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-02 PROTOCOL
Study Title:
An Umbrella Phase 1b, Open-label, Multi-Cohort Study to Evaluate 
Safety, Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals 
in Participants With HIV-1 Substudy-02: GS-1720
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
USA
IND Number:
162030
EudraCT Number:
Not applicable
ClinicalTrials.gov 
Identifier:
NCT05585307
Indication:
HIV-1 infection
Protocol ID:
GS-US-544-5905-02
Contact Information:
The medical monitor name and contact information will be provided on 
the Key Study Team Contact List.
Protocol Version/Date:
Original:
27 February 2023
Amendment 1:
02 March 2023
Amendment 2:
05 May 2023
A high-level summary of amendment history is provided in 
Appendix 11.3.
This study will be conducted under United States Food and Drug Administration investigational new drug 
application regulations (21 Code of Federal Regulations Part 312).
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The information contained in this document, particularly unpublished data, is the property or under 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.
GILEAU 

GS-1720 
Protocol GS-US-544-5905 Substudy-02 
Gilead Sciences, Inc. 
Final 
Amendment2 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ......................................................................................................................................... 3 
LIST OF IN-TEXT FIGURES ........................................................................................................................................ 3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................................. .4 
SUBSTUDY PROTOCOL SYNOPSIS .......................................................................................................................... 5 
SUBSTUDY-02 STUDY SCHEMA .............................................................................................................................. 8 
SUBSTUDY-02 STUDY PROCEDURES TABLE ....................................................................................................... 9 
1. 
INTRODUCTION ................................................................................................................................................ 11 
1.1. 
Rationale for Substudy-02 ....................................................................................................................... 11 
1.2. 
Background on Study Interventions Used in Substudy-02 ...................................................................... 11 
1.2.1. 
GS-1720 ................................................................................................................................. ll 
1.3. 
Rationale for Dose Selection of Study Drng ........................................................................................... 14 
1.4. 
Benefit-Risk Assessment for the Study ................................................................................................... 15 
2. 
OBJECTIVES AND ENDPOINTS ...................................................................................................................... 16 
3. 
STUDY DESIGN ................................................................................................................................................. 17 
3 .1. 
Study Design Overview ........................................................................................................................... 17 
3 .1.1. 
Dose Selection/Modification ................................................................................................. 18 
3.2. 
Duration oflnte1vention .......................................................................................................................... 18 
3 .3. 
Substudy-02 Specific Discontinuation Criteria ....................................................................................... 18 
Definitions for Time of Prima1y Endpoint and End of Study .............................................................................. 18 
4. 
PARTICIPANT POPULATION .......................................................................................................................... 19 
4.1. 
Number of Participants and Participant Selection for Substudy-02 ........................................................ 19 
4.2. 
Substudy-02-Specific Inclusion Criteria ................................................................................................. 19 
4.3. 
Substudy-02-Specific Exclusion Criteria ................................................................................................ 19 
5. 
STUDY INTERVENTIONS AND CONCOMITANT MEDICATIONS ........................................................... 20 
5.1. 
Enrollment and Treatment Code Access ................................................................................................. 20 
5.2. 
Description and Handling of GS-1720 and BVY .................................................................................... 20 
5.2.1. 
Fo1mulation ........................................................................................................................... 20 
5.2.2. 
Packaging and Labeling ........................................................................................................ 20 
5.2.3. 
Storage and Handling ............................................................................................................ 21 
5.2.4. 
Dosage and Ad1ninist1·ation ................................................................................................... 21 
5.3. 
Prior and Concoinitant Medications ........................................................................................................ 22 
5.4. 
Accountability for Study Drng Supplies: Study Drng and SOC ART Provided by the Sponsor 
(BVY) ...................................................................................................................................................... 22 
6. 
STUDY PROCEDURES ...................................................................................................................................... 23 
6.1. 
Instiuctions for Study Procedw·es ........................................................................................................... 23 
6.1.1. 
Phaimacokinetics ................................................................................................................... 23 
6.1.2. 
Subopti1nal Virologic Response ............................................................................................ 23 
6.1.3. 
Investigator Follow-up With Prima1y Health Care Provider ................................................ 24 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ................................................................................ 25 
7 .1. 
Toxicity Manage1nent .............................................................................................................................. 25 
7.1.1. 
Grade 1 and 2 Laborato1y Abnormalities or Clinical Events ................................................ 25 
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7.1.2. 
Grade 3 Laborato1y Abno1malities or Clinical Events .......................................................... 25 
7.1.3. 
Grade 4 Laborato1y Abno1malities or Clinical Events .......................................................... 25 
8. 
STATISTICAL CONSIDERATIONS ................................................................................................................. 27 
9. 
RESPONSIBILITIES ........................................................................................................................................... 28 
10. REFERENCES ..................................................................................................................................................... 29 
11. APPENDICES ...................................................................................................................................................... 30 
11.1. 
Pregnancy Precautions, Definition of Childbearing Potential, and Contraceptive Requirements .......... 30 
11.2. 
Management of Clinical and Laborat01y Adverse Events ...................................................................... 33 
11.3. 
Amendment Histo1y ................................................................................................................................ 34 
11.3.1. 
Amend1nent 2 (05 May 2023) ............................................................................................... 34 
11.3.2. 
Amend1nent 1 (02 March 2023) ............................................................................................ 34 
11.4. 
Investigator Signatw·e Page ..................................................................................................................... 35 
Table 1. 
Table 2. 
Table 3. 
Figure 1. 
Figure 2. 
CONFIDENTIAL 
LIST OF IN-TEXT TABLES 
Substudy-02 Study Procedw·es Table ........................................................................................ 9 
GS-US-615-6392: Prelimina1y PK Parameters of GS-1720 Following Single-Dose 
Administration of Oral GS-1720 (N = 8 Per Coho1t) in the Fasted Condition ....................... 13 
GS-1720 Dosage by Cohoit ..................................................................................................... 21 
LIST OF IN-TEXT FIGURES 
Overview of Visits, Dosing, and Key Assessments for Substudy-02 ....................................... 8 
GS-US-615-6392: Prelimina1y Mean (SD) GS-1720 Plasma Concentrntion-Time 
Profiles Following Single-Dose Administration of Oral GS-1720 (N = 8 Per Coho1t) 
in the Fasted Condition ............................................................................................................ 13 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ART
antiretroviral therapy
ARV
antiretroviral
AUC0-168h
area under the plasma drug concentration versus time curve from time zero to 168 hours 
postdose
%AUCexp
percentage of AUC extrapolated between AUClast and AUCinf
AUCinf
area under the plasma drug concentration versus time curve extrapolated to infinite time, 
calculated as AUClast + (Clast/z)
BVY
Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide; coformulated)
Cmax
maximum observed plasma drug concentration
EC95
95% effective concentration
ET
early termination
FIH
first in human
HIV
human immunodeficiency virus
HIV-1
human immunodeficiency virus type 1
IB
investigator’s brochure
INSTI
integrase strand-transfer inhibitor
IQ
inhibitory quotient
LA
long acting
paEC95
protein-adjusted 95% effective concentration
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PTM
placebo to match
PWH
people with HIV-1
RNA
ribonucleic acid
SAE
serious adverse event
SD
standard deviation
SOC
standard of care
SRT
safety review team
t1/2
terminal elimination half-life 
Tmax
observed time point of Cmax
US, USA
United States, United States of America

