An Umbrella Phase 1b, Open-label, Multi-Cohort Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1
Phase: PHASE1
Conditions: HIV-1-infection
Sponsor: Gilead Sciences

CLINICAL SUBSTUDY-03 PROTOCOL
Study Title:
An Umbrella Phase 1b, Open-label, Multicohort Study to Evaluate 
Safety, Pharmacokinetics, and Antiviral Activity of Novel 
Antiretrovirals in Participants With HIV-1; Substudy-03: GS-6212
Plain Language Short 
Title:
Study of GS-6212 in Participants With HIV-1
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
USA
IND Number:
162030
EU CT Number:
Not Applicable
ClinicalTrials.gov 
Identifier:
NCT05585307
Indication:
HIV-1 Infection
Protocol ID:
GS-US-544-5905-03
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol 
Version/Date:
Amendment 1:
18 August 2023
Amendment History:
Original:
08 June 2023
Amendment 1:
18 August 2023
High-level summaries of the history of amendment are provided in 
Appendix 11.4
This study will be conducted under United States Food and Drug Administration investigational 
new drug application regulations (21 Code of Federal Regulations Part 312); however, sites 
located in the European Economic Area, the United Kingdom, and Switzerland are not included 
under the investigational new drug application and are not considered to be investigational new 
drug application sites.
GILEAU 

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This study will be conducted in compliance with this protocol and in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki, and that are consistent with 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) and applicable 
regulatory requirements.
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
institutional review board or independent ethics committee. The information is only to be used 
by you in connection with authorized clinical studies of the investigational drug described in 
the protocol. You will not disclose any of the information to others without written 
authorization from Gilead Sciences, Inc., except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered.

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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................3
LIST OF IN-TEXT TABLES .........................................................................................................................................4
LIST OF IN-TEXT FIGURES........................................................................................................................................4
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...................................................................................5
SUBSTUDY PROTOCOL SYNOPSIS..........................................................................................................................7
SUBSTUDY-03 STUDY SCHEMA ............................................................................................................................11
STUDY PROCEDURES TABLE ................................................................................................................................12
1.
INTRODUCTION................................................................................................................................................14
1.1.
Rationale for Substudy-03.......................................................................................................................14
1.2.
Background on Study Interventions Used in Substudy-03......................................................................14
1.2.1.
GS-6212.................................................................................................................................14
1.3.
Rationale for Dose Selection of GS-6212 ...............................................................................................20
1.4.
Benefit-Risk Assessment for the Study...................................................................................................21
2.
OBJECTIVES AND ENDPOINTS......................................................................................................................22
3.
STUDY DESIGN.................................................................................................................................................22
3.1.
Study Design Overview...........................................................................................................................22
3.1.1.
Dose Selection/Modification.................................................................................................23
3.2.
Duration of Intervention..........................................................................................................................23
3.3.
Substudy-03–Specific Discontinuation Criteria......................................................................................23
3.4.
Definitions for Time of Primary Endpoint and End of Study .................................................................23
4.
PARTICIPANT POPULATION..........................................................................................................................24
4.1.
Number of Participants and Participant Selection for Substudy-03........................................................24
4.2.
Substudy-03–Specific Inclusion Criteria.................................................................................................24
4.3.
Substudy-03–Specific Exclusion Criteria................................................................................................24
5.
STUDY INTERVENTIONS AND CONCOMITANT MEDICATIONS ...........................................................25
5.1.
Enrollment and Treatment Code Access .................................................................................................25
5.2.
Description and Handling of GS-6212 and BVY....................................................................................25
5.2.1.
Formulation ...........................................................................................................................25
5.2.2.
Packaging and Labeling ........................................................................................................25
5.2.3.
Storage and Handling ............................................................................................................26
5.2.4.
Dosage and Administration ...................................................................................................26
5.3.
Fasting and Meals (GS-6212 Dosing) .....................................................................................................27
5.4.
Prior and Concomitant Medications........................................................................................................28
5.5.
Accountability for Study Drug Supplies: Study Drug and SOC ART Provided by the Sponsor 
(BVY)......................................................................................................................................................28
6.
STUDY PROCEDURES......................................................................................................................................29
6.1.
Instructions for Study Procedures ...........................................................................................................29
6.1.1.
Pharmacokinetics...................................................................................................................29
6.1.2.
Suboptimal Virologic Response............................................................................................29
6.1.3.
Poststudy Care.......................................................................................................................30
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT................................................................................31

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7.1.
Toxicity Management..............................................................................................................................31
7.1.1.
Grades 1 and 2 Laboratory Abnormalities or AEs ................................................................31
7.1.2.
Grade 3 Laboratory Abnormalities or AEs ...........................................................................31
7.1.3.
Grade 4 Laboratory Abnormalities or AEs ...........................................................................32
8.
STATISTICAL CONSIDERATIONS.................................................................................................................33
9.
RESPONSIBILITIES...........................................................................................................................................34
10.
REFERENCES.....................................................................................................................................................35
11.
APPENDICES......................................................................................................................................................36
11.1.
Investigator Signature Page.....................................................................................................................37
11.2.
Pregnancy Precautions, Definition of Childbearing Potential, and Contraceptive Requirements ..........38
11.3.
Management of Clinical and Laboratory Adverse Events ......................................................................41
11.4.
Amendment History ................................................................................................................................42
Amendment 1 (18 August 2023) .............................................................................................................42
11.5.
Sponsor Signature Page...........................................................................................................................43
LIST OF IN-TEXT TABLES
Table 1.
Substudy-03 Study Procedures Table......................................................................................12
Table 2.
Study GS-US-469-6401: Preliminary PK Parameters of GS-6212 Following Single- 
or Multiple-Dose Administration of Oral GS-6212 (N = 8 Per Cohort) Under Fasted 
and/or Fed Conditions .............................................................................................................19
Table 3.
GS-6212 Dosage by Cohort.....................................................................................................27
LIST OF IN-TEXT FIGURES
Figure 1.
Overview of Visits, Dosing, and Key Assessments for Substudy-03 .....................................11
Figure 2.
Study GS-US-469-6401: Preliminary Mean (SD) GS-6212 Plasma 
Concentration-Time Profiles Following Single-Dose Administration of Oral GS-
6212 (N = 8 Per Cohort) Under Fasted and/or Fed Conditions...............................................17
Figure 3.
Study GS-US-469-6401: Preliminary Mean (SD) GS-6212 Plasma 
Concentration-Time Profiles Following Multiple-Dose Administration of Oral GS-
6212 (N = 8 Per Cohort) Under Fasted Conditions.................................................................18

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ALT
alanine aminotransferase
ART
antiretroviral therapy
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated 
as AUClast + (Clast/λz)
BVY
bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®)
Cav,ss
average steady state plasma concentration during multiple dose administration
CLcr
creatinine clearance
Cmax
maximum observed concentration of drug
conc
concentration
CT
computed tomography
Ctrough
concentration at the end of the dosing interval
CV
coefficient of variation
D
Day
ECG
electrocardiogram
ET
early termination
EU
European Union
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV-1
human immunodeficiency virus type 1
IB
investigator’s brochure
ICH
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
IM
intramuscular
IND
investigational new drug
INSTI
integrase strand-transfer inhibitor
IQ
inhibitory quotient
LA
long-acting
LDL
low-density lipoprotein
MAD
multiple ascending dose
PEG
polyethylene glycol
PK
pharmacokinetic(s)
PWH
participant with HIV-1

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RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SC
subcutaneous
SD
standard deviation
SOC
standard of care
SRT
Safety Review Team
t1/2
terminal elimination half-life
Tmax
time (observed time point) of Cmax
US, USA
United States, United States of America
WFI
water for injection

