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during 
the Screening period to verify a result. 
27. Alanine aminotransferase (ALT) 1.5 times the upper limit of normal (ULN). 
28. Total Bilirubin 1.5 times the ULN. 
29.  Creatinine clearance of <50 mL/min/1.73 m2 via CKD-EPI method. 
30. Hemoglobin Grade 2 (Males: <10 g/dl; Females <9.5 g/dL). A single repeat test is 
allowed during the Screening period to verify a result. 
31. Platelets Grade 2 (<100,000 cells/mm3). A single repeat test is allowed during the 
Screening period to verify a result. 
32. PT Grade 2 (1.25 ULN). A single repeat test is allowed during the Screening 
period to verify a result. 
33. INR Grade 2 (1.5 ULN). A single repeat test is allowed during the Screening 
period to verify a result. 
34. Absolute Neutrophil Count (ANC) Grade 2 (ANC 799 cells/mm3). A single repeat 
test is allowed during the Screening period to verify a result. 

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35. The participant has a tattoo or other dermatological condition overlying potential 
injection sites which may interfere with interpretation of injection site reactions or 
administration of GSK3810109A. 
To assess any potential impact on participant eligibility with regard to safety, the 
investigator must refer to the IB and supplements, approved product labels, and/or local 
prescribing information for detailed information regarding warnings, precautions, 
contraindications, AEs, drug interactions, and other significant data pertaining to the 
study drugs. 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required. 
5.3.1. 
Meals and Dietary Restrictions 
• 
No dietary restrictions are required. 
5.3.2. 
Caffeine and Alcohol 
• 
There are no study-related restrictions on caffeine. Alcohol should be avoided for 24 
hours prior to dosing of GSK3810109A and for 24 hours prior to all scheduled study 
visits until the initiation of standard of care cART (SOC Initiation Visit). 
5.3.3. 
Activity 
• 
Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests. 
5.4. 
Screen Failures 
Screen failures are defined as individuals who consent to participate in the clinical study 
but are not subsequently randomized in the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any serious adverse 
events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened one time. Rescreened participants should be assigned a new 
participant number for re-screening. 
6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), intended to be 
administered to a study participant according to the study protocol. In this study, 
GSK3810109A is an experimental treatment for HIV-1 infected adults. 
GSK3810109A is a recombinant human IgG1 antibody which is expressed as a soluble 
glycoprotein secreted from a recombinant Chinese Hamster Ovary (CHO) DG44 cell line.  

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GSK3810109A is targeted against the CD4 binding site of the HIV gp120 envelope 
protein. 
6.1. 
Study Intervention(s) Administered 
GSK3810109A Injection, 600 mg/6mL is a solution for infusion or injection. It is 
supplied as a sterile aqueous solution manufactured from bulk drug substance containing 
a target of 100 mg/mL of GSK3810109A, 10 mM sodium citrate/citric acid, 50 mM 
sodium chloride, 150 mM arginine-HCl, and 0.002% polysorbate-80 at pH 6.5. 
GSK3810109A Injection, 600mg/6mL contains a fill volume of 6.25 mL (6.00 mL 
withdrawable volume) of solution filled into a 10-mL glass vial with a 13-mm 
fluorinated-polymer coated chlorobutyl rubber stopper and a 13 mm blue flip-off 
overseal. 
 
Table 2 
Study Interventions 
ARM 
Dose groups and cohorts within Part 1 and Part 2 
Intervention Name 
GSK3810109A 
Type 
Biologic 
Dose Formulation 
Solution for injection or infusion 
Unit Dose Strength(s) 
600 mg/6 mL 
Dosage Level(s) 
40 mg/kg, 280mg flat dose, other doses to be determined 
following Part 1 
Route of Administration 
IV infusion, SC injection 
Sourcing 
Provided centrally by the Sponsor 
Packaging and Labeling 
Study Intervention will be provided in vial. Each vial will be 
labeled as required per country requirement. 
[Current/Former Name(s) or 
Alias(es)] 
N6LS, N6LS bnAb (broadly neutralizing antibody), VRC-
HIVMAB091-00-AB 
6.2. 
Handling, Storage and Accountability of GSK3810109A 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study 
intervention are provided in the Study Procedures Manual.  
• 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. Take adequate precautions to 

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avoid direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or 
GSK study contact. 
• 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK. 
6.3. 
Pharmacy Procedures 
Refer to the IB for further information on GSK3810109A. 
Study Product and Administration Regimen 
GSK3810109A Injection, 600 mg/6 mL is a clear, slightly yellow solution for infusion or 
injection. It is supplied as a sterile aqueous solution manufactured from bulk drug 
substance containing a target of 100 mg/mL of GSK3810109A, 10 mM sodium 
citrate/citric acid, 50 mM sodium chloride, 150 mM arginine-HCl, and 0.002% 
polysorbate-80 at pH 6.5. GSK3810109A Injection, 600mg/6mL contains a fill volume of 
6.25 mL (6.00 mL withdrawable volume) of solution filled into a 10-mL glass vial with a 
13-mm fluorinated-polymer coated chlorobutyl rubber stopper and a 13 mm blue flip-off 
overseal. 
In calculating the dose to administer and number of vials to thaw, it should be assumed 
that the concentration is 100 mg/mL and that a volume of 6 mL can be withdrawn from a 
vial. For example, participants in Part 1, Group 1 will receive a dose of 40 mg/kg via IV 
route. Since each product vial contains at least 6 mL of 100mg/mL GSK3810109A, 
4 vials will be required for the dose preparation for participants up to 60kg. For 
participants with body weight >60 kg to 75kg, 5 vials will be required; for participants 
>75kg to 90kg, 6 vials will be required; for participants >90kg to 105kg, 7 vials will be 
required and for participants >105kg to 115kg, 8 vials will be required. 
Preparation of GSK3810109A for IV administration will require a 100 mL bag of 0.9% 
sodium chloride, United States Pharmacopeia (USP) (normal saline) and the correct dose 
of GS3810109A, as described in the IB. Preparation of GSK3810109A for SC 
administration will not require any diluent. 
GSK3810109A Vialed Product 
The product label designates the long-term storage temperature as -35°C to -15°C. 
Clinical site storage in a qualified, continuously monitored, temperature-controlled 
freezer. 
Following thaw, GSK3810109A vials may be stored for up to 24 hours at controlled 
room temperature (maximum 27°C) and/or up to 4 weeks at 2°C to 8°C. Product may not 
be stored in direct sunlight. If stored at 2-8°C, vials must be equilibrated at controlled 
room temperature (maximum 27°C) for a minimum of 60 minutes and may be held at 
room temperature for up to 8 hours prior to product preparation. 

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Temperature Excursions 
The site pharmacist must promptly report any storage temperature excursions outside of 
the normal allowance for the storage device to the study team. The affected product must 
be quarantined in a separate area. If the excursion results in thawed GSK3810109A 
material, DO NOT REFREEZE; store the thawed, vialed material at 2°C to 8°C. 
• 
Provide the following information regarding the excursion: lot number, fill volume 
and number of vials affected; temperature range and length of excursion, including 
data log reports; handling of materials post excursion (e.g. transfer to alternate 
storage, including times); visual inspection data of the materials (e.g. did the 
materials appear to have remained frozen, were vials cracked, etc.). The study team 
will notify the site pharmacist if continued clinical use of the product is acceptable. 
6.4. 
Preparation of Study Product Administration 
This section describes how the site pharmacist will prepare the study product for 
administration and how the clinician will administer the product.  
GSK3810109A is a highly concentrated protein solution and may develop white, opaque 
to translucent particles after thawing. When particles are observed, they may disappear 
after a few hours at room temperature or storage at 2C to 8C. 
The following instructions apply to thawing GSK3810109A: 
1. Thaw vial(s) for a minimum of 1.5 hours at controlled room temperature (maximum 
27°C) after removing from the freezer. 
2. Keep the material at room temperature during the entire preparation period until use, 
up to the maximum storage times described above in GSK3810109A Vialed Product. 
3. Prior to preparation for administration, vials should be swirled for 30 seconds with 
sufficient force to resuspend any visible particles yet avoiding foaming. DO NOT 
SHAKE THE VIALS. If particles are observed, return the vials to 2°C to 8°C storage. 
If the particles dissolve within the maximum storage times described in Section 6.3, 
the vials may be used for product preparation. If particles continue to be observed, 
do not use the vialed product for SC or IV administration. Refrigerated product 
must be equilibrated at controlled room temperature (maximum 27C) for a minimum 
of 60 minutes before preparation and must be used within 8 hours of any subsequent 
return to room temperature. 
4. If the thawed material is not administered within 24 hours of thaw, follow the storage 
information provided above in GSK3810109A Vialed Product. 
Preparation is to be done using aseptic technique, in a laminar flow biosafety cabinet. 
Assure that only the required vials are present in the preparation unit during dilution, and 
medication labels are strictly segregated to avoid mix-ups. More information on product 
preparation can be found in the GSK3810109A Investigators Brochure (IB). 

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Preparation for IV Administration 
For each IV infusion order, the participant’s weight, dose level, and study group code 
will be included in the pharmacy order. To prepare an IV infusion, the pharmacist will: 1) 
fill an empty sterile bag with 100 mL of normal saline, 2) calculate the total milligrams of 
GSK3810109A needed, 3) retrieve the minimum number of thawed and particle free vials 
required to prepare the full dose, 4) withdraw the necessary amount of GSK3810109A, 
and 5) add this volume to the sterile bag using good pharmacy practices to maintain 
sterility. If commercially available, a pre-filled 100 mL bag of normal saline may also be 
used. Prior to preparation for administration, vials of GSK3810109A should be gently 
swirled for 30 seconds while avoiding foaming. DO NOT SHAKE THE VIAL. 
An in-line filter infusion set must be used for IV product administrations and MUST 
comply with the following specifications: 1.2 micron PES (polyethersulfone) filter 
membrane, DEHP free, latex-free (equivalent to Braun #473994 filter extension set). 
When the in-line filter is added to the tubing, the administration set must then be primed. 
At the end of product administration, the IV administration set must be flushed with 
about 30 mL (or appropriate volume) of normal saline. 
The study product solution will typically be administered IV over approximately 30 
minutes using a volumetric pump. The total time needed to administer the dose may be 
longer based on factors such as participant tolerance. The rate of infusion may range from 
10-20 mg/kg/hr at the lowest dose level to 80 - 160 mg/kg/hr at the highest dose level. 
The mL/hr infusion rate may vary based on the total volume needed to administer a full 
dose. An infusion time greater than 30 minutes is permitted. 
Preparation for SC Administration 
For each SC administration order, the participant’s weight, dose level, and study group 
code will be included in the pharmacy order. To prepare a SC administration dose, the 
pharmacist will calculate the total mg needed and retrieve the minimum number of 
thawed, particle free vials needed to prepare the full dose. The maximum volume for SC 
injection is expected to be 2.5mL x 4 injections, but final dose will be determined 
following a review of data from Part 1. Prior to preparation for administration, vials 
should be gently swirled for 30 seconds avoiding foaming. DO NOT SHAKE THE 
VIALS. If particles are observed, follow instructions described in Section 6.4. 
The needed volume of GSK3810109A must be withdrawn from the vial into 1 to 4 
syringes (BD Luer-Lok 3 mL syringe; REF # 309657 or equivalent) using a 5-micron 
filter needle (BD Blunt Fill Needle – Filter, 18G 1 ½ inch; REF# 305211 or equivalent). 
A new filter needle must be used for each syringe. The filter needle must be discarded 
prior to dispensing and replaced with a needle suitable for SC injection at the time of 
administration. 
The product may be administered by direct SC injection with needle and syringe. The 
clinician will use proper SC technique to ensure administration into SC fatty layer and a 
slow push to minimize discomfort or the excessive distention of overlying skin. The 
length of time to complete the infusion will vary depending on the dose given and 
participant tolerance of the infusion rate. 

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Handling of Prepared Product for IV or SC Administration 
After product preparation in an IV bag, the prepared GSK3810109A may be stored at 
18°C to 27°C for a maximum of 8 hours total including the infusion time. Product may 
not be stored in direct sunlight. 
After preparation in syringes for SC administration, the prepared GSK3810109A may be 
stored at 2°C to 8°C up to 24 hours or at controlled room temperature (maximum 27°C) 
up to 4 hours. The product may not be stored in direct sunlight. 
Study Product Disposition 
The empty vials and the unused portion of a vial will be discarded in a biohazard 
containment bag and incinerated or autoclaved in accordance with the institutional or 
pharmacy policy. Any unopened vials that remain at the end of the study will be returned 
to the production facility or discarded at the discretion of the sponsor in accordance with 
policies that apply to investigational agents. Partially used vials will not be administered 
to other participants or used for in vitro experimental studies. These vials will be 
disposed of in accordance with institutional or pharmacy policy. 
6.5. 
Administration of GSK3810109A 
All study product administrations will be completed according to the assigned group. For 
participants of childbearing potential, a negative pregnancy test must be obtained prior to 
product administration that day. Prior to product administration, temperature, blood 
pressure, heart rate (pulse) and weight will be recorded, and a targeted physical 
examination will be conducted. In all study groups, the participant will be observed for at 
least 2 hours following each product administration. 
If a participant is assigned to an IV administration group, the IV access will be placed in 
an arm vein in an aseptic manner. A different site may be used for collection of PK blood 
samples; however, the same site may be used after flushing the line if another site is not 
available. GSK3810109A will be administered with approximately 100 mL of normal 
saline IV (as described in the IB) over approximately 30 minutes, with a target of 30 
minutes for the initial infusion for each participant. Infusions lasting longer than 30 
minutes are allowed. If the participant experiences side effects during the infusion, the 
rate of infusion may be slowed or stopped to alleviate the symptoms. 
If a participant is assigned to a SC administration group, the SC administration site(s) to 
be used must be assessed as acceptable by the clinician and the participant. The preferred 
SC administration site is the abdomen, but the upper arm or thigh may be used. The SC 
dose will be administered by standard needle in a maximum volume of about 2.5 mL per 
injection site. Up to 4 SC injection sites may be used if deemed necessary by the 
clinician. SC administration sites should be at least 2 inches apart. 
6.6. 
Measures to Minimize Bias: Randomization 
Participants in both Part 1 and Part 2: 

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Open-label 
using central 
randomization 
via 
(IVRS/IWRS) 
This is an open-label study; however, the specific intervention to be 
taken by a participant will be assigned using an IVRS/IWRS. The 
site will contact the IVRS/IWRS prior to the start of study 
intervention administration for each participant. The site will record 
the intervention assignment on the applicable case report form, if 
required. Potential bias will be reduced by the following steps: 
central randomization. 
6.7. 
Study Intervention Compliance 
• 
GSK3810109A will be intravenously or subcutaneously administered to participants 
at the site. Administration will be documented in the source documents and reported 
in the CRF. 
6.8. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency 
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 non-HIV 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 during or 
immediately after a scheduled visit, after all laboratory tests have been drawn, and only 
when scheduled visits are 4 weeks apart. This approach will minimize the risk of non-
specific increases in the level of plasma HIV-1 RNA at the next scheduled assessment. 
Clinical monitoring is recommended for participants taking methadone, as methadone 
maintenance therapy may need to be adjusted in some participants. 
Non-protocol defined treatments or medical interventions (e.g., physical therapy, 
radiotherapy, surgical procedures) are permitted during the study for appropriate medical 
management of the participant.  
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 

