Clinical trial NCT03739866
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences
Start date: 2018-11-26; Completion date: 2020-06-15
Enrollment: 53 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objectives of this study are:

Part A: To evaluate the short-term antiviral activity of lenacapavir (formerly GS-6207) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 compared to placebo in HIV-1 infected adults who are antiretroviral treatment naive or are experienced but capsid inhibitor (CAI) naive.

Part B: To evaluate the short-term antiviral activity of tenofovir alafenamide (TAF) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 in HIV-1 infected adult subjects who are antiretroviral treatment naïve or are experienced but without resistance to TAF.

Detailed description:

Arms: arm 1: Participants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225. arm 2: Participants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225. arm 3: Participants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225. arm 4: Participants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225. arm 5: Participants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225. arm 6: Participants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225. arm 7: Participants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225. arm 8: Participants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.
Interventions: intervention 1: Lenacapavir intervention 2: Placebo intervention 3: B/F/TAF intervention 4: TAF
Intervention descriptions: intervention 1: Administered subcutaneously in the abdomen intervention 2: Administered subcutaneously in the abdomen intervention 3: 50/200/25 mg tablets administered orally once daily intervention 4: Tablets administered orally

Protocol documents:
Prot_000.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov Identifier: 
Indication: 
Protocol ID: 
(rJ GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase lb Randomized, Double-Blinded, Placebo Controlled, 
Multi-Coho1t Study of the Safety, Phannacokinetics, and Antiviral Activity 
ofGS-6207 administered subcutaneously in HIV-1 Infected Subjects 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
136260 
Not Applicable 
NCT03739866 
HIV-1 Infection 
GS-US-200-4072 
Gilead Clinical Program Manager: 
Name: 
PPD 
PPU 
PPD 
Telephone: 
Fax: 
Gilead Medical Monitor: 
Name: 
Telephone: 
Fax: 
Cell: 
Gilead Clinical Study Director: 
Name: 
Telephone: 
Fax: 
Cell: 
Protocol Version/Date: 
Original: 
Amendment I: 
Amendment 2: 
Amendment 3: 
Amendment 4: 
PPD 
PPD 
PPD 
PPD 
PPD 
Pl'U 
PPD 
PPD 
14 September20l8 
20 December 2018 
13 March 2019 
21 May20l9 
13 June 2019 
CONFIDENTIALITY STATEMENT 
The info1mation contained in this document, paiiicularly unpublished data, is the prope1iy 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 infonnation is only to be used by you in 
connection with authorized clinical studies of the investigational diug described in the protocol. 
You will not disclose any of the infonnation to others without written authorization from 
Gilead Sciences, Inc., except to the extent necessaiy to obtain infonned consent from those 
persons to whom the dmg may be adininistered. 


GS-6207 and TAF 
Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
Final 
Amendment4 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ 4 
LIST OF IN-TEXT FIGURES ...................................................................................................................................... 5 
PROTOCOL SYNOPSIS .............................................................................................................................................. 6 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 13 
1. 
INTRODUCTION .............................................................................................................................................. 16 
1.1. 
Backgrowid ............................................................................................................................................ 16 
1.2. 
GS-6207 ................................................................................................................................................. 16 
1. 2 .1. 
General Infonnation ............................................................................................................. 16 
1.2.2. 
Additional Clinical Studies .................................................................................................. 17 
1.3. 
Tenofovir alafenamide (TAF) ................................................................................................................ 22 
1.3 .1. 
General Infonnation ............................................................................................................. 22 
1.4. 
Rationale for this Study .......................................................................................................................... 23 
1.4.1. 
Rationale for the development of GS-6207 .......................................................................... 23 
1.4.2. 
Rationale for the development of weekly oral TAF ............................................................. 24 
1.5. 
Rationale for the Dose Selection ............................................................................................................ 24 
1.5.1. 
GS-6207 ............................................................................................................................... 24 
1.5.2. 
TAF ...................................................................................................................................... 25 
1.6. 
Risk/Benefit Assessment for the Study .................................................................................................. 26 
1.7. 
Compliance ............................................................................................................................................ 26 
2. 
OBJECTIVES ..................................................................................................................................................... 27 
3. 
STUDY DESIGN ................................................................................................................................................ 28 
3.1. 
3.2. 
3.3. 
3.4. 
Endpoints ............................................................................................................................................... 28 
Study Design .......................................................................................................................................... 28 
Study Treatments ................................................................................................................................... 28 
Duration of Treatment ............................................................................................................................ 30 
4. 
SUBJECT POPULATION .................................................................................................................................. 31 
4.1. 
Number of Subjects and Subject Selection ............................................................................................ 31 
4.2. 
Inclusion Criteria (Paits A and B) .......................................................................................................... 31 
4.3. 
Exclusion Criteria (Parts A and B) ......................................................................................................... 33 
5. 
INVESTIGATIONAL MEDICINAL PRODUCT AND B/F/TAF ..................................................................... 34 
5.1. 
Randomization, Blinding and Treatment Codes .................................................................................... 34 
5.1.1. 
Procedures for Breaking Treatment Codes (Pait A) ............................................................. 34 
5.2. 
Description and Handling GS-6207, TAF and B/F/TAF ....................................................................... 35 
5.2.1. 
Foimulation .......................................................................................................................... 35 
5.2.2. 
Packaging and Labeling ....................................................................................................... 36 
5.2.3. 
Storage and Handling ........................................................................................................... 36 
5.3. 
Dosage and Administrntion of GS-6207 (Pait A, Cohoit s 1 - 5) ............................................................ 37 
5.4. 
Dosage and Administrntion ofTAF (Part B, Cohorts 6 - 8) ................................................................... 38 
5.5. 
Prior and Concomitant Medications ....................................................................................................... 38 
5.6. 
Dispensing, Accowitability, and Disposal or Return of GS-6207 and TAF (study dtugs) and 
B/F/TAF ................................................................................................................................................. 40 
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6.
STUDY PROCEDURES ....................................................................................................................................41
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................41
6.2.
Pretreatment Assessments......................................................................................................................41
6.2.1.
Screening Visit .....................................................................................................................41
6.3.
Treatment Assessments..........................................................................................................................42
6.3.1.
Day 1 ....................................................................................................................................42
6.3.2.
Assessments on Days 2, 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 
197 and 225..........................................................................................................................43
6.4.
Early Study Discontinuation Assessments.............................................................................................43
6.5.
Criteria for Discontinuation of Study.....................................................................................................44
6.6.
Clinical Laboratory Assessments ...........................................................................................................44
6.6.1.
Blood Samples......................................................................................................................45
6.6.2.
Urine Samples ......................................................................................................................47
6.7.
Management of Virologic Failure after Initiation of B/F/TAF on Day 10.............................................47
6.7.1.
Suboptimal Virologic Response (SVR)................................................................................47
6.7.2.
Virologic Rebound (VR)......................................................................................................48
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................49
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................49
7.1.1.
Adverse Events.....................................................................................................................49
7.1.2.
Serious Adverse Events........................................................................................................49
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................50
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................50
7.2.2.
Assessment of Severity ........................................................................................................51
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................51
7.4.
Gilead Reporting Requirements.............................................................................................................53
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments..................................................53
7.6.
Toxicity Management ............................................................................................................................54
7.7.
Special Situations Reports......................................................................................................................54
7.7.1.
Definitions of Special Situations..........................................................................................54
7.7.2.
Instructions for Reporting Special Situations.......................................................................55
8.
STATISTICAL CONSIDERATIONS................................................................................................................57
8.1.
Analysis Objectives and Endpoints........................................................................................................57
8.1.1.
Analysis Objectives..............................................................................................................57
8.1.2.
Primary Endpoint .................................................................................................................57
8.1.3.
Secondary Endpoint .............................................................................................................58
8.1.4.
Other Endpoints of Interest ..................................................................................................58
8.2.
Analysis Conventions.............................................................................................................................58
8.2.1.
Analysis Sets ........................................................................................................................58
8.3.
Data Handling Conventions ...................................................................................................................59
8.4.
Demographic Data and Baseline Characteristics ...................................................................................59
8.5.
Efficacy Analysis ...................................................................................................................................59
8.5.1.
Primary Analysis..................................................................................................................59
8.5.2.
Secondary Analyses .............................................................................................................60
8.6.
Safety Analysis.......................................................................................................................................60
8.6.1.
Duration of Exposure ...........................................................................................................60
8.6.2.
Adverse Events.....................................................................................................................60
8.6.3.
Laboratory Evaluations ........................................................................................................60
8.6.4.
Other Safety Evaluations......................................................................................................61
CCI
CCI-
-


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8.7.
Pharmacokinetic Analysis......................................................................................................................61
8.8.
Sample Size............................................................................................................................................61
8.9.
Analysis Schedule ..................................................................................................................................62
9.
RESPONSIBILITIES..........................................................................................................................................63
9.1.
Investigator Responsibilities ..................................................................................................................63
9.1.1.
Good Clinical Practice..........................................................................................................63
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................63
9.1.3.
Informed Consent.................................................................................................................63
9.1.4.
Confidentiality......................................................................................................................64
9.1.5.
Study Files and Retention of Records ..................................................................................64
9.1.6.
Case Report Forms...............................................................................................................65
9.1.7.
GS-6207 and TAF (Investigational Medicinal Product or Study Drug) and 
B/F/TAF Accountability and Return....................................................................................66
9.1.8.
Inspections............................................................................................................................66
9.1.9.
Protocol Compliance............................................................................................................66
9.2.
Sponsor Responsibilities ........................................................................................................................66
9.2.1.
Protocol Modifications.........................................................................................................66
9.2.2.
Study Report and Publications .............................................................................................67
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................67
9.3.1.
Payment Reporting...............................................................................................................67
9.3.2.
Access to Information for Monitoring..................................................................................67
9.3.3.
Access to Information for Auditing or Inspections ..............................................................68
9.3.4.
Study Discontinuation..........................................................................................................68
10.
REFERENCES ...................................................................................................................................................69
11.
APPENDICES ....................................................................................................................................................70
Appendix 1.
Investigator Signature Page....................................................................................................71
Appendix 2.
Study Procedures Table..........................................................................................................72
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................75
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities...............76
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) .............................98
Appendix 6.
GS-6207 Pregnancy Precautions (Part A), Definition for Female of Childbearing 
Potential, and Contraceptive Requirements............................................................................99
Appendix 7.
TAF Pregnancy Precautions (Part B), Definition for Female of Childbearing 
Potential, and Contraceptive Requirements..........................................................................101
LIST OF IN-TEXT TABLES
Table 1-1.
Study GS-US-200-4070 Preliminary Plasma Pharmacokinetic Parameters of 
GS-6207 Following Single Dose Administration of Subcutaneous Suspension of 
GS-6207, 30-450 mg ..............................................................................................................18
Table 1-2.
Study GS-US-200-4071 Preliminary Plasma Pharmacokinetic Parameters of 
GS-6207 Following Single and Multiple Dose Oral Administration of 30 mg 
(50 mg/mL) and 100 mg (50 mg/mL).....................................................................................19
Table 1-3.
Study GS-US-200-4071 Preliminary Plasma Pharmacokinetic Parameters of 
GS-6207 Following Single Dose Oral Administration in Cohorts 3 (300 mg, 
10 mg/mL) and 4 (7 mg, 100 mg/mL)....................................................................................20
Table 5-1.
List of medications that are prohibited due to the potential for drug-drug interaction 
with TAF ................................................................................................................................39


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LIST OF IN-TEXT FIGURES
Figure 1-1.
Preliminary Mean (SD) GS-6207 Plasma Concentration-Time Profiles Following 
Single-Dose Administration of Subcutaneous Suspension of GS-6207 30 mg, 
100 mg, 300 mg and 450mg (N=8 per cohort).......................................................................18
Figure 1-2.
Preliminary Mean (SD) GS-6207 Plasma Concentration-Time Profiles Following 
Single-Dose Administration of Oral GS-6207 at 30, 100, 300 and 75 mg 
(N=8/cohort)...........................................................................................................................20
Figure 1-3.
Preliminary Mean (SD) GS-6207 Plasma Concentration-Time Profiles Following 
Single-Dose Administration of Subcutaneous Solutions of GS-6207 at 300 mg 
(N=8/cohort); 300 mg/mL Free Acid and 300 mg/mL Na Salt ..............................................21


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 1b Randomized, Double-Blinded, Placebo Controlled, 
Multi-Cohort Study of the Safety, Pharmacokinetics, and Antiviral 
Activity of GS-6207 administered subcutaneously in HIV-1 Infected 
Subjects
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
136260
Not Applicable
NCT03739866
Study Centers 
Planned:
Approximately 15 centers in United States.
Objectives:
Part A (Cohorts 1 – 5)
The primary objective of this study is as follows:

To evaluate the short-term antiviral activity of GS-6207 compared 
to placebo GS-6207, with respect to the maximum reduction of 
plasma HIV-1 RNA (log10 copies/mL) from Day 1 through 
Day 10 in HIV-1 infected adult subjects who are antiretroviral 
treatment naïve or are experienced but capsid inhibitor (CAI) 
naïve.
The secondary objectives of this study are as follows: 

To investigate the safety and tolerability of GS-6207 as compared 
to placebo GS-6207 in HIV-1 infected subjects.

To characterize the plasma pharmacokinetics (PK) of GS-6207 in 
HIV-1 infected subjects.

To characterize the PK/pharmacodynamics relationship between 
GS-6207 concentration and the viral dynamics of HIV-1.

To determine the number and percentage of subjects ever 
achieving HIV-1 RNA < 50 copies/mL by Day 10 at each dose 
level.

To examine any emergence of capsid inhibitor (CAI) resistance.


GS-6207 and TAF 
Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
Study Design: 
Number of 
Paiiicipants 
Planned: 
Target Population: 
Duration of 
Treatment: 
Part B (Cohorts 6 - 8) 
The primaiy objective of this study is as follows: 
Final 
Amendment4 
• 
To evaluate the sho1i-te1m antiviral activity of TAF with respect 
to the maximum reduction of plasma HIV-1 RNA 
(log10 copies/mL) from Day 1 through Day 10 in HIV-1 infected 
adult subjects who ai·e antiretroviral treatment nai:ve or ai·e 
experienced but without resistance to T AF. 
The seconda1y objectives of this study are as follows: 
• 
To investigate the safety and tolerability of T AF in HIV-1 
infected subjects. 
• 
To characterize the phaimacokinetics (PK) ofTAF and its 
metabolites in HIV-1 infected subjects. 
• 
To examine any emergence of TAF resistance. 
Randomized, double-blinded, placebo-controlled, multi-coho1i study 
of GS-6207 (Paii A) and single aim study of TAF (Paii B) 
monotherapy in subjects with HIV-1 infection. 
Approximately 64 
HIV-1 infected subjects who are antiretroviral treatment nai:ve or 
experienced but integrase strand transfer inhibitor (INST!) nai:ve and 
CAI nai:ve (Paii A only), have not received any antiretroviral therapy 
(ART) within 12 weeks of screening, and have genotypic sensitivity 
to B/F/TAF (single tablet regimen of 
bictegravir/emtricitabine/tenofovir alafenamide) 
Single dose (Day 1) 
Diagnosis and Main 
Subjects with chronic HIV-1 infection and meet the following 
Eligibility Criteria: 
criteria: 
CONFIDENTIAL 
• 
Plasma HIV-1 RNA :::: 5,000 copies/mL but :S 400,000 copies/mL 
and CD4+ cell count > 200 cells/mm3 
• 
Treatment nai:ve or experienced but integrase strand transfer 
inhibitor (INST!) nai:ve and CAI naive (Part A only), and have not 
received any ART within 12 weeks of screening 
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GS-6207 and TAF
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CONFIDENTIAL
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
Screening genotype report must show sensitivity to B/F/TAF to 
allow TAF monotherapy (Part B) and initiation of B/F/TAF on 
Day 10 (Part A and Part B)

Screening genotype report must show sensitivity to at least 
one agent in either non-nucleoside reverse transcriptase inhibitor 
(NNRTI) or protease inhibitor (PI) class to allow its use as part of 
standard of care oral antiretroviral treatment in the future

Have adequate renal function (estimated GFR ≥70 mL/min)

No clinically significant abnormalities in ECG at Screening 

Not pregnant or lactating

Willing to initiate B/F/TAF on Day 10 after completion of all 
assessments
Study Procedures/
Frequency:
This study may enroll up to 5 cohorts in Part A and up to 3 cohorts in 
Part B, of approximately 8 unique subjects per cohort. All subjects 
will be enrolled after the completion of screening procedures and 
following confirmation of study eligibility. Within each Cohort (n=8)
in Part A, subjects will be randomized in a 3:1 ratio to receive active 
GS-6207 (n=6) or placebo (n=2). Within each Cohort (n=8) in Part B, 
subjects will be enrolled to receive active oral TAF.
Part A: A single dose of GS-6207 or placebo will be administered 
subcutaneously (SC) in the abdomen on Day 1. GS-6207 doses may 
be administered as multiple SC injections at different abdominal sites, 
as appropriate. In the case where multiple injections are administered 
for a given dose, the first and last injections should be no more than
30 minutes apart. If necessary for practical reasons, the period may be 
extended up to 45 minutes.
The Sponsor may elect to hold dosing, or stop study enrollment at any 
time based on review of preliminary safety and PK data.
Cohort
Treatment
1
150 mg GS-6207 or placebo
2
50 mg GS-6207 or placebo
3
450 mg GS-6207 or placebo
4
20 mg GS-6207 or placebo
5
750 mg GS-6207 or placebo