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SUBSTUDY PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: An Umbrella Phase 1b, Open-label, Multicohort Study to Evaluate Safety, 
Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1; 
Substudy-03: GS-6212
Plain Language Short Title: Study of GS-6212 in Participants With HIV-1
Regulatory Agency Identifier Number(s):
IND Number: 162030
EU CT Number: Not applicable
ClinicalTrials.gov Identifier: NCT05585307
Study Sites Planned: See master protocol synopsis for study centers planned.
Objectives and Endpoints: See master protocol synopsis for objectives and endpoints.
Study Design:
This substudy is being conducted as part of an umbrella study as described in the master 
protocol.
Substudy-03 is an open-label, Phase 1b, multiple-dose, multicohort study to evaluate the safety, 
pharmacokinetics (PK), and antiviral activity of GS-6212 given as monotherapy in participants 
with HIV-1 (PWH) who are either treatment-naive or treatment-experienced but naive to 
integrase strand-transfer inhibitors (INSTIs) and have not received any antiretroviral (ARV) 
therapy (ART) within 12 weeks of screening, including medications received for pre-exposure 
prophylaxis or postexposure prophylaxis. Any current or prior receipt of long-acting (LA) 
parenteral ARVs, such as monoclonal antibodies targeting HIV-1, injectable cabotegravir, or 
injectable rilpivirine, is exclusionary.
After screening and meeting all eligibility criteria, study drug dosing will be initiated on Day 1 in 
the clinic for each participant (Figure 1). Participants will be required to return to the clinic for 
visits on Days 2, 3, 4, 7, 8, 9, 10, and 11 (primary endpoint assessment). Doses of GS-6212 will 
be administered orally at the clinic under observation by site staff on clinic visit days/times and 
at home by the participant on nonclinic visit days/times at approximately the same time each day. 
In cohorts where GS-6212 is administered more than once daily, in-clinic observation of dosing 
will be conducted for the morning dose only. Participants will record at-home dosing details in a 
dosing log.

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After assessments on Day 11 or upon early termination (ET), participants will initiate a regimen 
of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide; BVY) provided by the sponsor or 
an alternative standard of care (SOC) ART regimen selected by the investigator. If participants 
are switching to BVY, a sufficient supply will be given to provide coverage for the remainder of 
the study. Participants will be required to return to the clinic for a follow-up visit on Day 25.
Overnight fasting (≥ 6 hours prior to dosing) is required for laboratory and/or PK analyses on 
Days 1 and 11. On all other days (Days 2 through 10), the AM doses should be taken on an 
empty stomach.
This substudy will enroll up to 5 cohorts, with at least 6 participants in each cohort. 
Initial participants will be enrolled in Cohort 1, with dosing in subsequent cohorts proceeding 
after Safety Review Team (SRT) review of emerging data from Cohort 1 and available data from 
the Phase 1a single ascending dose (SAD)/multiple ascending dose (MAD) 
Study GS-US-469-6401.
Sequential enrollment in cohorts, and order of assignment to substudies, are described in 
Section 5.1.1 of the master protocol.
The sponsor may elect to hold dosing, stop/pause substudy enrollment, or stop the study 
(or substudy, or specific cohort) at any time based on review of preliminary safety, efficacy, and 
PK data (see master protocol Section 5.1.1). If deemed unnecessary, the sponsor may choose not 
to initiate 1 or more cohorts.
Number of Participants Planned: Up to 5 cohorts, each containing at least 6 participants, will 
be enrolled.
Study Population: See master protocol synopsis for the target population.
Diagnosis and Main Eligibility Criteria: See master protocol for diagnosis and main eligibility 
criteria. For inclusion in this substudy, participants must also be willing to initiate BVY provided 
by the sponsor, or an alternative SOC ART regimen selected by the investigator, on Day 11 or 
upon ET, and be willing and able to comply with meal requirements.
Test Product, Dose, and Mode of Administration:
In Cohort 1, a 100-mg dose of GS-6212 will be administered orally twice daily (ie, once every 
12 hours ± 1 hour) on Days 1 through 10). The dose, dosing regimen, and meal requirements for 
administration of GS-6212 in Cohort 1 are provided in the table below. Subsequent cohort doses, 
dosing regimens, meal requirements (fasted or fed), and progression between cohorts will be 
adaptive. The maximum dose (to be administered each day at any given time) in subsequent 
cohorts will not exceed those indicated in the table below.
For participants who will be receiving GS-6212 once daily, study drug will be dispensed on 
Day 1. Bottles will be stored on site and administered in the clinic on Days 1 through 4. 
Participants will take doses at home on Days 5 and 6; doses on Days 7 through 10 will be 
administered in the clinic.

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For participants who will be receiving GS-6212 twice daily, study drug bottles will be dispensed 
on Day 1. Participants will take the bottles home after the morning dose at the clinic and then 
bring the bottles back to the clinic for the next day’s morning dose at the clinic for Days 1 
through 4 and Days 7 through 10. For Days 5 and 6, participants will keep the bottles at home.
Doses of GS-6212 will be administered orally at the clinic under observation by site staff on 
clinic visit days/times and at home by the participant on nonclinic visit days/times at 
approximately the same time each day. In cohorts where GS-6212 is administered more than 
once daily, in-clinic observation of dosing will be conducted for the morning dose only. 
Participants will record at-home dosing details in a dosing log. In addition to the dosing log, site 
staff can remind the participant of evening dosing via phone call/text message, if feasible. 
The timing of all doses on Days 5 and 6 should be recorded in a dosing log.
Cohort
Treatment
Cohort 1
100 mg oral doses BID (ie, once every 12 hours 
± 1 hour) on Days 1 through 10:
-
The first AM dose (on Day 1) should be taken 
following overnight fasting (≥ 6 hours).
-
All other AM doses (on Days 2 through 10) should 
be taken around the same time every morning on 
an empty stomach (fasting for ≥ 2 hours).
-
Each PM dose should be taken around the same 
time every evening with or without food. 
Participants are required to keep the pattern of 
study drug intake consistent throughout the 
10 days of dosing as much as possiblea.
Cohort 2
on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
Cohort 3
 on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
Cohort 4
 on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
Cohort 5
 on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
AM = before noon; BID = twice daily; PM = evening; QD = once daily
a
For instance, if a participant takes their first PM dose on an empty stomach, then they should try and take the remainder of 
their PM doses on an empty stomach and vice versa.
If BVY is initiated after assessments on Day 11 or upon ET, it will be administered orally, once 
daily, without regard to food.
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Reference Therapy, Dose, and Mode of Administration: Not applicable
Duration of Intervention: Up to 25 days
Study Procedures/Frequency: After screening and meeting all eligibility criteria, study drug 
dosing will be initiated on Day 1 in the clinic for each participant. Participants will be required to 
return to the clinic for visits on Days 2, 3, 4, 7, 8, 9, 10, and 11 (primary endpoint assessment). 
After assessments on Day 11 or upon ET, participants will initiate a regimen of BVY provided 
by the sponsor or an alternative SOC ART regimen selected by the investigator. Participants will 
be required to return to the clinic for a visit on Day 25.
The detailed schedule of procedures for Substudy-03 is provided in Table 1.
Statistical Methods: See master protocol synopsis for statistical methods.