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6.8.1. 
Prohibited Medications and Non-Drug Therapies 
The following concomitant medications or therapies are not permitted at any time during 
the study: 
• HIV immunotherapeutic vaccines are not permitted at any time during the study.  
• Other experimental agents, antiretroviral drugs not otherwise specified in the 
protocol, cytotoxic chemotherapy, or radiation therapy may not be administered.  
• Systemically administered immunomodulators (such as interleukin and interferon 
agents) are prohibited (a list of examples is provided in the SPM). This includes 
topical agents with substantial systemic exposure and systemic effects. Use of 
topical imiquimod is permitted. 
• 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. 
• For participants with an unanticipated requirement for HCV therapy during study, 
interferon or any other medications that have a potential for adverse drug-drug 
interactions with study treatment are prohibited during the conduct of the study. 
Consult with the Medical Monitor in cases where concurrent HCV therapy is 
required. 
• Acetaminophen (paracetamol) cannot be used in patients with acute viral hepatitis 
[James, 2009]. 
6.9. 
Dose Modification 
This protocol allows some alteration from the currently outlined dosing schedule and 
number of groups, however the maximum dose will not exceed 40 mg/kg. 
The decision to proceed to Part 2 will be made by the Safety and Dose Evaluation 
Committee and the study team based on viral load response (reduction in HIV-1 RNA).  
Additionally, safety, tolerability, and preliminary PK and/or pharmacodynamic data 
obtained in Part 1 will be used for dose selection in Part 2. 
6.10. 
Intervention in Follow-Up Period: Combination Oral ART 
Standard of Care Phase 
Participants who received GSK3810109A will continue to be followed for safety 
purposes according to the study schedule of activities. Initiation of standard of care, 2 or 
3-drug integrase-based oral ART will start at the end of the last assessment day in the 
Monotherapy Phase in Part 1 and Part 2.  
Participants will not be discontinued or replaced in the Long-Term Follow-Up period for 
initiating or changing ART. ART regimen changes will be documented in the 
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Participants who remain viremic on their oral ARTs will be encouraged to talk to their 
primary care provider about their ART regimen, per Department of Human and Health 
Services [DHHS, 2019] guidelines or local regulations. 
6.11. 
Intervention after the End of the Study 
The investigator is responsible for ensuring that consideration has been given to the 
poststudy care of the participant’s medical condition, whether or not ViiV 
Healthcare/GSK is providing specific post-study treatment. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
In Part 1 and Part 2 of the Monotherapy Phase, a single dose is administered, thus 
discontinuation of GSK3810109A is not applicable following the Day 1 IV infusion or 
SC injection. 
During the SOC Follow-up oral combination ART phase, investigators will manage their 
participants per standard of care, following relevant guidelines [DHHS, 2019] or local 
guidance, except as outlined below for cases of virologic failure (Section 7.1.2). Sites 
should contact the Medical Monitor to discuss the management of individual participants 
on ART, whenever necessary. 
Participants who received GSK3810109A, will continue to be followed for safety 
purposes according to the study schedule of activities (oral combination ART phase). 
Participants will not be discontinued or replaced in the study for initiating or changing 
ART. They will continue to be followed for safety purposes according to the study 
schedule of activities Section 1.3. ART regimen changes will be documented in the 
participant’s record. 
See the SOA, Section 1.3, for data to be collected at the time of study discontinuation. 
Emerging safety data will be reviewed in stream as the study progresses and any 
participant meeting the following criteria will result in a study pause whilst a full safety 
review is conducted and the findings and recommendations presented to ViiV Safety and 
Labelling Committee (VSLC) for endorsement: 
• Any Serious Adverse Event (SAE), regardless of its severity, that is considered be 
clinically significant and reasonably attributable to dosing with GSK3810109A, in 
the opinion of the Investigator and Sponsor. 
• Acute Allergic reaction or cytokine release syndrome (DAIDS criteria Grade 3-4) 
reasonably attributable to dosing with GSK3810109A, in the opinion of the 
Investigator and Sponsor. 
• Any AE of Grade 4 intensity assessed as related to GSK3810109A, as reported by 
the Investigator. 

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• Any participant meeting liver chemistry stopping criteria. 
• Any participant meeting QTc stopping criteria. 
Aggregate thresholds: 
• If ≥30% of participants within a dose group have a Grade 3 or higher AE trend or 
laboratory abnormality trend (with the exception of asymptomatic Grade 3 or 
higher cholesterol, triglyceride). 
• Any pattern of poorly tolerable, or clinically significant adverse events observed 
within a dose group are consistent across at least 50% of participants 
Relevant reporting and discussion with the Medical Monitor, relevant study team 
personnel, and the IRB/IEC will take place before resumption of dosing. Every effort will 
be made to take a blood sample at the time of the AE for PK analysis. 
7.1.1. 
QTc Stopping Criteria 
QTc stopping criteria is defined as a participant who has a QTc interval >550 msec 
considered causally related to IP. The QTc should be based on averaged QTc values of 
triplicate electrocardiograms obtained over a brief (e.g., 5 to 10 minute) recording period.   
When performing ECGs, the same QT correction formula must be used for each 
individual participant to determine eligibility for, and discontinuation from, the study.  
This formula may not be changed or substituted once the participant has been enrolled. 
For example, if a participant is eligible for the protocol based on QTcB, then QTcB must 
be used for discontinuation of this individual participant as well. 
Once the QT correction formula has been chosen for a participant’s eligibility, the same 
formula must continue to be used for that participant for all QTc data being collected for 
data analysis. Safety ECGs and other non-protocol specified ECGs are an exception. 
If a participant meets QTc stopping criteria, the participant will remain in the study to be 
evaluated for all the follow up per the SoA or until GSK3810109A is undetectable for 
appropriate procedures, including blood plasma PK sampling, and safety evaluations. The 
participant will not be removed from the study for medical reasons, unless they withdraw 
consent to continue participation. 
7.1.2. 
Virologic Failure 
Only plasma HIV-1 RNA values determined by the central laboratory will be used to 
assess virologic failure during the SOC follow up period. 

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7.1.3. 
Definition of Protocol-Defined Virologic Failure 
For the purposes of clinical management in this study, the criteria detailed below will 
apply during the SOC Follow-up period of the study. The virologic failure definition does 
not apply during Part 1/ Part 2. 
Suspected Virologic Failure: A single HIV-1 RNA value as defined by Virologic 
Nonresponse or Virologic Rebound. 
Confirmed Virologic Failure: Any of the below conditions are met once the Investigator 
has confirmed participant compliance:  
Virologic Non-Response Criteria:  
A decrease in plasma HIV-1 RNA from the SOC Initiation Visit (end of Monotherapy 
Phase) of less than 2.0 log10 c/mL at SOC Follow-up Week 8, with subsequent 
confirmation, unless plasma HIV-1 RNA is <200 c/mL,  
Confirmed plasma HIV-1 RNA ≥200c/mL on or after SOC Follow-up Week 12. 
Virologic Rebound Criteria:  
Confirmed rebound in plasma HIV-1 RNA ≥200c/mL after prior suppression to 
<200c/mL. 
Confirmatory testing of virologic non-response: 
The participant should have received full doses of ART treatment for at least two weeks 
at the time confirmatory plasma HIV-1 RNA is conducted, if possible. The current ART 
regimen should continue to be administered and no additional ART should be added 
during re-testing. 
Upon notification that a participant’s HIV-1 RNA plasma level initially meets one of the 
above criteria, the investigator should query the participant regarding intercurrent illness, 
recent immunization, interruption of therapy or inadequate adherence. 
All cases meeting “virologic management” criterion must be confirmed by a second 
measurement performed at least two weeks but not more than 4 weeks apart from the date 
of the original sample, unless delay is necessary to meet the requirements of confirmatory 
HIV-1 RNA testing as outlined below. 
The following guidelines should be followed for scheduling confirmatory HIV-1 RNA 
testing in an effort to avoid false-positive results: 
Confirmatory testing should be scheduled at least two weeks but not more than 4 weeks 
following resolution of any intercurrent illness, during which time the participant should 
receive full dose of all antiretrovirals in the regimen. 

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Confirmatory testing should be scheduled at least 4 weeks following any immunization, 
during which time the participant should receive full dose of all antiretrovirals in the 
regimen. 
If therapy is interrupted due to toxicity management, non-compliance, or other reasons, 
confirmatory testing should be scheduled 2-4 weeks following resumption of full dose of 
all antiretrovirals in the regimen. 
The participant should have received full doses of HAART for at least 2 weeks at the 
time confirmatory plasma HIV-1 RNA is done. 
Sites should contact the Medical Monitor to discuss individual participants, whenever 
necessary. 
7.1.4. 
Managing Virologic Failure 
Once a participant has been determined as meeting a protocol defined confirmed 
virologic failure criterion, a plasma sample from the suspected virologic failure time 
point will be sent for reverse transcriptase (RT)/ protease (PRO)/ integrase (IN) genotypic 
and phenotypic HIV-1 resistance testing and the result made known to the study 
investigator when available to advise on a new ARV-regimen. Plasma samples from 
storage will also be obtained at unscheduled visits including the time of Confirmed 
Virologic Failure criteria. 
Plasma HIV-1 RNA values determined by the central laboratory only will be used to 
assess virologic management criteria. Upon notification that a participant’s HIV-1 RNA 
plasma level qualifies him/her as meeting a virologic failure criterion, the investigator 
should query the participant regarding intercurrent illness, recent immunization, 
adherence, or interruption of therapy. 
Participants may continue to receive their SOC regimen at the discretion of the 
investigator until results of HIV-1 resistance testing are available. Based on the results of 
the resistance testing, the ART regimen may be modified by the investigator. 
A participant who meets virologic failure may remain in the study. 
Selection of ART regimen for participants meeting confirmed virologic failure criteria 
will be recorded in the eCRF. 
The protease RT/PRO/IN genotypic and phenotypic assays used in this study are not 
validated for plasma HIV-1 RNA levels <500 c/mL. Nevertheless, for all participants 
who meet confirmed virologic failure criteria, plasma samples will be analyzed in an 
attempt to obtain genotype/phenotype data on samples with HIV-1 RNA ≥200 c/mL, as 
possible. 
For participants meeting confirmed virologic failure, “Meeting Confirmed Virologic 
Failure” will be recorded in the eCRF as reason for the modification to a new ART-
regimen. 

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7.2. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology (in alignment with the FDA 
premarketing clinical liver safety guidance).  
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf 
In the monotherapy phase of Part 1 and Part 2, discontinuation of GSK3810109A is not 
possible for abnormal liver tests as this is a single-dose study. The expected duration of 
systemic exposure to GSK3810109A is 6 to 9 months. If a participant meets liver 
chemistry stopping criteria, the study will pause to conduct an evaluation of the relevant 
safety data. The findings and recommendations on dosing resumption will be presented to 
VSLC for endorsement. 
Discontinuation of ART in the Long-Term Follow-Up period for abnormal liver tests is 
required when: 
• a participant meets one of the conditions outlined in Section 10.7. 
• when in the presence of abnormal liver chemistries not meeting protocol-specified 
stopping rules, the investigator believes ART discontinuation and initiating a new 
ART is in the best interest of the participant.  
 

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Figure 1 
Phase 2a Liver Chemistry Stopping – Liver Stopping Event 
Algorithm 
 
Abbreviations: ALT = alanine transaminase; SAE = serious adverse event; ULN = upper limit of normal 
 
Refer to Appendix 7 for required Liver Safety Actions and Follow up Assessments. 
 
ART Restart: 
If participant meets liver chemistry stopping criteria, do not restart or rechallenge the 
participant with the ART in the Long-Term Follow-Up period unless: 
• ViiV Healthcare Safety and Labelling Committee (VSLC) approval is granted, 
• Ethics and/or IRB approval is obtained, if required, and 
• Separate consent for treatment restart is signed by the participant. 
• Refer to Section 10.7 for full guidance. 
If GSK/ViiV Medical Governance approval to restart/re-challenge participant with ART 
is not granted, then participant must discontinue their ART and initiate an alternate ART 
and may continue in the study with alternate ART interventions. 
7.2.1. 
Temporary Discontinuation 
As GSK3810109A is a single dose administration in Part 1 and Part 2 of the 
Monotherapy Phase, a temporary withdrawal of study drug is not applicable. 

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Participants may have a temporary interruption to their oral ART in the long-term follow-
up period for management of toxicities. Such interruption of ART does not require 
withdrawal from the study. However, consultation with the Medical Monitor is required. 
Start and stop dates of ART and reason for temporary interruption will be recorded in the 
eCRF. 
7.3. 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw consent and discontinue participation in this study at any 
time at his/her own request. The investigator may also, at his or her discretion, 
discontinue the participant from participating in this study at any time (e.g., safety, 
behavioral or administrative reasons). This is expected to be uncommon. If a participant 
withdraws from the study, he/she may request destruction of any samples taken, and the 
investigator must document this in the site study records. 
• 
All participants who discontinue prematurely from the study will be asked for 
additional information to establish the reason for withdrawal. Participants are 
not obligated to state the reason for withdrawal. However, the reasons for 
withdrawal, or failure to provide a reason, must be documented by the 
investigator on the Completion/Withdrawal section of the electronic case report 
form (eCRF). Every effort should be made by the investigator to follow-up 
participants who withdraw from the study. 
• 
At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA, Section 1.3 for data to be 
collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 
• 
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. 
• 
An in-clinic withdrawal visit will also be used to assess participants with 
ongoing AEs, and serious adverse events (SAEs) related & not related to study 
drug and also any laboratory abnormalities that are considered to be AEs or 
potentially harmful to the participant. 
7.4. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 

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• Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods).  These contact attempts should be 
documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of  Section 
10.1.9. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA, Section 1.3.  
Visits for participants in the monotherapy phase should occur as projected according to 
the Day 1 visit. However, in order to facilitate scheduling around weekends and holidays, 
the following visit windows have been stipulated: 

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Table 3 
Visit Windows 
Day 1, 3 Hour 
3 hours (30 minutes) from the start of infusion or time of 
injection(s) 
Day 1, 24 Hours 
24 hours (2 hours) from the start of infusion or time of 
injection(s) 
Day 3 
2 calendar days after Day 1 
Day 6 
5 calendar days (1 day) after Day 1  
Day 9 
8 calendar days (2 days) after Day 1 and at least one calendar 
day after the Day 6 visit 
Day 11 
10 calendar days (2 days) after Day 1 and at least one 
calendar day after the Day 9 visit 
Day 14 
13 calendar days (2 days) after Day 1 and at least one 
calendar day after the Day 11 visit 
Day 17 
16 calendar days (2 days) after Day 1 and at least one 
calendar day after the Day 14 visit 
Day 21 
20 calendar days (2 days) after Day 1 and at least one 
calendar day after the Day 17 visit 
Every 7 days while 
remaining in the 
monotherapy phase 
Target date (3 days) calculated from Day 1 
SOC Initiation Visit 
No visit window- this visit will be conducted either in place of a 
scheduled visit or as an unscheduled visit upon confirmation that 
a monotherapy endpoint has been reached. 
SOC Follow-up +1 Week 
1 week (3 days) after the SOC Initiation Visit 
SOC Follow-up +4 Weeks 
4 weeks (7 days) after the SOC Initiation Visit 
SOC Follow-up +8 Weeks 
8 weeks (7 days) after the SOC Initiation Visit 
SOC Follow-up +16 Weeks 
16 weeks (7 days) after the SOC Initiation Visit 
SOC Follow-up +24 Weeks 
24 weeks (7 days) after the SOC Initiation Visit 
SOC Follow-up +32 Weeks 
32 weeks (7 days) after the SOC Initiation Visit 
SOC Follow-up +48 Weeks 
48 weeks (7 days) after the SOC Initiation Visit 
 