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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, Multi-Cohort Study to Evaluate Safety, 
Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1 
Substudy-02: GS-1720 
Regulatory Agency Identifier Numbers:
IND Number: 162030
EudraCT Number: Not Applicable
ClinicalTrials.gov Identifier: NCT05585307
Study Centers Planned
See master protocol synopsis for study centers planned.
Objectives and Endpoints:
See master protocol synopsis for objectives and endpoints.
Study Design: See master protocol synopsis for the overview of this substudy design.
Substudy-02 is an open-label, Phase 1b, single/multiple-dose, multicohort study to evaluate the 
safety, pharmacokinetics (PK), and antiviral activity of GS-1720 given as monotherapy in 
people with HIV-1 who are either treatment-naive or treatment-experienced but naive to the 
study drug class, and have not received any antiretroviral therapy (ART) within 12 weeks of 
screening, including medications received for preexposure prophylaxis or postexposure 
prophylaxis. Any current or prior receipt of long-acting parenteral antiretrovirals, such as 
monoclonal antibodies targeting HIV-1, injectable lenacapavir or 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. 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 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 follow-up visits on 
Days 25, 39, and 60. 
Following study completion, the participant’s care will transfer to a primary health care 
provider who will determine the participant’s HIV long-term treatment plan. For participants 

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who complete the study, 6 and 12 months (± 1 month) after enrollment the investigator 
(or delegate) will contact the participant’s primary health care provider to request and record 
all available plasma HIV-1 RNA and resistance testing results and, if applicable, changes in 
HIV treatment regimen with date of change. 
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 review of emerging data from Cohort 1.
The doses and dosing regimen for GS-1720 in each cohort will be selected based on a review 
of available PK, cumulative safety, and HIV-1 RNA data through the primary endpoint 
(Day 11) and/or relevant and available safety and PK data from the ongoing Phase 1a 
first-in-human study of GS-1720.
Number of Participants Planned: Up to 40 participants
Target Population: See master protocol synopsis for the target population.
Duration of Intervention: Approximately 60 days
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 
on dosing 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 institute 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 follow-up visits on Days 25, 39, and 60. For participants who complete 
the study, 6 and 12 months (± 1 month) after enrollment the investigator (or delegate) will 
contact the participant’s primary health care provider to request and record all available 
plasma HIV-1 RNA and resistance testing results and, if applicable, changes in HIV treatment 
regimen with date of change.
The detailed schedule of procedures for Substudy-02 is provided in Table 1.