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SUBSTUDY-03 STUDY SCHEMA
Figure 1.
Overview of Visits, Dosing, and Key Assessments for Substudy-03
ART = antiretroviral therapy; BVY = bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®); 
PK = pharmacokinetic(s); SOC = standard of care
For Cohort 1, a dose of GS-6212 100 mg will be administered orally twice daily (ie, once every 12 hours ± 1 hour) on Days 1 
through 10 (for further details on dosing and meal requirements, see Section 5.2.4). Subsequent cohort doses, dosing regimens, 
meal requirements (fasted or fed), and progression between cohorts will be adaptive and determined as summarized in 
Section 3.1.1.
a
After assessments on Day 11 or upon early termination, participants will initiate a regimen of BVY provided by the sponsor 
or an alternative SOC ART regimen selected by the investigator. Participants who discontinue study drug before Day 11 
should start this regimen at the time of discontinuation (see Section 6.4.1 of the master protocol).
GS-6212 Treatment 
V 
Day 
-28 
Treatment 
1 
2 
3 
4 
5 
6 
7 
8 
9 10 11 
PK 
A A A A A A A A A A 
* 
* 
• 
Clinic visi1 
0 
No clinic visit 
A GS-6212 dosing 
V Primary endpoint 
Initiate BVY (B/FfTAF) or SOC 
* Intensive PK 
Trough PK sampling 
BVY or SOC ART Treatmenta ) 
25 

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STUDY PROCEDURES TABLE
Table 1.
Substudy-03 Study Procedures Table
Study Procedure
Screeninga
D1b
D2
D3
D4
D7
D8
D9
D10
D11b
D25
ETc
Visit Window
±2D
Written informed consent
X
Medical history and demography
X
Complete physical examination
X
X
X
X
Symptom-driven physical examinationd
X
X
X
X
Height 
X
Weight 
X
X
X
X
X
X
X
Vital signse
X
X
X
X
X
X
X
X
X
HBV blood panel and HCV serologyf
X
CD4 cell countf
X
X
X
X
X
Plasma sample for HIV-1 
genotyping/phenotypingf,g
X
X
X
Plasma HIV-1 RNAf
X
X
X
X
X
X
X
X
X
X
X
X
Hematologyf
X
X
X
X
X
X
X
Coagulation panelf
X
X
X
X
X
X
Chemistryf
X
X
X
X
X
X
X
Urinalysisf
X
X
X
X
X
X
X
Serum pregnancy testf,h
X
Urine pregnancy testf,h,i
X
X
X
Serum FSHf,j
X
12-Lead ECG
X
X
X
X
X
X
Intensive plasma PKk
X
X
Single trough plasma PKl
X
X
X
X
X
X
X
X
Review AEs and concomitant medicationsm
X
X
X
X
X
X
X
X
X
X
X
X
Study drug (GS-6212) dispensationn
X
Study drug (GS-6212) dosingo, p
X
X
X
X
X
X
X
X
BVY dispensation, as applicable
X

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Study Procedure
Screeninga
D1b
D2
D3
D4
D7
D8
D9
D10
D11b
D25
ETc
Visit Window
±2D
BVY or an alternative SOC administration
Xq
AE = adverse event; AM = before noon; BVY = bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®); CD4 = clusters of differentiation 4; 
D = Day; ECG = electrocardiogram; eCRF = electronic case report form; ET = early termination; FSH = follicle-stimulating hormone; HBV = hepatitis B virus; 
HCV = hepatitis C  virus; HIV-1 = human immunodeficiency virus type 1; PK = pharmacokinetic(s); RNA = ribonucleic acid; SAE = serious adverse event; SOC = standard of 
care
a
Prospective participants should be screened no more than 28 days prior to administration of the first dose of study drug.
b
Overnight fasting (≥ 6 hours prior to dosing) is required.
c
ET assessments will be performed within 72 hours of prematurely discontinuing from the study or study drug, as applicable.
d
Symptom-driven physical examinations will be performed as needed, based on reported signs and symptoms.
e
Vital signs include blood pressure, heart rate, respiration rate, and body temperature. Participants should be sitting down for 5 minutes before vital sign measurements are 
obtained.
f
See detailed list of laboratory assessments in Section 6.3.7 of the master protocol.
g
Participants who meet the criteria for virologic failure at Day 11 will be tested for the potential development of resistance against all components of the treatment regimen, 
including the study drug. See Section 6.3.9.1.3 of the master protocol for management of virologic failure.
h
Participants assigned female at birth and of childbearing potential only.
i
A negative urine pregnancy test is required prior to study drug dosing on Day 1. Positive urine pregnancy tests will be confirmed with a serum test.
j
A serum FSH test is required for participants assigned female at birth who are younger than 54 years, not on hormonal contraception, and who have stopped menstruating for 
≥ 12 months but do not have documentation of ovarian hormonal failure.
k
Intensive PK samples should be collected at these time points for all cohorts (relative to AM dosing): predose (≤ 30 minutes before dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 
12 hours postdose (
) on respective days of dosing (ie, Days 1 and 10). Please note that the 12-hour postdose sample (if collected) on 
Days 1 and 10 should be sampled prior to the administration of the PM dose, as applicable.
l
Single trough PK sample should be drawn prior to AM drug dosing (as applicable) on the indicated dosing days (ie, Days 2, 3, 4, 7, 8, 9, and 11).
m
From the time of obtaining informed consent through the first administration of study drug, record all SAEs, as well as any nonserious AEs related to protocol-mandated 
procedures, on the AE eCRF. All other untoward medical occurrences observed during the screening period, including exacerbation or changes in medical history are to be 
captured on the medical history eCRF. See Section 7, Adverse Events and Toxicity Management, for additional details.
n
Study drug bottles of GS-6212 will be dispensed on Day 1 (see Section 5.2.4).
o
For Cohort 1, a 100-mg dose of GS-6212 will be administered twice daily (ie, once every 12 hours ± 1 hour) on Days 1 through 10 (for further details on dosing and meal 
requirements, see Section 5.2.4). Subsequent cohort doses, dosing regimens, meal requirements (fasted or fed), and progression between cohorts will be adaptive and 
determined as summarized in Section 3.1.1.
p
Participants will take their study drug doses at home on Days 5 and 6.
q
After assessments on Day 11 or upon ET, participants will initiate a regimen of BVY provided by the sponsor or an alternative SOC ART regimen selected by the 
investigator. Participants who discontinue study drug before Day 11 should start this regimen at the time of discontinuation (see Section 6.4.1 of the master protocol).
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1.
INTRODUCTION
Substudy-03, conducted under the GS-US-544-5905 master protocol, will evaluate the safety, 
pharmacokinetics (PK), and antiviral activity of GS-6212 given as monotherapy in participants 
with HIV-1 (PWH) who are either treatment-naive or treatment-experienced but naive to the 
integrase strand-transfer inhibitor (INSTI) class, and have not received any antiretroviral (ARV) 
therapy (ART) within 12 weeks of screening (full population details provided in Section 4).
1.1.
Rationale for Substudy-03
An overall rationale for the development of long-acting (LA) ARV agents is provided in the 
GS-US-544-5905 master protocol.
A rationale for the development of GS-6212 is provided below in Section 1.2.1.
1.2.
Background on Study Interventions Used in Substudy-03
1.2.1.
GS-6212
1.2.1.1.
General Information
Integrase strand-transfer inhibitors have played an ever-growing role in disease treatment and are 
currently a key component of combination ARV therapies. There are currently 5 INSTIs 
approved for the treatment of HIV-1 infection. GS-6212 is a potent and selective INSTI with a 
favorable nonclinical pharmacology profile that supports its clinical development as a novel 
ARV agent for the treatment of HIV-1 infection, with the potential for injectable dosing once 
every 3 months. A broad spectrum of representative HIV-1 mutant variants resistant to 
nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, 
protease inhibitors, or capsid inhibitors remained fully sensitive to GS-6212, indicating that the 
compound should retain full antiviral potency against mutant variants from these ARV classes. 
Developing the novel INSTI GS-6212 to be combined with other LA ARVs would fulfill an 
unmet medical need for people with HIV-1 to provide safe and effective regimens that can be 
administered less frequently. For further information, refer to the current GS-6212 investigator’s 
brochure (IB), including the following:
1) Nonclinical PK
2) Nonclinical pharmacodynamics
3) Nonclinical toxicology
1.2.1.2.
Nonclinical Pharmacology and Toxicology
Nonclinical pharmacology and toxicology studies are provided in the GS-6212 IB.