There are visit windows in the SOC follow-up phase from the projected visit dates. 
However, the number of tablets dispensed should be considered when scheduling the next 
visit to assure continuity of cART until the next scheduled visit 
• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
The maximum amount of blood collected from each participant (weighing 
50 - 115kg) will not exceed approximately 500 ml over a 2-week period during 
the Monotherapy Phase. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples such that they are not viable for assessment. 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
6 5  
 
•  
Sc r e e ni n g Ass ess me nts:  
All p artici p a nts will b e s cre e n e d f or el i gi bilit y b ef ore b ei n g ra n d o miz e d, prefera bl y 
wit hi n 2 8 d a ys of t h e Scre e ni n g visit. Ra n d o miz ati o n o n D a y 1 m a y o c c ur as s o o n as all 
Scre e ni n g pr o c e d ures h a v e b e e n c o m plete d a n d res ults are a v aila ble a n d o n file. T h e 2 8 -
d a y s cre e ni n g p eri o d m a y b e e xte n de d  (i. e., u p t o 3 5 d a ys) t o all o w re c ei pt of all 
Scre e ni n g ass ess m e nt res ults a n d t o a c c o m m o d ate s c h e d uli n g.  
•  
All s cre e ni n g e v al u ati o ns m ust b e c o m plete d a n d re vie we d t o c o nfir m t h at p ote ntial 
p artici p a nts m e et all eli gi bilit y criteria. T h e i n v esti gat or will m ai ntai n a s cre e ni n g 
l o g t o re c or d d etails of all p artici p a nts s cre e ne d a n d t o c o nfir m eli gi bilit y or re c or d 
re as o ns f or s cre e ni n g f ail ure, as a p plic a ble.  
•  
Pr o c e d ures c o n d ucte d as p art of t h e p artici pa nt’s r o uti n e cli nic al m a n a ge m e nt (e. g., 
bl o o d c o u nt) a n d o btai n e d b ef ore si g ni n g of I C F m a y b e utiliz e d f or s cre e ni n g or 
b as eli n e p ur p os es pr o vi d e d t h e pr o c e d ure m et t h e pr ot o c ol -s pe cifie d criteria a n d w as 
p erf or m e d wit hi n t h e ti m e fra m e d efi ne d i n t h e S o A ( Se cti o n 1. 3 ). 
•  
Pr ot o c ol w ai v ers or e x e m pti o ns are n ot all o w e d.  
•  
D a y 1 Ass ess me nts  
O n D a y 1 , t he f oll o wi n g ass ess m e nts m ust b e c o m plete d pri or t o d osi n g: c o nfir m 
p artici p a nt m e ets all i n cl usi o n a n d e x cl usi o n criteria, v ital si g ns, w ei g ht, te m p erat ure, a n d 
la b orat or y ass ess m e nts. 
F or all ass ess m e nts o n D a y 1, s e e t h e D a y 1 S o A i n Se cti o n 1. 3. 2 . Se e Se cti o n 6  f or 
pre p arati o n a n d a d mi nistrati o n of G S K 3 8 1 0 1 0 9 A.  
Part 1 of t h e st u d y will e v al u ate t w o d os es of G S K 3 8 1 0 1 0 9 A a d mi nistere d b y I V i nf usio n 
o n D a y 1 i n t h e 2 gr o u ps . E nr oll m e nt i n Part 1 will c o nti n u e u ntil a p pr o xi m atel y 1 0  
e v al u a ble p artici p a nts are c o nfir me d i n Gr o u p 1 t o s u p p ort t h e G o / N o G o criteria (s e e 
Se cti o n  4. 4  a n d Se cti o n 9. 5 ). Partici p a nts will b e ra n d o miz e d e q uall y ( 1: 1) b et w ee n 
Gr o u p 1 a n d 2.  
•  Part 1 Gr o u p 1 ( hi g h d os e gr o u p) will ass ess  a 4 0  m g/ k g I V i nf usi o n of 
G S K 3 8 1 0 1 0 9 A.   
•  Part 1 Gr o u p 2 will ass ess G S K 3 8 1 0 1 0 9 A a d mi nistere d at a re d u c e d flat d os e 
( 2 8 0 m g) I V i nf usi o n.  
F oll o wi n g c o m pleti o n of a pre -d efi ne d i nf or m al i nteri m a n al ysis of d ata fr o m Part 1 a n d 
a c c or di n g t o criteria d efi n e d i n Se cti o n 4. 4  a n d Se cti o n 9. 5 , f urt her g r o u ps of 
a p pr o xi m atel y  1 0 p artici p a nts will t h e n b e st u die d i n Part 2 a cr oss a ra n ge of d os e 
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infusion levels (depending upon the data obtained in Part 1), and a dose administered 
subcutaneously. Participants will be randomized equally between all groups in Part 2. 
The exact doses in Part 2 will be defined based on data from Part 1. 
As in Part 1, after the infusion or SC injection in Part 2, samples will be collected as per 
the SoA. 
Standard of Care Long Term Follow-up Phase 
For all assessments in the Standard of Care Follow-up Phase, see the SoA in 
Section 1.3.3. 
All participants will initiate an oral integrase-based ART (dolutegravir + lamivudine 
regimens will be provided by the study; alternative integrase inhibitor-based regimens 
may be reimbursed after discussion and agreement with the Medical Monitor) after 
monotherapy phase on the day of the SOC Initiation Visit. PK-enhancing agents will not 
be counted as part of the ART regimen. 
Participants who remain viremic on antiretroviral therapies (ARTs) will be encouraged to 
talk to their primary care provider about their ART regimen, per Department of Human 
and Health Services (DHHS, 2019) guidelines or other local regulations. 
Participants who receive the study product will continue to be followed for safety 
purposes according to the study schedule of evaluations. Participants will not be 
discontinued or replaced in the study for initiating or changing ARTs. They will continue 
to be followed for safety purposes according to the study schedule of evaluations. ART 
regimen changes will be documented in the participant’s record. 
8.1. 
Efficacy Assessments 
8.1.1. 
Plasma HIV-1 RNA 
Plasma for quantitative HIV-1 RNA will be collected according to the Schedule of 
Activities (Section 1.3). Methods to be used may include but are not limited to the Abbott 
Realtime HIV-1 Assay lower limit of quantitation 40 c/mL. In some cases, (e.g., where 
the plasma HIV-1 RNA is below the lower limit of detection for a given assay) additional 
exploratory methods may be used to further characterize plasma HIV-1 RNA levels. 
8.1.2. 
Lymphocyte Subsets 
Lymphocyte subsets will be collected for assessment by flow cytometry (total 
lymphocyte counts, percentage, and absolute CD4+ and CD8+ lymphocyte counts, 
CD4+/CD8+ ratio) according to the Schedule of Activities (Section 1.3). 
8.1.3. 
Pharmacokinetics 
GSK3810109A serum levels will be evaluated per the schedule in the SoA. See Section 
8.5 for details. 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
6 7  
 
8. 2.  
S af et y A s s e s s m e nt s  
Pla n n e d ti m e p oi nts f or all s af et y ass ess m e nts are pr o vi d e d i n t h e S o A ( Se cti o n 1. 3 ). 
8. 2. 1.  
P h y si c al E x a mi n ati o n s  
•  
A c o m plete p h ysical e x a mi nati o n will i n cl u d e, at a mi ni m u m, ass ess m e nts of the 
S k i n, Car di o v as c ular, Res pirat or y, G astr oi ntesti n al a n d N e ur ol o gic al s yste ms. 
Car di o v as c ular ris k f act ors (ass ess m e nts i n cl u de s m o ki n g stat us a n d hist or y, 
f a mil y hist or y of c ar dia c e v e nts), re c e nt [6 m o nt hs] illicit dr u g us e, i ntra v e n o us 
dr u g us e, gastr oi nt esti n al dis e as e, m eta b olic, ps yc hiatric, re n al, b o n e, a n d 
n e ur ol o gic dis or d ers will b e c olle cte d.  
•  
H ei g ht a n d w ei g ht will als o b e m e as ure d a n d re c or de d. S h o es s h o ul d b e 
re m o v e d f or h ei g ht a n d w ei g ht m e as ure me nts. 
•  
I n v esti gat ors s h o ul d p a y s p ecial atte nti o n to cli nic al si g ns relate d t o pre vi o us 
s eri o us ill n ess es. 
8. 2. 2.  
Vit al Si g n s  
•  
Vital si g ns will b e m e as ure d i n a s e mi -s u pi n e p ositi o n after 5 mi n utes rest i n a 
q uiet s etti n g wit h o ut distra cti o ns (e. g., tele visi o n, c ell p h o nes) a n d will i n cl u d e 
te m p erat ure, s yst olic an d diast olic bl o o d pressure, a n d p uls e.  Res pirat or y rate 
a n d S P O 2 will als o b e m e as ure d d uri n g t h e i n -cli nic p eri o d o n D a y 1.   
8. 2. 3.  
C D C HI V -1 Cl a s sifi c ati o n a n d HI V A s s o ci at e d C o n diti o n s  
HI V -ass o ciate d c o n diti o ns will b e re c or d e d as p er t h e Sc h e d ule of A cti viti es 
( Se cti o n 1. 3. 1 ). HI V ass o ciate d c o n diti o ns will b e ass ess e d a c c or di n g t o t h e 2 0 1 4 C D C 
Re vis e d Classific ati o n S yste m f or HI V I nfe cti o n i n A d ults  [C D C , 2 0 1 4]. W h e n ass essi n g 
C D C sta ge at Scre e ni n g, c o nsi d er o nl y t h e latest a v aila ble C D 4 + T -c ell c o u nt, e x ce pt 
w h e n t h e p artici p a nt h a d a n a cti v e Sta ge 3 e v e nt. I n dic at ors of cl i nic al dis e as e 
pr o gressi o n are d efi n e d as:  
C D C Sta ge 1 at e nr ol m e nt → Sta ge 3 e v e nt;  
C D C Sta ge 2 at e nr ol m e nt → Sta ge 3 e v e nt;  
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CDC Stage 3 at enrolment → New Stage 3 Event; 
CDC Stage 1, 2 or 3 at enrolment → Death. 
8.2.4. 
Electrocardiograms 
• 
Triplicate 12-lead ECG will be obtained as outlined in the SoA (Section 1.3) 
using an ECG machine that automatically calculates the heart rate and measures 
PR, QRS, QT, and QTc intervals.  
• 
The ECG should be read locally and be centrally archived. Please contact the 
Medical Monitor if any concerns.  
• 
Refer to Section 7.1.1 for ECG management criteria and additional QTc 
readings that may be necessary. 
8.2.5. 
Clinical Safety Laboratory Assessments 
• 
Refer to Section 10.2 for the list of clinical laboratory tests to be performed and 
to the SoA (Section 1.3) for the timing and frequency.  
• 
For visits with fasting labs, an overnight fast is preferred; however, a minimum 
of a 6-hour fast is acceptable. 
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or medical monitor. If such values do not return to normal/baseline 
within a period of time judged reasonable by the investigator, the etiology 
should be identified and the sponsor notified. 
• 
All protocol-required laboratory assessments, as defined in the Study Reference 
Manual (SRM), must be conducted in accordance with the laboratory manual, 
through the central laboratory (Q2 Solutions), and the SoA (Section 1.3). 
8.2.6. 
Immunogenicity Assessments 
Anti-GSK3810109A antibodies (ADA) will be evaluated in serum samples collected 
from all participants according to the SoA (Section 1.3). Additionally, serum samples 
should also be collected at the final visit from participants who were withdrawn from the 
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regarding sample collection, processing, storage, and shipment will be provided in the 
SRM or equivalent. 
Serum samples will be tested using a tiered testing scheme (ie, screen, confirm, titer). 
First, all samples will be tested in the screening assays. Next, samples that screen positive 
will be tested in a confirmation assay to determine the specificity. Finally, samples that 
confirm positive will be titrated to quasi-quantitate the amount of anti-GSK3810109A 
antibodies in the sample. The results (e.g., positive or negative) and titer values will be 
reported. Other analyses may be performed to characterize the ADA further. 
• 
The detection and characterization of antibodies to GSK3810109A will be 
performed using validated assays. Blood samples will also be collected and 
analyzed for GSK3810109A concentrations at the same time points as the 
immunogenicity samples to enable interpretation of the ADA data (SoA, Section 
1.3). 
8.2.7. 
Suicidal Ideation and Behavior Risk Monitoring 
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 INs, including DTG. Therefore, it is appropriate to monitor participants for 
suicidality before and during treatment.  
Participants should be monitored appropriately and observed closely for suicidal ideation 
and behavior or any other unusual changes in behavior. It is recommended that the 
investigator consider mental health consultation or referral for participants who 
experience signs of suicidal ideation or behavior. Participants presenting with new 
onset/treatment emergent depression should be advised to contact the investigator 
immediately if symptoms of severe acute depression (including suicidal 
ideation/attempts) develop, because medical intervention and discontinuation of the study 
medication may be required. 
Additionally, the investigator will collect information using the Possible Suicidality-
Related AE (PSRAE) eCRF form in addition to the AE (non-serious or SAE) eCRF form 
on any participant that experiences a possible suicidality-related AE while participating 
in this study. This may include, but is not limited to, an event that involves suicidal 
ideation, a preparatory act toward imminent suicidal behavior, a suicide attempt, or a 
completed suicide. The investigator will exercise his or her medical and scientific 
judgment in deciding whether an event is possibly suicide-related. PSRAE forms should 
be completed and reported to GSK/ViiV Healthcare within 1 week of the investigator 
diagnosing a possible suicidality-related AE. Sites should have a plan in place for 
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8.3. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Section 10.3. As described in Appendix 
3, intensity of AEs (and lab abnormalities) will be graded using the division of AIDS 
(DAIDS) Grading table. 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study (see Section 7). 
For Adverse Events related to COVID-19, please see Section 10.10.5.2. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of study intervention until the last visit 
at the time points specified in the SoA (Section 1.3). However, any SAEs 
assessed as related to study participation (e.g., study intervention, protocol-
mandated procedures, invasive tests, or change in existing therapy) or related to 
a GSK product will be recorded from the time a participant consents to take part 
in the study.  
• 
All AEs will be collected from the start of intervention until last study visit at 
the time points specified in the SoA (Section 1.3). 
• 
Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the case report form (CRF) not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in Section 
10.3.5. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
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• 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence. Appropriate questions include: 
• “How are you feeling?”  
• “Have you had any (other) medical problems since your last visit/contact?” 
• “Have you taken any new medicines, other than those provided in this study, 
since your last visit/contact?” 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special 
interest, will be followed until the event is resolved, stabilized, otherwise explained, or 
the participant is lost to follow-up (as defined in Section 7.4). Further information on 
follow-up procedures is given in Section 10.3.4. 
AEs of special interest include: injection site reactions, infusion related reactions, 
serious/severe immune reactions (including anaphylaxis and cytokine release syndrome). 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met.  
• 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators. 
• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary. 
• 
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAE) from the 
sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate according to local requirements. 
8.3.5. 
Pregnancy 
• 
Details of all pregnancies in female participants at birth will be collected after the 
start of study intervention and until completion of the long-term follow-up period. 
• 
If a pregnancy is reported, the investigator should inform GSK within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Section 
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• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE. 
8.3.6. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Section 10.3.3 and all deaths, whether or not 
they are considered SAEs, specific Cardiovascular (CV) and Death of the CRF will be 
required to be completed. These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death.  
The CV CRFs are presented as queries in response to reporting of certain CV MedDRA 
terms. The CV information should be recorded in the specific cardiovascular section of 
the CRF within one week of receipt of a CV Event data query prompting its completion. 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
8.3.7. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
The events or outcomes listed in the CDC Classification System for HIV-1 Infections 
[Section 10.8] will be recorded on the HIV-Associated Conditions eCRF page if they 
occur. However, these individual events or outcomes, as well as any sign, symptom, 
diagnosis, illness, and/or clinical laboratory abnormality that can be linked to any of these 
events or outcomes are not reported to GSK as AEs and SAEs even though such event or 
outcome may meet the definition of an AE or SAE, unless the following conditions 
apply: 
• 
The event or outcome is in the investigator’s opinion of greater intensity, frequency 
or duration than expected for the individual participant, or 
• 
The investigator considers that there is a reasonable possibility that the event was 
related to treatment with the investigational product, or 
• 
Death occurring for any reason during a study, including death due to a disease-
related event, will always be reported promptly. 
• 
Lymphomas and invasive cervical carcinomas are excluded from this exemption; 
they must be reported as SAEs even if they are considered to be HIV-related. 
If either of the above conditions is met, then record the Disease Related Event on the 
SAE page rather than the HIV Associated Conditions eCRF page and report 
promptly [Section 8.3.1] to GSK. 
8.3.8. 
Specific Toxicities/Adverse Event Management 
8.3.8.1. 
Injection/ Infusion Site Reactions (ISRs) 
Injection or infusion site reactions will be managed through investigator assessment 
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beyond 2 weeks must be discussed with the Medical Monitor to determine etiology and 
assess appropriate continued study participation. 
Digital photographs may be documented where possible on all participants who have an 
injection site reaction, with observable findings, that is either serious or Grade 3 or 
higher, or that persists beyond 2 weeks. Dermatology will be consulted on all participants 
who have an injection site reaction considered serious, Grade 3 or above, or if clinically 
significant and persistent beyond 30 days and others if the Investigator or Medical 
Monitor feels it is medically necessary. 
Details regarding photo collection and any other follow up will be given by the Medical 
Monitor at the time of assessment. 
ISR discomfort can be managed symptomatically (e.g., cold/warm compress, 
acetaminophen, ibuprofen) if the reaction is interfering with the participant’s ability to 
perform activities of daily living. The required intervention should be documented on the 
appropriate eCRF page. 
Diary Cards 
Participants will complete a diary card following GSK3810109A infusion/injection. This 
allows participants to record and score the severity of any reactions, record the impact of 
the infusion/injection on normal daily activities as well as any action taken such as use of 
analgesic medication following the infusion/ injection. 
Participants will be required to bring the original completed diary cards to the next clinic 
visit and hand over to the investigator/site staff who will enter the information from the 
ISR diary cards into the relevant ISR Diary section of the eCRF within the same 
timeframe as normal eCRF data entry (1 working week of the visit). 
8.3.8.2. 
Severe Immune Reactions 
Intravenous access will be placed in an arm vein in an aseptic manner. GSK3810109A 
will be administered with approximately 100 mL of normal saline IV over approximately 
30 minutes. Infusions lasting longer than 30 minutes are allowed. If the participant 
experiences side effects during the infusion, the rate of infusion may be slowed or 
stopped to alleviate the symptoms.  
Vital signs will be monitored during the infusion and prompt treatment of anaphylaxis is 
critical, with subcutaneous or intramuscular epinephrine and intravenous fluids. 
Adjunctive measures include airway protection, antihistamines, steroids, and beta 
agonists. Some symptoms may be treated by slowing or stopping the infusion. Supportive 
treatment may also be indicated for some signs and symptoms. Medication administered 
during anaphylactic reaction will be recorded in CRF. 
Patients with anaphylaxis should be closely monitored for the possibility of recurrent 
symptoms after initial resolution. Urinary and serum histamine levels and plasma tryptase 
levels drawn after onset of symptoms may assist in diagnosis. 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
7 4  
 