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Test Product, Dose, and Mode of Administration: 
Single or multiple doses of GS-1720 will be administered starting on Day 1. The dose, dose 
regimen, and meal requirements for administration of GS-1720 in Cohort 1 are provided 
below. Subsequent cohort dosing, dosing regimen (ie, single or multiple doses), meal 
requirements (fasted, or with a low-fat or high-fat meal), and progression between cohorts will 
be adaptive. Doses in subsequent cohorts will not exceed the doses indicated below.
Single or multiple doses of GS-1720 will be administered orally by site staff, at approximately 
the same time each day, with or without regard to food (as appropriate). The GS-1720 dose 
used in any cohort will not be higher than those previously evaluated in the Phase 1a study 
GS-US-615-6392.
•
Cohort 1: Single dose of GS-1720 450 mg administered on both Day 1 and Day 2 in the 
fasted condition 
•
Cohort 2: Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
•
Cohort 3: Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
•
Cohort 4: Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
•
Cohort 5: Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
Reference Therapy, Dose, and Mode of Administration: Not applicable.
Statistical Methods: See master protocol for statistical methods.

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SUBSTUDY-02 STUDY SCHEMA
Figure 1.
Overview of Visits, Dosing, and Key Assessments for Substudy-02
ART = antiretroviral therapy; BVY = bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®); 
PK = pharmacokinetic; SOC = standard of care
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. 
b
Additional intensive PK visits may be required for cohorts with more than 1 day of dosing of GS-1720.
For Cohort 1, a single 450-mg dose of GS-1720 will be administered on both Day 1 and Day 2 in the fasted condition. The doses, 
dosing regimen (single or multiple doses), and meal requirements for GS-1720 in each subsequent cohort will be selected based 
on a review of available PK, cumulative safety, and HIV-1 RNA data through the primary endpoint (Day 11), and/or relevant and 
available safety and PK data from the ongoing Phase 1a first-in-human study of GS-1720 (Section 3.1.1). 
Day 
Treatment 
PK 
GS-1720 Treatment 
f f f f 
T f 
-28 
2 
3 
4 
7 
• 
* 
• 
Clinic visit 
• 
Initiate GS-1720 dosing (single or multiple doses) 
V Primary endpoint 
Initiate BVY (B/F/TAF) or SOC 
* Intensive PKb 
Single anytime plasma PK 
T 
I BVY or SOC ART Treatmenta > 
V 
f f 
T 
T 
T 
10 
11 
25 
39 
60 

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SUBSTUDY-02 STUDY PROCEDURES TABLE
Table 1.
Substudy-02 Study Procedures Table
Study Procedure
Screeninga
D1b
D2
D3b
D4
D7b
D8
D9
D10
D11b
D25b
D39b
D60b
ETc
Visit Window
± 2D
± 2D
± 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
X
X
Vital signse
X
X
X
X
X
X
X
X
X
X
HBV blood panel and HCV serologyf
X
CD4 cell countf
X
X
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
X
X
Hematologyf
X
X
X
X
X
X
X
X
X
Coagulation panelf
X
X
X
X
X
X
Chemistryf
X
X
X
X
X
X
X
X
X
Urinalysisf
X
X
X
X
X
X
X
X
X
Serum pregnancy testf,h
X
Urine pregnancy testf,h,i
X
X
X
X
Serum FSHf,j
X
12-Lead ECG
X
X
X
X
X
X
Intensive plasma PKk,l
X