GS-6207 and TAF
Protocol GS–US-200-4072
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Gilead Sciences, Inc. 
Amendment 4
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The doses to be evaluated in Cohorts 2 through 5 will be determined 
based on cumulative safety (through at least Day 14), available PK 
and viral kinetic data from previous cohorts as well as available 
safety (through at least Day 14) and pharmacokinetic data from 
Study GS-US-200-4070 (Phase 1, first-in-human, single ascending 
dose study of GS-6207 SC suspension formulation, in which 
GS-6207 30 to 450 mg was administered subcutaneously). As such, 
Cohorts 2-5 may be initiated in parallel. Selected doses will be either 
lower than, or no more than 3-fold higher than, previously evaluated 
doses either in this study or in Study GS-US-200-4070; the same SC 
suspension formulation is being administered in both studies. The 
highest proposed dose in this study, GS-6207 900 mg, represents a 
2-fold dose escalation over GS-6207 450 mg, which has been shown 
to be safe and well tolerated in Study GS-US-200-4070, based on a 
blinded review of safety data. 
Observed GS-6207 or placebo (study drug) dosing is required at 
Day 1.
Part B: A single dose of TAF will be administered orally on Day 1. 
The Sponsor may elect to hold dosing, or stop study enrollment at any 
time based on review of preliminary safety and PK data.
The doses to be evaluated in Cohorts 7-8 will be determined based on 
cumulative safety (through at least Day 14), available PK and viral 
kinetic data from previous cohorts. Selected doses will be either 
lower than, or no more than 3-fold higher than, previously evaluated 
doses in this study. Cohorts 7 and 8 may be run in parallel.
Observed TAF dosing is required at Day 1.
In Part A, following screening and Day 1 visits, subjects will be 
required to visit the clinic on Days 2, 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 
85, 113, 141, 169, 197 and 225. 
In Part B, following screening and Day 1 visits, subjects will be 
required to visit the clinic on Days 2, 3, 4, 5 (if possible), 6 (if 
possible), 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 225.
Cohort
Treatment
6
200 mg TAF
7
Up to 600 mg TAF
8
Up to 600 mg TAF


GS-6207 and TAF 
Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
CONFIDENTIAL 
Final 
Amendment4 
Adverse events, concomitant medications, complete or 
symptom-directed physical examinations, and HIV-1 RNA will be 
perfonned at Screening, Day 1, and all subsequent study visits. 
CD4+ cell count will be perfonned at Screening, Day 1, Day 10, and 
all subsequent study visits. Other laborato1y analyses (hematology, 
chemistiy, and urine chemistiy) will be perfonned at Screening, 
Days 1, 3, 7, 10, 14, and all subsequent study visits. Fasting is 
required for laborato1y analyses at Days 1, 3, 7, 10, 85, 169 and 225. 
ECGs will be perfo1med at Screening, Days 1 (pre-dose), 2, 10, 29, 
57, 85, 169, and 225. 
A plasma sample for genotypic and phenotypic testing of HIV-1 
capsid (Paii A) or HIV-1 RT (Paii B) will be collected at Screening 
and Day 10 for all subjects to dete1mine eligibility and to evaluate the 
potential emergence of resistance against GS-6207 (Paii A) or T AF 
(Part B). The screening plasma sample will also be used for genotypic 
testing ofHIV-1 PR, RT, and IN to dete1mine eligibility. 
A whole blood sample for potential HIV DNA genotyping will be 
collected at Days 85, 169 and 225. 
Subjects who meet the criteda for virologic failure after Day 10 will be 
tested for the potential development of resistance against all 
components of the ti·eatinent regimen, including GS-6207. 
GS-6207 PK sampling (Part A, Cohorts 1 -5 ): 
Blood samples will be collected to dete1mine GS-6207 PK 
(and metabolites, if applicable) in plasma at the following time points 
relative to study diug dosing: 
• 
Day 1: 0 (pre-dose), 1, 2, 4, 8, 12, and 24 hours post dose. 
• 
Days 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 
225: a single anytime PK sample will be collected. 
TAF PK sampling (Part B, Cohorts 6 - 8): 
Plasma PK samples will be collected to detennine PK of T AF and its 
metabolite, TFV, at the following time points relative to study diug 
dosing: 
• 
Day 1: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 and 48 hours 
post dose. 
• 
Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, and 10 at 
approximately the same time in the morning as pre-dose on 
Day 1. 
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GS-6207 and TAF
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Amendment 4
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PBMC PK samples will be collected to determine PK of TFV-DP at 
the following time points relative to study drug dosing:

Day 1: 0 (pre-dose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose.

Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, and 10 at 
approximately the same time in the morning as pre-dose on 
Day 1.
All subjects will initiate B/F/TAF on Day 10 after completion of all 
assessments.
Test Product, Dose, 
and Mode of 
Administration:
Part A:
Study drug will be administered SC in the morning without regard to 
food. Observed study drug dosing is required.
Cohort 1: GS-6207 150 mg 
Cohort 2: GS-6207 50 mg 
Cohort 3: GS-6207 450 mg
Cohort 4: GS-6207 20 mg
Cohort 5: GS-6207 750 mg
Part B:
Study drug will be administered orally in the morning under fasted 
conditions. Observed study drug dosing is required.
Cohort 6: TAF 200 mg
Cohort 7: TAF up to 600 mg
Cohort 8: TAF up to 600 mg
Reference Therapy, 
Dose, and Mode of 
Administration:
Part A:
Study drug will be administered SC in the morning without regard to 
food. Observed study drug dosing is required.
Cohort 1: Placebo GS-6207 150 mg 
Cohort 2: Placebo GS-6207 50 mg 
Cohort 3: Placebo GS-6207 450 mg
Cohort 4: Placebo GS-6207 20 mg
Cohort 5: Placebo GS-6207 750 mg
Part B:
None
Criteria for 
Evaluation:
Safety:
Adverse events, vital signs, clinical laboratory tests, ECG


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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13 June 2019
Efficacy:
Maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from 
Day 1 through Day 10
Pharmacokinetics:
Part A: The following GS-6207 PK parameters in plasma will be 
calculated: 
AUC0-t, AUCinf, AUClast, CL/F, t1/2, z, Vz/F, Cmax, Tmax, Clast, CD10, 
Tlast
Part B: The following PK parameters will be calculated for TAF and 
TFV in plasma, or TFV-DP in PBMCs, as appropriate:
AUC0-t, AUCinf, AUClast, CL/F, t1/2, z, Vz/F, Cmax, Tmax, Clast, CD10, 
Tlast
Statistical Methods:
Data from the placebo recipients in all Cohorts will be combined to 
form one placebo group for analysis purposes. Each GS-6207 
(Part A) and TAF (Part B) dose group will be compared to the 
placebo group in Part A with respect to the efficacy endpoints. 
Incidence of treatment emergent AEs and graded laboratory toxicities 
will be summarized by treatment group.
GS-6207 and TAF (and metabolites, as applicable) PK parameters 
will be summarized by treatment group using descriptive statistics. 
Part A: A sample size of 6 subjects in each GS-6207 dose group and 
a total of 10 subjects in the placebo group will provide 99% power to 
detect a treatment difference of 2.79 log10 copies/mL in maximum 
reduction of HIV-1 RNA between at least one of the GS6207 dose 
groups and the placebo group. In this power analysis, it is assumed 
that a common standard deviation for maximum reduction in HIV-1 
RNA is 0.526 log10 copies/mL (based on Study GS-US-141-1219) 
and a 2-sided t-test is conducted at an alpha level of 0.05.
Part B: A sample size of 8 subjects in each TAF dose group and a 
total of 10 subjects in the placebo group will provide 99% power to 
detect a treatment difference of 1.43 log10 copies/mL in maximum 
reduction of HIV-1 RNA between at least one of the TAF dose 
groups and the placebo group from Part A. In this power analysis, it is 
assumed that a common standard deviation for maximum reduction in 
HIV-1 RNA is 0.52 log10 copies/mL (based on Studies
GS-US-120-0104 and GS-US-120-1101) and a 2-sided t-test is 
conducted at an alpha level of 0.05.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
AE
adverse event
AIDS
acquired immune deficiency syndrome
ALT
alanine aminotransferase
ART
antiretroviral therapy
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration versus 
time curve
B
bictegravir
B/F/TAF
bictegravir/emtricitabine/tenofovir alafenamide
BUN
blood urea nitrogen
CAI
capsid inhibitor
CBC
complete blood count
CFR
FDA code of federal regulations
CI
confidence interval
CK
creatine kinase
Clast
last measurable plasma concentration
CD10
concentration at Day 10
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRO
contract (or clinical) research organization 
CSR
clinical study report
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DLT
Dose-limiting toxicity
DNA
deoxyribonucleic acid
DP
diphosphate
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination
FSH
follicle stimulating hormone


GS-6207 and TAF
Protocol GS–US-200-4072
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Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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FTC
emtricitabine
GCP
Good Clinical Practice (Guidelines)
GSI, Gilead
Gilead Sciences, Inc.
HAART
highly active antiretroviral therapy
HBV
hepatitis B virus
HBcAb
hepatitis B core antibody
HBeAB
hepatitis B virus e-antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IMP, study drug
investigational medicinal products
INSTI
integrase strand-transfer inhibitor
INR
international normalized ratio
IRB
institutional review board
IUD
intrauterine device
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LDL
low density lipoprotein
LLT
lower level term
LSM
least-squares mean
MAD
multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
Mg
milligram
Min
minute
mtDNA
mitochondrial DNA
NNRTI
non-nucleoside reverse transcriptase inhibitor
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
N(t)RTI
nucleos(t)ide reverse transcriptase inhibitor
PBMC
peripheral blood mononuclear cell
PI
protease inhibitor
PK
pharmacokinetic
PVE
Phamacovigilance and Epidemiology
PXR
pregnane X receptor
QD
once daily
RNA
ribonucleic acid


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Gilead Sciences, Inc. 
Amendment 4
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RT
reverse transcriptase
SAD
single ascending dose
SADR
serious adverse drug reaction
SAE
serious adverse event
SC
subcutaneously
SOP
standard operating procedures
SUSAR
Suspected Unexpected Serious Adverse Reaction
SVR
suboptimal virologic rebound
Tmax
the maximum time that a drug is present at the maximum concentration in serum
TAF
tenofovir alafenamide
TAM
thymidine analogue mutations
TDF
tenofovir disoproxil fumarate, Viread
TE
treatment experienced
TFV
tenofovir
Tlast
time (observed time point) of Clast
ULN
upper limit of the normal range
US
United States
USPI
United States prescribing information
WHO
World Health Organization


GS-6207 and TAF
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Amendment 4
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1.
INTRODUCTION
1.1.
Background
Human Immunodeficiency Virus (HIV)-1 infection is a life-threatening and serious disease of 
major public health significance, with approximately 37 million people infected worldwide, and
approximately 15.8 million on antiretroviral (ARV) treatment {Centers for Disease Control 
(CDC) 2017, UNAIDS 2016}. Advances in combination antiretroviral therapy (ART) for HIV 
have led to significant improvements in morbidity and mortality by suppressing viral replication, 
preserving immunologic function, and averting disease progression to acquired 
immunodeficiency syndrome (AIDS). Standard-of-care for the treatment of HIV-1 infection 
involves the use of a combination of oral ARV drugs (ie, 2 NRTIs plus a third agent) to suppress 
viral replication to below detectable limits, increase CD4 cell counts, and delay disease 
progression. 
While combination ARV therapy for the treatment of HIV-1 infection is efficacious and well 
tolerated, these agents need to be taken every day and require near perfect adherence to minimize 
the emergence of drug resistant variants. In addition, “treatment fatigue” can occur, defined as 
“decreased desire and motivation to maintain vigilance in adhering to a treatment regimen” 
among patients prescribed chronic or life-long treatment {Claborn 2015}, which can lead to 
nonadherence and treatment failure. As such, there remains a significant medical need for ARVs 
that can be administered less frequently (ie, long acting drug products), thereby providing an 
alternative treatment option for HIV-1 infected individuals.
The viral capsid (CA) protein plays multiple essential roles in the HIV-1 replication cycle, 
including the assembly and maturation of new virions, the encapsidation of the viral RNA 
genome and replicative enzymes into a protective conical capsid shell, the controlled 
disassembly of the capsid shell following viral entry to help coordinate reverse transcription of 
the viral genome, and the active trafficking of viral DNA to the nucleus via a nuclear pore to 
enable formation of an integrated provirus.
1.2.
GS-6207
GS-6207 is a novel, first-in-class, selective inhibitor of HIV-1 capsid function, which has potent 
antiviral activity, low human clearance, and physicochemical properties well suited for 
extended-release parenteral or oral formulations.
1.2.1.
General Information
For further information on GS-6207, please refer to the investigator’s brochure (IB). Information 
in the IB includes:

Nonclinical pharmacology and toxicology 

Nonclinical pharmacokinetics (PK) and in vitro metabolism

Preclinical pharmacology, pharmacokinetics, and toxicology 

Clinical experience


GS-6207 and TAF
Protocol GS–US-200-4072
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Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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1.2.2.
Additional Clinical Studies
As of January 10, 2019, 3 Phase 1 clinical studies in healthy volunteers and 1 study in subjects 
with HIV infection were ongoing:
GS-US-200-4070, a Phase 1 Randomized, Blinded, Placebo-Controlled, Single Ascending Dose
Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Subcutaneous GS-6207 
(Aqueous Suspension) in Healthy Subjects
GS-US-200-4071, a Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability 
and Pharmacokinetics of Oral GS-6207, and the Effect of Food on GS-6207 Pharmacokinetics
GS-US-200-4538, a Phase 1 Randomized, Blinded, Placebo-Controlled, Single Ascending Dose 
Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Subcutaneous GS-6207 
(Solution Formulations) in Healthy Subjects
GS-US-200-4072, a Phase 1b randomized, double-blinded, placebo-controlled, multi-cohort 
study of the safety, pharmacokinetics, and antiviral activity of GS-6207 administered as a 
subcutaneous injectable suspension in HIV-1 infected subjects.
A brief summary of the available data from these studies is presented.
1.2.2.1.
GS-US-200-4070 Summary
Study GS-US-200-4070 is an ongoing, Phase 1 study in healthy volunteers evaluating the safety, 
tolerability, and PK of single ascending doses of a GS-6207 subcutaneous suspension. 40 unique 
subjects across 4 dosing cohorts have received either SC GS-6207 or placebo (4:1 ratio). 
Administration of single SC doses of GS-6207 30 mg (Cohort 1), 100 mg (Cohort 2), 300 mg. 
(Cohort 3) and 450 mg (Cohort 4) is complete. PK sampling for Cohorts 1 and 2 (through 
Day 169 [24 weeks] post dose) is complete and ongoing for Cohorts 3 and 4 (through Day 225 
[32 weeks] post dose). Preliminary PK profiles and PK parameters of subcutaneous GS-6207 
administered as single doses of 30 mg, 100 mg, 300 mg and 450 mg are presented in Figure 1-1
and Table 1-1 below. Preliminary PK data are available for 168 days post dose for Cohorts 1, 2 
and 4, and through 196 days post-dose for Cohort 3. 
GS-6207 PK profiles (Table 1-1) are consistent with sustained delivery. The PK is characterized 
by prolonged exposure, with measureable concentrations for up to 196 days [28 weeks], to date. 
The median apparent terminal t1/2 is 30-43 days. Increases in GS-6207 mean Cmax and AUCinf are 
approximately dose proportional over the dose range of 30-450 mg.
In a preliminary blinded review of the available safety data through February 1, 2019 (n=40), no 
deaths, serious adverse events (SAEs), or Grade 3-4 adverse events (AEs) have been reported. 
Injection site reactions occurred in 21 of 40 subjects (53%) these included injection site erythema 
(15 subjects, 38%), injection site pain (14 subjects, 35%), injection site nodules (9 subjects,
23%), injection site induration (8 subjects, 20%), and injection site swelling (7 subjects, 18%). 
The only other AE that was reported by more than 10% of subjects was headache (5/40, 13%).