GS-6212
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Amendment 1
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1.2.1.3.
Clinical Studies of GS-6212
1.2.1.3.1.
Study GS-US-469-6161
Study GS-US-469-6161 is an ongoing, Phase 1a, first-in-human, randomized, blinded 
(sponsor unblinded), placebo-controlled clinical study. In this study, healthy participants 
received or will receive single ascending doses (SAD) of GS-6212 using the following 
formulations and parenteral routes of administration: GS-6212 polyethylene glycol (PEG)/water 
for injection (WFI) suspension formulation (400 mg/mL) administered subcutaneously 
(SC, Part A), GS-6212 oil suspension formulation (350 mg/mL) administered SC (Part B), 
GS-6212 PEG/WFI suspension formulation (225 mg/mL) administered intramuscularly 
(IM, Part C), and GS-6212 PEG/WFI suspension formulation (400 mg/mL) administered IM 
(Part D). The study remains blinded, with follow-up ongoing.
Preliminary PK Summary
To characterize the PK of GS-6212 for injection, plasma samples will be collected up to Day 301 
in each cohort. Interim PK analysis of samples until at least Day 7 postdose from cohorts that 
have been dosed thus far in Parts A, B, C, and D is ongoing.
Safety Summary
As of 12 May 2023, 75 participants have received either GS-6212 or placebo (randomized 4:1) 
by injection in Part A (n = 30; 200, 600, and 1200 mg), Part B (n = 20; 200 and 525 mg), Part C 
(n = 20; 
and 225 mg) and Part D (n = 5; 200 mg). There have been no deaths, serious 
adverse events (SAEs), Grade 3 or higher adverse events (AEs), or discontinuations due to AEs 
reported. In a preliminary review of available safety data for 75 participants, as of 12 May 2023, 
the most common study drug (GS-6212 or placebo)–related AEs have been mild to moderate 
(Grade 1 and Grade 2) injection site reactions related to SC or IM administration and reported in 
30% to 100% of participants across the different cohorts. Noninjection-site reaction study 
drug-related AEs were reported as follows: headache (n = 6), rash and pruritis (n = 1), and 
diarrhea (n = 1); all were Grade 1 and resolved without intervention. Other AEs included 
1 participant who experienced presyncope related to micturition and 1 participant with 
asymptomatic atrial flutter at a Day 56 follow-up visit related to illicit drug use (cocaine). 
Both AEs resolved without intervention and were considered to be unrelated to GS-6212.
There were no clinically relevant changes from predose in values for hematology, clinical 
chemistry, urinalysis, or coagulation parameters in this preliminary review. Five participants had 
Grade 3 laboratory abnormalities; 3 participants had increased fasting low-density lipoprotein 
(LDL), 2 participants had increased fasting triglycerides, 1 participant had a decrease in CLcr and 
a corresponding increase in serum creatinine from baseline but both values remained in the 
normal range. None of these Grade 3 laboratory abnormalities were considered clinically 
relevant. No Grade 4 laboratory abnormalities were reported.
No notable changes from predose were observed in vital signs (systolic and diastolic blood 
pressure, pulse, temperature, and weight).
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GS-6212 
Protocol GS-US-544-5905-03 
Gilead Sciences, Inc. 
1.2.1.3.2. 
Study GS-US-469-6401 
Final 
Amendment 1 
Study GS-US-469-6401 is an ongoing, Phase la, randomized, blinded (sponsor unblinded), 
placebo-contrnlled clinical study. In this study, healthy paii icipants received or will receive SAD 
or multiple ascending doses (MAD) of oral GS-6212. This study is being conducted in 2 pa1is 
(SAD Coho1is 1 through 4 and MAD Coho1is 5 through 7) that will include up to 7 coho1is. 
Additionally, Cohorts 2 and 3 will be conducted as a 2-period fixed-sequence design of the same 
single-dose levels of oral GS-6212 to assess any potential food effect. 
Preliminary PK Summary 
Prelimina1y GS-6212 plasma concentration-time profiles and associated PK 
followin administration of single oral doses of 100 mg (Coho1i 1 
under fasted and/or fed conditions, and 
under fasted conditions ai·e presented 
in Figure 2, Figure 3, and Table 2 based on PK data available from Study GS-US-469-6401 as of 
21 April 2023. Phannacokinetic sainples were collected for up to 72 hours postdose. 
Following oral administration of GS-6212 with or without food, GS-6212 was absorbed quickly 
with Tmax observed from 1.0 to 4.0 hours postdose. The median oral GS-6212 t112 ranged from 
approximately-
hours across the evaluated dose levels. All but 1 paiiicipant attained 
~rotein-adjusted 95% effective concentration or inhibito1y quotient (IQ) 
-
for GS-6212 by up to 2.0 hours postdose across all coho1is. 
Over the dose range evaluated, the increase in AUC and Cma.x was less than dose-propo1i ional in 
the fasted state. These less than dose-proportional increases in exposure suggest that oral 
GS-6212 exhibits nonlineai·ity in the dose-exposure relationship likely due to solubility-limited 
absorption. 
Based on data from a limited sain le size, GS-6212 exp~as assessed by AUCinfand Cmax) 
followin 
of a GS-6212-
dose with a hi h-fat meal was on 
average, approxrmate y 
o er relative to GS-6212 
dosed in fasted 
conditions. In compai·ison, 
of a GS-6212 
dose with a 
high-fat meal led to,~ 
approximate 
increase in GS-6212 exposure 
relative to GS-6212- dosed in fasted conditions. 
In line with the observed t112 values, minimal accumulation in GS-6212 exposures was observed 
following 10 days of once-daily dosing in Cohorts 5 and 6. 
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Final
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CONFIDENTIAL
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Final
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Amendment 1
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GS-6212 
Protocol GS-US-544-5905-03 
Gilead Sciences, Inc. 
-
Cohort 1 
Cohort 2 
(100 mg; -
Fasted) 
1590 
2790 
(17.2) 
(14.8) 
2.00 
2.00 
(1.00, 
(1.25, 
2.75) 
3.00) 
8.32 
26.1 
(44.5) 
(37.4) 
1.60 
3.94 
(26.7) 
(82.1) 
48.0 
72.0 
(39.0, 
(54.0, 
48.0) 
72.0) 
6420 
14,400 
(28.2) 
(19.1) 
6500 
14,800 
(28.1) 
(19.5) 
6520 
15,000 
(28.1) 
(20.5) 
0.259 
1.05 
(37.1) 
(213) 
6.42 
8.43 
(5.01, 
(6.68, 
10.1) 
12.5) 
Cohort 2 
.
; 
1830 
(37.8) 
3.00 
(1.25, 
4.00) 
25.2 
(56.0) 
4.06 
(94.8) 
72.0 
(54.0, 
72.0) 
11,200 
(38.4) 
11,600 
(39.1) 
11,600 
(39.2) 
0.440 
(46.7) 
9.33 
(8.15, 
14.8) 
Cohort 5 
Cohort 3 
Cohort 3 - · 
-
; 
.
; 
Day 1; 
Fasted) 
4720 
5140 
1430 
(37.8) 
(41.2) 
(47.8) 
2.50 
4.00 
1.00 
(2.00, 
(3.00, 
(0.625, 
3.00) 
4.00) 
3.50) 
120 
366 
12.7 
(195) 
(198) 
(78.2) 
2.87 
5.63 
12.7 
(1 18) 
(109) 
(78.2) 
72.0 
72.0 
24.0 
(72.0, 
(72.0, 
(24.0, 
72.0) 
72.0) 
24.0) 
26,200 
40,700 
6590 
(32.9) 
(48.9) 
(51.1) 
27,000 
42,900 
6590 
(35.2) 
(51.2) 
(51.1) 
27,100 
43,000 
6660 
(35.3) 
(51.2) 
(51.2) 
0.201 
0.183 
1.02 
(81.0) 
(55.4) 
(40.7) 
14.4 
11.4 
3.77 
(12.2, 
(7.20, 
(3.33, 
15.7) 
13.2) 
4.14) 
h = hom·; PK = phanuacokinetic(s); Ql = first qua1tile; Q3 = third qua1tile; QD = once daily 
Cohort 5 -
QD x 
10 days, 
Day 10; 
Fasted) 
1640 
(32.3) 
2.00 
(2.00, 
3.75) 
15.5 
(58.1) 
1.73 
(24.1) 
72.0 
(48.0, 
72.0) 
7460 
(38.6) 
7650 
(38.6) 
8.84 
(7.25, 
10.5) 
Final 
Amendment 1 
Cohort 6 
- · 
Day l ; 
Fasted) 
2900 
(37.2) 
2.00 
(0.625, 
3.75) 
17.0 
(55.0) 
17.0 
(55.0) 
24.0 
(24.0, 
24.0) 
13,400 
(40.3) 
13,400 
(40.3) 
13,500 
(40.4) 
0.597 
(26.8) 
3.46 
(3.28, 
3.55) 
PK parameters presented to 3 significant figures as mean (%CV) except t112, T1as1, and Tmax which are presented as median 
(Ql, Q3). 
Note: Analysis was conducted using nominal time points. 
Safety Summary 
As of21 April 2023, 50 paiiicipants have received at least 1 dose of either GS-6212 or-
acebo 
in SAD Coho1is 1 2 and 3 (100 mg, 
) and MAD Coho1is 5 and 6 
• 
and-
for 10 days). Preliminaiy GS-6212 exposures for each coho1i ai·e found 
m Table 2 wit t e 1 
est estimated exposure (preliminaiy AUCuu) of 43,000 h•ng/mL in 
Coho1i 3. In a preliminaiy blinded review of available safety data collected for 50 paiiicipants 
(SAD Coho1is 1, 2, and 3 and MAD Cohorts 5 and 6) as of 21 April 2023, there have been no 
deaths, SAEs, Grade 3 or higher AEs, or discontinuations due to AEs repo1ied. One paiiicipant 
experienced a study diug (GS-6212 or placebo )- related treatment-emergent AE of Grade 1 
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Gilead Sciences, Inc.
Amendment 1
CONFIDENTIAL
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headache, which resolved. One participant in Cohort 6 experienced treatment-emergent AEs of 
Grade 1 nausea and vomiting, along with headache and dizziness, on Days 1 and 2 respectively, 
which resolved without treatment and were judged by the investigator to be related to study drug 
(GS-6212 or placebo). This same participant experienced Grade 3 laboratory abnormalities for 
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) on Day 13 which returned 
to baseline on retesting by Day 25; bilirubin levels and international normalized ratio remained 
normal, and acute viral hepatitis testing was negative.
Three participants had Grade 3 laboratory abnormalities; 1 participant had increased ALT and 
AST (discussed above) and a Grade 3 decrease in CLcr from baseline with normal serum 
creatinine and normal CLcr, 1 participant had increased LDL, which returned to baseline on 
retesting, and 1 participant had an increased triglyceride level that decreased on repeat testing. 
With the exception of the participant with elevated ALT and AST, no Grade 3 laboratory 
abnormalities were clinically significant or judged to be related to study drug. There were no 
other clinically relevant changes from predose in values for hematology, clinical chemistry, 
urinalysis, or coagulation parameters. No notable changes from predose were observed in vital 
signs (systolic and diastolic blood pressure, pulse, temperature, and weight).
1.3.
Rationale for Dose Selection of GS-6212
Selection of the GS-6212 doses for this study takes into consideration the available safety, 
tolerability, and PK data for GS-6212 from the ongoing Phase 1a oral SAD and MAD study in 
healthy volunteers (Study GS-US-469-6401), as well as emerging preliminary safety and 
antiviral activity data in this substudy (as applicable).
As of 21 April 2023, 30 participants (24 active and 6 placebo) have received a 
 of 
either GS-6212 
 or placebo in SAD Cohorts 1, 2, and 3, and 20 participants 
(16 active and 4 placebo) have received multiple oral doses of either GS-6212 
 