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Single anytime plasma PKm
X
X
X
X
X
X
X
X
X
X
X
X
Review AEs and concomitant medicationsn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Initiate study drug (GS-1720) dosingo
X
BVY dispensation
X
BVY or SOC self-administration
Xp
Investigator (or delegate) follow-up with 
primary health care provider
For participants who complete the study, 6 and 12 months (± 1 month) after enrollment the investigator (or delegate) will 
contact the participant’s primary health care provider to request and record all available plasma HIV-1 RNA and resistance 
testing results and, if applicable, changes in HIV treatment regimen with date of change.
AE = adverse event; BVY = bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®); D = Day; ECG = electrocardiogram; eCRF = electronic case report form; 
ET = early termination; FSH = follicle-stimulating hormone; HBV = hepatitis B virus; HCV = hepatitis C virus; PK = pharmacokinetic(s); 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) 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 after Day 11 will be tested for the potential development of resistance against all components of the treatment regimen, 
including the evaluated compound. See Section 6.3.9.1.3 of the master protocol for management of virologic failure.
h
Participants assigned female at birth 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
Serum FSH test is required for participants assigned female at birth and < 54 years old, not on hormonal contraception, and who have stopped menstruating for ≥ 12 months 
but do not have documentation of hormonal ovarian failure.
k
Intensive PK samples should be collected at these time points for all cohorts: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose 
) on 
respective days of dosing. Additional intensive PK visits may be required for cohorts with more than 1 day of dosing of GS-1720.
l
For Cohort 1, intensive PK visits will be required for Day 1 and Day 2.
m
Single anytime PK sampling will occur relative to study drug dosing on Day 1. Single anytime PK sampling will not be done if drug dosing and intensive PK sampling are 
performed on the same day.
n
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.
o
For Cohort 1, a single 450-mg dose of GS-1720 will be administered on both Day 1 and Day 2 in the fasted condition (Section 5.2.4). Subsequent cohort dose, dosing regimen 
(ie, single or multiple dose), meal requirements (fasted or with a low-fat or high-fat meal), and progression between cohorts will be adaptive and determined as summarized in 
Section 3.1.1. 
p
BVY or SOC will be initiated on Day 11. Participants who discontinue study drug before Day 11 should start this regimen at the time of discontinuation (Section 6.4.1 of 
master protocol).
CCI
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1.
INTRODUCTION
Substudy-02, conducted under the GS-US-544-5905 master protocol, will evaluate the safety, 
pharmacokinetics (PK), and antiviral activity of GS-1720 given as monotherapy in people 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-02
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-1720 is provided below in Section 1.2.1.
1.2.
Background on Study Interventions Used in Substudy-02
1.2.1.
GS-1720
1.2.1.1.
General Information
Integrase strand-transfer inhibitors play an ever-growing role in HIV-1 treatment, and are a key 
component of combination ARV therapies. Currently, there are 5 INSTIs approved for the 
treatment of HIV infection. As a class, INSTIs exhibit strong antiviral activity and excellent 
clinical tolerability. Notably, all approved oral INSTIs require once or twice daily dosing. 
Therefore, developing novel INSTIs with optimal oral LA PK that can be combined with other 
LA oral ARVs would fulfill an unmet medical need; ie, the availability of regimens that can be 
administered less frequently. GS-1720 is a novel potent and selective LA INSTI, engineered to 
have a long t1/2 (projected to be approximately 240 hours), with a favorable nonclinical 
pharmacology profile that supports clinical development as a once weekly, oral ARV agent for 
the treatment of HIV infection.
For further information, refer to the current investigator’s brochure (IB), including the following:
1. Nonclinical PK
2. Nonclinical pharmacodynamics (PD)
3. Nonclinical toxicology
1.2.1.2.
Nonclinical Pharmacology and Toxicology
Nonclinical pharmacology and toxicology studies are provided in the IB.

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1.2.1.3.
Clinical Studies of GS-1720
1.2.1.3.1.
GS-US-615-6392
Study GS-US-615-6392 is an ongoing, first-in-human (FIH), Phase 1a study in healthy 
participants to evaluate the safety, tolerability, and PK of single and multiple ascending oral 
doses of GS-1720 up to 1350 mg. The study is planned to include up to 9 cohorts, each 
comprising at least 9 participants. Currently, participants have been enrolled in single ascending 
dose Cohorts 1 to 3 (n = 10/cohort) and received GS-1720 50-, 150-, and 450-mg doses 
(with Cohort 4 scheduled to receive GS-1720 1350 mg by 01 March 2023) (or placebo to match 
[PTM]), respectively, and multiple ascending dose Cohorts 5 and 6 (n = 9/cohort) and received, 
or are receiving, GS-1720 150- and 450-mg doses (or PTM), respectively, once weekly for 
6 doses. 
Preliminary PK Summary
Preliminary GS-1720 plasma concentration-time profiles and preliminary PK parameters after 
administration of single oral doses of 50 mg (Cohort 1), 150 mg (Cohort 2), and 450 mg 
(Cohort 3) GS-1720 in the fasted condition are presented in Figure 2 and Table 2, based on PK 
data available on 03 February 2023.
Median time to Tmax of GS-1720 occurred between 3.5 and 4.0 hours. A 9-fold increase in dose 
(from 50 to 150 to 450 mg) resulted in a 3.5-fold higher Cmax and 3.6-fold higher AUC0-168h. Less 
than dose-proportional increases observed in Cmax and AUC0-168h suggest that GS-1720 exhibits 
nonlinearity in dose-exposure relationship due to solubility-limited absorption.