8. 4.  
T r e at m e nt of O v er d o s e  
F or t his st u d y, a n y d os e of G S K 3 8 1 0 1 0 9 A gre ater t h a n 4 0  m g/ k g wit hi n a 2 w e e k p eri o d 
will b e c o nsi d ere d a n o v er d os e.  
T h e I n v esti gat or s h o ul d us e cli nic al j u d ge m e nt i n tre ati n g o v er d ose, as Vii V H e alt h c are 
is u n a ble t o re c o m me n d s p ecific tre at m e nt ot h er t h a n s u p p orti v e c are.  
I n t h e e v e nt of a n o v er d os e, t h e i n v esti gat or/tre ati n g p h ysicia n s h o ul d: 
1.  C o nta ct t h e Me dic al M o nit or i m m e diatel y.  
2.  M o nit or vital si g ns re g ularl y f or s e v eral h o urs after t h e o v er d os e  
3.  Cl os el y m o nit or t h e p art ici p a nt f or A E/ S A E a n d la b orat or y a b n or m alities u ntil 
G S K 3 8 1 0 1 0 9 A c a n n o l o n ger b e d etecte d s yste mic all y.  
4.  O btai n a s er u m s a m ple f or P K a n al ysis fr o m t h e d ate of t h e o v er d ose of st u d y 
i nter v e nti o n if re q u este d b y t h e Me dic al M o nit or ( d eter mi ne d o n a c as e-b y -
c as e b asis).  
5.  D o c u m e nt t h e q u a ntit y of t h e e x cess d os e as w ell as t h e d urati o n of t h e 
o v er d osi n g i n t h e C R F.  
Si n c e t his is a si n gle d os e a d mi nistrati o n of G S K 3 8 1 0 1 0 9 A, t h ere will b e n o d os e 
i nterr u pti o ns or m o dific ati o ns. 
8. 5.  
P h ar m a c o ki n eti c s  
•  
W h ole bl o o d s a m ples of a p pr o xi matel y 2 m L will b e c olle cte d f or m e as ure m e nt of 
s er u m c o n c e ntrati o ns of G S K 3 8 1 0 1 0 9 A at t h e ti m e p oi nts s p e cifie d i n t h e S o A 
( Se cti o n 1. 3 ). T h e ti mi n g of P K s a m ples  m a y b e altere d a n d/ or P K s a m ples m a y b e 
o btai n e d at a d diti o n al ti m e p oi nts d uri n g t h e st u d y t o e ns ure t h or o u g h P K m o nit ori n g 
if w arra nte d a n d a gre e d u p o n b et w ee n t h e i n v esti gat or a n d t h e s p o ns or. I nstr u cti o ns 
f or t h e c olle cti o n a n d h a n dli n g of bi ol o gic al s a m ples will b e pr o vi d e d b y t h e s p o ns or. 
T h e a ct u al d ate a n d ti m e ( 2 4 -h o ur cl o c k ti m e) of e a c h s a m ple will b e re c or d e d.  
•  Sa m ples will b e us e d t o e v al u ate t h e s yste mic P K of G S K 3 8 1 0 1 0 9 A. Ea c h s er u m 
s a m ple will b e c olle cte d e q u all y i nt o 2 ali q u ots wit h o n e al i q u ot as a b a c k u p t o b e 
st ore d at sites a n d s hi p p e d later. Sa m ples c olle cte d f or a n al yses of G S K 3 8 1 0 1 0 9 A 
s er u m c o n c e ntrati o n m a y als o b e us e d t o e v al uate s afet y or effic a c y as pe cts 
relate d t o c o n c er ns arisi n g d uri n g or after t h e st u d y. 
C CI

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
7 5  
 
C CI

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
7 6  
 
P h e n ot y pic a n d f u n cti o n al pr o p erties of T c ells  will b e i n v esti gate d b y a n al y zi n g c yt o kine 
s e creti o n i n res p o ns e t o HI V a nti ge ns b ef ore a n d at s e v eral ti m e p oi nts p ost a nti b o d y 
i nf usi o n. 
8. 7. 3.  
B -c ell R e s p o n s e s  
W h ole v e n o us bl o o d s a m ples will b e o btai n e d fr o m e a c h p artici pa nt  a c c or di n g t o t h e 
Sc h e d ule of A cti v ities i n Se cti o n 1. 3 . D etails c o nc er ni n g t h e h a n dli n g, la b eli n g a n d 
s hi p pi n g of t h es e s a m ples will b e s u p plie d s e p aratel y. 
P h e n ot y pic a n d f u n cti o n al pr o p erties of B c ells will b e i n v esti gate d b y m e as uri n g t h e 
h eter ol o g o us n e utraliz ati o n pr ofile b ef ore a nti b o d y i nf usi o n a n d at t h e S O C F oll o w -U p 
We e k 4 8 ti m e p oi nt.  T h e h eter ol o g o us n e utraliz ati o n pr ofile a n al ysis m a y b e c arrie d o ut 
b y M o n o gra m Bi os cie n c es . 
8. 8.  
Vir al G e n ot y pi n g a n d P h e n ot y pi n g  
At Scre e ni n g, s a m ples will b e c olle cte d f or HI V -1 R T/ P R O/I N  ge n ot y p e a n d p h e n ot y p e. 
Res ults will b e pr o vi d e d t o t h e I n v esti gat or t o assist i n t h e s ele cti o n of t h e sta n dar d of 
c are re gi m e n t h at will b e i nitiate d at t h e e n d of Part 1 a n d Part 2. Res ults will als o b e 
m a d e a v aila ble f or s cre e n e d p artici pa nt s w h o d o n ot m e et ot h er eli gi bilit y f or st u d y 
i n cl usi o n i n or d er t o i nf or m i nitial HI V tre at m e nt pla ns o utsi de of st u d y. Resista n ce test 
d ata s h o ul d b e re vie w e d as s o o n as a v aila ble. If oral A R T h as b e e n i nitiate d pri or t o 
res ults b e c o mi n g a v aila ble, i n v esti gat or s h oul d d eter mi n e if a p artici p a nt’s re gi m e n 
s h o ul d b e m o difie d. 
D uri n g t h e S O C F oll o w -U p,  p artici p a nts e x p erie n ci n g c o nfir m e d vir ol o gic f ail ure will 
h a v e plas m a s a m ples teste d f or HI V -1 R T/ P R O/I N  ge n ot y p e a n d p h e n ot y pe fr o m 
s a m ples c olle cte d at t h e ti m e of s u s p e cte d vir ol o gic f ail ure; t h es e res ults will b e re p orte d 
t o t h e I n v esti gat or as s o o n as a v aila ble t o pr o vi d e g ui d a nc e f or ele cti o n of a s witc h 
re gi m e n. 
D etails c o n c er ni n g t h e h a n dli n g, la b eli n g a n d s hi p pi n g of t h es e s a m ples will b e s u p plie d 
s e p aratel y. G en ot y pic a n d p h e n ot y pic a nal ys es m a y b e c arrie d o ut b y M o n o gra m 
Bi os cie n c es usi n g, b ut n ot li mite d t o, t h eir Sta n d ar d P h e n os e ns e testi n g m et h o ds f or 
pr ote as e ( P R O) a n d re v ers e tra ns cri ptas e ( R T), or wit h t h eir G e n e Se q I nte gras e a n d 
P h e n o Se ns e I nte gras e ass a ys.  
C CI

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
7 7  
 
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
St ati sti c al H y p ot h e s e s  
N o f or m al statistic al h y p ot h eses will b e teste d, a n d st u d y c o ncl usi o ns wil l b e b as e d o n 
esti m ati o n. T h e pri m ar y tre at m e nt effe ct t o b e esti m ate d is t h e m a xi m u m p las ma HI V-1 
R N A d e cli n e fr o m b as eli n e o ver t h e M o n ot hera p y P h as e f or e a c h d ose le v el a n d m et h o d 
of a d mi nistrati o n (i ntra v e n o us or s u bc uta n e o us).  
9. 2.  
S a m pl e Si z e D et er mi n ati o n  
A n esti m ate d 5 0 p artici p a nts will b e ra n d o ml y assi g n e d t o G S K 3 8 1 0 1 0 9 A a cr oss 
a p pr o xi m atel y 5  gr o u ps t o a c hie v e a p pr o xi m atel y 1 0 e val u a ble p artici pa nts f or e a c h 
gr o u p.  
T h e s a m ple siz e of a p pr o xi m atel y 1 0 e v al ua ble p artici p a nts f or Gr o u p 1 w as c h os e n t o 
all o w f or a n a c c urate esti m ate of t h e pri m ar y tre at m e nt effe ct of t h e hi g h est d os e. A 
s a m ple siz e of a p pr o xi m atel y 1 0 f or t h e re m ai ni n g gr o u ps w as c h os e n pri m aril y b as e d o n 
C CI

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feasibility in order to explore approximately 4 additional groups at varying dose 
concentrations and modes of delivery (IV and subcutaneous). The required sample size of 
approximately 10 for Group 1 is to be able to account for the possibility of some 
participants being non-sensitive to GSK3810109A, and to accurately estimate the 
primary treatment effect among the sensitive-only subgroup.  
Based on viral load decline data from 3 previous POC studies with bNAbs (VRC01: 
[Lynch, 2015]; 10-1074: [Caskey, 2017]; 3BNC117: [Caskey, 2015]), we assumed a 
target value viral load decline (VLD) for individual participants from the highest dose 
(Group 1) to be 1.3 log10 when analysing all participants regardless of their sensitivity to 
GSK3810109A. We also assumed a minimum value of 1 log10 VLD to represent a 
clinically meaningful change. Alternatively, a target value of 1.4 log10 VLD among 
participants sensitive to GSK3810109A represents a meaningful decline to proceed with 
the study. In the absence of sensitivity data during the study we use a 0.5 log10 decrease 
as a proxy for sensitivity for our interim analysis. We used these thresholds in our interim 
Go/No Go criteria, detailed in Section 9.5 and powered the study to make a decision on 
whether to proceed to Part 2 based on the VLD observed in Part 1 among the high-dose 
group (Group 1). 
To determine the operating characteristics of the interim decision and inform our sample 
size, we simulated trial data as arising from a mixture of 2 normal distributions to 
describe the VLD among a population consisting of both sensitive and non-sensitive 
individuals. The mixing parameter is the proportion of non-sensitive individuals in the 
population and the mean VLD varying for sensitive individuals and 0.2 for non-sensitive 
individuals, both with SD=0.4. We simulated data with mixing parameters of 0.10 or 0.30 
and mean VLD for sensitive individuals ranging from 0.2 to 2 as listed in Table 4.  
We simulated 10,000 trials for each unique combination of the above parameter values.  
For each unique scenario, we calculated the proportion of trials with Go, No-Go, and 
Consider for the informal interim analysis described in Section 9.5. These proportions 
estimate the probabilities of each decision and are shown below in Table 4. 
Table 4 
Probability Decision at Interim Based on a Sample Size of 10 
% non-sensitive 
participants in 
population 
True VLD for sensitive 
participants in population 
Probability of Decision at Interim 
Go 
No-Go 
Consider 
 