GS-6207 and TAF 
Protocol GS-US-200-4072 
Final 
Gilead Sciences, Inc. 
Amendment 4 
Figure 1-1. 
Preliminary Mean (SD) GS-6207 Plasma Concentration-Time Proflles 
Following Single-Dose Administration of Subcutaneous Suspension of 
GS-6207 30 mg, 100 mg, 300 mg and 450mg (N=8 per cohort) 
-
...I 
E -
Cl) 
C: -
,-.. 
0 
N 
<9 
(/) 
(!) 
100 
10 
1 
....,. Cohort 1 : 30 mg 
....,. Cohort 2: 100 mg 
-+ Cohort 3: 300 mg 
.. Cohort 4: 450 mg 
0.1+-...... -
............ -
...... -----------.-----.,-----
0 
14 28 42 56 
70 84 98 112 126 140 154 168 182 196 
Time, day 
Table 1-1. 
Study GS-US-200-4070 Preliminary Plasma Pharmacokinetic 
Parameters of GS-6207 Following Single Dose Administration of 
Subcutaneous Suspension of GS-6207, 30-450 mg 
Coho11 l 
Cohort 2 
Cohort 3 
N=8 
N=8 
N=8 
Dose (Injection Volume) 
30 mg (1 X 0.3 
l00mg(lxlmL) 
300 mg (3 x 1 mL) 
mL) 
PK Parameter 
Mean (%CV) 
AUCinf (hr*ng/mL) 
7740 (8.75)" 
27600 (40.4)h 
86300 (18.5)c 
AUC1as1 (hr*ng/mL) 
6800 (13.1) 
25900 (44.6) 
81300 (18.0) 
AUC %Extrapolated(%) 
12.3 (36.3) 
6.92 (70.5) 
5.45 (113) 
Cmax (ng/mL) 
3.24 (39.8) 
14.7 (58.4) 
47.9 (27.7) 
Cmo(ng/mL) 
2.28 (36.7) 
10.7 (57.7) 
31.4 (35.2) 
tmax ( day) t 
35.0 (22.3, 36.8) 
21.0 (11.8, 36.8) 
31.5 (17.5, 35.0) 
t112(day)t 
35.5 (31.5, 40.2)" 
30.3 (23.6, 48.2)h 
43.1 (26.5, 46.5)° 
Pha1macokinetic parameters are presented as Mean (%CV), and shown to 3 significant digits 
fMedian (Ql ,Q3); •n=4; bn=6; c n=7; ND= Not yet dete1mined 
CONFIDENTIAL 
Page 18 
Cohort 4 
N=8 
450 mg (3 X 1.5 mL) 
111000 (25. 7)° 
102000 (21.0) 
6.79 (68.4) 
58.4 (22.9) 
47.1 (44.7) 
14.0 (6.50, 29.8) 
39.9 (32.8, 48.8)° 
13 June 2019 


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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1.2.2.2.
GS-US-200-4071 Summary
Study GS-US-200-4071 is an ongoing, Phase 1 study in healthy volunteers evaluating the safety,
tolerability, and PK of single and multiple ascending doses of a GS-6207 oral capsule. As of 
January 10, 2019, a total of 40 unique subjects have received GS-6207 in Cohorts 1-4.
In Cohorts 1 and 2, each subject was randomized to receive either GS-6207 (N=8; 50 mg/mL) or 
matching placebo (N=2); a single dose was administered under fasted conditions on Day 1 
followed by a 10-day washout period, then 10 days of once-daily doses on Days 11-20.
Preliminary single dose PK profiles from Cohorts 1 and 2 (Figure 1-2) suggested that the 10 day 
washout period was not sufficient to allow for characterization of the elimination phase 
following a single oral dose of GS-6207. As a result, the protocol was amended to limit 
evaluation of GS-6207 PK to single ascending doses with extended PK sampling to allow for 
characterization of the single dose oral PK prior to any further multiple dosing.
A summary of the preliminary PK parameters of oral GS-6207 after administration of single and 
multiple doses of 30 mg (50 mg/mL; Cohort 1) and 100 mg (50 mg/mL; Cohort 2) are presented 
in Table 1-2 below. Maximum plasma concentrations of GS-6207 (Cmax) occurred between 3.5 
and 29 hours (median Tmax). Following multiple dosing, the mean Cmax and AUC0-24 were at least 
10-fold higher than those after a single dose.
Table 1-2.
Study GS-US-200-4071 Preliminary Plasma Pharmacokinetic 
Parameters of GS-6207 Following Single and Multiple Dose Oral 
Administration of 30 mg (50 mg/mL) and 100 mg (50 mg/mL)
Cohort 1 (N=8)
Cohort 2 (N=8)
30 mg SD 
30 mg MD
100 mg SD
100 mg MD
Cmax (ng/mL)
1.16 (23.9)
12.2 (17.1)
2.70 (55.4)
41.3 (53.8)
tmax (hr)†
29.0 (4.00, 90.0)
3.50 (1.89, 10.0)
26.0 (4.00, 96.0)
4.00 (4.00, 10.5)
AUC0-24hr (hr*ng/mL)
17.6 (19.7)
232 (17.9)
34.8 (47.3)
843 (56.5)
AUClast (hr*ng/mL)
147 (29.0)
-
319 (46.0)
-
Pharmacokinetic parameters are presented as Mean (%CV), and shown to 3 significant digits
AUC0-24hr= AUC from time zero through 24 hours post dose; AUClast = AUC from time zero to Day 7 post dose for single dose
†Median (Q1,Q3)
In Cohorts 3 and 4, each subject was randomized to receive a single dose of either GS-6207 
(N=8; 100 mg/mL) or matching placebo (N=2).
PK profiles and preliminary PK parameters of GS-6207 after administration of single oral doses 
of 300 mg (100 mg/mL; Cohort 3) and 75 mg (100 mg/mL; Cohort 4) are presented in Figure 1-2
and Table 1-3 below. Maximum plasma concentrations of GS-6207 (Cmax) occurred between 
6.00 and 38 hours (median Tmax). The increase in Cmax was less than dose proportional between 
75 and 300 mg. Based on the available PK from Cohort 3, the estimated terminal t1/2 of GS-6207 
is approximately 16 days.


GS-6207 and TAF 
Protocol GS-US-200-4072 
Final 
Gilead Sciences, Inc. 
Amendment 4 
Figure 1-2. 
Preliminary Mean (SD) GS-6207 Plasma Concentration-Time Proflles 
Following Single-Dose Administration of Oral GS-6207 at 30, 100, 300 
and 75 mg (N=8/cohort) 
10 
.....,_ Cohort 1, 30 mg (50 mg/ml) 
_....,_ Cohort 2, 100 mg (50 mg/ml) 
...J 
...... Cohort 3, 300 mg (100 mg/ml) 
E 
O> 
---
Cohort 4, 75 mg (100 mg/ml) 
C 
,-..-
0 
1 
<'I 
<!) 
U) 
C) 
0.1 .... ----------------
0 
7 
Table 1-3. 
Parameter 
Cmax(ng/mL) 
tmax (hr) t 
AUC1as1 (hr*ng/mL) 
AUCw (hr*ng/mL) 
AUC %Extrapolated (%) 
t112t(days) 
14 
21 
28 
35 
Time, day 
Study GS-US-200-4071 Preliminary Plasma Pharmacokinetic 
Parameters of GS-6207 Following Single Dose Oral Administration in 
Cohorts 3 (300 mg, 10 mg/mL) and 4 (7 mg, 100 mg/mL) 
Coho11 3 (N=S) 
Cohort 4 (N=S) 
300 mg SD 
75 mg SD 
2.33 (31.9) 
1.33 (41.7) 
6.00 (4.00, 16.5) 
38.0 (4.00-72.0) 
877 (46.4) 
217 (56.3) 
1200 (29.1) 
TBD• 
29.3 (39.9) 
52.9 (20.7) 
15.7 (11.1, 17.5) 
TBD• 
Pha1macokinetic parameters are presented as Mean (%CV), and shown to 3 significant digits; TBD = to be dete1mined, fMedian 
(Ql,Q3); • AUC % extrapolated is currently too large to provide estimates of AUCini and ti12, parameters will be calculated upon 
availability of data 
In a prelimimuy blinded review of safety data to date as of January 10, 2019 of Cohoits 1-4, 
no deaths, serious adverse events (SAEs), or Grade 2-4 adverse events (AEs) have been repo1ted; 
no AE has been repo1ted in more than 1 subject. 
CONFIDENTIAL 
Page 20 
13 June 2019 


GS-6207 and TAF 
Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
1.2.2.3. 
GS-US-200-4538 Summaiy 
Final 
Amendment4 
Study GS-US-200-4538 is an ongoing, Phase 1 study in healthy volunteers evaluating the safety, 
tolerability, and PK of single ascending doses of GS-6207 subcutaneous solution fo1m ulations. 
40 unique subjects across 4 dosing cohorts have received either SC GS-6207 or placebo 
(4:1 ratio). Single SC doses of three fo1m ulations (300 mg/mL free acid; Coho1i 1, 300 mg/mL 
Na salt; Coho1i 5, and 150 mg/mL Na salt; Coho1i 9) of GS-6207 have been administered at a 
300 mg dose. Coho1i 6 has received a 900 mg dose of 300 mg/mL Na salt. PK samples will be 
collected for up to 450 days. PK analysis is ongoing. 
Preliminaiy PK profiles of GS-6207 after administration of single 300 mg SC doses of 
300 mg/mL free acid (Coho1i 1) and 300 mg/mL Na salt (Coho1i 5) are presented in Figure 1-3 
below. To date, there is insufficient data to calculate PK pai·ameters from these solution 
fo1mulations. Plasma concentrations of GS-6207 over the first 42 days were at least 5 fold lower 
than those following a 300 mg dose of the GS-6207 SC suspension evaluated in Study 
GS-US-200-4070 (Figure 1-1). 
In a preliminaiy blinded review of safety data as of Januaiy 10, 2019 (n=20) no deaths, serious 
adverse events (SAEs), or Grade 3-4 adverse events (AEs) have been reported. Preliminaiy 
info1mation provided by the investigator after 14 days of follow up indicates a favorable safety 
profile in subjects who received a 900 mg dose of GS-6207 in Coho1i 6. 
Figure 1-3. 
100 
...J 
-E 
10 
0) 
C 
" 
0 N 
co 
J, 
1 
0 
Preliminary Mean (SD) GS-6207 Plasma Concentration-Time Proflles 
Following Single-Dose Administration of Subcutaneous Solutions of 
GS-6207 at 300 mg (N=8/cohort); 300 mg/mL Free Acid and 
300 mg/mL Na Salt 
• 
Cohort 1; 300 mg (300mg/ml Free Acid) 
Cohort 5; 300 mg (300mg/ml Na salt) 
0.1---------------
0 
7 
CONFIDENTIAL 
14 
21 
Time, day 
28 
35 
42 
Page 21 
13 June 2019 


GS-6207 and TAF
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Final
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Amendment 4
CONFIDENTIAL
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13 June 2019
1.2.2.4.
GS-US-200-4072 Summary
Study GS-US-200-4072 is an ongoing, Phase 1b randomized, double-blinded, 
placebo-controlled, multi-cohort study of the safety, pharmacokinetics, and antiviral activity of 
GS-6207 administered as a subcutaneous injectable suspension in HIV-1 infected subjects 
conducted under IND 136260 (injectable). The primary objective of this study is to evaluate the 
short-term antiviral activity of GS-6207 compared to placebo GS-6207, with respect to the 
maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 in 
HIV-1 infected adult subjects who are antiretroviral treatment naïve or are treatment-experienced 
but not currently taking ARV treatment. This study may enroll up to 40 subjects across 5 cohorts 
of 8 unique subjects per cohort. 
All subjects will receive Biktarvy as a standard-of-care oral combination antiretroviral therapy 
immediately after completing the assessment of the primary endpoint (ie, Day 10) in order to 
minimize the risk of exposing subjects to GS-6207 monotherapy for an extended period of time. 
This study is currently enrolling.
In a preliminary blinded review of the available safety data as of February 26, 2019 when the 
first cohort had all completed Day 10 of GS-6207 150 mg, no deaths, serious adverse events 
(SAEs), or Grade 2-4 adverse events (AEs) have been reported. The preliminary safety data 
indicate a favorable safety profile in subjects with HIV-1 infection. Preliminary blinded HIV-1
RNA data showed a mean (range) 1.76 (1.49-2.06) log10 copies/mL decline in HIV-1 RNA at 
Day 10.
1.3.
Tenofovir alafenamide (TAF)
Following its release from the prodrug TAF, TFV is metabolized intracellularly to the active 
metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor of HIV-1 reverse 
transcriptase that terminates the elongation of the viral DNA chain during the process of 
retroviral replication.
1.3.1.
General Information
For further information on TAF, please refer to the investigator’s brochure (IB). Information in 
the IB includes:

Nonclinical pharmacology and toxicology 

Nonclinical pharmacokinetics (PK) and in vitro metabolism

Preclinical pharmacology, pharmacokinetics, and toxicology

Clinical experience


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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1.4.
Rationale for this Study
Current oral combination ARV therapy can achieve and maintain virologic suppression in the 
majority of patients and even provide second or third line regimens after they fail their first line 
regimen for efficacy or safety reasons. However, there still remains a significant unmet medical 
need for heavily treatment experienced (TE) HIV patients, which can be met with an 
antiretroviral agent with a new mechanism of action. As there is no cross-resistance with agents 
in existing classes, such agents can be used in patients who develop resistance to agents in 
existing classes or in virologically suppressed patients without concern for losing certain classes 
altogether even if they develop resistance. 
While current oral combination ARV therapy for the treatment of HIV-1 infection is efficacious 
and generally well tolerated, these agents need to be taken every day and require near-perfect
adherence to achieve and maintain virologic suppression and minimize the emergence of 
drug-resistant variants. Given the potency of contemporary ART, a detectable viral load 
identified during chronic care for a patient with stable access to ART is most likely the result of 
poor adherence {The Department of Health and Human Services (DHHS) Panel on 
Antiretroviral Guidelines for Adults and Adolescents 2017}. As such, there remains a significant 
medical need for ARVs that can be administered less frequently (i.e., long-acting drug products)
for all patients. 
1.4.1.
Rationale for the development of GS-6207
GS-6207 is a selective, multi-stage inhibitor of HIV-1 capsid function being developed as a 
novel therapeutic for the treatment of HIV-1 infection. GS-6207 is characterized by potent 
antiviral activity, a novel resistance profile, low predicted human clearance, low potential for 
drug-drug interactions, and low aqueous solubility. GS-6207 is anticipated to be active against 
all major types of HIV-1, including those that have developed resistance to existing classes of 
ARVs (eg, nucleoside reverse transcriptase inhibitors [NRTIs], nonnucleoside reverse 
transcriptase inhibitors [NNRTIs], protease inhibitors [PIs], and integrase strand-transfer
inhibitors [INSTIs]). This makes GS-6207 a useful antiretroviral agent for heavily treatment 
experienced patients with few options due to multiclass resistant HIV-1 infection. In addition, 
the physicochemical characteristics allow GS-6207 to be well suited for an extended-release
parenteral formulation that can potentially be used as a novel long-acting antiretroviral (ARV)
treatment administered monthly or less frequently. 
To date, Gilead evaluated GS-6207 only in healthy volunteers and has not observed any safety 
signal of concern (see Section 1.2.2). The current study (GS-US-200-4072) is the first study of 
GS-6207 in humans with HIV-1 infection. This study will assess the safety, tolerability, PK, and 
antiviral activity of GS-6207 in treatment naïve or experienced but capsid inhibitor (CAI) and 
integrase strand transfer inhibitor (INSTI) naive. The study involves 10 days of monotherapy that 
will allow for the assessment of antiviral activity over a range of GS-6207 exposures in HIV-1 
infected subjects. The study will also allow for the evaluation of the safety and PK of GS-6207 in 
HIV-1 infected subjects. The data from this study will support dose selection for Phase 2 and 
3 studies.


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1.4.2.
Rationale for the development of weekly oral TAF
TAF is a next generation oral prodrug of TFV that, compared to TDF, delivers increased 
intracellular levels of TFV-DP, in conjunction with lower systemic TFV exposure. TAF provides 
enhanced delivery of TFV to peripheral blood mononuclear cells (PBMCs), lymphatic organs, 
and hepatocytes, resulting in higher intracellular levels of the active phosphorylated moiety 
TFV-DP, more effective suppression of residual viral replication in a wider range of reservoir 
and anatomic sanctuaries of HIV, and lower systemic circulating levels of TFV, resulting in a 
better overall profile. 
The combination of low circulating TFV and high intracellular TFV-DP (as compared with TDF) 
raises the prospect that less frequent administration of higher dose TAF may be a safe and 
effective alternative for patients for whom daily adherence is challenging.
While current oral combination ARV therapy for the treatment of HIV-1 infection is efficacious 
and generally well tolerated, these agents need to be taken every day and require near-perfect
adherence to achieve and maintain virologic suppression and minimize the emergence of 
drug-resistant variants. Given the potency of contemporary ART, a detectable viral load 
identified during chronic care for a patient with stable access to ART is most likely the result of 
poor adherence {The Department of Health and Human Services (DHHS) Panel on 
Antiretroviral Guidelines for Adults and Adolescents 2017}. As such, there remains a significant 
medical need for ARVs that can be administered less frequently (i.e., long-acting drug products)
for all patients. An oral ARV which could be administered weekly might offer the potential for 
improved treatment for some patients. If so, viral suppression for 10 days after a single dose can 
support a weekly administration. 
1.5.
Rationale for the Dose Selection
1.5.1.
GS-6207
Selection of the GS-6207 SC suspension doses for this study takes into consideration the 
available safety, tolerability and PK data for SC GS-6207 from the ongoing SC single ascending 
dose study in healthy volunteers (GS-US-200-4070), as well as preliminary safety and antiviral 
activity data in this study following administration of GS-6207 150 mg to HIV-1 infected 
subjects (GS-US-200-4072).
As of February 1, 2019, 40 subjects (32 active and 8 placebo) have received a single dose of 
GS-6207 via subcutaneous injection (SC 30 to 450 mg). All subjects have completed at least 
168 days of follow up or discontinued the study. In the blinded review of safety data, GS-6207 
was generally well-tolerated. There have been no deaths, serious adverse events (SAEs), or 
Grade 3-4 adverse events (AEs) reported. Injection site reactions occurred in 21 of 40 subjects 
(53%) these included injection site erythema (15 subjects, 38%), injection site pain (14 subjects, 
35%), injection site nodules (9 subjects, 23%), injection site induration (8 subjects, 20%), and 
injection site swelling (7 subjects, 18%). The only other AE that was reported by more than 10% 
of subjects was headache (5/40, 13%).