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Figure 2.
GS-US-615-6392: Preliminary Mean (SD) GS-1720 Plasma 
Concentration-Time Profiles Following Single-Dose Administration of 
Oral GS-1720 (N = 8 Per Cohort) in the Fasted Condition
IQ1, IQ5 = inhibitory quotient 1- or 5-fold higher than the protein-adjusted 95% effective concentration against wild-type HIV-1 
virus (paEC95: 1938 ng/mL)
Table 2.
GS-US-615-6392: Preliminary PK Parameters of GS-1720 Following 
Single-Dose Administration of Oral GS-1720 (N = 8 Per Cohort) in the 
Fasted Condition
Parameter
Cohort 1
(50 mg, Fasted)
Cohort 2
(150 mg, Fasted)
Cohort 3
(450 mg, Fasted)
Cmax (ng/mL)
4300 (28.3)
6860 (28.1)
15,000 (21.5)
Tmax (h)
3.50 (2.25, 5.50)
4.00 (2.25, 5.50)
4.00 (3.00, 4.00)
AUC0-168h (h•ng/mL)
370,000 (35.5)
636,000 (33.0)
1,340,000 (22.2)
AUCinf (h•ng/mL)
944,000 (46.1)
1,680,000 (41.1)
3,490,000 (29.4)
%AUCexp
0.74 (24.5)
8.17 (70.4)
40.3 (14.2)
t1/2 (h) [days]
227 (206, 239) [9.47]
225 (206, 271) [9.37]
235 (218, 248) [9.77]
%CV = percentage coefficient of variation; PK = pharmacokinetics; Q1 = first quartile; Q3 = third quartile.
PK parameters presented to 3 significant figures as mean (%CV), except for Tmax, and t1/2, which are presented as median 
(Q1, Q3) hours, with [median days] for t1/2. Note: Preliminary analysis was conducted using nominal time points.
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• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • IQ5 (9690 ng/mL) 
240 
480 
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960 
1200 
1440 
1680 
Time (hr) 

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Safety Summary
In a preliminary blinded review of available safety data for 39 participants, as of 
14 February 2023, no deaths, serious adverse events (SAEs), Grade 3 or higher adverse events 
(AEs), or discontinuations due to AEs were reported. Study drug (GS-1720 or PTM)-related AEs 
were reported for 3 participants; headache and vertigo were reported for 1 participant each in 
Cohort 3 (GS-1720 450 mg or PTM, single dose), and decreased appetite and paresthesia of the 
right foot were reported for 1 participant in Cohort 5 (GS-1720 150 mg or PTM, once weekly 
dose). None of these study drug-related AEs was serious.
There were no clinically relevant changes from predose in values for hematology, clinical 
chemistry, urinalysis, or coagulation parameters in this preliminary review. Three participants, 
all in Cohort 2 (GS-1720 150 mg or PTM, single dose), had Grade 3 laboratory abnormalities; 
1 participant had glycosuria and a decrease in creatinine clearance, 1 participant had increased 
direct bilirubin (with no other signs or symptoms of hepatotoxicity), and 1 participant had an 
increase in creatine kinase. None of these Grade 3 laboratory abnormalities was 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).
1.3.
Rationale for Dose Selection of Study Drug
Selection of GS-1720 doses for this study takes into consideration the available safety, 
tolerability, and PK data for GS-1720 from the ongoing FIH study with oral single and multiple 
ascending doses in healthy volunteers (Study GS-US-615-6392), as well as emerging preliminary 
safety and antiviral data in this substudy.
As of 14 February 2023, 30 participants (24 active and 6 placebo) had received a single oral dose 
of GS-1720 (50 to 450 mg) or PTM, and 9 participants (6 active and 3 placebo) had received 
multiple oral doses of GS-1720 (150 mg) or PTM. In a preliminary blinded review of available 
safety data from 39 participants, as of 14 February 2023, GS-1720 was generally well tolerated. 
No deaths, SAEs, Grade 3 or higher AEs, or discontinuations due to AEs were reported. Three 
participants had Grade 3 laboratory abnormalities, none of which was considered clinically 
relevant. No Grade 4 laboratory abnormalities were reported.
As of 17 February 2023, available preliminary PK data from Study GS-US-615-6392 showed 
less than dose-proportional PK of GS-1720 following single doses of 50, 150, and 450 mg 
(Figure 2 and Table 2). Based on modeling and simulation, a 450-mg dose of GS-1720 given on 
both Day 1 and Day 2 is expected to result in a GS-1720 plasma concentration at Day 11 
(ie, 240 h from the first dose) that is approximately 5-fold the inhibitory quotient (IQ), defined as 
the in vitro-derived protein-adjusted 95% effective concentration against the wild-type HIV-1 
virus (paEC95: 1938 ng/mL), and is selected for evaluation in Cohort 1 of this substudy. GS-1720 
exposures projected for Cohort 1 (450 mg on Day 1 and 450 mg on Day 2, taken approximately 
24 h apart) are expected to be well covered by exposures in multiple ascending dose Cohort 6 in 
the FIH study. Preliminary clinical safety and PK data from Cohort 6, in which participants are 