0.2: No treatment effect 
0.0% 
99.8% 
0.2% 
10% 
1.1 
24.1% 
61.7% 
14.2% 
1.25 
58.0% 
26.3% 
15.7% 
1.4 
83.0% 
7.5% 
9.5% 
2 
96.3% 
0.0% 
3.7% 
30% 
1.1 
5.4% 
87.4% 
7.2% 
1.25 
19.0% 
64.4% 
16.7% 
1.4 
35.1% 
37.3% 
27.6% 
2 
57.5% 
0.6% 
41.9% 
 

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To assess the sensitivity of the above analysis to the sample size and parameter 
assumptions we assessed the operating characteristics under the following 4 scenarios: 
1. There is no effect on VLD (mean VLD=0 for entire population). 
2. GSK3810109A has mean VLD of 1.4 among sensitive population, but 50% of the 
population is non-sensitive to GSK3810109A. 
3. GSK3810109A has mean VLD of 1.4 among sensitive population and only 10% 
of the population is non-sensitive to GSK3810109A. 
4. GSK3810109A has mean VLD of 1.4 among the entire population (i.e. entire 
population is sensitive to GSK3810109A).  
For each scenario we calculated the operating characteristics above for sample sizes of 8, 
10, 20, and 50 to see how sensitive the operating characteristics are to sample size. The 
results are shown in Table 5.  
Table 5 
Sensitivity to Sample Size and Parameter Assumptions 
Scenario 
N 
Prob. Go 
Prob. No Go 
Prob. Consider 
Treatment doesn’t work VLD=0 for 
all 
8 
0.0% 
99.8% 
0.2% 
10 
0.0% 
99.8% 
0.2% 
20 
0.0% 
99.9% 
0.1% 
50 
0.0% 
100.0% 
0.0% 
Treatment works well for sensitive 
participants and 50% non-sensitive 
(sensitive VLD=1.4 and non-
sensitive VLD=0.2) 
8 
9.3% 
58.3% 
32.4% 
10 
7.1% 
65.8% 
27.1% 
20 
2.6% 
79.8% 
17.7% 
50 
0.0% 
91.1% 
8.9% 
Treatment works well for sensitive 
participants and 10% non-sensitive 
(sensitive VLD=1.4 and non-
sensitive VLD=0.2) 
8 
80.7% 
6.5% 
12.8% 
10 
83.0% 
7.5% 
9.5% 
20 
89.4% 
4.1% 
6.5% 
50 
87.1% 
0.2% 
12.8% 
Treatment works well and all 
participants sensitive (sensitive 
VLD=1.4) 
8 
97.6% 
0.7% 
1.7% 
10 
97.9% 
0.4% 
1.7% 
20 
99.2% 
0.0% 
0.9% 
50 
99.9% 
0.0% 
0.1% 
The false positive rates (Prob. Go in scenarios 1 and 2) and false negative rates (scenarios 
3 and 4 Prob. No Go) are well controlled <10% across all sample sizes tested. 
Additionally, an increase in sample size under scenario 3 does not drastically improve 
power (Prob. Go). Therefore, a sample size of approximately 10 for Group 1 is sufficient 
for this analysis. 
9.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 

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Population 
Description 
Screened  
All participants who were screened for eligibility 
Randomized 
• 
All participants who were randomly assigned to treatment in the 
study. 
• 
This population will be based on the treatment the participant was 
randomized to. 
Safety 
• 
All participants who received at least one dose of study treatment. 
• 
This population will be based on the treatment the participant 
actually received. 
Note: Participants who were not randomized but 
received at least one dose of study treatment should be 
listed. 
Full Analysis Set 
(FAS) 
• 
All randomized participants who received at least one dose of study 
treatment. 
• 
This population will be based on the treatment the participant was 
randomized to. 
Any participant who receives a treatment 
randomization number will be considered to have been 
randomized. 
Per-Protocol (PP) 
• 
All participants in the FAS population who comply with the protocol. 
• 
Protocol deviations that would exclude participants from the PP 
population will be defined in the Reporting and Analysis Plan.  
Pharmacokinetic (PK) 
All participants in the Safety population who had at 
least 1 non-missing PK assessment (Non-quantifiable 
[NQ] values will be considered as non-missing values). 
 
9.4. 
Statistical Analyses 
9.4.1. 
Efficacy Analyses 
Plasma HIV-1 RNA values will be used for the efficacy analysis based on the FAS 
population (and the PP population if it differs from FAS). Change from baseline in 
plasma HIV-1 RNA will be calculated for each participant on each assessment visit of the 
trial. Maximum change from baseline during the monotherapy period will also be 
calculated for each evaluable participant. A randomized participant is considered 
evaluable if plasma HIV-1 RNA measurements are available at baseline and at least 3 out 
of the 4 scheduled monotherapy timepoints from Day 3 through Day 11 inclusive. Based 
on Part 1 data, the definition of evaluable for Part 2 may be changed. In this case, the 
definition of evaluable for Part 2 will be updated in the statistical analysis plan. 
Maximum change in plasma HIV-1 RNA from baseline among evaluable participants 
will be summarized by treatment. Change in plasma HIV-1 RNA from baseline will be 
summarized by treatment at each visit/assessment. 

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Plasma HIV-1 RNA will be listed by treatment, participant, and time point and 
summarized by treatment and time point along with change from baseline. 
Change in CD4+ T cell counts will be summarized by treatment, over time.  
9.4.2. 
Safety Analyses 
All safety analyses will be performed on the Safety Population. Safety data will be 
presented in tabular format and summarized descriptively according to GSK’s Integrated 
Data Standards Library. No formal statistical analysis of the safety data will be 
conducted. 
9.4.2.1. 
Immunogenicity Analyses 
For each participant, the results and titers of ADA will be listed for each assessment time 
point, along with the time-matched drug concentration. The frequency and percentage of 
participants with positive and negative results will be summarized for each assessment 
time and overall for each participant by dose group. Additional analyses may be 
conducted as appropriate to the data. Information detailing the analyses will be included 
in the statistical analysis plan. 
9.4.2.2. 
Pharmacokinetic Analyses 
The single dose systemic exposure of GSK3810109A will be estimated over the 
monotherapy duration. Relevant PK parameters such AUC, Cmax and Tmax will be 
summarized based on available data. The systemic drug concentrations may subsequently 
be utilized for a PK/PD analysis to characterize the exposure-response relationship 
between GSK3810109A exposure and viral load decline. 
9.4.3. 
Other Analyses 
Pharmacokinetic, pharmacodynamic, virology, and biomarker analyses will be described 
in the statistical analysis plan. The population PK analysis and pharmacodynamic 
analyses will be presented separately from the main clinical study report (CSR).  
Additionally, special statistical and data analysis considerations may be warranted in the 
event that the COVID-19 or related epidemics or natural disasters may affect the study 
and data integrity. To the extent possible, these will be described in the main study 
statistical analysis plan (SAP); alternatively, a separate SAP focusing on modified data 
handling rules (eg, changes to analysis populations, visit windows and endpoints) and 
analyses (eg, sensitivity analyses to assess impact of and account for missing data) may 
be prepared, taking in to account applicable regulatory guidance and industry best 
practices for handling such situations. 
9.5. 
Interim Analyses 
An informal interim analysis of preliminary antiviral activity will occur after the earlier 
of the Day 21 visit or end of monotherapy of the last high-dose (Group 1) participant. 
Antiviral activity will be measured by maximum viral load decline (VLD) from baseline 

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during monotherapy (Part 1) in evaluable participants in the high dose group (Group 1). 
This analysis will decide Go/No Go based on emerging evidence of efficacy. The Safety 
and Dose Evaluation Committee (SDEC) will also consider emerging safety data from 
both dosing groups before deciding whether to proceed with Part 2 of the trial. 
The subgroup for the efficacy Go/No Go decision as well as the criteria used will depend 
on the proportion of evaluable participants who are non-responders, defined as those 
participants with a maximum VLD less than 0.5 log10. If less than 30% of evaluable 
participants are non-responders, then the analysis will be based on all evaluable 
participants in Group 1 (Scenario 1) from the FAS population. If 30% or more of 
participants are non-responders, then the analysis will include only those participants in 
Group 1 from the FAS population with a VLD of at least 0.5 log10 (Scenario 2).  
For this analysis, the Bayesian posterior probabilities of the mean maximum log10 VLD 
(based on the Group 1 data used in each scenario) exceeding/not exceeding certain 
thresholds will be calculated. For the Bayesian calculation, we assume the maximum 
VLD follows a normal distribution (mean, standard deviation) and the assumed priors are 
taken to be non-informative, with Normal (0, 100) for mean and Inverse Gamma (0.01, 
0.01) for standard deviation. The following decision criteria will be used: 
Scenario 1 (< 30% of evaluable participants are non-responders): 
If Prob. (maximum log10 VLD >1) 70% AND Prob. (maximum log10 VLD>1.3) 
 10%, the trial will proceed (GO). 
If Prob. (maximum log10 VLD>1) <70% AND Prob. (maximum log10 VLD>1.3) 
<10%, the trial will not proceed (STOP). 
Otherwise, the study team will consider the whole preliminary clinical data (e.g. 
safety, tolerability and PK, as available) and decide whether to proceed 
(CONSIDER). 
Scenario 2 (>=30% of evaluable participants are non-responders): 
If Prob. (maximum log10 VLD <1.4) >50%, the trial will not proceed (STOP).  
Otherwise, the study team will consider the whole preliminary clinical data and 
decide whether to proceed (CONSIDER). In this scenario the team will also 
determine whether to include a pre-screen for GSK3810109A sensitivity if the 
decision is to proceed with the trial. 
If the decision based on Group 1 data is to proceed with the trial, then the antiviral 
activity of both Group 1 and Group 2 will be reviewed to aid dose selection and mode of 
administration of monotherapy for the subsequent groups in Part 2. 
At the Part 1 interim analysis stage, safety Go / No-Go criteria from the Safety 
Population are pre-defined as: 

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No Go: 
• If ≥35% of treated participants in Part 1 receiving GSK3810109A have a 
clinically significant Grade 3 or higher AE trend or laboratory abnormality trend 
(with the exception of asymptomatic Grade 3 or higher cholesterol, triglyceride) 
determined by the SDEC 
Go:  
• The above safety ‘no go’ criteria is not met. 
The safety interim analysis will be based on all available safety data from the 
monotherapy phase of Part 1 participants at the time of the interim efficacy data cut-off. 
>65% of Part 1 participants must complete monotherapy without a clinically significant 
Grade 3 or lab abnormality trend before the study can proceed with Part 2 (Go decision). 
Additional ongoing safety data from Part 1 participants until their monotherapy 
completion will be added to the interim safety analysis until a definitive decision (Go or 
No Go) can be reached. 

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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 Consideration 
• 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 
• 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
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 his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding 
the study. 
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent 
that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, 
and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study.  
A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative.  
Participants who are rescreened are required to sign a new ICF. 
GSK/ViiV Healthcare (alone or working with others) may use participant’s coded study 
data and samples and other information to carry out this study; understand the results of 
this study; learn more about GSK3810109A or about HIV; publish the results of these 
research efforts; work with governmental agencies or insurers to have GSK3810109A 
approved for medical use or approved for payment coverage. 
10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
The participant must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the participant.  
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 

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before submission. This allows the sponsor to protect proprietary information and to 
provide comments.  
The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
10.1.6. 
Dissemination of Clinical Study Data 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a ViiV Healthcare/GSK site or other 
mutually-agreeable location. 
ViiV Healthcare/ GSK will also provide the investigator with the full summary of the 
study results.  The investigator is encouraged to share the summary results with the study 
participants, as appropriate. 
The procedures and timing for public disclosure of the protocol and results summary and 
for development of a manuscript for publication for this study will be in accordance with 
ViiV Healthcare/ GSK Policy. 
ViiV Healthcare/ GSK intends to make anonymized patient-level data from this trial 
available to external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve patient care. This helps ensure the data 
provided by trial participants are used to maximum effect in the creation of knowledge 
and understanding. 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF. This includes 
accurate and timely transcription of the data recorded on the participant-
completed ISR Diary cards into the relevant section of the study eCRF.    
• Guidance on completion of CRFs will be provided in the Study Reference 
Manual. 
• Quality tolerance limits (QTLs) will be pre-defined in the quality tolerance limits 
plan to identify systematic issues that can impact participant safety and/or 
reliability of study results. These pre-defined parameters will be monitored during 
and at the end of the study and all deviations from the QTLs and remedial actions 
taken will be summarized in the clinical study report. 