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GS-6207 PK was shown to be dose proportional across the dose range of 30 to 450 mg in Study 
GS-US-200-4070. Based on the PK data from Study GS-US-200-4070, GS-6207 150 mg is 
expected to result in a GS-6207 concentration at Day 10 (Ct) that is 4-fold higher than the protein 
adjusted EC95 against wild type HIV virus (paEC95; 3.8 ng/mL), and was selected for evaluation 
in Cohort 1 (Table 1-1) of this study. PK analysis is ongoing. Preliminary blinded data from 
Cohort 1 demonstrated a favorable safety profile and a mean decrease of 1.76 log10 copies/mL 
in HIV-1 RNA at Day 10 following administration of 150 mg GS-6207. Based on these data, a 
dose of 50 mg and 450 mg have been selected for Cohorts 2 and 3, respectively. Doses of 20 mg 
and 750 mg were subsequently selected for Cohorts 4 and 5 respectively.
1.5.2.
TAF
The PK, safety and efficacy of TAF have been comprehensively characterized across several 
TAF-containing clinical development programs including in combination with B/F/TAF used in 
this study. The results of clinical studies, including the proof-of-concept TAF monotherapy 
evaluation in HIV-infected subjects, informed selection of TAF oral doses for this study.
Briefly, Phase 1 studies demonstrated a favorable safety profile and approximately dose 
proportional increases in exposure for TAF, TFV and TFV-DP (active intracellular metabolite) 
across the dose range of 8 to 125 mg. In Phase 3 clinical studies, TAF 25 mg exhibited a 
favorable safety profile when dosed in subjects with chronic hepatitis B infection (CHB) or in 
combination with other ARV agents for the treatment of HIV.
The results from the two TAF proof-of-concept short-term (10-14 day) monotherapy studies in 
treatment-naïve HIV-1 subjects showed dose-dependent mean reductions in HIV-1 RNA of 0.99, 
1.43, 1.52 log10 copies/mL on Day 10 at TAF doses of 8 mg, 25 mg, 40 mg QD, respectively, and 
a mean decrease of 1.48 log10 copies/mL on Day 10 at TAF 120 mg QD (GS-US-120-0104 and 
GS-US-120-1101) {Ruane 2013}. Based on these data, a single dose of TAF 200 mg was chosen 
for the initial evaluation in this study (Part B, Cohort 6). Assuming dose proportionality, TAF 
200 mg is predicted to provide intracellular exposure of the active metabolite, TFV-DP, at 
Day 10 similar to that observed following daily dosing of 25 mg TAF; and as such achieve 
comparable viral load reduction through Day 10.
TAF doses to be evaluated in adaptive cohorts 7 and 8 (up to 600 mg single dose) will be 
selected based on cumulative safety, antiviral activity and available pharmacokinetic data from 
previous cohorts in Part B. These doses will be either lower than, or no more than 3-fold higher 
than, previously evaluated doses. Following administration of 600 mg TAF, predicted TFV Cmax
(236 ng/mL) is projected to be similar to predicted average daily TFV exposures (1033 ng/mL) 
and up to 50% lower, respectively, than that observed following daily administration of TDF 
300 mg (Cmax: 300 ng/mL and average daily exposure: 2290 ng/mL); accordingly, doses of up to 
600 mg TAF are supported by clinical safety data from the TDF 300 mg development program 
{STRIBILD® 2019, VIREAD 2019}.


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The proposed dose range allows for sufficient dose-separation between cohorts for examining 
safety, antiviral activity and pharmacokinetics of a single dose of oral TAF, and maximizes the 
probability of observing a dose/exposure -response relationship. Since there are sufficient 
subjects in the placebo group from Part A, and the safety of TAF >125 mg is unknown, all 
subjects in Part B will be enrolled to receive TAF.
1.6.
Risk/Benefit Assessment for the Study
Potential risks associated with the study include unknown adverse events (AEs), including 
injection site reaction, general risks associated with frequent clinic visits and laboratory blood 
draws, and the associated pain and discomfort of multiple phlebotomies. Strategies to mitigate 
these risks include close monitoring of lab values as well as AEs. Parameters for monitoring of
AEs will be well defined and closely followed.
In addition, potential risks to HIV positive subjects include prolonged exposure (weeks to 
months) to subtherapeutic concentrations of GS-6207, which can lead to HIV-1 developing 
resistance to GS-6207. Strategies to mitigate these risks include initiation of B/F/TAF, which is 
an FDA-approved single tablet regimen with established efficacy and safety profile, on Day 10. 
With the initiation of B/F/TAF most subjects are expected to achieve virologic suppression 
within a few weeks, which substantially reduces the risk of HIV-1 developing resistance.
Similarly, subjects receiving TAF monotherapy have a risk of developing TAF resistance. 
However, TAF has a shorter half-life than GS-6207 and the same mitigation strategy of initiation 
of B/F/TAF at Day 10 will be used.
There is no direct benefit to subjects participating in this study; however, data from this study
will support the development of GS-6207 and weekly TAF for the treatment of HIV-1 infection. 
Potential benefits may include the participant’s contribution to understanding the antiviral 
activity, safety, tolerability, and pharmacokinetics of GS-6207 (Part A) or TAF (Part B)
(i.e. how much GS-6207 or TAF gets into the blood stream).
Given the above, the benefit-risk balance for this study is considered positive.
1.7.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


GS-6207 and TAF 
Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
2. 
OBJECTIVES 
Part A (Cohorts 1 - 5) 
The prima1y objective of this study is as follows: 
Final 
Amendment4 
• 
To evaluate the sho1t-te1m antiviral activity of GS-6207 compared to placebo GS-6207, with 
respect to the maximum reduction of plasma HIV-I RNA (log10 copies/mL) from Day 1 
through Day 10 in HIV-I infected adult subjects who are antiretroviral treatment na'ive or are 
experienced but capsid inhibitor (CAI) na'ive. 
The secondaiy objectives of this study ai·e as follows: 
• 
To investigate the safety and tolerability of GS-6207 as compai·ed to placebo GS-6207 in 
HIV-I infected subjects 
• 
To chai·acterize the plasma phannacokinetics (PK) of GS-6207 in HIV-I infected subjects 
• 
To chai·acterize the PK/phaimacodynamics of GS-6207 concentration and viral dynamics of 
HIV-I. 
• 
To dete1mine the number and percentage of subjects ever achieving HIV-I RNA 
< 50 copies/mL by Day 10 at each dose level 
• 
To exainine any emergence of capsid inhibitor (CAI) resistance 
Part B (Cohorts 6 - 8) 
The prima1y objective of this study is as follows: 
• 
To evaluate the sho1t-tenn antiviral activity ofTAF with respect to the maximum reduction 
of plasma HIV-I RNA (log10 copies/mL) from Day 1 through Day 10 in HIV-I infected adult 
subjects who ai·e antiretroviral treatment na'ive or ai·e experienced but without resistance to 
TAF. 
The secondaiy objectives of this study ai·e as follows: 
• 
To investigate the safety and tolerability of T AF in HIV-I infected subjects 
• 
To chai·acterize the phannacokinetics (PK) ofTAF and its metabolites in HIV-I infected 
subjects 
• 
To exainine any emergence of T AF resistance. 
I 
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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint is the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from 
Day 1 through Day 10.
Secondary endpoints include: 

Incidences of adverse events and graded laboratory abnormalities

PK parameters of GS-6207 (Part A) and TAF (and its metabolites, as appropriate) (Part B)

Correlation between Ct (concentration at Day 10) of GS-6207 (Part A) and the maximum 
reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 

Number and percentage of subjects ever achieving HIV-1 RNA < 50 copies/mL by Day 10
(Part A)

Incidences of any emergence of CAI resistance (Part A)

Incidences of any emergence of TAF resistance (Part B)
3.2.
Study Design
Randomized, double-blinded, placebo-controlled, multi-cohort study of GS-6207 (Part A) and 
single-arm study of TAF (Part B) monotherapy in subjects with HIV-1 infection
3.3.
Study Treatments
This study may enroll up to 5 cohorts in Part A and up to 3 cohorts in Part B, of approximately 
8 unique subjects per cohort. All subjects will be enrolled after the completion of screening 
procedures and following confirmation of study eligibility. Within each Cohort (n=8) in Part A, 
subjects will be randomized in a 3:1 ratio to receive active GS-6207 (n=6) or placebo (n=2).
Within each Cohort (n=8) in Part B, subjects will be enrolled to receive active oral TAF.
Part A: A single dose of GS-6207 or placebo will be administered subcutaneously (SC) in the 
abdomen on Day 1. GS-6207 doses may be administered as multiple SC injections at different 
abdominal sites, as appropriate. In the case where multiple injections are administered for a 
given dose, the first and last injections should be no more than 30 minutes apart. If necessary for 
practical reasons, the period may be extended up to 45 minutes. 


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Cohort
Treatment
1
150 mg GS-6207
2
50 mg GS-6207
3
450 mg GS-6207
4
20 mg GS-6207
5
750 mg GS-6207
The Sponsor may elect to hold dosing, or stop study enrollment at any time based on review of 
preliminary safety and PK data.
The doses to be evaluated in Cohorts 2 through 5 will be determined based on cumulative safety 
(through at least Day 14), available PK and viral kinetic data from previous cohorts as well as
available safety (through at least Day 14) and pharmacokinetic data from Study 
GS-US-200-4070 (Phase 1, first-in-human, single ascending dose study of GS-6207 SC 
suspension formulation). Cohorts 2-5 may be initiated in parallel. Selected doses will be either 
lower than, or no more than 3-fold higher than, previously evaluated doses either in this study or 
in Study GS-US-200-4070; the same SC suspension formulation is being administered in both 
studies. The highest proposed dose in this study, GS-6207 900 mg, represents a 2-fold dose 
escalation over GS-6207 450 mg, which has been shown to be safe and well tolerated in 
Study GS-US-200-4070, based on a blinded review of safety data. 
Observed study drug dosing is required at Day 1.
Part B: A single dose of TAF will be administered orally on Day 1.
The Sponsor may elect to hold dosing, or stop study enrollment at any time based on review of 
preliminary safety and PK data.
The doses to be evaluated in Cohorts 7-8 will be determined based on cumulative safety 
(through at least Day 14), available PK and viral kinetic data from previous cohorts. Selected 
doses will be either lower than, or no more than 3-fold higher than, previously evaluated doses in 
this study. Cohorts 7 and 8 may be run in parallel.
Observed TAF dosing is required at Day 1.
Cohort
Treatment
6
200 mg TAF
7
Up to 600 mg TAF
8
Up to 600 mg TAF


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Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
3.4. 
Duration of Treatment 
Final 
Amendment4 
Regardless of Coho1t in this study, the procedmes are identical. Following screening and Day 1 
visits, subjects will be required to visit the clinic on Days 2, 3, 4, 5 (Pait B only, if possible), 
6 (Pait B only, if possible), 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 225. 
All subjects will be dosed with either active GS-6207 or placebo (Pait A) or TAF (Pait B) on 
Day 1. 
-
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 64 subjects who meet all the eligibility criteria will be enrolled. 
Replacement subjects may be enrolled for subjects who do not complete all procedures for 
reasons other than discontinuation due to monotherapy treatment related adverse events.
4.2.
Inclusion Criteria (Parts A and B)
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) The ability to understand and sign a written informed consent form, which must be obtained 
prior to initiation of study procedures
2) Must be between 18 and 65 years of age, inclusive on the date of the screening visit
3) Cohorts 1 - 5: Antiretroviral treatment naïve OR experienced but capsid inhibitor (CAI) and 
integrase strand transfer inhibitor (INSTI) naïve and have not received any anti-HIV 
treatment, including antiretroviral medications received for prevention (PrEP) or post 
exposure prophylaxis (PEP), within 12 weeks prior to screening
Cohorts 6 - 8: Antiretroviral treatment naïve OR experienced but integrase strand transfer 
inhibitor (INSTI) naïve and have not received any anti-HIV treatment, including 
antiretroviral medications received for prevention (PrEP) or post exposure prophylaxis 
(PEP), within 12 weeks prior to screening
4) Plasma HIV-1 RNA ≥ 5,000 copies/mL but < 400,000 copies/mL 
5) CD4+ cell count > 200 cells/mm3
6) Cohorts 1 - 5: Screening HIV-1 capsid genotypic report provided by Gilead must not show 
any mutation known to be associated with in vitro resistance to GS-6207 (L56I, M66I, 
Q67H, Q67Y, K70N, N74D, N74S, A105E, or T107N in HIV-1 capsid)
Cohorts 6 - 8: HIV-1 capsid genotyping criteria do not apply
7) Must be willing to initiate B/F/TAF on Day 10
8) Screening genotype report provided by Gilead must show genotypic sensitivity to the 
components of B/F/TAF at Screening to allow its initiation on Day 10
9) No documented or suspected resistance to the components of B/F/TAF to allow its initiation 
on Day 10


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10) Screening genotype report provided by Gilead must show genotypic sensitivity to at least 
one agent in the non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor 
(PI) classes such that a viable standard-of-care ARV regimen can be constructed in the future
11) Normal ECG (if abnormal, determined by the Investigator to be not clinically significant)
12) Adequate renal function:
Estimated glomerular filtration rate 70 mL/min according to the Cockcroft-Gault formula
{Cockcroft 1976}:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
13) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
14) Alkaline phosphatase ≤ULN
15) Total bilirubin 1.5 mg/dL, or normal direct bilirubin
16) Adequate hematologic function (absolute neutrophil count 750/mm3; platelets 
50,000/mm3; hemoglobin 8.5 g/dL) (Those with chronic neutropenia with no clinical 
significance can enroll at the discretion of the investigator.)
17) Females of childbearing potential (as defined in Appendix 6 for Cohorts 1 - 5, and 
Appendix 7 for Cohorts 6 - 8) must have a negative serum pregnancy test at screening.
18) Male and female subjects of childbearing potential who engage in heterosexual intercourse 
must agree to utilize protocol specified method(s) of contraception as described in 
Appendix 6 for Cohorts 1 - 5, and Appendix 7 for Cohorts 6 - 8.
19) Female subjects must refrain from egg donation and in vitro fertilization during treatment 
and until at least:

300 days following the dose of study drug, for Cohorts 1 – 5

7 days following the last dose of Biktarvy on the study, for Cohorts 6 – 8
20) Cohorts 1 - 5: Male subjects must refrain from sperm donation during treatment and until at 
least 360 days following the dose of study drug.
Cohorts 6 - 8: Male subjects must refrain from sperm donation during treatment on the 
study.


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4.3.
Exclusion Criteria (Parts A and B)
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Anticipated to start HIV-1 therapy between Days 1 and 9
2) Participation in any other clinical trial, including observational studies, without prior approval 
from the sponsor is prohibited while participating in this trial
3) Recent use of any approved or investigational antiretroviral drugs within 12 weeks prior to 
screening
4) Have taken any prescription medications or over-the-counter medications, including herbal 
products, within 42 days prior to start of study drug dosing without prior approval form the 
sponsor, with the exception of vitamins and/or acetaminophen and/or hormonal contraceptive 
medications
5) Known hypersensitivity to the study drug, the metabolites or formulation excipients, or to 
B/F/TAF
6) A new AIDS-defining condition diagnosed within the 30 days prior to screening (refer to
Appendix 5)
7) Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
8) Chronic Hepatitis B Virus (HBV) infection, as determined by either:

Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV 
core antibody status, at the screening visit 

Positive HBV core antibody and negative HBV surface antibody, regardless of HBV 
surface antigen status, at the screening visit.
9) Pregnant or lactating females
10) Have an implanted defibrillator or pacemaker
11) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance
12) A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy 
other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive 
cutaneous squamous carcinoma. Subjects with cutaneous KS are eligible, but must not have 
received any systemic therapy for KS within 42 days of Day 1 and must not be anticipated to 
require systemic therapy during the study
13) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 42 days prior to Day 1


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5.
INVESTIGATIONAL MEDICINAL PRODUCT AND B/F/TAF
5.1.
Randomization, Blinding and Treatment Codes
Part A
Subjects will be assigned a screening number at the time of consent. It is the responsibility of the 
investigator to ensure that the subject is eligible for the study prior to enrollment.
Following completion of screening procedures, eligible subjects will be randomized in a 3:1 ratio 
within each cohort to receive either GS-6207 (n=6) or placebo (n=2) on Day 1, and assigned a 
subject number. 
All screening tests and procedures must be completed and reviewed by the investigator prior to 
the administration of the study drug on Day 1. Once a subject number has been assigned to a 
subject, it will not be reassigned to another subject. If necessary, replacement subjects may be 
enrolled after discussion and approval from Sponsor. A new unique subject number will be 
assigned to the replacement subject. 
The study pharmacist, or designee will remain unblinded throughout the study to prepare the 
study drug. The designated site staff administering the study drug will also remain unblinded. 
For additional information on maintaining the study blind, please refer to the study Pharmacy 
Manual. The Pharmacokinetics File Administrator, or designee, who facilitates data transfer of
PK files between Gilead and vendors, will remain unblinded. 
Part B
Subjects will be assigned a screening number at the time of consent. It is the responsibility of the 
investigator to ensure that the subject is eligible for the study prior to enrollment.
Following completion of screening procedures, eligible subjects will be enrolled to receive TAF 
and will be assigned a subject number. 
All screening tests and procedures must be completed and reviewed by the investigator prior to 
the administration of the study drug on Day 1. Once a subject number has been assigned to a 
subject, it will not be reassigned to another subject. If necessary, replacement subjects may be 
enrolled after discussion and approval from Sponsor. A new unique subject number will be 
assigned to the replacement subject.
5.1.1.
Procedures for Breaking Treatment Codes (Part A)
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the IWRS system 
for that subject. Gilead recommends but does not require that the investigator contact the Gilead
medical monitor before breaking the blind. Treatment assignment should remain blinded unless 


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that knowledge is necessary to determine subject emergency medical care. The rationale for 
unblinding must be clearly explained in source documentation and on the case report form/ 
electronic case report form (eCRF), along with the date on which the treatment assignment was 
obtained. The investigator is requested to contact the Gilead medical monitor promptly in case of 
any treatment unblinding.
All subjects will be followed until study completion unless consent to do so is specifically 
withdrawn by the subject.
Gilead Pharmacovigilance and Epidemiology (PVE) may independently unblind cases for 
expedited reporting of suspected unexpected serious adverse reactions (SUSARs).
5.2.
Description and Handling GS-6207, TAF and B/F/TAF
5.2.1.
Formulation
5.2.1.1.
GS-6207 and Placebo
GS-6207 injectable suspension, 100 mg/mL is a sterile, preservative-free, white to off-white to 
tan suspension for subcutaneous injection. In addition to the active ingredient, the suspension 
contains the following inactive ingredients: poloxamer 188, sodium chloride, phosphate buffer, 
and water for injection.
The placebo is a sterile, clear, colorless solution for subcutaneous injection. The solution 
contains the following inactive ingredients: poloxamer 188, sodium chloride, phosphate buffer, 
and water for injection.
5.2.1.2.
TAF
TAF tablets, 25 mg, are yellow, round, film-coated tablets debossed with "GSI" on one side of 
the tablet and "25" on the other side of the tablet. In addition to the active ingredient, the tablets 
contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, 
croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene 
glycol, talc, and iron oxide yellow.
5.2.1.3.
Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF, 50/200/25 mg)
Bictegravir /Emtricitabine /Tenofovir Alafenamide (B/F/TAF, 50/200/25 mg) tablets 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, 200 mg of 
emtricitabine, and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the 
B/F/TAF 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.