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given a 450-mg dose of GS-1720 once weekly for 6 weeks (initial dosing completed on 
23 February 2023), will be reviewed by the safety review team [SRT]. Higher and/or lower doses 
will be evaluated in subsequent cohorts to target a range of IQ values that characterize the 
PK-PD relationship between GS-1720 PK and changes from baseline in HIV-1 viral load. Doses 
in Cohorts 2 to 5 will be determined by the SRT based on cumulative safety, PK, and virologic 
data from Cohort 1, as well as safety and available PK data from the FIH study (Study 
GS-US-615-6392). Doses selected for Cohorts 2 to 5 will be adaptive and have projected 
exposures within the range of observed exposures in the FIH study.
1.4.
Benefit-Risk Assessment for the Study
Potential risks to participants may include prolonged exposure (several weeks) to subtherapeutic 
concentrations of study drug. This could lead to the development of resistance to the study drug 
and, potentially, the study drug class, which could limit future treatment options. Strategies to 
mitigate this risk, and additional benefit-risk assessments applicable to Substudy-02 and 
GS-1720, 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.

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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-02 is an open-label, Phase 1b, single/multiple-dose, multicohort study to evaluate the 
safety, PK, and antiviral activity of GS-1720 given as monotherapy in PWH who are either 
treatment-naive or treatment-experienced but naive to the study drug class and have not received 
any ART within 12 weeks of screening, including medications received for preexposure 
prophylaxis or postexposure prophylaxis. Any current or prior receipt of LA parenteral ARVs, 
such as monoclonal antibodies targeting HIV-1, injectable lenacapavir or 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). 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 follow-up visits on Days 25, 39, and 60. 
Overnight fasting (≥ 6 hours) is required for laboratory analyses prior to visits on Days 1, 3, 7, 
11, 25, 39, and 60.
Following study completion, the participant’s care will transfer to a primary health care provider 
who will determine the participant’s HIV long-term treatment plan. For participants who 
complete the study, 6 and 12 months (± 1 month) after enrollment the investigator (or delegate) 
will contact the participant’s primary health care provider to request and record all available 
plasma HIV-1 RNA and resistance testing results and, if applicable, changes in HIV treatment 
regimen with date of change.
The selection of doses and dosing regimens for GS-1720 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, as described in Section 3.1.1.
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).

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3.1.1.
Dose Selection/Modification
Enrollment and dosing with GS-1720 will begin with Cohort 1. The dose and regimen of 
GS-1720 for Cohort 1 is defined in Section 5.2.4.
A summary of 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 Substudy-02 for 60 days.
Participants will receive single or multiple doses of GS-1720, starting on Day 1. Participants will 
then initiate a BVY or alternative SOC regimen following study assessments on Day 11 for the 
remainder of the study. Participants will be required to return to the clinic for follow-up visits on 
Days 25, 39, and 60.
3.3.
Substudy-02 Specific Discontinuation Criteria
Criteria for early discontinuation from the substudy for individual participants are described in 
Section 3.3.1 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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4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection for Substudy-02
In Substudy-02, 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-02-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: 
S02-1. Willing to initiate an SOC ART regimen on Day 11 or upon ET as stated in Section 4.2 in 
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.
S02-2. Willing and able to comply with meal requirements on dosing days.
4.3.
Substudy-02-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:
S02-1. Requirement for ongoing therapy with any prohibited medication listed in Section 5.3.