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• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• Monitoring details describing strategy including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. This includes the participant-completed ISR Diary cards (source documents) 
and the data transcribed from the dairy cards into the eCRF. The investigator may need to 
request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
Definition of what constitutes source data can be found in the Monitoring Plan. 
10.1.9. 
Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 

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• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further study intervention development. 
10.1.10. 
Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials Registers and 
Publication 
• Study information from this protocol will be posted on publicly available 
clinical trial registers before enrolment of participants begins. 
• Where required by applicable regulatory requirements, an investigator 
signatory will be identified for the approval of the clinical study report.  The 
investigator will be provided reasonable access to statistical tables, figures, 
and relevant reports and will have the opportunity to review the complete 
study results at a GSK site or other mutually-agreeable location. 
• GSK will also provide the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study participants, as appropriate. 
• The procedures and timing for public disclosure of the results summary and 
for development of a manuscript for publication will be in accordance with 
GSK Policy. 
• A manuscript will be progressed for publication in the scientific literature if 
the results provide important scientific or medical knowledge. 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
8 9  
 
1 0. 2.  
A p p e n di x 2: Cli ni c al L a b or at or y T e st s  
T h e tests d etaile d i n Ta ble 6  will b e p erf or m e d b y t h e c e ntral la b orat or y.  
Pr ot o c ol -s p e cific re q uire me nts f or i n cl usi o n or e x cl usi o n of p artici p a nts are d etaile d i n 
Se cti o n 5  of t h e pr ot o c ol . 
A d diti o n al tests m a y b e p erf or m e d at a n y ti m e d ur i n g t h e st u d y as d eter mi ne d n e c ess ar y 
b y t h e i n v esti gat or or re q uire d b y l o c al re g ulati o ns.  
Pre g n a n c y Testi n g: Ref er t o Se cti o n 5. 1  I n cl usi o n Criteria f or s cre e ni n g pre g n a n c y 
criteria. A d diti o n al s er u m or uri n e pre g n a nc y tests m a y b e p erf or m e d, as d eter mi n e d 
n e c ess ar y b y t h e i n v esti gat or or re q uire d b y l o c al re g ulati o n, t o esta blis h t h e a bs e nc e of 
pre g n a n c y at a n y ti m e d uri n g t h e p artici p a nt's p artici p ati o n i n t h e st u d y.  
T a bl e 6  
Pr ot o c ol -R e q uir e d S af et y L a b or at or y A s s e s s m e nt s  
H e m at olo gy  
Plat elet co u nt  
Aut o m at e d W B C diff er e ntial:  
R B C co u nt  
N e utr o p hils  
W B C co u nt ( a bsolut e)  
Ly m p h ocyt es 
H e m o glo bin  
M o n ocyt es  
H e m at ocrit  
Eosin o p hils  
M C V  
Baso p hils  
M C H  
% R eticulocyt es  
Cli ni c al C h e mi stry  
B U N  
Pot assiu m  
A S T  
T ot al bilir u bin a 
Cr e atinin e  
C hlorid e  
AL T  
Alb u min  
Glucose c 
T ot al C O 2 
Alkalin e p h osp h at ase  
Cr e atin e p h osp h okin ase  
So diu m  
Lip ase  
Ph osp h at e  
Cr e atinin e cle ar a nce b 
C alciu m  
 
 
 
F a sti n g Li pi d Pa nel d 
T ot al ch olest er ol  
H D L ch olest er ol  
L D L ch olest er ol 
Triglycerid es  
Ot h er T e st s  
Plas m a HI V -1 R N A  
HI V -1 g e n otyp e/ p he n otyp e ( R T/ P R O/I NI)  
C D 4 + a n d C D 8 + cell co u nts [ C D 4/ C D 8 r atio]  
Perip h er al Blo o d M o n o n ucle ar C ells ( P B M Cs)  
H e p atitis B ( H Bs Ag), a nti -H Bc, a nti -H Bs Ag, a n d h e p atitis C a ntib o dy e 
Syp hilis ser olo gy + R eflex R a pid Plas m a R e a gin ( R P R)  
Pr ot hr o m bin Ti m e ( P T)/I nter natio n al N or malize d R atio (I N R)/ Partial T hro mb o plastin Ti me ( P T T) 
Pr e g n a ncy t est f or w o m e n of child b e arin g p ot ential f 
Urin alysis, urin e alb u min/cr e atinin e r atio, a n d urine pr ot ein/cr eatinin e r atio, urin e p h osp hat e  
Ge n etics Sa m ple  
F ollicle sti m ulatin g h or m o n e ( F S H) a n d estr a diol  ( o nly f or inst a nces w h e n p ost m e no p ausal st at us is q u estio n a ble) 
ntib o dies ( A D A) 
G S K3 8 1 0 1 0 9 A P K a n alysis  
C O VI D -1 9 P C R or a ntig en  t estin g 
C CI
C CI
C CI

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AST=aspartate aminotransferase, ALT = alanine aminotransferase, CO2 = carbon dioxide, HDL = high density 
lipoprotein, LDL = low density lipoprotein, HBsAg= hepatitis B virus surface antigen, PT/INR = prothrombin 
time/international normalized ratio. 
a) 
Direct bilirubin will be reflexively performed for all total bilirubin values >1.5 ×ULN. 
b) 
Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) [Levey, 2009]. 
c) 
For fasting glucose assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments. 
d) 
For fasting lipids assessments, an overnight fast is preferred; however, a minimum of a 6-hour fast is 
acceptable for participants with afternoon appointments. 
e) 
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). 
f) 
Urine pregnancy test/ serum pregnancy test will be performed according to the SoA (Section 1.3). 
g) 
The intention is to utilize these biomarker data for research purposes; the sponsor will not be reporting real-
time results of these assessments to the investigator 
 

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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital 
signs measurements), including those that worsen from baseline, considered 
clinically significant in the medical and scientific judgment of the investigator 
(i.e., not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including 
either an increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study intervention administration 
even though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
study intervention or a concomitant medication. Overdose per se will not be 
reported as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will 
not be reported as an AE or SAE. Such instances will be captured in the 
efficacy assessments. However, the signs, symptoms, and/or clinical sequelae 
resulting from lack of efficacy will be reported as AE or SAE if they fulfill the 
definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal 
safety assessments which are associated with the underlying disease, unless 

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judged by the investigator to be more severe than expected for the participant’s 
condition. 
• 
The disease/disorder being studied or expected progression, signs, or 
symptoms of the disease/disorder being studied, unless more severe than 
expected for the participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social 
and/or convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
o Results in death 
o Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been detained 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
Results in persistent or significant disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 

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• 
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events 
that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
• 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development 
of drug dependency or drug abuse. 
Is associated with liver injury and impaired liver function defined as: 
• ALT  3xULN and total bilirubin*  2xULN (>35% direct), or 
• ALT  3xULN and INR** > 1.5. 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick.  If fractionation is unavailable and 
ALT  3xULN and total bilirubin  2xULN, then the event is still to be reported as an 
SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants. If INR measurement is obtained, the value is to 
be recorded on the SAE form. 
10.3.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 

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• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 
10.3.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review 
all documentation (e.g. hospital progress notes, laboratory, and diagnostics 
reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records 
before submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information. Whenever possible, the 
diagnosis (not the individual signs/symptoms) will be documented as the 
AE/SAE. 
• 
Participant-completed Value Evidence and Outcomes questionnaires and the 
collection of AE data are independent components of the study. 
• 
Responses to each question in the Value Evidence and Outcomes questionnaire 
will be treated in accordance with standard scoring and statistical procedures 
detailed by the scale’s developer. 
• 
The use of a single question from a multidimensional health survey to 
designate a cause-effect relationship to an AE is inappropriate. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with 
normal everyday activities. 

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• 
Severe: An event that prevents normal everyday activities. An AE that is 
assessed as severe should not be confused with an SAE. Severe is a category 
utilized for rating the intensity of an event; and both AE and SAE can be 
assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study 
intervention and each occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, 
evidence, and/or arguments to suggest a causal relationship, rather than a 
relationship cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and 
other risk factors, as well as the temporal relationship of the event to study 
intervention administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or 
Product Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is 
very important that the investigator always make an assessment of 
causality for every event before the initial transmission of the SAE data to 
GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as medically indicated or as 
requested by GSK to elucidate the nature and/or causality of the AE or SAE as 
fully as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
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• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 
10.3.5. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE 
data collection tool (see next section) in order to report the event within 24 
hours. 
• 
The site will enter the SAE data into the electronic system as soon as it 
becomes available. 
• 
The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and 
verification of the relationship of each SAE to IP/study participation 
(causality) within 72 hours of SAE entry into the eCRF. 
• 
After the study is completed at a given site, the electronic data collection tool 
will be taken off-line to prevent the entry of new data or changes to existing 
data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection 
tool has been taken off-line, then the site can report this information on a paper 
SAE form (see next section) or to the medical monitor/SAE coordinator by 
telephone. 
• 
Contacts for SAE reporting can be found at the beginning of this protocol on 
the Sponsor/Medical Monitor Contact Information page. 
 
SAE Reporting to GSK via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to 
transmit this information to the medical monitor or the SAE coordinator. 
• 
In rare circumstances and in the absence of facsimile equipment, notification 
by telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 

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• 
Initial notification via telephone does not replace the need for the investigator 
to complete and sign the SAE CRF pages within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found at this beginning of the protocol on 
the Sponsor/Medical Monitor Contact Information page. 
 

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10.4. 
Appendix 4: Toxicity Management 
Adverse events that occur during the trial should be evaluated by the investigator and 
graded according to the DAIDS toxicity scales [DHHS, 2019]. Additional information 
regarding detecting, documenting and reporting AEs and SAEs are available in Section 
8.3. 
Monotherapy Phase 
In Part 1 and Part 2 of the Monotherapy Phase, a single dose is administered, thus 
discontinuation of GSK3810109A is not applicable following the Day 1 IV infusion or 
SC injection. Participants who received GSK3810109A, will continue to be followed for 
safety purposes according to the study schedule of activities (oral combination ART 
phase). Participants will not be discontinued or replaced in the study for initiating or 
changing ART. They will continue to be followed for safety purposes according to the 
study schedule of evaluations Section 1.3.1. ART regimen changes will be documented in 
the participant’s record. Participants that meet participant level stopping criteria outlined 
in Section 7.1 will result in a study pause whilst a review of all relevant safety data is 
performed with the outcomes and recommendations on dosing resumption presented to 
VSLC for endorsement. 
SoC Follow-Up Phase 
In the follow-up phase, SoC may be interrupted at the discretion of the investigator and 
according to the severity of the AE. If one or more ART medication is held due to 
toxicity or AEs, all ART medications should be held to reduce the risk of development of 
resistance taking into account the length of the planned interruptions and the PK half-life 
of each ART of the regimen, in order to minimize the risk of development of resistance. 
Guidance is provided below on participant management based on the severity of the AE 
for specific toxicities in the SOC follow-up phase. All changes in SoC 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 will continue to be 
followed for safety purposes according to the study schedule of evaluations (oral 
combination ART phase). 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 SOC, dosing may continue after discussion with the medical monitor. 

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Participants who develop a Grade 3 AE or toxicity that the investigator considers related 
or possibly related to the SOC should have SOC withheld and be rechecked each week 
until the AE returns to Grade 2. Once the AE is Grade ≤2, SOC may be restarted. 
Should the same Grade 3 AE recur within 28 days in the same participant, SOC should be 
permanently discontinued. Changes in SOC will for safety or virologic failure will be 
made in consultation with the medical monitor and follow international guidelines.  
Exceptions are noted for lipid abnormalities in Section 7.1. 
Grade 4 Toxicity/Adverse Event 
Subjects who develop a Grade 4 AE or toxicity should have SOC discontinued. Changes 
in SOC will for safety or virologic failure will be made in consultation with the medical 
monitor and follow international guidelines. However, if the investigator has compelling 
evidence that the AE is not causally related to the study drugs, dosing may continue after 
discussion with and assent from the medical monitor. Subjects should be rechecked each 
week until the AE returns to Grade 2. 
Subjects with asymptomatic Grade 4 laboratory abnormalities should be investigated for 
all potential non-drug related causes, and, following discussion with the medical monitor, 
may continue therapy if the investigator has compelling evidence that the toxicity is not 
related to study treatment. Exceptions are noted for lipid abnormalities in Section 7.1. 
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.  
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 and Section 10.7. 

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

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10.5.2. 
Contraception Guidance: 
Participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in Table 
7. 
Table 7 
Highly Effective Contraceptive Methods 
• 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
• 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per 
year when used consistently and correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationb 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)b 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner: 
• 
Note: Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the participant of childbearing potential and 
the absence of sperm has been confirmed. If not, an additional highly effective method 
of contraception should be used. Spermatogenesis cycle is approximately 90 days. 
• 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly. 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
oral 
• 
injectable 
• 
Sexual abstinence 
• 
Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant. 
• 
ACCEPTABLE METHODSd 
• 
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action 

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• 
Male or female condom with or without spermicidee 
• 
Cervical cap, diaphragm, or sponge with spermicide 
• 
A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods)c 
 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c. 
If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of action. 
d. 
Considered effective, but not highly effective - failure rate of ≥1% per year. Periodic abstinence (calendar, 
sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhoea method (LAM) are not acceptable methods of contraception. 
e. 
Male condom and female condom should not be used together (due to risk of failure with friction). 
10.5.3. 
Collection of Pregnancy Information: 
Male participants with partners who become pregnant 
• 
Investigator will attempt to collect pregnancy information on any male 
participant’s female partner of a male study participant who becomes pregnant 
while participating in this study. This applies only to male participants who 
receive study intervention. 
• 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the 
partner’s pregnancy.  
• 
The female partner will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to 
GSK. 
• 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of 
fetal status (presence or absence of anomalies) or indication for procedure.  
Female Participants who become pregnant 
• 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study. 
• 
The initial information will be recorded on the appropriate form and submitted to 
GSK within 24 hours of learning of a participant's pregnancy. 
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which 
will be forwarded to GSK Generally, follow-up will not be required for longer 
than 6 to 8 weeks beyond the estimated delivery date. 

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• 
Any termination of pregnancy will be reported, regardless of fetal status 
(presence or absence of anomalies) or indication for procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
• 
A spontaneous abortion (occurring at < 22 weeks gestational age) or still birth 
(occurring at > 22 weeks gestational age) is always considered to be an SAE and 
will be reported as such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study intervention by the investigator, will be reported 
to GSK as described in Section 10.3. While the investigator is not obligated to 
actively seek this information in former study participants, he or she may learn of 
an SAE through spontaneous reporting.  
Any female participant who becomes pregnant while participating   
• 
will discontinue study intervention or be withdrawn from the study. 

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10.6. 
Appendix 6: Genetics 
• 
USE/ANALYSIS OF DNA 
• 
Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and IRB/IEC allow, a blood sample will be collected for DNA 
analysis. 
• 
DNA samples may be used for research related to GSK3810109A or HIV and related 
diseases. They may also be used to develop tests/assays including diagnostic tests 
related to GSK3810109A or study interventions of this drug class and HIV. Genetic 
research may consist of the analysis of one or more candidate genes or the analysis 
of genetic markers throughout the genome or analysis of the entire genome (as 
appropriate). 
• 
DNA samples may be analyzed if it is hypothesized that this may help further 
understand the clinical data. 
• 
DNA samples may be analyzed for effects on GSK3810109A PK or PD responses, 
or on HIV susceptibility, severity, or progression. Additional analyses may be 
conducted if it is hypothesized that this may help further understand the clinical data.  
• 
Therefore, samples may be analyzed as part of a multi-study assessment of genetic 
factors involved in the response to GSK3810109A. The results of genetic analyses 
may be reported in the clinical study report or in a separate study summary. 
• 
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
• 
The samples will be retained while research on GSK3810109A (or study 
interventions of this class) or HIV continues but no longer than 15 years after the last 
participant last visit or other period as per local requirements. 