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5.2.2.
Packaging and Labeling
5.2.2.1.
GS-6207 and Placebo
GS-6207 injectable suspension, 100 mg/mL, and placebo solution are each filled into a 3 mL 
borosilicate glass vial and closed with a rubber stopper and aluminum seal with a polypropylene 
flip-off cap. Each single use vial contains sufficient volume (1.2 mL) to allow withdrawal of 
1 mL of GS-6207 injectable suspension or placebo solution. 
The vials are labeled and placed into secondary packaging for storage.
Study drug to be distributed to centers in the US shall be labeled to meet requirements of the 
US Food and Drug Administration (FDA) and/or other local regulations as applicable.
5.2.2.2.
TAF 
TAF tablets are packaged in white, high density polyethylene (HDPE) bottles. Each bottle 
contains 30 tablets and a 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 US shall be labeled to meet requirements of the 
US Food and Drug Administration (FDA) and/or other local regulations as applicable.
5.2.2.3.
Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF, 50/200/25 mg)
Bictegravir /Emtricitabine /Tenofovir Alafenamide (B/F/TAF, 50/200/25 mg) is packaged in 
white, high density polyethylene (HDPE) 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.
B/F/TAF to be distributed to centers in the US shall be labeled to meet requirements of the 
US Food and Drug Administration (FDA) and/or other local regulations as applicable.
5.2.3.
Storage and Handling
5.2.3.1.
GS-6207 and Placebo
GS-6207 100 mg/mL injectable suspension and placebo solution vials should be stored 
refrigerated at 2 °C to 8 °C (36 °F to 46 °F). Storage conditions are specified on the label. Until 
dispensed for dosing, all vials of study drugs should be stored in a securely locked area, 
accessible only to authorized site personnel. 
To ensure the sterility, stability, and proper identification, study drug(s) should not be stored in a 
container other than the container in which they were supplied.
Measures that minimize drug contact with the body should always be considered during 
handling, preparation, and disposal procedures.


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5.2.3.2.
TAF 
TAF tablets should be stored at controlled room temperature of 25°C (77°F); excursions are 
permitted between 15°C and 30°C (59°F and 86°F). Storage conditions are specified on the label.
Until dispensed to the subjects, all bottles of study drugs should be stored in a securely locked 
area, accessible only to authorized site personnel.Measures that minimize drug contact with the 
body should always be considered during handling, preparation, and disposal procedures.
5.2.3.3.
Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF, 50/200/25 mg)
Bictegravir /Emtricitabine /Tenofovir Alafenamide (B/F/TAF, 50/200/25 mg) stored at 
controlled room temperature of 25°C (77°F); excursions are permitted between 15°C and 30°C 
(59°F and 86°F). Storage conditions are specified on the label. Until dispensed to the subjects, all 
bottles of B/F/TAF should be stored in a securely locked area, accessible only to authorized site 
personnel.
To ensure the stability and proper identification, B/F/TAF should not be stored in a container
other than the container in which they were supplied. Keep the bottle tightly closed to protect
from moisture.
Measures that minimize drug contact with the body should always be considered during 
handling, preparation, and disposal procedures.
5.3.
Dosage and Administration of GS-6207 (Part A, Cohorts 1 - 5)
Part A of this study may enroll up to 5 cohorts of approximately 8 unique subjects per cohort. All 
subjects will be enrolled after the completion of screening procedures and following 
confirmation of study eligibility. Within each Cohort (n=8) in Part A, subjects will be 
randomized in a 3:1 ratio to receive active GS-6207 (n=6) or placebo (n=2).
A single dose of GS-6207 or placebo will be administered subcutaneously (SC) in the abdomen 
on Day 1. GS-6207 doses may be administered as multiple SC injections at different abdominal 
sites, as appropriate. In the case where multiple injections are administered for a given dose, the 
first and last injections should be no more than 30 minutes apart. If necessary for practical 
reasons, the period may be extended up to 45 minutes.
Cohort
Treatment
1
150 mg GS-6207 or placebo
2
50 mg GS-6207 or placebo
3
450 mg GS-6207 or placebo
4
20 mg GS-6207 or placebo
5
750 mg GS-6207 or placebo
The Sponsor may elect to hold dosing, or stop study enrollment at any time based on review of 
preliminary safety data.


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The doses to be evaluated in Cohorts 2 through 5 will be determined based on cumulative safety 
(through at least Day 14), available PK and viral kinetic data from previous cohorts as well as
available safety (through at least Day 14) and pharmacokinetic data from Study 
GS-US-200-4070 (Phase 1, first-in-human, single ascending dose study of GS-6207 SC 
suspension formulation). Cohorts 2-5 may be initiated in parallel. Selected doses will be either 
lower than, or no more than 3-fold higher than, previously evaluated doses either in this study or 
in Study GS-US-200-4070; the same SC suspension formulation is being administered in both 
studies. The highest proposed dose in this study, GS-6207 900 mg, represents a 2-fold dose 
escalation over GS-6207 450 mg, which has been shown to be safe and well tolerated in Study 
GS-US-200-4070, based on a blinded review of safety data. 
5.4.
Dosage and Administration of TAF (Part B, Cohorts 6 - 8)
Part B of this study may enroll up to 3 cohorts of approximately 8 unique subjects per cohort. All 
subjects will be enrolled after the completion of screening procedures and following 
confirmation of study eligibility. Within each Cohort (n=8) in Part B, subjects will be enrolled to 
receive active oral TAF.
A single dose of TAF will be administered orally on Day 1.
The Sponsor may elect to hold dosing, or stop study enrollment at any time based on review of 
preliminary safety and PK data.
The doses to be evaluated in Cohorts 7-8 will be determined based on cumulative safety 
(through at least Day 14), available PK and viral kinetic data from previous cohorts. Selected 
doses will be either lower than, or no more than 3-fold higher than, previously evaluated doses in 
this study. Cohorts 7 and 8 may be run in parallel.
Observed TAF dosing is required at Day 1.
5.5.
Prior and Concomitant Medications
The following medications are excluded while subjects are participating in Part A:

Any prescription medications and over-the-counter medications, including herbal products, 
with the exception of vitamins, and/or acetaminophen and/or ibuprofen and/or hormonal 
contraceptive medications. However, the short-term use of topical hydrocortisone cream or 
AD ointment to treat minor skin irritation due to ECG leads will be allowed. If a subject 
requires use of a disallowed medication, a request for such use must be reviewed by the 
Sponsor and if approved, subjects may continue to participate in the study. 

Any and all illegal or illicit drug use, including use of prescription drugs outside the care of 
the prescribing physician.
Cohort
Treatment
6
200 mg TAF
7
Up to 600 mg TAF
8
Up to 600 mg TAF


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For Part A, if a subject discontinues B/F/TAF between the Day 10 and Day 225 visits, they can 
switch to an alternative ARV regimen, which should not contain the following prohibited ARVs: 
Prohibited ARVs
HIV Protease Inhibitors
RTV or COBI containing regimens
Efavirenz
Etravirine
Nevirapine
The following medications are excluded while subjects are participating in Part B: 

TAF is a substrate of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) 
transporters {DESCOVY® 2017}. Drugs that inhibit or induce Pgp or BCRP activity may 
lead to increases or decreases, respectively, in TAF absorption. In vitro data suggest TAF 
may inhibit or induce CYP3A at doses up to 600 mg, however, given its short half-life and 
transient exposure, clinically relevant changes in CYP3A substrates are not expected 
following co-administration with a single dose TAF. 

Medications that are potent inhibitors or inducers of Pgp/BCRP are prohibited, and use of 
herbal/natural supplements are excluded while subjects are participating in this study. 
Table 5-1 contains examples of medications that are to be excluded while subjects are 
participating in the study in Part B. As this table is not exhaustive, all concomitant 
medications are to be reviewed with the sponsor until Day 10. After Day 10, the investigator 
should follow the current USPI for B/F/TAF {BIKTARVY® 2018}.

Any and all illegal or illicit drug use, including use of prescription drugs outside the care of 
the prescribing physician, are prohibited.
Table 5-1.
List of medications that are prohibited due to the potential for 
drug-drug interaction with TAF
Medication Class
Disallowed Medications
Anti-arrhythmics
Amiodarone, Dronedarone, Propafenone
Anti-anginal agents
Ranolazine
Anti-biotics
Clarithromycin
Anti-convulsants
Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin
Anti-fungals
Itraconazole
Anti-malarials
Quinidine
Anti-mycobacterials
Rifapentine, Rifabutin, Rifampin
Anti-retroviral agents
Any antiretroviral drug that is not part of the study regimen
Beta blockers
Carvedilol
Ca channel blockers
Verapamil
Herbal/Natural Supplements
St. John’s Wort, Echinaccea, Milk thistle (i.e., silymarin), Chinese herb sho-saiko-to 
(or Xiao-Shai-Hu-Tang)


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5.6.
Dispensing, Accountability, and Disposal or Return of GS-6207 and TAF 
(study drugs) and B/F/TAF
The investigator (or designee, eg, study center pharmacist) will acknowledge receipt of the study 
drugs and B/F/TAF (after reviewing the shipment’s content and condition) from Gilead 
(or designee). The investigator will maintain an accurate inventory of all study drug and 
B/F/TAF. The study drug will be administered at the study center by qualified study center staff. 
The dose of study drug administered to subjects in the clinic under the supervision of staff will 
be accurately recorded on the Study Drug Accountability form provided by Gilead (or on 
equivalent documentation maintained by the study center), which indicates the date and quantity 
of each dosage formulation dispensed to individual subjects.
Where possible, study drug and B/F/TAF should be destroyed at the site. If the site does not have 
acceptable procedures in place for drug destruction, arrangements will be made between the site 
and Gilead Sciences (or Gilead Sciences’ representative) for return of unused study drug supplies
and B/F/TAF. The study monitor will provide instructions for return.
The study monitor will evaluate each study center’s study drug disposal procedures and provide 
appropriate instruction for destruction of unused study drug supplies. If the site has an 
appropriate standard operating procedure (SOP) for drug destruction as determined by Gilead , 
the site may destroy used (empty or partially empty) and unused study drug supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for central files.
If study drug or B/F/TAF is destroyed on site, the investigator must maintain accurate records for 
all drug destroyed. Records must show the identification and quantity of each unit destroyed, the 
method of destruction, and the person who disposed of the drugs. Upon study completion, copies 
of the study drug accountability records must be filed at the site. Another copy will be returned 
to Gilead. Refer to the Pharmacy Binder for study drug disposal/return instructions. The study 
monitor will review study drug supplies and associated records at periodic intervals.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. Additional information is 
provided in the study procedures manual.
The investigator must document any deviation from protocol procedures and notify the sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
Entry into screening does not guarantee enrollment into the study. In order to manage the total 
trial enrollment, Gilead, at its sole discretion, may suspend screening and/or enrollment at any 
site or trial-wide at any time.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 42 days prior to Day 1 to determine eligibility for participation
in the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events and prior 
medications within 42 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature)

12-lead ECG performed supine

Height and Weight

Obtain blood and urine samples as described in Section 6.6

Review of AEs and concomitant medications
Once eligibility is confirmed, each subject will be assigned a unique subject number. Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. 
Prior to or during the Day 1 visit in Part A the Investigator or designee will enroll the subject 
using the Interactive Web Response System (IWRS). In Part B, the Investigator will contact 
Gilead Sciences to obtain the subject number. The subject number assignment may be performed 
up to 7 days prior to the in-clinic Day 1 visit provided that all screening procedures have been 
completed and subject eligibility has been confirmed.


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Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 42 days after screening for Day 1 assessments. Subjects will be instructed to fast 
overnight (6 hours) prior to the Day 1 visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (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.
6.3.
Treatment Assessments
Subjects will be required to visit the clinic on Days 1, 2, 3, 4, 5 (Part B only, if possible), 
6 (Part B only, if possible), 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 225.
Subjects will be required to fast overnight (> 6 hours) prior to visit on Days 1, 3, 7, 10, 85, 169, 
and 225 for laboratory analyses.
6.3.1.
Day 1 
The following procedures are to be completed at the Day 1 visit prior to study drug dosing.

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature)

Weight

12-lead ECG performed supine (pre-dose)

Obtain blood and urine samples as described in Section 6.6 (Note: all blood and urine 
samples should be collected pre-dose on Day 1, except for PK samples as noted in 
Section 6.6)

Part B: A single dose of TAF will be administered orally on Day 1 at the study center under 
fasted conditions, with 240 mL of water following an overnight fast (no food or drink, except 
water, for at least 6 hours).
On Day 1, subjects will be restricted from food intake until after collection of the 4-hour 
blood draw. Additionally, subjects will be restricted from water consumption 1 hour before 
and 2 hours after dosing, except for the 240 mL of water given with the study drug. Subjects 
will fast until 2 hours after study drug administration. Water may be freely consumed 
following the 2-hour blood draw and for the remainder of the collection period. Subjects may 
eat after the 4 hour post-dose blood draw.


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6.3.2.
Assessments on Days 2, 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 
and 225
Subjects will be required to fast overnight (> 6 hours) prior to visit on Days 3, 7, 10, 85, 
169 and 225 for laboratory analyses. Study visit Days 29, 43, 57, 85, 113, 141, 169 and 197 may 
be completed within ± 2 days of the protocol-specified visit date. 
The following procedures are to be completed at all visits unless otherwise specified: 

Review of AEs and changes in concomitant medications

Symptom directed physical examination 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature)

Weight

12-lead ECG performed supine (Days 2, 10, 29, 57, 85, 169 and 225)

Obtain blood and urine samples as described in Section 6.6

All subjects will initiate B/F/TAF on Day 10 after completion of all assessments.
B/F/TAF will be dispensed at Days 10, 43, 85, 141 and 197. 
6.4.
Early Study Discontinuation Assessments
If a subject discontinues their participation prior to Day 225, Early Termination Visit should be 
performed. 
However, if there are any abnormal laboratory results indicating that there is a possible or 
probable causal relationship with the study drug, every attempt should be made to keep the 
subject in the study and repeat those laboratory tests weekly (or as often as deemed prudent by 
the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained.
If this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study.
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The following evaluations should be performed at the Early Termination Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature)

Weight

Obtain blood and urine samples as described in Section 6.6

Counsel subject regarding the importance of continuing a complete ARV therapy in 
accordance to standard of care, and refer patient to an appropriate HIV treatment facility
6.5.
Criteria for Discontinuation of Study 
Study may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator.

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Subject request to discontinue for any reason

Subject noncompliance with B/F/TAF

Pregnancy during the study; refer to Appendix 6 and Appendix 7

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)
6.6.
Clinical Laboratory Assessments
Blood and urine samples will be collected throughout the study as outlined below, within 
Section 6, and in Appendix 2 Study Procedures Table.