 or placebo in MAD Cohorts 5 and 6. In a preliminary blinded review of available safety 
data collected for 50 participants (Cohorts 1 through 3, and 5 and 6) as of 21 April 2023, 
GS-6212 dosed orally was generally safe and well-tolerated. A summary of preliminary safety 
data from Study GS-US-469-6401 is included in Section 1.2.
As of 21 April 2023, preliminary SAD PK data are available from Cohorts 1 through 3 at doses 
ranging from 100 
, and MAD PK data are available from Cohorts 5 and 6 at 
 
 doses from Study GS-US-469-6401 (Figure 2, Figure 3, and Table 2). For the purposes 
of dose selection, both Ctrough and the Cav,ss were taken into consideration given that steady state 
is attained rapidly via the oral route in comparison to the SC/IM profiles that are expected to be 
relatively flatter with sustained exposures spanning over a wider interval. This may facilitate the 
extrapolation of the antiviral GS-6212 data from oral dosing to relevant clinical concentrations 
achieved with SC or IM formulations. Based on modeling and simulation using a preliminary 
population PK model, a 100-mg dose of GS-6212 administered orally twice daily (ie, once every 
12 hours) from Days 1 through 10 will be used for Cohort 1 of this substudy. Modeling predicts 
that this regimen will result in a median GS-6212 Ctrough at Day 11 that is approximately 4.7-fold 
above the IQ, with the median Cav,ss predicted to be approximately 5.0-fold above the IQ5 
(the estimated therapeutic threshold). The mean Cmax of GS-6212 attained following a single oral 
CCI
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-

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Gilead Sciences, Inc.
Amendment 1
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dose of 100 mg was approximately 1590 ng/mL (Table 2). Based on the available data, 
accumulation for GS-6212 exposures following twice daily dosing of 100 mg is expected to be 
minimal; the predicted median GS-6212 AUC and Cmax for the proposed 
 
 is approximately 3.0- to 3.5-fold lower than the highest observed AUC and Cmax from 
the available preliminary analysis of Study GS-US-469-6401. Overall, GS-6212 exposures 
projected for Cohort 1 of the current study are well covered by the systemic levels of GS-6212 
that have been shown to be safe in Study GS-US-469-6401 (see Section 1.2).
As part of this substudy, higher and/or lower GS-6212 doses/exposures relative to Cohort 1 will 
be evaluated in subsequent cohorts to target a wide range of IQ values that characterize the 
PK/pharmacodynamic relationship between GS-6212 PK and changes from baseline in HIV-1 
viral load. Doses in Cohorts 2 to 5 (as applicable) will be determined by the Safety Review Team 
(SRT) based on cumulative safety, PK, and virologic data from Cohort 1, as well as relevant and 
available safety and PK data from the Phase 1a study (GS-US-469-6401). Doses selected for 
Cohorts 2 to 5 will be adaptive and will have projected GS-6212 exposures approximately at or 
below the observed exposures in the Phase 1a study.
1.4.
Benefit-Risk Assessment for the Study
Potential risks to participants may include limited exposure to subtherapeutic concentrations of 
study drug. This could lead to the HIV-1 virus developing resistance to the study drug, and 
potentially to the study drug class, which could limit future treatment options. Strategies to 
mitigate this risk, and additional risk/benefit assessments applicable to Substudy-03 and 
GS-6212, are described in Section 1.4 of the master protocol.
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2.
OBJECTIVES AND ENDPOINTS
Objectives and endpoints are described in Section 2 of the master protocol.
3.
STUDY DESIGN
3.1.
Study Design Overview
This substudy is being conducted as part of an umbrella study as described in the master 
protocol.
Substudy-03 is an open-label, Phase 1b, multiple-dose, multicohort study to evaluate the safety, 
PK, and antiviral activity of GS-6212 given as monotherapy in PWH who are either 
treatment-naive or treatment-experienced but naive to INSTIs and have not received any ART 
within 12 weeks of screening, including medications received for pre-exposure prophylaxis or 
postexposure prophylaxis. Any current or prior receipt of LA parenteral ARVs, such as 
monoclonal antibodies targeting HIV-1, injectable cabotegravir, or injectable rilpivirine, is 
exclusionary.
After screening and meeting all eligibility criteria, study drug dosing will be initiated on Day 1 in 
the clinic for each participant (Figure 1). Participants will be required to return to the clinic for 
visits on Days 2, 3, 4, 7, 8, 9, 10, and 11 (primary endpoint assessment). Doses of GS-6212 will 
be administered orally at the clinic under observation by site staff on clinic visit days/times and 
at home by the participant on nonclinic visit days/times at approximately the same time each day. 
In cohorts where GS-6212 is administered more than once daily, in-clinic observation of dosing 
will be conducted for the morning dose only. Participants will record at-home dosing details in a 
dosing log.
After assessments on Day 11 or upon early termination (ET), participants will initiate a regimen 
of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide; BVY) provided by the sponsor or 
an alternative standard of care (SOC) ART regimen selected by the investigator. If participants 
are switching to BVY, a sufficient supply will be given to provide coverage for the remainder of 
the study. Participants will be required to return to the clinic for a follow-up visit on Day 25.
Overnight fasting (≥ 6 hours prior to dosing) is required for laboratory and/or PK analyses on 
Days 1 and 11 (see Section 5.3). On all other days (Days 2 through 10), the AM doses should be 
taken on an empty stomach (for additional details see Section 5.3).
The selection of doses and dosing regimens for GS-6212 is described in Section 3.1.1.
This substudy will enroll up to 5 cohorts, with at least 6 participants in each cohort. 
Initial participants will be enrolled in Cohort 1, with dosing in subsequent cohorts proceeding 
after SRT review of emerging data from Cohort 1 and available data from the Phase 1a 
SAD/MAD Study GS-US-469-6401, as described in Section 3.1.1.