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10.7. 
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments 
Study treatment refers to all drugs evaluated in the study and therefore includes ViiV 
study intervention and non-ViiV ART therapies that can be used in combination with 
ViiV products or other ART interventions. 
A liver stopping event is an occurrence of predefined liver chemistry changes (ALT, 
bilirubin) that trigger discontinuation of study treatment and requirement of additional 
actions and follow up assessments to be performed. 
A liver monitoring event is as an occurrence of predefined liver chemistry changes (ALT, 
bilirubin and or INR) that triggers increased monitoring of the participant’s liver 
chemistries, but no action is taken with study treatment unless liver chemistry stopping 
criteria are met. 
Table 8 
Phase 2a Liver Chemistry Stopping Criteria: Required Actions and 
Follow up Assessments 
Liver Chemistry Stopping Criteria 
 
ALT-absolute 
 
ALT≥3xULN 
If ALT≥3xULN AND bilirubin1,2  2xULN (>35% direct 
bilirubin), Report as an SAE. 
See additional Actions and Follow Up Assessments listed below 
Required Actions and Follow up Assessments 
Actions 
Follow Up Assessments 
Immediately discontinue study 
intervention 
 
Report the event to GSK within 24 
hours 
Complete the liver event CRF, and 
complete an SAE data collection tool if 
the event also meets the criteria for an 
SAE2 
Perform liver event follow up 
assessments 
Monitor the participant until liver 
chemistries resolve, stabilise, or return 
Viral hepatitis serology3 
Obtain INR and recheck with each 
liver chemistry assessment until the 
transaminases values show downward 
trend 
Obtain blood sample for 
pharmacokinetic (PK) analysis, 
obtained CAB of last dose4 
Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH). 
Fractionate bilirubin, if total 
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to within baseline (see MONITORING 
below) 
MONITORING: 
If ALT≥3xULN AND bilirubin  2xULN 
or INR >1.5 
Repeat liver chemistries (include ALT, 
aspartate transaminase [AST], alkaline 
phosphatase, bilirubin and INR) and 
perform liver event follow up 
assessments within 24 hours 
Monitor participant twice weekly until 
liver chemistries resolve, stabilise or 
return to within baseline 
A specialist or hepatology consultation is 
recommended 
 
If ALT≥3xULN AND bilirubin < 2xULN 
and INR ≤1.5: 
Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, bilirubin 
and INR) and perform liver event follow 
up assessments within 24-72 hours 
Monitor participant weekly until liver 
chemistries resolve, stabilize or return 
to within baseline 
Obtain complete blood count with 
differential to assess eosinophilia 
Record the appearance or worsening 
of clinical symptoms of liver injury, or 
hypersensitivity, on the AE report 
form 
Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications. 
Record alcohol use on the liver event 
alcohol intake case report form 
 
If ALT≥3xULN AND bilirubin  
2xULN or INR >1.5: 
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 high 
performance liquid chromatography 
(HPLC) assay (quantifies potential 
acetaminophen contribution to liver 
injury in participants with definite or 
likely acetaminophen use in the 
preceding week) [James, 2009]. 
Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) and /or liver biopsy to 
evaluate liver disease; complete Liver 
Imaging and/or Liver Biopsy CRF 
forms. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT 3xULN and bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary bilirubin on 
dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. 
All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN, which may indicate 
severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of hepatic impairment or 
cirrhosis). 

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3. 
Includes: Hepatitis A immunoglobulin (gM) antibody; HBsAg and HBcAb; Hepatitis C RNA; Cytomegalovirus IgM 
antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile antibody or 
monospot testing) and Hepatitis E IgM antibody  
4. 
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 SRM. 
 
References 
Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury: the 
attractive hazard.  Expert Opin Drug Saf. 2009; 8:709-714. 
Hunt, CM.  Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: A systematic review. Hepatol. 2010; 52:2216-
2222. 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, et.al. 
Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen Overdose 
and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784. 
Papay JI, Clines D, Rafi R, Yuen N., Britt S.D., Walsh J.S., Hunt C.M. Drug-induced 
liver injury following positive drug rechallenge. Regul Tox Pharm. 2009; 54:84-90. 

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10.8. 
Appendix 8: CDC Classification for HIV-1 Infection (2014) 
• 
Note that the CD4+ T-lymphocyte count takes precedence over the CD4+ T-
lymphocyte percentage in HIV infection stages 1, 2, and 3. The CD4+ T-lymphocyte 
percentage should only be considered if the count is missing. 
• 
HIV infection, stage 0 
• 
Indicates early HIV infection, inferred from a negative or indeterminate HIV test 
result within 180 days of a positive result. The criteria for stage 0 supersede and 
are independent of criteria used for other stages. 
• 
HIV infection, stage 1 
• 
Laboratory confirmation of HIV infection with no AIDS-defining condition, 
and 
o CD4+ T-lymphocyte count of ≥500 cells/L, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of ≥26%. 
• 
HIV infection, stage 2 
• 
Laboratory confirmation of HIV infection with no AIDS-defining condition, and 
o CD4+ T-lymphocyte count of 200 to 499 cells/L, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of 14% to 25%. 
• 
HIV infection, stage 3 (AIDS) 
• 
Laboratory confirmation of HIV infection, and 
o CD4+ T-lymphocyte count of <200 cells/L, or 
o CD4+ T-lymphocyte percentage of total lymphocytes of <14%, or 
o Documentation of an AIDS-defining condition (see below). 
• 
Documentation of an AIDS-defining condition supersedes a CD4+ T-
lymphocyte count of >200 cells/L and a CD4+ T-lymphocyte percentage of 
total lymphocytes of >14%.  
• 
HIV infection, stage unknown 
• 
Laboratory confirmation of HIV infection, and 
o No information on CD4+ T-lymphocyte count or percentage, and 
o No information on presence of AIDS-defining conditions. 
• 
Stage-3-defining opportunistic illnesses in HIV infection 
• 
Candidiasis of bronchi, trachea, or lungs  
• 
Candidiasis of oesophagus  
• 
Cervical cancer, invasive 

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• 
Coccidioidomycosis, disseminated or extrapulmonary  
• 
Cryptococcosis, extrapulmonary  
• 
Cryptosporidiosis, chronic intestinal (>1 month's duration) 
• 
Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 
month 
• 
Cytomegalovirus retinitis (with loss of vision) 
• 
Encephalopathy, HIV-related  
• 
Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, 
or oesophagitis (onset at age >1 month) 
• 
Histoplasmosis, disseminated or extrapulmonary  
• 
Isosporiasis, chronic intestinal (>1 month's duration)  
• 
Kaposi's sarcoma  
• 
Lymphoma, Burkitt's (or equivalent term)  
• 
Lymphoma, immunoblastic (or equivalent term)  
• 
Lymphoma, primary, of brain  
• 
Mycobacterium avium complex or Mycobacterium kansasii, disseminated or 
extrapulmonary  
• 
Mycobacterium tuberculosis of any site, pulmonary, disseminated or 
extrapulmonary  
• 
Mycobacterium, other species or unidentified species, disseminated or 
extrapulmonary 
• 
Pneumocystis jirovecii pneumonia  
• 
Pneumonia, recurrent 
• 
Progressive multifocal leukoencephalopathy  
• 
Salmonella septicaemia, recurrent  
• 
Toxoplasmosis of brain, onset at age >1 month  
• 
Wasting syndrome attributed to HIV. 

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10.9. 
Appendix 9: Child-Pugh Classification 
A participant is classified with mild hepatic impairment (Class A) if their overall sum of 
scores is 5-6 points, moderate hepatic impairment (Class B) if their overall sum of scores 
is 7-9 points, and severe hepatic impairment (Class C) if their overall sum of scores is 10-
15 based on the Child-Pugh system [Pugh, 1973] scoring described in the following table 
(Table 9). For participants requiring anticoagulation therapy, discussion with the study 
medical monitor will be required. 
Table 9 
Child-Pugh System 
Finding  
Points Scored for Each Observed Finding  
 
1 
2 
3 
Encephalopathy Grade1  
None 
1 or 2 
3 or 4 
Ascites 
Absent 
Slight 
Moderate 
Serum bilirubin, SI units (μmol/L),  
Serum bilirubin, conventional units (mg/dL)  
<34 
<2 
34 to 52 
2 to 3 
>52 
>3 
Serum albumin, SI units (g/L)  
Serum albumin, conventional units (mg/dL)  
>35 
>3.5 
28 to 35 
2.8 to 3.5 
<28 
<2.8 
 Prothrombin Time (seconds prolonged) or 
INR  
<4 
<1.7 
4 to 6 
1.7 to 2.3 
>6 
>2.3 
1. 
Grade 0: normal consciousness, personality, neurological examination, electroencephalogram 
Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles per second waves 
Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves 
Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves 
Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cycles per second delta activity 
[Pugh, 1973; Lucey, 1997] 
 
References 
Lucey MR, Brown KA, Everson GT, et al. Minimal criteria for placement of adults on 
the liver transplant waiting list: a report of a national conference organized by the 
American Society of Transplant Physicians and the American Association for the Study 
of Liver Diseases. Liver Transpl Surg 1997; 3:628-37. 
Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the 
oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60:646-9. 
 

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10.10. 
Appendix 10: COVID-19 Pandemic and Clinical Trial 
Continuity 
Background 
The COVID-19 pandemic presents significant logistical challenges for many clinical sites 
around the world, with variable restrictions being placed on site resources and operations, 
and on an individual participants ability to attend clinic visits.  In some places, medical 
visits are occurring, and in others, research clinics are operating with only emergency 
staff. 
Based on these challenges, it may be necessary to adopt additional measures and 
procedures to protect participant safety, and to ensure that there are no gaps in HIV-1 
treatment for participants enrolled in this clinical study, through continuous access to 
antiretroviral therapy. 
In order to maintain the scientific integrity of the study, and adhere to updated guidance 
from regulators, procedures have also been put into place to ensure that the actions taken 
to mitigate against any impact of COVID-19 are well documented in the trial database. 
This appendix outlines the measures which are approved for implementation within this 
clinical trial, to protect patient safety and to ensure the integrity of the clinical trial, as a 
result of COVID-19 only. These measures may be implemented in accordance with any 
requirements and expectations set out by local Independent Review Boards/Independent 
Ethics Committees and National Competent Authorities, as necessary. 
This appendix does not apply to participant management issues that are unrelated to a 
specific, and documented, impact from COVID-19.  
10.10.1. 
Changes to Study Visits and Study Procedures 
If central laboratory testing cannot be performed at a particular visit, and monitoring for 
safety is required, tests may be performed at an appropriately authorised/accredited local 
laboratory (or other relevant clinical facility), if this can be done within local restrictions 
on physical distancing. The site should proactively inform the sponsor about such 
instances. Local laboratory results may be used to inform safety decisions. Results should 
be retained in source records. 
When on-site visits are reduced, it is important that the investigator continue collecting 
relevant clinical information, including adverse events, from the participant through 
alternative means, e.g. by telephone contact. 
There may be cases where the current principal investigator (PI) of a site is indisposed for 
a period and may need to delegate parts of his/her duties temporarily, e.g. to a sub-
investigator. Any such changes should be documented in the site’s source records. Any 
permanent changes in PI should be communicated to the sponsor. 
There may also be circumstances where immediate actions are required by the sponsor 
and/or investigator, outside of what is contemplated in the protocol, in order to protect a 

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study participant from immediate hazard. Any such measures will be carefully 
documented and conducted in accordance with the National Competent Authority 
(NCA)/IRB/IEC regulations. 
10.10.2. 
Changes to Informed Consent 
Informed consent should continue per normal procedure and as described in the main 
body of the protocol, to the extent possible. However, there may be circumstances where 
re-consent of participants is needed, and a physical signature on site is not possible. In 
these cases, alternative ways of obtaining such re-consent should be considered, such as 
the participant sending a picture of his/her written consent to the investigator, or the 
investigator contacting the participant by telephone or video call and obtaining verbal 
consent, supplemented with email confirmation.   
Any updated informed consent form or other participant-facing materials should be 
provided to participants by e-mail, mail or courier before re-consent is obtained. Any 
consent obtained this way should be documented in source records and confirmed by way 
of normal consent procedure at the earliest opportunity when participants attend their 
next on-site study visit. 
Any alternative informed consent procedure must be undertaken only after site 
IRB/Ethics Committee agreement and approval. 
10.10.3. 
COVID-19 Vaccines 
Any active trial participant who has access via local guidelines to a COVID-19 vaccine 
that has received emergency, conditional, or standard market authorization may receive 
that vaccine, if requested by the site investigator and trial participant. 
Ideally, when COVID-19 vaccinations are given, administration should occur at least 
2 weeks before or after a study visit to allow for a distinctive assessment of any possible 
ISRs. 
As of January 2021, there is limited publicly available information on the reduction of 
severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) transmission after 
vaccination. Therefore, until further evidence is available and/or local guidance changes, 
COVID-19 precautions (e.g., masking, social distancing) should be maintained after a 
vaccination series is completed. 
10.10.4. 
COVID-19 Experimental Agents 
If any treatments for COVID-19 are planned for a study participant, please consult with 
the study medical monitor to ensure that relevant drug interactions are considered and to 
ensure that continued study participation remains appropriate. 

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10.10.5. 
COVID-19 Specific Data Capture 
10.10.5.1. Capturing COVID-19 Specific Protocol Deviations 
Please refer to your study procedure manual for specific details on capturing protocol 
deviations as a result of COVID-19. 
10.10.5.2. Capturing COVID-19 Specific AEs and SAEs 
It is important for the study team to describe COVID‑19 related adverse events/serious 
adverse and their impact on study data and outcomes. Standardization of case definitions 
will facilitate future data analysis.  
Please use the following guidance:  
1. AEs should continue to be evaluated as to whether they meet SAE criteria as defined 
in the protocol, and if so, submitted according to established SAE reporting 
requirements. SAEs and AEs should be submitted following usual study procedures 
and timelines. 
2. When an in-person clinic visit is not possible, please conduct a remote telehealth visit 
to assess for, and document any AEs/SAEs. 
3. Investigators should use the WHO definition to classify COVID-19 cases. The 
definition below, released March 20, 2020, represents a time point for standardized 
collection. We recognize definitions are likely to continue to evolve. When reporting 
both serious and non- serious adverse events (related to COVID-19 infection, 
investigators should use the following Verbatim terms:  
a. Suspected COVID-19 infection; or 
b. Probable COVID-19 infection; or 
c. Confirmed COVID-19 infection 
4. Sites should contact the study Medical Monitor for questions related to definitions 
and reporting, and decisions around impact to study drug continuation. 
5. A new COVID-19 infection Case Report Form will be added to the eCRF to collect 
additional details about the reported COVID-19 AE or SAE data. It is important to 
collect the correct information from each participant reporting a COVID-19 AE or 
SAE. Therefore, please use the CRF templates to help you collect this information, 
once available. 
WHO Case Definition - March 20, 2020 Version (https://www.who.int/publications-
detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov)): 

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Suspected case:  
A. A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or 
residence in a location reporting community transmission of COVID-19 disease 
during the 14 days prior to symptom onset;  
OR  
B. A patient with any acute respiratory illness AND in contact (see definition of 
“contact” below) with a confirmed or probable COVID-19 case (see definition of 
contact) in the last 14 days prior to symptom onset;  
OR  
C. A patient with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation.  
Probable case:  
A. A suspect case for whom testing for the COVID-19 virus is inconclusive 
(Inconclusive being the result of the test reported by the laboratory).  
OR  
B. A suspect case for whom testing could not be performed for any reason. 
Confirmed case:  
A person with laboratory confirmation of COVID-19 infection, irrespective of clinical 
signs and symptoms.  
Covid-19 Contact: 
A contact is a person who experienced any one of the following exposures during the 2 
days before and the 14 days after the onset of symptoms of a probable or confirmed case: 
1. Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes; 
2. Direct physical contact with a probable or confirmed case; 
3. Direct care for a patient with probable or confirmed COVID-19 disease without 
using proper personal protective equipment; OR 
4. Other situations as indicated by local risk assessments.  