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6.6.1.
Blood Samples

Blood sample collection for the following laboratory analyses will be performed at every 
visit, unless specified:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be randomized (Screening and Days 29, 57, 85, 113, 141, 169,
197 and 225)
Serum FSH test (required for female subjects who have stopped menstruating for 
≥12 months but do not have documentation of ovarian hormonal failure) 
(Screening only)
Urine pregnancy test (females of childbearing potential only). If the test is positive, 
confirmatory serum test should be sent and study drug dosing should be delayed until 
results obtained (Day 1)
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN)
(All visits except Days 2, 4, 8 and 9). Subjects will be required to fast overnight 
(> 6 hours) prior to visit on Days 3, 7, 10, 85, 169 and 225.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
Creatinine clearance (All visits except Days 2, 4, 8 and 9)
Male: (140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
Hematology profile: complete blood count (CBC) with differential and platelet count
(All visits except Days 2, 4, 8 and 9)
CD4+ cell count (Screening and Days 1, 10, 29, 43, 57, 85, 113, 141, 169, 197 and 225)
Plasma HIV-1 RNA. Any subsequent HIV-1 genotype and phenotype testing will be 
performed as described in Section 6.7.
HIV-1 genotype and phenotype for PR, RT, IN, and capsid (Screening only)
HIV-1 capsid genotype and phenotype (Day 10)
HIV DNA genotyping (Days 85, 169 and 225)


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Hepatitis B virus (HBV) serologies (HBV surface antigen, HBV core antibody, HBV 
surface antibody) (Screening only)
Hepatitis C virus (HCVAb) serology (Screening only)
Plasma storage samples for safety and virology testing (HIV-1 capsid genotype and 
phenotype) (Not collected at Screening visit)
GS-6207 PK Sampling (Part A, Cohorts 1 – 5)
Blood samples to determine PK in plasma:
■
The exact time of study drug administration and the exact time points (date and 
24-hour clock) of collection of plasma samples must be carefully recorded.
■
Day 1: Time 0 (pre-dose), 1, 2, 4, 8, 12 and 24 hours post dose (relative to study drug 
dosing time) blood sample collection to determine pharmacokinetics (PK) in plasma
on Day 1 
■
Days 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197 and 225: a single 
anytime PK sample will be collected.
TAF PK sampling (Part B, Cohorts 6 - 8): 
Plasma PK samples will be collected to determine PK of TAF and its metabolite, TFV, at 
the following time points relative to study drug dosing:
■
Day 1: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 and 48 hours post dose.
■
Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, and 10 at approximately the same time 
in the morning as pre-dose on Day 1.
PBMC PK samples will be collected to determine PK of TFV-DP at the following time 
points relative to study drug dosing:
■
Day 1: 0 (pre-dose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose.
■
Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, and 10 at approximately the same time 
in the morning as pre-dose on Day 1.
CCI


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Urine Samples 
Final 
Amendment4 
Urine samples will be collected for the following laborato1y analyses at eve1y study visit, unless 
othe1wise specified: 
• 
Urinalysis and urine Chemistiy: including color & clarity, specific gravity, pH, glucose, 
ketones, bilimbin, urobilinogen, blood, niu-ite, leukocyte esterase and microscopic 
(if microscopic elements are seen), urine protein, albumin, creatinine, phosphate, calcium, 
magnesium and uric acid (All visits except Days 2, 4, 8 and 9) 
• 
Urine pregnancy test (females of childbearing potential only). If the test is positive, 
confinnato1y sernm test should be sent and study diug dosing should be delayed until results 
obtained (Day 1) 
• 
Urine storage (All visits except Screening, Days 2, 4, 8 and 9) 
-
6.7. 
Management ofVirologic Failure after Initiation of B/F/TAF on Day 10 
Subjects who experience either suboptimal virologic response (SVR) or virologic rebound (VR) 
after initiating B/F/TAF, as defined below, will be considered to have virologic failure. 
6.7.1. 
Suboptimal Virologic Response (SVR) 
• 
HIV-1 RNA~ 50 copies/mL and less than l log10 HIV-1 RNA reduction from Day 10 at the 
Day 57 visit 
Following the first instance of SVR at Day 57, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood di·aw (2 to 3 weeks after first SVR visit) for confnmation of 
SVR. A plasma sample from either the first instance or the SVR confm nation visit will be tested 
for HIV-1 capsid genotypic and phenotypic resistance. In addition, if SVR is confnmed, a 
plasma sample from the SVR confnmation visit will be tested for HIV-1 PR, RT, and IN 
genotypic and phenotypic resistance. 
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6.7.2.
Virologic Rebound (VR) 

At any visit, after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA to
≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled 
visit; OR

At any visit, a > 1 log10 increase in HIV-1 RNA from the nadir which is subsequently
confirmed at the following scheduled or unscheduled visit.
At any visit after achieving HIV-1 RNA < 50 copies/mL, if the HIV-1 RNA is ≥50 and
< 200 copies/mL, a reflex HIV-1 RNA repeat test will be conducted on stored plasma samples, 
if available. If the repeat result is < 50 copies/mL, no further action is required. If the repeat 
result is ≥ 50 copies/mL subjects will be asked to return to the clinic for a scheduled or 
unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted in HIV-1 
RNA VR) for confirmation of VR. 
A plasma sample from either the first instance or the VR confirmation visit will be tested for 
HIV-1 capsid genotypic and phenotypic resistance. In addition, if VR is confirmed, a plasma 
sample from the VR confirmation visit will be tested for HIV-1 PR, RT, and IN genotypic and 
phenotypic resistance.


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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered a medicinal product, which does not necessarily have a causal relationship with the
treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease 
temporally associated with the use of a medicinal product, whether or not considered related to 
the medicinal product. AEs may also include pre- or post-treatment complications that occur as a 
result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or 
occupational exposure. Preexisting events that increase in severity or change in nature during or 
as a consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an adverse event and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.7)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to IMP
therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of adverse event reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures (eg., venipuncture).


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7.2.2.
Assessment of Severity
AE severity should be recorded and graded according to the Gilead Grading Scale for Severity of
Adverse Events and Laboratory Abnormalities (Appendix 4). 
The distinction between the seriousness and the severity of an adverse event should be noted.
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For
example, a headache may be severe in intensity, but would not be classified as serious unless it
met one of the criteria for serious events.
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead 
Requirements for collection prior to study drug initiation:
After informed consent, but prior to administration of study drug, the following types of events 
should be reported on the case report form (eCRF): all SAEs and adverse events related to 
protocol-mandated procedures.
Adverse Events
Following administration of study drug, all AEs, regardless of cause or relationship, that occur 
on or before the last posttreatment follow-up visit, or in the case of early termination, 225 days 
after the administration of study drug must be reported to the eCRF database as instructed.
All AEs should be followed up until resolution or until the adverse event is stable, if possible. 
Gilead Sciences may request that certain AEs be followed beyond the protocol defined follow up 
period.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Pharmacovigilance and Epidemiology (PVE) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Any SAEs and deaths that occur on or before the last post-treatment follow-up visit, or in the 
case of early termination, 225 days after the administration of study drug, regardless of causality, 
should also be reported. 


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Final 
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Investigators are not obligated to actively seek SAEs after the protocol defined follow up period. 
However, if the investigator learns of any SAEs that occur after study paiiicipation has 
concluded and the event is deemed relevant to the use ofIMP, he/she should promptly document 
and report the event to Gilead PVE. 
• 
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
Electronic Serious Adverse Event ( eSAE) Repo1iing Process 
• 
Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
infonnation to Gilead PVE within 24 hours of the investigator's knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines. 
• If it is not possible to record and submit the SAE info1mation electr·onically, because the 
eCRF database cannot be accessed or is not available (including at study staii), record the 
SAE on the paper serious adverse event repo1iing fonn and submit within 24 hours to: 
Gilead PVE contact infonnation: 
Email: 
Fax: 
PPD 
PPD 
• 
As soon as it is possible to do so, any SAE reported via paper must be tr·anscribed into the 
eCRF Database according to instructions in the eCRF completion guidelines. 
• If an SAE has been repo1ied via a paper fonn because the eCRF database has been locked, 
no finiher action is necessaiy. 
• 
For fatal or life-threatening events, copies of hospital case repo1is, autopsy repo1is, and other 
documents ai·e also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
repo1is. 
• 
Any medications necessaiy for tr·eatinent of the SAE must be recorded onto the concomitant 
medication section of the subject's eCRF and the event description section of the SAE fonn. 
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Standard of Care Adverse Event Reporting 
Final 
Amendment4 
This is a study in which B/F/TAF will be administered as standard of care treatment for HIV. 
Investigators are encouraged to repo1i any special situations, including pregnancy, and adverse 
events associated with B/F/TAF or any other collllllercially available Gilead product 
administered as part of standard-of-care treatment to Gilead PVE. 
Gilead PVE conta.ct infonnation: 
Email: 
Fax: 
7.4. 
Gilead Reporting Requirements 
IPIPD 
IPIPD 
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other countiy-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulato1y agencies repo1is of SAEs, serious adverse dmg reactions (SADRs ), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulato1y 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
cmTent regulations. 
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
infonnation specified in the investigator's brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR repo1is associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR repo1is as soon as 
is practical, where this is required by local regulato1y agencies, and in accordance with the local 
institutional policy. 
7.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments 
Laborato1y abno1malities without clinical significance are usually not recorded as AEs or SAEs. 
However, laborato1y abnonnalities ( eg, clinical cheinistiy, hematology, and urine cheinistiy) 
independent of the underlying medical condition that require medical or surgical intervention or 
lead to investigational study discontinuation must be recorded as an AE, as well as an SAE, 
if applicable. In addition, laborato1y or other abnonnal assessments ( eg, ECG, X-rays, vital 
signs) that are associated with signs and/or symptoms must be recorded as an AE or SAE if they 
meet the definition of an AE ( or SAE) as described in Sections 7 .1.1 and 7 .1.2. If the laborato1y 
abno1mality is pa1i of a syndrome, record the syndrome or diagnosis (ie, aneinia), not the 
laborato1y result (ie, decreased hemoglobin). 
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Severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4). For AEs associated with laboratory 
abnormalities, the event should be graded on the basis of the clinical severity in the context of 
the underlying conditions; this may or may not be in agreement with the grading of the 
laboratory abnormality.
7.6.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3, and as outlined below.
 

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 4). 

Treatment-emergent toxicities will be noted by the investigator and brought to the attention 
of the Gilead medical monitor. Whether or not considered treatment-related, all subjects 
experiencing AEs must be monitored periodically as clinically indicated, until symptoms 
subside, and until any abnormal laboratory values have resolved or returned to baseline levels 
or they are considered irreversible, or until there is a satisfactory explanation for the changes 
observed.

Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results, unless such a delay is not consistent with 
good medical practice.
Any questions regarding toxicity management should be directed to the Gilead medical monitor.
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, and pregnancy reports regardless of an 
associated AE.
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
CCI


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An overdose is defined as an accidental or intentional administration of a quantity of a medicinal 
product given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labelling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy except in cases in which the investigator has 
reason to suspect that the subject has taken the additional dose(s).
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the medicinal product.
Occupational exposure with an AE is defined as exposure to a medicinal product as a result of
one’s professional or non-professional occupation.
7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
administration of study drug and throughout the study, including the post study drug follow-up 
period, to the Gilead PVE using the pregnancy report form within 24 hours of becoming aware 
of the pregnancy.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.1.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post study
must be reported to Gilead PVE.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to or Gilead PVE using the pregnancy outcome 
report form. If the end of the pregnancy occurs after the study has been completed, the outcome 
should be reported directly to Gilead PVE. Gilead PVE contact information is as follows: 
Email:
 and Fax: 
PPD
PPD


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Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead PVE using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead PVE, 
fax number
 or email 
 
Refer to Appendix 6 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study IMP and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications do not need to be reported on 
the special situations report form; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
PPD
PPD


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8. 
STATISTICAL CONSIDERATIONS 
8.1. 
Analysis Objectives and Endpoints 
8.1.1. 
Analysis Objectives 
Part A (Cohorts 1 - 5): 
Final 
Amendment4 
The prima1y analysis objective of this study is to evaluate the sho1t-tenn antiviral activity of 
GS-6207 compared to placebo administered subcutaneously (SC) in the abdomen on Day 1, with 
respect to the maximum reduction of plasma HIV-I RNA (log10 copies/mL) from Day 1 through 
Day 10 in HIV-I infected adult subjects who are antiretroviral treatment na'ive or are experienced 
but capsid inhibitor (CAI) na'ive. 
The secondaiy analysis objectives of this study are to investigate the safety and tolerability of 
GS-6207 as compai·ed to placebo, to characterize the plasma phaimacokinetic (PK) of GS-6207 
and the PK/phaimacodynamic (PD) (or dose-response) relationship between GS-6207 
concentration at Day 10 and the viral dynainics of HIV-I, to dete1mine the number and 
percentage of subjects ever achieving HIV-I RNA < 50 copies/mL by Day 10, and to examine 
any emergence of CAI resistance. 
Part B (Cohorts 6 - 8): 
The prima1y analysis objective of this study is to evaluate the short-tenn antiviral activity of a 
single dose of oral T AF with respect to the maximum reduction of plasma HIV-I RNA 
(log10 copies/mL) from Day 1 through Day 10 in HIV-I infected adult subjects who ai·e 
antiretroviral treatment na'ive or are experienced but without resistance to TAF. 
The secondaiy analysis objectives of this study are to investigate the safety and tolerability of 
TAF, to chai·acterize the PK of TAF, and to exainine any emergence of TAF resistance. 
8.1.2. 
Primary Endpoint 
The prima1y endpoint is the maximum reduction of plasma HIV-I RNA (log10 copies/mL) from 
Day 1 through Day 10. 
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8.1.3.
Secondary Endpoint
Secondary endpoints include: 

Incidences of adverse events and graded laboratory abnormalities

PK parameters of GS-6207 (Part A) and TAF (and its metabolites, as appropriate) (Part B)

Correlation between Ct (concentration at Day 10) of GS-6207 (Part A) and the maximum 
reduction of plasma HIV-1 RNA (log10 copies/mL) from baseline through Day 10

Number and percentage of subjects ever achieving HIV-1 RNA < 50 copies/mL by Day 10
(Part A)

Incidences of any emergence of CAI resistance (Part A)

Incidences of any emergence of TAF resistance (Part B)
8.1.4.
Other Endpoints of Interest
The correlation between AUC of TAF, and its metabolites, as appropriate, and the maximum 
reduction of plasma HIV-1 RNA (log10 copies/mL) from baseline through Day 10. 
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
Analysis sets define which subjects are included in an analysis. The assignment of subjects to 
analysis sets will be done before the study blind is broken for analysis.
8.2.1.1.
Efficacy
The primary analysis set for efficacy analysis is defined as full analysis set (FAS), which 
includes all subjects who are randomized and receive full dose of randomized study drug. 
Subjects with major eligibility violations that are identifiable based on pre-randomization 
characteristics may be excluded. Subjects will be grouped according to the treatment to which 
they are randomized.
8.2.1.2.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which includes all 
subjects who are randomized and receive any dose of study drug. Subjects who receive treatment 
other than that intended will be analyzed according to treatment received.


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8.2.1.3.
Pharmacokinetics
The primary analysis set for PK analyses is defined as GS-6207 or TAF PK analysis set, which 
includes all subjects who are randomized, receive any dose of GS-6207 or TAF, and have at least 
1 nonmissing post baseline concentration value for GS-6207 or TAF, or its metabolites. 
8.2.1.4.
Pharmacokinetic/Pharmacodynamic Analysis Set 
The PK/PD analysis set includes all subjects who are in full analysis set and have both 
nonmissing Ct of GS-6207 and the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) 
from Day 1 through Day 10.
8.3.
Data Handling Conventions
Logarithm (base 10) transformation will be applied to HIV-1 RNA levels for efficacy analysis. 
Natural logarithm transformation for all PK parameters of GS-6207, TAF, and its metabolites 
(eg, Cmax, Ct, and AUC0-t, as applicable) will be applied for pharmacokinetic analysis.
For summary statistics, PK concentration values below the limit of quantitation (BLQ) will be 
treated as zero at pre-dose and one-half of the lower limit of quantitation (LLOQ) for post dose 
time points.
Laboratory data that are continuous in nature but are less than the LLOQ or above the upper limit 
of quantitation will be imputed to the value of the lower or upper limit minus or plus 1 
significant digit, respectively (eg, if the result of a continuous laboratory test is < 20, a value of
19 will be assigned; if the result of a continuous laboratory test is < 20.0, a value of 19.9 will be 
assigned).
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized and descriptive statistics will be 
provided.
Demographic summaries will include sex, race, ethnicity, and age.
Baseline data will include a summary of body weight, height, and body mass index.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
Data from the placebo recipients in all cohorts will be combined to form one placebo group for
the purpose of analysis. Each of the GS-6207 and TAF treatment group will be compared to the 
pooled placebo group with respect to the primary efficacy endpoint, the maximum reduction of 
plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10, using the 2-sided t-test 
conducted at an alpha level of 0.05.