GS-6212
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Amendment 1
CONFIDENTIAL
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Sequential enrollment in cohorts, and order of assignment to substudies, are described in 
Section 5.1.1 of the master protocol.
The sponsor may elect to hold dosing, stop/pause substudy enrollment, or stop the study 
(or substudy, or specific cohort) at any time based on review of preliminary safety, efficacy, and 
PK data (see master protocol Section 5.1.1). If deemed unnecessary, the sponsor may choose not 
to initiate 1 or more cohorts.
3.1.1.
Dose Selection/Modification
Enrollment and dosing with GS-6212 will begin with Cohort 1. The dose and regimen of 
GS-6212 for Cohort 1 is defined in Section 5.2.4.
A summary of planned SRT reviews, dose decisions, and cohort progression applicable to this 
substudy is included in Section 3.1.1 of the master protocol.
3.2.
Duration of Intervention
Participants will be under evaluation in this Substudy-03 for 25 days.
Participants will receive doses of GS-6212 from Days 1 through 10; dosage and frequency will 
be specified as described in Section 5.2.4. Participants will then initiate a BVY or alternative 
SOC regimen following study assessments on Day 11 or upon ET for the remainder of the study. 
Participants will be required to return to the clinic for a follow-up visit on Day 25.
3.3.
Substudy-03–Specific Discontinuation Criteria
Criteria for early discontinuation for individual participants, each substudy, and each substudy 
cohort are described in Section 3.3 of the master protocol.
3.4.
Definitions for Time of Primary Endpoint and End of Study
Definitions for the time of the primary endpoint and end of study for each substudy are described 
in Section 3.4 of the master protocol.

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Amendment 1
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4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection for Substudy-03
In Substudy-03, up to 5 cohorts, each containing at least 6 participants, will be enrolled. 
Participant replacement is described in Section 4.1.1 of the master protocol.
4.2.
Substudy-03–Specific Inclusion Criteria
Inclusion criteria applicable to all substudies are provided in Section 4.2 of the master protocol. 
In addition to meeting the inclusion criteria in the master protocol, participants must also meet 
the following inclusion criteria to be eligible for participation in this substudy:
S03-1. Willing to initiate an SOC ART regimen on Day 11 or upon ET as stated in Section 4.2 
of the master protocol. For this substudy, willing to initiate BVY provided by the sponsor or an 
alternative SOC ART regimen selected by the investigator on Day 11 or upon ET.
S03-2. Willing and able to comply with meal requirements.
4.3.
Substudy-03–Specific Exclusion Criteria
Exclusion criteria applicable to all substudies are provided in Section 4.3 of the master protocol. 
In addition to not meeting any of the exclusion criteria in the master protocol, participants must 
not meet the following exclusion criterion to be eligible for participation in this substudy:
S03-1. Requirement for ongoing therapy with any prohibited medication listed in Section 5.4.

GS-6212 
Protocol GS-US-544-5905-03 
Gilead Sciences, Inc. 
5.1. 
STUDY INTERVENTIONS AND CONCOMITANT 
MEDICATIONS 
Enrollment and Treatment Code Access 
Final 
Amendment 1 
Paiiicipant emollment procedures ai·e described in Section 5 .1 of the master protocol. 
5.2. 
Description and Handling of GS-6212 and BVY 
BVY will be provided by the sponsor for use during the study, as applicable. 
5.2.1. 
Formulation 
BVY tablets (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) ai·e 
capsule-shaped, film-coated, pmp lish brown, de bossed with "GSI" on one side of the tablet and 
"9883" on the other side of the tablet. Each tablet core contains 50 mg of bictegravir 
(equivalent to 52.5 mg ofbictegravir sodium), 200 mg of emtricitabine, and 25 mg of tenofovir 
alafenamide (equivalent to 28 mg oftenofovir alafenamide fumai·ate). In addition to the active 
ingredients, the BVY tablets contain croscannellose sodium, magnesium stearate, and 
microc1ystalline cellulose. The tablet cores ai·e film-coated with iron oxide red, iron oxide black, 
PEG, polyvinyl alcohol, talc, and titanium dioxide. Additional details are provided in local 
prescribing infonnation for BVY product. 
5.2.2. 
Packaging and Labeling 
GS-6212 tablets ai·e packaged in white, high-density polyethylene bottles. Each bottle contains 
30 tablets and a silica gel desiccant. Each bottle is enclosed with a white, continuous-thread, 
child-resistant screw cap with an induction-sealed, aluminum-faced liner. GS-6212 
-
bottle configurations contain polyester packaging material. GS-6212 
bottle configuration does not contain polyester packaging material. 
BVY tablets ai·e packaged in white, high-density polyethylene bottles. Each bottle contains 
30 tablets, silica gel desiccant, and polyester packaging material. Each bottle is enclosed with a 
white, continuous-thread, child-resistant polypropylene screw cap with an induction-sealed and 
aluminum-faced liner. 
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Study drug(s) to be distributed to study sites in the United States (US) and other participating 
countries shall be labeled to meet applicable requirements of the US Food and 
Drug Administration (FDA), European Union (EU) Guideline to Good Manufacturing 
Practice-Annex 13 (Investigational Medicinal Products) for Common Technical Document, or 
Annex 6 for Clinical Trial Regulation, as applicable, and/or other local regulations.
5.2.3.
Storage and Handling
GS-6212 tablets should be stored below 30 °C. BVY should be stored according to the storage 
conditions specified on the label.
GS-6212 and BVY should be stored in a securely locked area, accessible only to authorized site 
personnel. To ensure the stability of GS-6212 and BVY and proper identification, the drug 
product should not be stored in a container other than that in which it is supplied.
5.2.4.
Dosage and Administration
In Cohort 1, a dose of GS-6212 100 mg will be administered orally twice daily (ie, once every 
12 hours ± 1 hour) on Days 1 through 10. The dose, dosing regimen, and meal requirements for 
administration of GS-6212 in Cohort 1 are provided in Table 3. Subsequent cohort doses, dosing 
regimens, meal requirements (fasted or fed), and progression between cohorts will be adaptive, 
as described in Section 3.1.1. The maximum dose (to be administered each day at any given 
time) in subsequent cohorts will not exceed those indicated in Table 3.
For participants who will be receiving GS-6212 once daily, study drug will be dispensed on 
Day 1. Bottles will be stored on site and administered in the clinic on Days 1 through 4. 
Participants will take doses at home on Days 5 and 6; doses on Days 7 through 10 will be 
administered in the clinic.
For participants who will be receiving GS-6212 twice daily, study drug bottles will be dispensed 
on Day 1. Participants will take the bottles home after the morning dose at the clinic and then 
bring the bottles back to the clinic for the next day’s morning dose at the clinic for Days 1 
through 4 and Days 7 through 10. For Days 5 and 6, participants will keep the bottles at home.
Doses of GS-6212 will be administered orally at the clinic under observation by site staff on 
clinic visit days/times and at home by the participant on nonclinic visit days/times at 
approximately the same time each day. In cohorts where GS-6212 is administered more than 
once daily, in-clinic observation of dosing will be conducted for the morning dose only. 
Participants will record at-home dosing details in a dosing log. In addition to the dosing log, 
site staff can remind the participant of evening dosing via phone call/text message, if feasible. 
The timing of all doses on Days 5 and 6 should be recorded in a dosing log.