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5.
STUDY INTERVENTIONS AND CONCOMITANT 
MEDICATIONS
5.1.
Enrollment and Treatment Code Access
Participant enrollment procedures are described in Section 5.1 of the master protocol.
5.2.
Description and Handling of GS-1720 and BVY 
BVY will be provided by the sponsor for use during the study, as applicable.
5.2.1.
Formulation
GS-1720 tablets are available in strengths of 10, 50, and 250 mg. GS-1720 10- and 50-mg tablets 
are round, plain-faced, film-coated, beige tablets. GS-1720 250-mg tablets are capsule-shaped, 
plain-faced, film-coated, beige tablets. In addition to the active ingredient, GS-1720 tablets also 
contain lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl 
cellulose, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, 
iron oxide red, iron oxide yellow, and ferrosoferric oxide.
BVY tablets (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) are 
capsule-shaped, film-coated, purplish-brown, debossed 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 of bictegravir sodium), 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide 
(equivalent to 28 mg of tenofovir alafenamide fumarate). In addition to the active ingredients, the 
BVY tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. 
The tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, 
polyvinyl alcohol, talc, and titanium dioxide. Additional details are provided in local prescribing 
information for BVY product.
5.2.2.
Packaging and Labeling
GS-1720 tablets are packaged in white, high-density polyethylene bottles containing silica gel 
desiccant and polyester packing material. Each bottle is sealed with a white, continuous-thread, 
child-resistant, polypropylene screw cap with an induction-sealed, aluminum-faced liner.
BVY tablets are packaged in white, high-density polyethylene bottles. Each bottle contains 
30 tablets, silica gel desiccant, and polyester packing material. Each bottle is enclosed with a 
white, continuous-thread, child-resistant polypropylene screw cap with an induction-sealed and 
aluminum-faced liner.
Study drug to be distributed to centers in the United States (US) and other participating countries 
will be labeled to meet applicable requirements of the US Food and Drug Administration and/or 
other local regulations as applicable.

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5.2.3.
Storage and Handling
GS-1720 tablets should be stored below 30 °C. BVY should be stored according to the storage 
conditions specified on the label. 
GS-1720 and BVY should be stored in a securely locked area, accessible only to authorized site 
personnel. To ensure the stability of GS-1720 and BVY and proper identification, the drug 
products should not be stored in a container other than that in which they are supplied. 
5.2.4.
Dosage and Administration 
Single or multiple doses of GS-1720 will be administered starting on Day 1. The dose, dosing 
regimen, and meal requirements for administration of GS-1720 in Cohort 1 are provided in 
Table 3. Subsequent cohort doses, dosing regimens (ie, single or multiple doses), meal 
requirements (fasted, or with a low-fat or high-fat meal), and progression between cohorts will 
be adaptive, as described in Section 3.1.1. Doses in subsequent cohorts will not exceed those 
indicated in Table 3.
Single or multiple doses of GS-1720 will be administered orally by site staff, at approximately 
the same time each day (in the case of multiple dose regimens), with or without regard to food 
(as appropriate). The GS-1720 dose used in any cohort will not be higher than those previously 
evaluated in the Phase 1a Study GS-US-615-6392.
A low-fat/moderate calorie breakfast (400-500 calories; 100-125 calories from fat) or a 
high-fat/high-calorie breakfast (800-1000 calories; 500-600 calories from fat) may be initiated 
30 minutes prior to study drug administration. Participants may be administered GS-1720 at or 
within 5 minutes of participants consuming the meal.
Table 3.
GS-1720 Dosage by Cohort
Cohort
Treatment
Cohort 1
A single dose of GS-1720 450 mg will be administered on both Day 1 and Day 2 
in the fasted condition
Cohort 2
Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
Cohort 3
Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
Cohort 4
Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
Cohort 5
Single or multiple doses of GS-1720 up to 1350 mg administered in the fasted 
condition or with food (low-fat or high-fat meal)
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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5.3.
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 11 through the end of the study.
From Day 11 through the last visit, the investigator should follow local prescribing information 
for BVY or other ART taken as SOC by an individual participant. 
5.4.
Accountability for Study Drug Supplies: Study Drug and SOC ART 
Provided by the Sponsor (BVY)
Guidance related to accountability, return, and disposal for study drug supplies (study drug 
[GS-1720 for this substudy] and SOC ART provided by the sponsor [BVY for this substudy]) is 
provided in Section 5.4 of the master protocol.

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STUDY PROCEDURES 
Final 
Amendment2 
Study procedures applicable to all studies are listed in Section 6 of the master protocol. Study 
procedures specific to Substudy-02 are listed in the sections below. The time points for study 
procedures are specified in Table 1. A substudy-specific infonned consent fo1m will be required 
for Substudy-02. 
6.1. 
6.1.1. 
Instructions for Study Procedures 
Pharmacokinetics 
Blood samples will be collected to detennine GS-1720 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.
Investigator Follow-up With Primary Health Care Provider 
For participants who complete the study, 6 and 12 months (± 1 month) after enrollment the 
investigator (or delegate) will contact the participant’s primary health care provider to request 
and record all available plasma HIV-1 RNA and resistance testing results and, if applicable, 
changes in HIV treatment regimen with date of change. At each time point, the investigator 
(or delegate) should make and document at least 3 attempts of contact over a period of 4 weeks.
These data are derived from secondary use data (previously collected for other purposes), 
therefore collection and submission of AEs are not required. 