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Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days 
before through the 14 days after the date on which the sample was taken which led to 
confirmation. 
 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
1 1 6  
 
1 0. 1 1.  
A p p e n di x  1 1 : A b br e vi ati o n s a n d T r a d e m ar k s 
A b br e vi ati o n s  
A C T G  
I nter n ati o n al AI D S S o ciet y 
A D A  
A nti -dr u g a nti b o d y  
A E  
A d v ers e e v e nt  
AI D S  
A c q uire d i m m u n o deficie n c y s y n dr o me  
A L P  
Al k ali n e P h os p h atas e  
A L T  
Ala ni n e a mi n otra nsferas e  
A nti -H Bc  
H e p atitis B C ore A nti b o d y  
A R V  
A ntiretr o viral  
A R T  
A ntiretr o viral t h era p y  
A S T  
As p artate a mi n otra nsferas e  
A U C  
Are a u n d er t h e c ur v e  
B MI  
B o d y Mass I n d e x  
b N A b  
Br o a dl y n e utralizi n g a nti b o d y  
B U N  
Bl o o d Ure a Nitr o ge n  
C A  
C o m p ete nt A ut h orit y  
C A B G  
C or o n ar y arter y b y p ass grafti n g  
c A R T 
C o m bi n ati o n a ntiretr o viral t h era p y  
c/ m L 
C o pies/ milliliter  
C D C  
Ce nters f or Dis e as e C o ntr ol a n d Pre v e nti o n  
C H O  
C hi n es e H a mster O v ar y  
CI O M S  
C o u n cil f or I nter n ati o nal Or ga niz ati o ns of Me dic al Scie n c es  
C K D -E PI  
C hr o nic Ki d n e y Dis e as e E pi d e mi ol o g y C olla b orati o n  
C R F  
Cas e Re p ort F or m  
C m a x  
Ma xi m u m c o n c e ntrati o n  
C O N S O R T  
C o ns oli d ate d Sta n d ar ds of Re p orti n g Trials  
C P K  
Cre ati n e p h os p h o ki n as e  
Cr Cl  
Cre ati ni n e Cle ara n c e  
C R S  
C yt o ki n e Rele as e S y n dr o m e  
C S R  
Cli nic al St u d y Re p ort  
C V  
Car di o v as c ular  
D AI D S  
Di visi o n of A c q uire d I m m u n o d eficie nc y S y n dr o me 
D DI  
Dr u g -Dr u g I ntera cti o n  
d L  
D e ciliter  
D H H S  
D e p art m e nt of H e alt h a n d H u m a n Ser vic es  
DI LI  
Dr u g i n d u c e d li v er i nj ur y  
D N A  
D e o x yri b o n ucleic a ci d  
D S C  
D os e Sele cti o n C o m mitte e  
E C  
Et hics C o m mitte e  
E C G  
Ele ctr o c ar di o gra m  
E C L  
Ele ctr o c h e mil u mi n esc e nc e  
C CI

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eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
ELISA 
Enzyme-linked immunosorbent assay 
FAS 
Full analysis set 
FBS 
Fetal bovine serum 
FDA 
Food and Drug Administration 
FSH 
Follicle stimulating hormone 
FTIH 
First Time in Human 
GCP 
Good Clinical Practice 
GCSP 
GSK’s Global Clinical Safety and Pharmacovigilance 
GSK 
GlaxoSmithKline 
GSK3810109A N6LS 
GFR 
Glomerular Filtration rate 
HAART 
Highly active antiretroviral therapy 
HBsAg 
Hepatitis B surface Antigen 
HBV 
Hepatitis B virus 
hCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HDPE 
High density polyethylene 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
HRT 
Hormonal replacement therapy 
HSR 
Hypersensitivity reaction 
IAS 
International AIDS Society 
IB 
Investigator’s Brochure 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
ICF 
Informed Consent Form  
IgG 
Immunoglobulin G 
IgG1 
Immunoglobulin G1 
IgM 
Immunoglobulin M 
INI 
Integrase Inhibitor 
INR 
International normalized ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ISR 
Infusion/ Injection Site Reaction 
ITT-E 
Intent-to-treat exposed 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-replacing system 
IV 
Intravenously 
IWRS/IWRS 
Interactive Voice/Web Recognition System 
LDL  
Low density lipoprotein 
LOAEL 
Lowest observed adverse effect level  
mAb 
Monoclonal antibody 
MCH 
Mean corpuscular hemoglobin 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
1 1 8  
 
M C V  
Me a n c or p us c ular v ol u m e  
Me d D R A  
Me dic al dicti o n ar y f or re g ulat or y a cti vities  
M ol/ L  
Micr o m ole/ Liter  
m g  
Milli gra m  
m g/ d L  
Milli gra m p er d e ciliter  
m g/ mi n  
Milli gra m p er mi n ute  
M S D  
Mes o Sc ale Dis c o v er y  
M V  
Mi ni m u m V al u e  
N A b  
N e utralizi n g A nti b o d y  
n g/ m L  
N a n o gra m p er milliliter  
N m  
N a n o m eter  
N N R TI  
N o n -n u cle osi de re v erse tra ns cri ptas e i n hi bit or 
O C  
O bs er v e d Cas e  
P B S  
P h os p h ate b uffere d s ali n e  
P D  
P h ar m a c o d y na mic  
P E P  
P ost -e x p os ure pr o p h yla xis  
P K  
P h ar m a c o ki n etic  
P O C  
Pr o of of C o n c e pt  
P O C B P  
Partici p a nts of c hil d b e ari n g p ote ntial  
P P  
Per pr ot o c ol  
Pr E P  
Pre -e x p os ure pr o p h yla xis  
P R O  
Pr ote as e  
P S R A E  
P ossi ble s uici d alit y -relate d a d vers e e v e nt 
P T  
Pr ot hr o m bi n Ti m e  
P T C A  
Perc uta n e o us tra nsl u mi n al c or o n ar y a n gi o plast y  
P T T  
Partial T hr o m b o plasti n Ti m e  
Q Tc  
C orre cte d Q T i nter v al  
R A P  
Re p orti n g a n d A n al ysis Pla n  
R B C  
Re d bl o o d c ell  
R N A  
Ri b o n u cleic a ci d  
R P R  
Ra pi d plas m a re a gi n  
R T  
Re v ers e Tra ns cri ptas e  
S A E  
Seri o us a d v ers e e v e nt  
S A P  
Statistic al A n al ysis Pla n  
S A R S C o V -2  
Se v ere a c ute res pirat or y s y n dr o me c or o n a vir us -2  
S C  
S u b c uta n e o us  
S D  
Sta n d ar d D e viati o n  
S D E C  
Saf et y a n d D os e E v al u ati o n C o m mitte e  
S D M  
S y m pt o m Distress M o d ule  
S o A  
Sc h e d ule of A cti vities  
SJ S  
Ste v e ns -J o h ns o n s y n dr o m e 
S R M  
St u d y Ref ere n c e Ma n ual  
S U S A R  
S us p e cte d u n e x pe cte d s eri o us a d v ers e re a cti o ns  
T m a x  
Ti m e t o m a xi m al c o n c e ntrati o n  
C CI
C CI

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TV 
Target Value 
ULN 
Upper limit of normal 
VLD 
Viral load decline 
VRC 
Vaccine Research Center 
VSLC 
ViiV Safety and Labelling Committee 
WBC 
White blood cell 
WHO 
World Health Organization 
 
Trademark Information 
Trademarks of ViiV Healthcare 
 
Trademarks not owned by the  
ViiV Healthcare 
Dovato 
 
ACCEPT 
 
 
GeneSeq 
 
 
GenoSure 
 
 
MedDRA 
 
 
PAXGENE 
 
 
PhenoSense 
 
 
SAS 
 
 
WinNonlin 

T M F -1 3 8 9 4 6 7 4  
C O N FI D E N TI A L  
 
 
 
2 0 7 9 5 9  
 
1 2 0  
 
1 0. 1 2.  
A p p e n di x 1 2 : Pr ot o c ol A m e n d m e nt Hi st or y  
T h e Pr ot o c ol A m e n d m e nt S u m m ar y of C h a n ges Ta ble f or t h e c urre nt a m e n d me nt is 
l o c ate d dire ctl y b ef ore t h e Ta ble of C o nte nts ( T O C). 
A me n d me nt 1 : 0 1 -S E P -2 0 2 0  
T his a m e n d m e nt is c o nsi d ere d t o b e s u bsta ntial b as e d o n t h e criteria s et f ort h i n A rticle 
1 0(a) of Dire cti v e 2 0 0 1/ 2 0/ E C of t h e E ur o pe a n Parlia m e nt a n d t h e C o u n cil of t h e 
E ur o p e a n U ni o n.  
O v e r all R ati o n ale f o r A me n d me nt  1 : Li v er s af et y criteria h a v e b e e n u p date d t o ali g n 
wit h c urre nt Vii V Saf et y a n d La b elli n g C o m mitte e g ui d a n c e.  Clarific at i o n of all o w a ble 
visit wi n d o ws is als o pr o vi d e d.  
Se cti o n # 
a n d N a m e  
D e s cri pti o n of C h a n g e  
Brief R ati o n ale  
5.2 Excl usi o n 
Criteri a  
Eli gi bility criteri a h ave b e e n 
u p d ate d to refl ect curre nt AL T a n d 
T otal Biliru bi n eli gi bility criteri a as 
p er Vii V Safety a n d L a b elli n g 
C o m mitte e  (V SL C ) G ui d a nce.  
C h a n g es ma d e to ali g n to curre nt V SL C 
G ui d a nce.  
7.2 Liver 
C h e mistry 
Sto p pi n g 
Criteri a  
Liver sto p pi n g criteri a h ave b e e n 
u p d ate d to refl ect curre nt AL T a n d 
T otal Biliru bi n eli gi bility criteri a as 
p er V SL C G ui d a nce.  
C h a n g es ma d e to ali g n to curre nt V SL C 
G ui d a nce.  
8 Stu dy 
Assess me nts 
a n d 
Proce d ures  
Cl arificati o n th at visit wi n d o ws are 
calcul ate d fro m start of i nfusi o n 
(I V) or ti me of i nj ecti o n ( S C) 
C h a n g es ma d e to ali g n with 
p h ar macoki n etics a n alysis pl a n.  
 
A me n d me nt 2:  0 5 -N O V -2 0 2 0  
C CI

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Section # 
and Name 
Description of Change 
Brief Rationale 
1.3.1 
Screening 
Schedule of 
Activities 
Sample for PBMC collection has 
been added at the Screening visit. 
Sample will be used to support 
immunology (cell-based) analyses in 
subjects who enrol in the study. Samples 
from subjects who do not enrol in the 
study will be destroyed. 
1.3.2 
Monotherapy 
Phase 
Schedule of 
Activities 
Body weight and height has been 
added at Day 1 (Pre-dose). 
CDC Classification has been 
removed at SOC Initiation and 
Early Discontinuation visits. 
Footnote 3 updated regarding 
timing of initiation of SOC cART. 
Changes made for clarification. 
1.3.3 
Standard of 
Care Follow-
Up Phase 
Schedule of 
Activities 
HIV Associated conditions have 
been added at Weeks 4, 8, 16 and 
32. 
PBMC collection has been moved 
from Week 16 to Week 4. 
Changes made for clarification and to 
adjust immunology sampling timepoints to 
most relevant timings following SOC 
initiation. 
6.3 Pharmacy 
Procedures 
Storage conditions have been 
updated to remove temperature 
excursion allowance. 
Changes made to align storage conditions 
to current product specifications. 
8 Study 
Assessments 
and 
Procedures 
Visit windows descriptions have 
been altered. 
Changes made for clarity in calculating 
visit windows. (Actual visit windows have 
not changed) 
8.7.2 T-cell 
Responses 
T cell investigation description has 
been updated. 
Changes made for clarity. 
 
 
Amendment 3: 11-MAR-2021 
This amendment is considered to be substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for Amendment 3: Additional exclusion criteria and study 
participant monitoring during Day 1 has been included in this amendment. Clarifications 
regarding parallel enrollment during Parts 1 and 2, study pause criteria, use of COVID-19 
vaccines during the study, and choice of standard of care ART have been included. 

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Section # 
and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
Study cohorts within Part 1 and 
Part 2 will be enrolled as parallel, 
randomized groups. 
A “No Go” decision by SDEC will 
apply to all subsequent dosing 
groups 
Changes made for clarification. 
 
1.3.2 
Monotherapy 
Phase 
Schedule of 
Activities 
Study participants will be required 
to remain in clinic from Pre-dose 
through 4 hours for monitoring of 
vital signs. 
Vital signs of blood pressure, 
heart rate, body temperature and 
SPO2 will be recorded in the 
eCRF during and for up to 4 hours 
following the infusion/injection. 
Vital signs including blood 
pressure, heart rate, body 
temperature, respiratory rate and 
SpO2 must be obtained every 15 
minutes during the infusion period 
(only required Pre-Dose and Post-
Dose for SC injections), every 30 
minutes for two hours following 
the start of the infusion/ injection, 
and then hourly for another two 
hours; vital signs should be 
recorded in the medical record. 
Additional monitoring requirements have 
been added during Day 1. 
4.1.3 
Standard of 
Care Follow-
Up Phase  
A regimen of dolutegravir + 
lamivudine will be provided 
through the study if deemed 
appropriate by the investigator 
and consistent with local 
guidelines. 
Clarification that choice of SOC regimen 
should be consistent with applicable 
guidelines. 
4.2 Scientific 
Rationale for 
Study Design  
Oral dolutegravir + lamivudine 
(Dovato™) will be provided in the 
study for use during the SOC 
follow-up period, if appropriate 
and consistent with local 
Guidelines. 
Clarification that choice of SOC regimen 
should be consistent with applicable 
guidelines. 

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Section # 
and Name 
Description of Change 
Brief Rationale 
4.4 Interim Go 
/ No Go 
Criteria and 
Dose 
Selection 
If a No Go decision is reached, 
this will apply to all subsequent 
planned cohorts. 
Clarification that No Go decision will apply 
to all subsequent cohorts. 
5.2 Exclusion 
Criteria 
Hemoglobin  Grade 2 (Males: 
<10 g/dl; Females <9.5 g/dL). A 
single repeat test is allowed during 
the Screening period to verify a 
result. 
Platelets Grade 2 (<100,000 
cells/mm3). A single repeat test is 
allowed during the Screening 
period to verify a result. 
PT Grade 2 (1.25 ULN). A 
single repeat test is allowed during 
the Screening period to verify a 
result. 
INR Grade 2 (1.5 ULN). A 
single repeat test is allowed during 
the Screening period to verify a 
result. 
Absolute Neutrophil Count (ANC) 
Grade 2 (ANC 799 cells/mm3). 
A single repeat test is allowed 
during the Screening period to 
verify a result. 
 
Changes made to exclude subjects at 
elevated risk of infection or bleeding 
disorder. 
6.1 Study 
Intervention(s) 
administered 
Study arm updated, and dose 
formulation changed to “Solution 
for injection or infusion” 
Clarification of the descriptors within 
Table 2. 

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Section # 
and Name 
Description of Change 
Brief Rationale 
10.10.3 
COVID-19 
Vaccines 
COVID-19 vaccines approved 
under emergency, conditional or 
standard authorization are 
allowed, in addition to guidance on 
timing and transmission reduction 
strategies. 
Clarification on the use of COVID-19 
vaccines during the study. 
 
 

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11. 
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