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Amendment 1
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Table 3.
GS-6212 Dosage by Cohort
Cohort
Treatment
Cohort 1
100 mg oral doses BID (ie, once every 12 hours 
± 1 hour) on Days 1 through 10:
-
The first AM dose (on Day 1) should be taken 
following overnight fasting (≥ 6 hours).
-
All other AM doses (on Days 2 through 10) should 
be taken around the same time every morning on 
an empty stomach (fasting for ≥ 2 hours; 
see Section 5.3).
-
Each PM dose should be taken around the same 
time every evening with or without food. 
Participants are required to keep the pattern of 
study drug intake consistent throughout the 
10 days of dosing as much as possiblea 
(see Section 5.3).
Cohort 2
 on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
Cohort 3
 on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
Cohort 4
 on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
Cohort 5
 on 
Days 1 through 10; dosing intervals and meal 
requirements (fasted or fed) to be determined based on 
relevant and available data from earlier cohorts.
AM = before noon; BID = twice daily; PM = evening; QD = once daily
a
For instance, if a participant takes their first PM dose on an empty stomach, then they should try and take the remainder of 
their PM doses on an empty stomach and vice versa.
If BVY is initiated after assessments on Day 11 or upon ET, it will be administered orally, once 
daily, without regard to food.
5.3.
Fasting and Meals (GS-6212 Dosing)
Cohort 1:
All GS-6212 doses will be administered at approximately the same time on each day 
(morning/evening) with 240 mL of water.
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AM dosing:
The first AM dose of the study drug (on Day 1) should be administered following an overnight 
fast (no food or drinks, except water) for at least 6 hours. Participants should continue to fast 
until after collection of the 2-hour intensive PK sample, relative to time of dosing on Day 1. 
Additionally, participants will be restricted from water consumption 1 hour before and until 
1 hour after dosing, except for the 240 mL given with the study drug on Day 1.
On all other days (ie, Days 2 through 10), participants should take the study drug on an empty 
stomach (no food or drinks except water, for at least 2 hours) and continue to fast until 1-hour 
postdose.
PM dosing:
Study drug should be taken every evening on an empty stomach (no food or drinks, except water, 
for at least 2 hours and continue to fast until 1-hour postdose) or with food. Additionally, 
overnight fasting (no food or drinks, except water) for at least 6 hours, is required for safety 
assessments on Day 11.
Participants are required to keep the pattern of study drug intake consistent throughout the 
10 days of dosing as much as possible (for instance, if a participant takes their first PM dose on 
an empty stomach, then they should try and take the remainder of their PM doses on an empty 
stomach and vice versa).
Note: Fasting and meal requirements for the subsequent cohorts will be confirmed following 
availability of data from Cohort 1, and relevant and available data from the Phase 1a SAD/MAD 
Study GS-US-469-6401.
5.4.
Prior and Concomitant Medications
See Section 5.3 of the master protocol for information on prior or concomitant medication rules 
applicable to this substudy, including restricted medications through Day 11. The investigator 
should reach out to the sponsor for guidance prior to the use of any concomitant medication from 
Day 1 through the end of study.
From Day 11 (following administration of BVY or an alternative SOC) through the last visit, the 
investigator should follow the local prescribing information for BVY or other ART taken as SOC 
(as applicable) by an individual participant.
5.5.
Accountability for Study Drug Supplies: Study Drug and SOC ART 
Provided by the Sponsor (BVY)
Guidance related to accountability, return, and disposal of study drug supplies (study drug 
[GS-6212 for this substudy] and SOC ART provided by the sponsor [BVY for this substudy]) is 
provided in Section 5.4 of the master protocol.

GS-6212 
Protocol GS-US-544-5905-03 
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STUDY PROCEDURES 
Final 
Amendment 1 
Study procedures applicable to all substudies are listed in Section 6 of the master protocol. 
Study procedures specific to Substudy-03 are listed in the sections below. The time points for 
study procedures are specified in Table 1. Substudy-specific info1med consent fo1ms will be 
required for Substudy-03. 
6.1. 
6.1.1. 
Instructions for Study Procedures 
Pharmacokinetics 
Blood samples will be collected to detennine GS-6212 PK (and metabolites, if appropriate) in 
plasma as indicated in Table 1. 
6.1.2. 
Suboptimal Virologic Response 
Management of suboptimal virologic response is described in Section 6.3 .9 .1.3 of the master 
protocol. 
6.1.2.1. 
Management ofVirologic Rebound 
Management ofvirologic rebound is described in Section 6.3.9.1.3 of the master protocol. 
6.1.2.2. 
Resistance Analysis at Paiiicipant's Last Visit 
Resistance analysis at a paiiicipant's last visit is described in Section 6.3.9.1.3 of the master 
protocol. 
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6.1.3.
Poststudy Care
The investigators will counsel and refer the participants to long-term care, including a human 
immunodeficiency virus treatment facility, and any medication assistance programs. Please see 
Section 3.5 of the master protocol.

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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
Adverse events are specified in Section 7 of the master protocol. Information regarding toxicity 
management that is specific to GS-6212 is described below and included in Appendix 11.3. 
Pregnancy precautions, definition of childbearing potential, and contraceptive requirements 
specific to GS-6212 are included in Appendix 11.2.
7.1.
Toxicity Management
All clinically significant laboratory toxicities will be managed according to uniform guidelines 
detailed in Appendix 11.3 and as outlined below.
•
Grade 3 or 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing as soon as possible, and preferably within 3 calendar days after receipt of the original 
test results. The study drug may be continued without dose interruption for a clinically 
insignificant Grade 3 or 4 laboratory abnormality (eg, creatine kinase elevation after 
strenuous exercise, triglyceride elevation that is nonfasting or can be medically managed). 
Recurrences of laboratory abnormalities considered unrelated to study drug may not require 
permanent discontinuation.
•
Grade 3 or 4 AEs, if considered unrelated to study drug, may not require dose interruption; 
continuation of study drug is at the discretion of the investigator.
7.1.1.
Grades 1 and 2 Laboratory Abnormalities or AEs
•
Continue study drug dosing at the discretion of the investigator.
7.1.2.
Grade 3 Laboratory Abnormalities or AEs
•
For a Grade 3 clinically significant laboratory abnormality confirmed by repeat testing that is 
considered related to study drug, the study drug should be permanently discontinued, and the 
investigator should consult the medical monitor and manage as clinically indicated. BVY or 
an alternative SOC should be initiated if clinically appropriate.
•
For a Grade 3 AE considered to be related to the study drug, the study drug should be 
permanently discontinued, and the investigator should consult the medical monitor and 
manage as clinically indicated. BVY or an alternative SOC should be initiated if clinically 
appropriate.