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8.5.2.
Secondary Analyses
Correlation between Ct of GS-6207 and the maximum reduction of HIV-1 RNA
(log10 copies/mL) from Day 1 through Day 10 will be assessed using the Pearson correlation 
analysis. Analysis will be done for each treatment group.
The percentage of subjects ever achieving HIV-1 RNA < 50 copies/mL by Day 10 (for Part A 
only) will be summarized by treatment group. Fisher exact test will be used for comparison 
between treatment groups.
Percentage of subjects with any emergence of CAI resistance and TAF resistance, respectively, 
will be summarized by treatment group.
8.6.
Safety Analysis
All safety data collected on or after the first dose date will be summarized by treatment 
according to the study drug received. Data for the pretreatment period will be included in data 
listings.
8.6.1.
Duration of Exposure
A subject’s extent of exposure to study drug data will be generated from the study drug 
administration eCRF form. Exposure data will be listed.
8.6.2.
Adverse Events
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). System Organ Class (SOC), High-Level Group Term 
(HLGT), High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be 
attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
adverse event will be defined as any adverse event that begins on or after the date of first dose of 
study drug.
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
and PT) will be provided by treatment group. Additional summaries will include summaries for 
adverse events by grade, Investigator’s assessment of relationship to study drug, and effect on 
study drug dosing. 
8.6.3.
Laboratory Evaluations
Selected laboratory data will be summarized using only observed data. Data and change from 
baseline at all scheduled time points will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities attached in Appendix 4. 


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Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline, will be summarized by treatment group. 
If baseline data are missing, any graded abnormality (ie, at least a Grade 1) will be considered 
treatment emergent. The post baseline maximum toxicity grade will be summarized by 
laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug will be included in a data 
listing.
8.6.4.
Other Safety Evaluations
Vital sign and safety ECG data will be summarized and/or listed as appropriate.
8.7.
Pharmacokinetic Analysis
The plasma concentration data of GS-6207 and TAF, and its metabolites, will be summarized by 
nominal sampling time and treatment using descriptive statistics. Pharmacokinetic and PBMC 
parameters will be listed and summarized using descriptive statistics (eg, sample size, arithmetic 
mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and 
maximum) by treatment group. The concentrations of the study drug in plasma over time will be 
plotted in semi-logarithmic and linear formats as mean standard deviation and median 
(Q1, Q3), respectively.
8.8.
Sample Size
Part A: A sample size of 6 subjects in each GS-6207 treatment group and a total of 10 placebo 
subjects from all cohorts combined will provide 99% power to detect a treatment difference of 
2.79 log10 copies/mL in maximum reduction of HIV-1 RNA between at least one of the GS-6207 
treatment groups and the placebo group. In this power analysis, it is assumed that a common 
standard deviation for maximum reduction in HIV-1 RNA is 0.526 log10 copies/mL (based on 
Study GS-US-141-1219) and a 2-sided t-test is conducted at an alpha level of 0.05.
Part B: A sample size of 8 subjects in each TAF dose group and a total of 10 subjects in the 
placebo group will provide 99% power to detect a treatment difference of 1.43 log10 copies/mL 
in maximum reduction of HIV-1 RNA between at least one of the TAF dose groups and the 
placebo group from Part A. In this power analysis, it is assumed that a common standard 
deviation for maximum reduction in HIV-1 RNA is 0.52 log10 copies/mL (based on Studies 
GS-US-120-0104 and GS-US-120-1101) and a 2-sided t-test is conducted at an alpha level of 
0.05.


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8.9.
Analysis Schedule
Interim Unblinded Analyses
Prior to the final analysis, a few selected individuals from Gilead will be unblinded to assess the 
interim safety, efficacy, and PK of study drug. This group will consist of at least 
one representative from Clinical Research, Biostatistics, Clinical Pharmacology, and 
Pharmacovigilance/Epidemiology, and may include other personnel as necessary. Details of 
unblinding (eg, memberships, responsibilities, analysis schedules) will be defined in a charter.
1) To select the doses for Cohorts 2 through 5 in Part A
After at least 50% of the subjects and/or after all subjects within each cohort complete the 
Day 10 visit, the Sponsor will conduct interim unblinded analyses to select the GS-6207 doses to 
evaluate in each subsequent cohort. The Sponsor will review cumulative safety (through at least
Day 14), available viral kinetic, and available PK data. The results from these analyses may be 
submitted to regulatory agencies to facilitate the clinical development program or to scientific 
meetings or journals to disseminate the findings. 
2) To select the doses for Cohorts 7 and 8 in Part B
After at least 50% of the subjects in each cohort and/or after all subjects within each cohort 
complete the Day 10 visit, the Sponsor will conduct interim analyses to select the TAF doses to 
evaluate in each subsequent cohort. The Sponsor will review cumulative safety (through at least
Day 14), available viral kinetic, and available PK data. The results from these analyses may be 
submitted to regulatory agencies to facilitate the clinical development program or to scientific 
meetings or journals to disseminate the findings.
3) To select the dose(s) for further clinical development
After the last subject in the study completes Day 10 visit, the Sponsor may conduct an interim 
unblinded analysis of cumulative safety, viral kinetic, and PK data to select the dose(s) for 
further clinical development (e.g. Phase 2 or 3 studies).
Final analysis
The Sponsor will conduct a final analysis of all data after the last subject in the study completes 
the last visit (Day 225) or prematurely discontinues from the study.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and 
South Africa), International Conference on Harmonisation (ICH) guidelines, or with the laws and 
regulations of the country in which the research is conducted, whichever affords the greater 
protection to the study subject. The investigator will ensure adherence to the basic principles of 
Good Clinical Practice, as outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and 
Investigators,” 21 CFR, part 50, 1998, and 21 CFR, part 56, 1998.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, 1998, 
providing documentation of their financial interest or arrangements with Gilead, or proprietary 
interests in the investigational drug under study. This documentation must be provided prior to 
the investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB. The investigator will not begin any study subject activities until 
approval from the IRB has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB any modifications made to the protocol or any accompanying material to be provided to 
the subject after initial IRB approval, with the exception of those necessary to reduce immediate 
risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 
investigator must use the most current IRB approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately signed 
and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB or local 
requirements. The consent form will inform subjects about pharmacogenomic testing and sample 
retention, and their right to receive clinically relevant pharmacogenomic analysis results.


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9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB, or laboratory. Laboratory specimens 
must be labeled in such a way as to protect subject identity while allowing the results to be 
recorded to the proper subject. Refer to specific laboratory instructions. NOTE: The investigator 
must keep a screening log showing codes, names, and addresses for all subjects screened and for 
all subjects enrolled in the trial. Subject data will be processed in accordance with all applicable 
regulations
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, and any other study information, remain the 
sole and exclusive property of Gilead during the conduct of the study and thereafter. This 
information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, and 
(2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, IRB 
and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, physical examination, and 
confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;


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
Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all adverse events and other safety parameters (start and end date, and including 
causality and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, United States, Europe, or Japan) and until there are no pending or planned 
marketing applications in an ICH region; or, if no application is filed or if the application is not 
approved for such indication, until 2 years after the investigation is discontinued and regulatory
authorities have been notified. Investigators may be required to retain documents longer if 
specified by regulatory requirements, by local regulations, or by an agreement with Gilead. The 
investigator must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF casebook will be completed by an authorized study staff 
member whose training for this function is completed in EDC. The eCRF casebook will only 
capture the data required per the protocol schedule of events and procedures. The 
Inclusion/Exclusion Criteria and Enrollment eCRFs should be completed only after all data 
related to eligibility have been received. Subsequent to data entry, a study monitor will perform 
source data verification within the EDC system. System-generated or manual queries will be 
issued to the investigative site staff as data discrepancies are identified by the monitor or internal 
Gilead staff, who routinely review the data for completeness, correctness, and consistency. The 
site coordinator is responsible for responding to the queries in a timely manner, within the 
system, either by confirming the data as correct or updating the original entry, and providing the 
reason for the update (e.g. data entry error). Original entries as well as any changes to data fields 


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Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 66
13 June 2019
will be stored in the audit trail of the system. Prior to any interim time points or database lock 
(as instructed by Gilead), the investigator will use his/her log in credentials to confirm that the 
forms have been reviewed, and that the entries accurately reflect the information in the source 
documents. At the conclusion of the trial, Gilead will provide the site with a read-only archive 
copy of the data entered by that site. This archive must be stored in accordance with the records 
retention requirements outlined in Section 9.1.5.
9.1.7.
GS-6207 and TAF (Investigational Medicinal Product or Study Drug) and 
B/F/TAF Accountability and Return
Where possible, IMP and B/F/TAF should be destroyed at the site. If the site has an appropriate 
SOP for drug destruction as determined by Gilead, the site may destroy used (empty or partially 
empty) and unused IMP and B/F/TAF supplies in accordance with that site’s approved SOP. A 
copy of the site’s approved SOP will be obtained for central files. If IMP and/or B/F/TAF are
destroyed on site, the investigator must maintain accurate records for all IMP and/or B/F/TAF 
destroyed. Records must show the identification and quantity of each unit destroyed, the method 
of destruction, and the person who disposed of the IMP. Upon study completion, copies of the 
IMP accountability records must be filed at the site. Another copy will be returned to Gilead. If 
the site does not have an appropriate SOP for drug destruction, used and unused IMP and 
B/F/TAF supplies are to be sent to the designated disposal facility for eventual destruction. The 
study monitor will provide instructions for return.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRB, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB in 
accordance with local requirements and receive documented IRB approval before modifications 
can be implemented.


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Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency. Gilead will 
ensure that the report meets the standards set out in the ICH Guideline for Structure and Content 
of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:
the results of the study in their entirety have been publicly disclosed by or with the consent of 
Gilead in an abstract, manuscript, or presentation form or the study has been completed at all 
study sites for at least 2 years
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, e.g. attendance at Investigator's Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 68
13 June 2019
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures and notify the appropriate 
regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the investigator 
will assure that adequate consideration is given to the protection of the subjects’ interests.


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 69
13 June 2019
10.
REFERENCES
BIKTARVY®, Gilead Sciences Inc. BIKTARVY® (bictegravir, emtricitabine, and tenofovir 
alafenamide) tablets, for oral use. US Prescribing Information (USPI). Foster 
City, CA. Revised: February.  2018:
Centers for Disease Control (CDC). HIV Surveillance Report: Diagnoses of HIV Infection in the 
United States and Dependent Areas, 2015. Volume 27. Available at: 
http://www.cdc.gov/hiv/library/reports/surveillance/.  Accessed: 30 January.  
2017.
Claborn KR, Meier E, Miller MB, Leffingwell TR. A Systematic Review Of Treatment Fatigue 
Among HIV-Infected Patients Prescribed Antiretroviral Therapy. Psychology, 
health & medicine 2015;20 (3):1-11.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
DESCOVY®, Gilead Sciences Inc. DESCOVY® (emtricitabine and tenofovir alafenamide) 
tablets, for oral use. U. S. Prescribing Information. Foster City, CA. Revised: 
September.  2017:
Ruane PJ, Dejesus E, Berger D, Markowitz M, Bredeek UF, Callebaut C, et al. Antiviral 
Activity, Safety, and Pharmacokinetics/Pharmacodynamics of Tenofovir 
Alafenamide as 10-Day Monotherapy in HIV-1-Positive Adults. J Acquir Immune 
Defic Syndr 2013;63 (4):449-55.
Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT. Revised 
surveillance case definitions for HIV infection among adults, adolescents, and 
children aged <18 months and for HIV infection and AIDS among children aged 
18 months to <13 years--United States, 2008. MMWR Recomm Rep 2008;57 
(RR-10):1-12.
STRIBILD®, Gilead Sciences Inc. STRIBILD® (elvitegravir, cobicistat, emtricitabine, tenofovir 
disoproxil fumarate) Tablets, for Oral Use. U. S. Prescribing Information. Foster 
City, CA. Revised: January.  2019:
The Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for 
Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults 
and Adolescents Living with HIV. Available at: 
http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Last 
Updated: 17 October.  2017.
UNAIDS. Fact Sheet 2016: Global Statistics-2015. Available at: 
http://www.unaids.org/en/resources/documents/2016/UNAIDS_FactSheet.  2016.
VIREAD, Gilead Sciences Inc. VIREAD® (tenofovir disoproxil fumarate) Tablets, for Oral Use. 
VIREAD® (tenofovir disoproxil fumarate) Powder, for Oral Use. U. S. 
Prescribing Information. Foster City, CA. Revised: April.  2019:


GS-6207 and TAF
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Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 70
13 June 2019
11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)
Appendix 6.
GS-6207 Pregnancy Precautions (Part A), Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
Appendix 7.
TAF Pregnancy Precautions (Part B), Definition for Female of Childbearing 
Potential, and Contraceptive Requirements


GS-6207 and TAF 
Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
Final 
Amendment4 
A Phase 1 b Randomized, Double-Blinded, Placebo Controlled, Multi-Cohort Study of the 
Safety, Pharmacokinetics, and Antiviral Activity of GS-6207 administered subcutaneously in 
HIV-1 Infected Subjects 
GS-US-200-4072, Amendment 4, 13 June 2019 
This protocol has been approved by Gilead Sciences, lnc. The following signature documents 
this approval. 
PPD 
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 folly informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 71 
13June2019 


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 72
13 June 2019
Appendix 2.
Study Procedures Table
Screeninga
Day 1b, h
Day 2
Day 3h
Day 4
Day 7 h
Day 8
Day 9
Day 10h
Day 14
Day 29
Day 43
Day 57
Day 85 h
Day 113
Day 141
Day 169 h
Day 197
Day 225 h
Early 
Terminationd
Written Informed 
Consent
X
Medical History 
X
Complete Physical 
Examination
X
X
X
Symptom Directed 
Physical Examination
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signsj
(including weight)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
X
X
X
Height
X
Hematologyf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistryg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Estimated GFRc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis and Urine 
Chemistryk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Storage Sample
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Teste
X
X
X
X
X
X
X
X
X
X
Serum FSHi
X
Urine Pregnancy test
X
HBV, HCV Testing
X
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV-1 
Genotyping/Phenotyping
X
HIV-1 capsid 
Genotype/Phenotyper
X
X
CCI


GS-6207 and TAF 
Protocol GS-US-200-4072 
Final 
Gilead Sciences, Inc. 
Amendment4 
... 
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HIV DNA genotyping 
X 
X 
X 
Plasma HIV-1 RNA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma Storage Sample 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Intensive PK Plasma 
xi 
Collection (Part A) 
Single Anytime PK 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma Sample (Pait A)n 
PK Plasma Sample 
X 
X 
X 
X 
X 
X 
X 
X 
(Part B) 0 ·-· 
·----------
X 
X 
X 
X 
X 
X 
••--- ---••········· 
• • • • 
• 
X 
T AF Administration 
X 
(PartB) 
BIFITAF dispensation 
X 
X 
X 
X 
X 
Adverse Events/ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Meds 
a 
Screening evaluations must be completed within 42 days prior to Day 1. 
b 
Day 1 tests and procedm·es must be completed prior to administration of the dose of study drug 
c 
According to the Cockcroft-Gault fo1mula 
d 
Within 72 hom·s of pe1manently discontinuing study. Counsel subject regarding the importance of continuing a complete ARV therapy in accordance to standard of care, and 
refer patient to an appropriate HIV treatment facility. 
e 
Females of childbearing potential only 
f 
Hematology: CBC with differential and platelet count 
g 
Chemistries: Alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and indirect bilimbin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, phosphoms, magnesium, potassium, sodium, tu-ic acid, and amylase (reflex lipase testing if total amylase > 1.5 x ULN). 
h 
Fasting ovemight (;?: 6 hotu·s) required for Days 1, 3, 7, 10, 85, 169 and 225 
CONFIDENTIAL 
Page 73 
13 June 2019 


GS-6207 and TAF 
Protocol GS-US-200-4072 
Gilead Sciences, Inc. 
FSH test is required for female subjects who have stopped menstruating for :C:: 12 months but do not have documentation of ovarian honuonal failure. 
J 
Vital signs - blood pressm·e, pulse, respiration rate, and temperattu·e, weight 
Final 
Amendment4 
k 
Urinalysis and Urine Chemistry: including color & clarity, specific gravity, pH, glucose, ketones, bilimbin, m·obilinogen, blood, nitrite, leukocyte esterase and microscopic 
(if microscopic elements are seen), mine protein, albmu.in, creatinine, phosphate, calcium, magnesimu and uric acid 
I 
n 
0 
p 
I 
r 
Patt A: Serial blood samples to detenu.ine phanuacokinetics (PK) in plasma will be collected at the following time points relative to study dmg dosing O (pre-dose), I, 2,4, 8, 
12 and 24 hom-s ost dose. 
Patt A: Smg e Anytnue PK samp e to e co ecte at t 1e Day 3, 4, an 7 t u·ou 1 225 VISlts. 
Patt B: Plasma PK-am 
!es to be collected at the following time points relative to study dmg dosing: 0 (pre-dose), 0.5, I, 2, 3, 4, 6, 8, IO, 12, 24 and 48 hours post dose; as 
well as at Days 4, 
7, 8, 9 and IO at approximately the same time in the moming as pre-dose on Day I. 
Patt B: PBMC PK sam es to e co ecte at e following time points relative to stlldy dmg dosing: 0 (pre-dose), I, 2, 4, 6, 8, 12, 24 and 48 hom·s post dose, as well as at 
Da s 4 
7 8 9 and IO at a 
roximatel the same time in the moming as pre-dose on Day I. 
1 1ty pnor to randomization. Pait B: the capsid genotype/phenotype will be completed for 
CONFIDENTIAL 
Page 74 
13 June 2019 