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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-1720 is described below, and included in Appendix 11.2. 
Pregnancy precautions, definition of female of childbearing potential, and contraceptive 
requirements specific to GS-1720 are included in Appendix 11.1.
7.1.
Toxicity Management 
All clinically significant laboratory toxicities will be managed according to uniform guidelines 
detailed in Appendix 11.2 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 multiple-dose 
cohorts for a clinically insignificant Grade 3 or 4 laboratory abnormality (eg, creatine kinase 
elevation after strenuous exercise, or 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 clinical events, if considered unrelated to study drug, may not require dose 
interruption; continuation of study drug for multiple-dose cohorts is at the discretion of the 
investigator.
7.1.1.
Grade 1 and 2 Laboratory Abnormalities or Clinical Events
•
Continue study drug at the discretion of the investigator for multiple-dose cohorts, as 
applicable.
7.1.2.
Grade 3 Laboratory Abnormalities or Clinical Events
•
For a Grade 3 clinically significant laboratory abnormality confirmed by repeat testing that is 
considered related to study drug, the study drug should be withheld in multiple-dose cohorts 
and the medical monitor consulted.
7.1.3.
Grade 4 Laboratory Abnormalities or Clinical Events
•
For a Grade 4 clinical event or clinically significant laboratory abnormality confirmed by 
repeat testing considered related to study drug, the study drug should be permanently 
discontinued in multiple-dose cohorts 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.

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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
11.1.
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 female participant 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-1720 is contraindicated in pregnancy as any malformative effect is unknown. There is no 
suspicion of human teratogenicity based on class effects or genotoxic potential. GS-1720 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 investigator’s brochure (IB) for additional information.
b.
Contraception Requirements for Participants Assigned Female at Birth of 
Childbearing Potential
The inclusion of participants assigned female at birth 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 female participants 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 one 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.
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.

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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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11.2.
Management of Clinical and Laboratory Adverse Events
Grade 1 
___ 
G_r_a_d_e_2 __ _.I I 
Grade 3 
I I 
Grade 4 
r 
Continue study 
drug dosing at 
the discretion of 
the inve~tigator 
l 
Repeat lab to confirm 
toxicity grade 
l 
If confirmed, and possibly or probably rel<1ted to study 
drug(s), discontinue study(s) dosing permanently, and 
manage subject according to local practice. Subject 
should be followed as clinically indicated until the 
laboratory abnormality returns to baseline, or is 
otherwise explained 

GS-1720
Protocol GS-US-544-5905 Substudy-02
Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
Page 34
05 May 2023
11.3.
Amendment History
High-level summaries of the history of this study’s amendments are provided in tabular form in 
the subsections below (from most recent amendment to oldest), 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 protocol amendment 1 to this 
amendment will be made available upon the publication of this protocol.
11.3.1.
Amendment 2 (05 May 2023)
Rationale for Key Changes Included in Amendment 2
Affected Sections
Per Food and Drug Administration (FDA) request, additional language included 
noting following study completion, the participant’s care will transfer to a primary 
health care provider who will determine the participant’s HIV long-term treatment 
plan. For those participants who complete the study, 6 and 12 months after 
enrollment the investigator (or delegate) will contact the participant’s primary 
health care provider to request and record all available plasma HIV-1 RNA and 
resistance testing results and, if applicable, changes in HIV regimen with date of 
change. 
Synopsis, Table 1, 
Sections 3.1 and 6.1.3
Minor changes included to correct typographic errors.
Throughout, as required
11.3.2.
Amendment 1 (02 March 2023)
Rationale for Key Changes Included in Amendment 1
Affected Sections
References to the United States prescribing information for Biktarvy® 
(bictegravir/emtricitabine/tenofovir alafenamide; BVY) removed as sites outside 
of the United States will be involved; replaced with reference to local prescribing 
information. Added details on BVY formulations, packaging, labeling, storage 
conditions, and administration.
Sections 5.2, 5.2.1, 5.2.2, 
5.2.3, 5.2.4, and 5.3 

GS-1720
Protocol GS-US-544-5905 Substudy-02
Final
Gilead Sciences, Inc. 
Amendment 2
CONFIDENTIAL
Page 35
05 May 2023
11.4.
Investigator Signature Page
GILEAD SCIENCES, INC.
333 LAKESIDE DRIVE
FOSTER CITY, CA 94404
USA
STUDY ACKNOWLEDGMENT
An Umbrella Phase 1b, Open-label, Multi-Cohort Study to Evaluate Safety, Pharmacokinetics, 
and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1 Substudy-02: 
GS-1720
Amendment 2, 05 May 2023
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval.
Name (Printed)
Signature
Director, Clinical Development
Date
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
PPD

Prot GS-US-544-5905-02 amd-2
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Development
eSigned
05-May-2023
15:21:22
PPD