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7.1.3.
Grade 4 Laboratory Abnormalities or AEs
•
For a Grade 4 AE or clinically significant laboratory abnormality confirmed by repeat testing 
considered related to study drug, the study drug should be permanently discontinued, BVY or 
an alternative SOC should be initiated if clinically appropriate, and the participant managed 
according to local practice. The participant should be followed as clinically indicated until 
the laboratory abnormality returns to baseline or is otherwise explained, whichever comes 
first. A clinically significant Grade 4 laboratory abnormality that is not confirmed by repeat 
testing should be managed according to the algorithm for the new toxicity grade.
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the sponsor’s medical monitor, and the appropriate course of action will be discussed and 
decided. Whether or not considered treatment-related, all participants experiencing an AE must 
be monitored periodically until symptoms subside, any abnormal laboratory values have resolved 
or returned to baseline levels or are considered irreversible, or until there is a satisfactory 
explanation for the changes observed.
Any questions regarding toxicity management should be directed to the sponsor’s medical 
monitor.

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8.
STATISTICAL CONSIDERATIONS
Details of statistical methods will be provided in the statistical analysis plan for this substudy, 
including any deviations from the original statistical analyses planned. Statistical considerations 
for this substudy are described in Section 8 of the master protocol.

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9.
RESPONSIBILITIES
Details regarding responsibilities are specified in Section 9 of the master protocol.

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10.
REFERENCES
None.

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11.
APPENDICES

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11.1.
Investigator Signature Page
GILEAD SCIENCES, INC.
333 LAKESIDE DRIVE
FOSTER CITY, CA 94404
USA
An Umbrella Phase 1b, Open-label, Multicohort Study to Evaluate Safety, Pharmacokinetics, 
and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1; Substudy-03: 
GS-6212
Amendment 1, 18 August 2023
CLINICAL STUDY PROTOCOL ACKNOWLEDGMENT
INVESTIGATOR STATEMENT
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated.
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study.
Principal Investigator Name (Printed)
Signature
Date
Site Number

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11.2.
Pregnancy Precautions, Definition of Childbearing Potential, and 
Contraceptive Requirements
1)
Definitions
a.
Definition of Childbearing Potential
For the purposes of this study, a participant assigned female at birth is considered of childbearing 
potential following the initiation of puberty (Tanner Stage 2) until becoming postmenopausal, 
unless the participant is permanently sterile or has medically documented ovarian failure.
Participants assigned female at birth are considered to be in a postmenopausal state when they 
are at least 54 years of age with cessation of previously occurring menses for at least 12 months 
without an alternative cause. In addition, participants assigned female at birth younger than 
54 years of age with amenorrhea of at least 12 months may also be considered postmenopausal if 
their follicle-stimulating hormone level is in the postmenopausal range and they are not using 
hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a participant assigned female at birth of any age.
b. Definition of Fertility in a Participant Assigned Male at Birth
For the purposes of this study, a participant assigned male at birth is considered fertile after the 
initiation of puberty unless the participant is permanently sterile by bilateral orchidectomy or 
medical documentation.
2)
Contraception Requirements for Participants Assigned Female at Birth
a.
Study Drug Effects on Pregnancy and Hormonal Contraception
GS-6212 is contraindicated in pregnancy, as a malformative effect due to human 
teratogenicity/fetotoxicity is unknown. GS-6212 has insufficient data to exclude the possibility 
of a clinically relevant interaction with hormonal contraception that results in reduced 
contraception efficacy. Therefore, hormonal contraception is not recommended as a 
contraceptive method either solely or as a part of a contraceptive regimen. Refer to the latest 
version of the GS-6212 investigator’s brochure for additional information.
Refer to the prescribing information for pregnancy and contraception information for the 
standard of care regimen.
b.
Contraception Requirements for Participants Assigned Female at Birth of 
Childbearing Potential
The inclusion of participants assigned female at birth and of childbearing potential requires the 
use of highly effective contraceptive measures with a failure rate of less than 1% per year. 
They must also not rely on hormone-containing contraceptives as a form of birth control during 
the study. They must have a negative serum pregnancy test at screening and a negative urine 
pregnancy test at the Day 1 visit before enrollment. Pregnancy tests will be performed at monthly 
intervals thereafter until the end of contraception requirement.

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Duration of required contraception for participants assigned female at birth in this clinical study 
should start from the screening visit until the end of the protocol-defined follow-up period.
Participants assigned female at birth and of childbearing potential must agree to 1 of the 
following contraceptive methods:
Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the participant’s preferred and usual 
lifestyle.
Or
Consistent and correct use of any of the following methods of birth control listed below:
•
Nonhormonal intrauterine device
•
Bilateral tubal occlusion (upon medical assessment of surgical success)
•
Vasectomy in the partner assigned male at birth (upon medical assessment of surgical 
success)
Inclusion of methods of contraception in this list of permitted methods does not imply that the 
method is approved in any country or region. Methods should only be used if locally approved.
Participants assigned female at birth and of childbearing potential must also refrain from egg 
donation and in vitro fertilization during treatment and until the end of contraception 
requirement.
3)
Contraception Requirements for Participants Assigned Male at Birth
It is theoretically possible that a relevant systemic concentration of study drug may be achieved 
in a partner assigned female at birth from exposure to the participant’s seminal fluid and pose a 
potential risk to an embryo/fetus. A participant assigned male at birth with a partner assigned 
female at birth and of childbearing potential must use condoms during treatment and until the 
end of the protocol-defined follow-up period. If the partner assigned female at birth and of 
childbearing potential is not pregnant, additional contraception recommendations should also be 
considered.
Participants assigned male at birth must also refrain from sperm donation and cryopreservation 
of germ cells during treatment and until the end of contraception requirement.

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4)
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. A female condom and a male condom should not be used 
together.
5)
Procedures to be Followed in the Event of Pregnancy
Participants assigned female at birth will be instructed to notify the investigator if they become 
pregnant or suspect they are pregnant at any time from the start of the study until the end of the 
protocol-defined follow-up period.
Participants assigned male at birth whose partner has become pregnant or suspects they are 
pregnant from start of study until the end of the protocol-defined follow-up period must also 
report the information to the investigator. Instructions for reporting pregnancy, partner 
pregnancy, and pregnancy outcome are outlined in Section 7.4.2.3 of the master protocol.

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11.3.
Management of Clinical and Laboratory Adverse Events
BVY = bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®); SOC = standard of care
Grade 1 
Continue study drng 
dosing at the discretion of 
the investigator 
Grade 2 
Grade 3 
I 
I 
Grade 4 
l 
l 
Repeat laboratmy test to 
confum toxicity grade 
For Grade 3 or 4 clinically significant laboratmy 
abno1malities confumed by repeat testing and 
considered to be related to study diug or adverse 
events considered to be related to study diug, the 
study di·ug should be pe1manently discontinued, and 
the investigator should consult tl1e medical monitor 
and manage as clinically indicated. 
BVY or another SOC should be initiated if clinically 
appropriate. 

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11.4.
Amendment History
A high-level summary of this amendment is provided in tabular form in the subsection below, 
with changes listed in order of importance. Minor changes such as the correction of typographic 
errors, grammar, or formatting are not detailed.
A separate tracked change (red-lined) document comparing the original protocol to this 
amendment will be made available upon the publication of this protocol.
11.4.1.
Amendment 1 (18 August 2023)
Rationale for Key Changes Included in Amendment 1
Affected Sections
A formulation for the new GS-6212 
 has been added.
Sections 5.2.1 and 5.2.2
Minor changes such as the correction of typographic errors, grammar, or 
formatting.
Throughout, as needed.
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11.5.
Sponsor Signature Page
GILEAD SCIENCES, INC.
333 LAKESIDE DRIVE
FOSTER CITY, CA 94404
USA
An Umbrella Phase 1b, Open-label, Multicohort Study to Evaluate Safety, Pharmacokinetics, 
and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1; Substudy-03: 
GS-6212
Amendment 1, 18 August 2023
APPROVAL OF CLINICAL STUDY PROTOCOL
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval.
[See appended electronic signature]
Name (Printed)
Senior Director, Clinical Development
Signature
[See appended electronic signature]
Date
PPD

Prot-GS-US-544-5905-03-amd-1
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Project Team
Leader eSigned
18-Aug-2023
22:26:00
PPD