GS-6207 and TAF 
Protocol GS-US-200-4072 
Final 
Gilead Sciences, Inc. 
Amendment 4 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
Grade 1 
Grade 2 
H 
' .. 
May continue on t he study 
at the discretion of t he 
investigator 
CONFIDENTIAL 
Page 75 
Grade 3 
V 
Repeat lab to confirm 
toxicity grade 
V 
Grade 4 
If confirmed, then monitor 
periodically until resolved 
or ret urned to baseline or is 
otherwise explained 
13 June 2019 


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 76
13 June 2019
Appendix 4.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Antiviral Toxicity Grading Scale Version: 01 April 2015
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
HIV POSITIVE
Adult and Pediatric 
57 Days
8.5 to 10.0 g/dL 
85 to 100 g/L
7.5 to 8.5 g/dL 
75 to 85 g/L
6.5 to 7.5 g/dL 
65 to 75 g/L
6.5 g/dL
65 g/L
HIV NEGATIVE
Adult and Pediatric 
57 Days 
10.0 to 10.9 g/dL
100 to 109 g/L
OR
Any decrease from Baseline
2.5 to 3.5 g/dL
25 to 35 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
OR
Any decrease from Baseline
3.5 to 4.5 g/dL
35 to 45 g/L
7.0 to 9.0 g/dL
70 to 90 g/L
OR
Any decrease from Baseline
4.5 g/dL
45 g/L
7.0 g/dL
70 g/L
Infant, 36–56 Days
(HIV POSITIVE OR
NEGATIVE)
8.5 to 9.4 g/dL
85 to 94 g/L
7.0 to 8.5 g/dL
70 to 85 g/L
6.0 to 7.0 g/dL
60 to < 70 g/L
6.0 g/dL
< 60 g/L
Infant, 22–35 Days
(HIV POSITIVE OR
NEGATIVE)
9.5 to 10.5 g/dL
95 to 105 g/L
8.0 to 9.5 g/dL
80 to 95 g/L
7.0 to 8.0 g/dL
70 to 80 g/L
7.0 g/dL
70 g/L
Infant, 1–21 Days
(HIV POSITIVE OR
NEGATIVE)
12.0 to 13.0 g/dL
120 to 130 g/L
10.0 to 12.0 g/dL
100 to 120 g/L
9.0 to 10.0 g/dL
90 to 100 g/L
9.0 g/dL
90 g/L
Absolute Neutrophil Count 
(ANC)
Adult and Pediatric, 
≥ 7 Months#
1000 to 1300/mm3
750 to 1000/mm3
500 to 750/mm3
500/mm3
1.00 to 1.30 GI/L
0.75 to 1.00 GI/L
0.50 to 0.75 GI/L
0.50 GI/L
Absolute CD4+ Count
HIV NEGATIVE ONLY
Adult and Pediatric 
> 13 Years
300 to 400/mm3
300 to 400/μL
200 to 300/mm3
200 to 300/μL
100 to 200/mm3
100 to 200/μL
100/mm3
100/μL


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Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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13 June 2019
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects. Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 78
13 June 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia 
130 to <LLN mEq/L
125 to 130 mEq/L
121 to 125 mEq/L
121 mEq/L
130 to <LLN mmol/L
125 to 130 mmol/L
121 to 125 mmol/L
121 mmol/L
Hypernatremia 
>ULN to 150 mEq/L
150 to 154 mEq/L
154 to 159 mEq/L
159 mEq/L
>ULN to 150 mmol/L
150 to 154 mmol/L
154 to 159 mmol/L
159 mmol/L
Hypokalemia 
Adult and Pediatric
1 Year
3.0 to <LLN mEq/L
2.5 to 3.0 mEq/L
2.0 to 2.5 mEq/L
2.0 mEq/L
3.0 to <LLN mmol/L
2.5 to 3.0 mmol/L
2.0 to 2.5 mmol/L
2.0 mmol/L
Infant <1 Year 
3.0 to 3.4 mEq/L
3.0 to 3.4 mmol/L
2.5 to 3.0 mEq/L
2.5 to <3.0 mmolL
2.0 to 2.5 mEq/L
2.0 to <2.5 mmolL
2.0 mEq/L
<2.0 mmolL
Hyperkalemia 
Adult and Pediatric
1 Year
5.6 to 6.0 mEq/L
5.6 to 6.0 mmol/L
6.0 to 6.5 mEq/L
6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Infant <1 Year
>ULN to 6.0 mEq/L
>ULN to 6.0 mmol/L
> 6.0 to 6.5 mEq/L
> 6.0 to 6.5 mmol/L
6.5 to 7.0 mEq/L
6.5 to 7.0 mmol/L
7.0 mEq/L
7.0 mmol/L
Hypoglycemia
Adult and Pediatric
1 Month
55 to 64 mg/dL
3.03 to 3.58 mmol/L
40 to 55 mg/dL
2.20 to 3.03 mmol/L
30 to 40 mg/dL
1.64 to 2.20 mmol/L
30 mg/dL
1.64 mmol/L
Infant, 1 Month
50 to 54 mg/dL
2.8 to 3.0 mmol/L
40 to 50 mg/dL
2.2 to 2.8 mmol/L
30 to 40 mg/dL
1.7 to 2.2 mmol/L
30 mg/dL
1.7 mmol/L
Hyperglycemia, Nonfasting 
116 to 160 mg/dL
160 to 250 mg/dL
250 to 500 mg/dL
500 mg/dL
6.42 to 8.91 mmol/L
8.91 to 13.90 mmol/L
13.90 to 27.79 mmol/L
27.79 mmol/L
Hyperglycemia, Fasting
110 to 125 mg/dL
6.08 to 6.96 mmol/L
>125 to 250 mg/dL
>6.96 to 13.90 mmol/L
>250 to 500 mg/dL
>13.90 to 27.79 mmol/L
>500 mg/dL
>27.79 mmol/L


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 79
13 June 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Hypocalcemia 
(corrected for albumin if 
appropriate*)
Adult and Pediatric
2 Years
7.8 <LLN mg/dL
1.94 to <LLN mmol/L
7.0 to 7.8 mg/dL
1.74 to 1.94 mmol/L
6.1 to 7.0 mg/dL
1.51 to 1.74 mmol/L
6.1 mg/dL
1.51 mmol/L
Pediatric ≥7 days -2 Years
7.8 to 8.4 mg/dL
1.94 to 2.10 mmol/L
7.0 to <7.8 mg/dL
1.74 to <1.94 mmolL
6.1 to <7.0 mg/dL
1.51 to < 1.74 mmolL
< 6.1 mg/dL
< 1.51 mmol/L
Infant, 7 Days
6.5 to 7.5 mg/dL
1.61 to 1.88 mmol/L
6.0 to 6.5 mg/dL
1.49 to < 1.61 mmol/L
5.5 to 6.0 mg/dL
1.36 to < 1.49 mmol/L 
5.5 mg/dL
< 1.36 mmol/L
Hypercalcemia (corrected 
for albumin if appropriate*)
Adult and Pediatric 
7 Days
>ULN to 11.5 mg/dL
11.5 to 12.5 mg/dL
12.5 to 13.5 mg/dL
13.5 mg/dL
>ULN to 2.88 mmol/L
2.88 to 3.13 mmol/L
3.13 to 3.38 mmol/L
3.38 mmol/L
Infant, 7 Days
11.5 to 12.4 mg/dL
2.86 to 3.10 mmol/L
12.4 to 12.9 mg/dL
> 3.10 to 3.23 mmol/L
12.9 to 13.5 mg/dL
> 3.23 to 3.38 mmol/L
13.5 mg/dL
> 3.38 mmol/L
Hypocalcemia (ionized)
3.0 mg/dL to LLN
2.5 to < 3.0 mg/dL
2.0 to 2.5 mg/dL
2.0 mg/dL
0.74 mmol/L to LLN
0.62 to 0.74 mmol/L
0.49 to 0.62 mmol/L
0.49 mmol/L
Hypercalcemia (ionized)
ULN to 6.0 mg/dL
6.0 to 6.5 mg/dL
6.5 to 7.0 mg/dL
7.0 mg/dL
ULN to 1.50 mmol/L
1.50 to 1.63 mmol/L
1.63 to 1.75 mmol/L
1.75 mmol/L
Hypomagnesemia
1.40 to <LLN mg/dL
1.2 to <LLN mEq/L
1.04 to 1.40 mg/dL
0.9 to 1.2 mEq/L
0.67 to 1.04 mg/dL
0.6 to 0.9 mEq/L
0.67 mg/dL
0.6 mEq/L
0.58 to <LLN mmol/L
0.43 to 0.58 mmol/L
0.28 to 0.43 mmol/L
0.28 mmol/L
Hypophosphatemia
Adult and Pediatric
14 Years
2.0 to < LLN mg/dL
0.63 to LLN mmol/L
1.5 to 2.0 mg/dL
0.47 to 0.63 mmol/L
1.0 to 1.5 mg/dL
0.31 to 0.47 mmol/L
1.0 mg/dL
0.31 mmol/L
Pediatric 1 Year–14 Years 
3.0 to <LLN mg/dL
0.96 to <LLN mmol/L
2.5 to 3.0 mg/dL
0.80 to < 0.96 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 80
13 June 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
Pediatric 1 Year
3.5 to <LLN mg/dL
1.12 to <LLN mmol/L
2.5 to 3.5 mg/dL
0.80 to < 1.12 mmol/L
1.5 to 2.5 mg/dL
0.47 to < 0.80 mmol/L
1.5 mg/dL
< 0.47 mmol/L
Hyperbilirubinemia 
Adult and Pediatric 
> 14 Days
1.0 to 1.5 ULN 
1.5 to 2.5 ULN
2.5 to 5.0 ULN 
5.0 ULN 
Infant, 14 Days
(non-hemolytic)
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 to 30.0 mg/dL
> 428 to 513 μmol/L
30.0 mg/dL
> 513 μmol/L
Infant, 14 Days
(hemolytic)
NA
NA
20.0 to 25.0 mg/dL
342 to 428 μmol/L
25.0 mg/dL
> 428 μmol/L
Blood Urea Nitrogen
1.25 to 2.50 ULN 
2.50 to 5.00 ULN 
5.00 to 10.00 ULN 
10.00 ULN
Hyperuricemia
>ULN to 10.0 mg/dL 
10.0 to 12.0 mg/dL 
12.0 to 15.0 mg/dL 
15.0 mg/dL
>ULN to 597 μmol/L
597 to 716 μmol/L
716 to 895 μmol/L
895 μmol/L
Hypouricemia
Adult and Pediatric
≥ 1 year
Infant < 1 Year
1.5 mg/dL to LLN
87 μmol/L to LLN
1.0 to 1.5 mg/dL
57 to 87 μmol/L
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
N/A
1.0 mg/dl to <LLN-
57 μmol to <LLN
0.5 to 1.0 mg/dL
27 to 57 μmol/L
0.5 mg/dL
27 μmol/L
Creatinine** 
1.50 to 2.00 mg/dL
133 to 177 μmol/L
2.00 to 3.00 mg/dL
177 to 265 μmol/L
3.00 to 6.00 mg/dL 
265 to 530 μmol/L
6.00 mg/dL
530 μmol/L
Bicarbonate
Adult and Pediatric 
≥ 4 Years
16.0 mEq/L to LLN 
11.0 to 16.0 mEq/L
8.0 to 11.0 mEq/L
8.0 mEq/L
16.0 mmol/L to LLN
11.0 to 16.0 mmol/L
8.0 to 11.0 mmol/L
8.0 mmol/L
Pediatric < 4 Years
NA
11.0 mEq/Lto <LLN
8.0 to 11.0 mEq/L
8.0 mEq/L
11.0 mmol/L to <LLN
8.0 to 11.0 mmol/L
8.0 mmol/L
Triglycerides
(Fasting)
NA
500 to 750 mg/dL
5.64–8.47 mmol/L
750 to 1200 mg/dL
8.47–13.55 mmol/L
1200 mg/dL
13.55 mmol/L


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 81
13 June 2019
CHEMISTRY
Grade 1
Grade 2
Grade 3
Grade 4
LDL (Fasting)
Adult
130 to 160 mg/dL
>160 to 190 mg/dL
> 190 mg/dL
NA
3.35 to 4.15 mmol/L
>4.15 to 4.92 mmol/L
>4.92 mmol/L
LDL (Fasting)
Pediatric >2 to <18 years
110 to 130 mg/dL
>130 to 190 mg/dL
> 190 mg/dL
NA
2.84 to 3.37 mmol/L
>3.37 to 4.92 mmol/L
>4.92 mmol/L
Hypercholesterolemia
(Fasting)
200 to 239 mg/dL
239 to 300 mg/dL
300 mg/dL
NA
5.16 to 6.19 mmol/L
6.19 to 7.77 mmol/L
7.77 mmol/L
Pediatric 18 Years
170 to 199 mg/dL
4.39 to 5.15 mmol/L
199 to 300 mg/dL
5.15 to 7.77 mmol/L
300 mg/dL
7.77 mmol/L
NA
Creatine Kinase
3.0 to 6.0 ULN
6.0 to 10.0 ULN
10.0 to 20.0 ULN
20.0 ULN
*
Calcium should be corrected for albumin if albumin is < 4.0 g/dL
**
An overlap between the Grade 1 scale and the Lab’s normal range for creatinine may result for Male subjects >70 yrs. Please follow the Gilead convention of grading any 
result within the LLN and ULN a 0.


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 82
13 June 2019
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
ALT (SGPT) 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
GGT
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Alkaline Phosphatase 
1.25 to 2.50 ULN
2.50 to 5.00 ULN
5.00 to 10.00 ULN
10.00 ULN
Total Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Pancreatic Amylase
1.0 to 1.5 ULN
1.5 to 2.0 ULN
2.0 to 5.0 ULN
5.0 ULN
Lipase 
1.0 to 1.5 ULN
1.5 to 3.0 ULN
3.0 to 5.0 ULN
5.0 ULN
Albumin
Pediatrics <16 years 
≥ 16 years
-
2.0 to LLN g/dL
20 to LLN g/L
2.0 g/dL
20 g/L
NA
3.0 g/dL to LLN
30 g/L to LLN
2.0 to 3.0 g/dL
20 to 30 g/L
2.0 g/dL
20 g/L
NA


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 83
13 June 2019
URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Hematuria (Dipstick) 
1
2
3-4+
NA
Hematuria (Quantitative) 
See Note below
Females
>ULN - 10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Males
6-10 RBC/HPF
10-75 RBC/HPF
> 75 RBC/HPF
NA
Proteinuria (Dipstick)
1
2–3
4
NA
Proteinuria, 24 Hour Collection
Adult and Pediatric 
10 Years
200 to 999 mg/24 h
>999 to 1999 mg/24 h
>1999 to 3500 mg/24 h
3500 mg/24 h
Pediatric 3 Mo to 
< 10 Years
201 to 499 mg/m2/24 h
>499 to 799 mg/m2/24 h
>799 to 1000 mg/m2/24 h
1000 mg/ m2/24 h
Glycosuria (Dipstick)
1+
2-3
4
NA
Notes:

Toxicity grades for Quantitative and Dipstick Hematuria will be assigned by Covance Laboratory, however for other laboratories, toxicity grades will only be assigned to 
Dipstick Hematuria.

With the exception of lipid tests, any graded laboratory test with a result that is between the LLN and ULN should be assigned Grade 0.

If the severity of a clinical AE could fall under either one of two grades (eg,., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE.


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
Page 84
13 June 2019
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Arrhythmia (general)
(By ECG or physical exam)
Asymptomatic AND No 
intervention indicated
Asymptomatic AND 
Non-urgent medical 
intervention indicated
Symptomatic, 
non-life-threatening AND 
Non-urgent medical 
intervention indicated 
Life-threatening arrhythmia 
OR Urgent intervention 
indicated
Cardiac-ischemia/Infarction
NA
NA
Symptomatic ischemia 
(stable angina) OR Testing 
consistent with ischemia 
Unstable angina OR Acute 
myocardial infarction
Hemorrhage (significant acute 
blood loss)
NA
Symptomatic AND No 
transfusion indicated
Symptomatic AND 
Transfusion of 2 units 
packed RBCs (for children 
10 cc/kg) indicated 
Life-threatening hypotension 
OR Transfusion of 2 units 
packed RBCs indicated (for 
children 10 cc/kg) indicated
Hypertension (with repeat 
testing at same visit)
140–159 mmHg systolic 
OR 
90–99 mmHg diastolic
159–179 mmHg systolic 
OR 
99–109 mmHg diastolic
179 mmHg systolic 
OR 
109 mmHg diastolic
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization (other than 
ER visit) indicated
Pediatric 17 Years (with 
repeat testing at same visit)
NA
91st–94th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
≥95th percentile adjusted 
for age, height, and gender 
(systolic and/or diastolic)
Life-threatening consequences 
(eg, malignant hypertension) 
OR Hospitalization indicated 
(other than emergency room 
visit)
Hypotension
NA
Symptomatic, corrected with 
oral fluid replacement
Symptomatic, IV fluids 
indicated
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure
Pericardial Effusion
Asymptomatic, small 
effusion requiring no 
intervention
Asymptomatic, moderate or 
larger effusion requiring no 
intervention
Effusion with non-life-
threatening physiologic 
consequences OR Effusion 
with nonurgent intervention 
indicated
Life-threatening consequences 
(eg, tamponade) OR Urgent 
intervention indicated


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Prolonged PR Interval
PR interval 
0.21 to 0.25 sec
PR interval
0.25 sec
Type II 2nd degree AV 
block OR Ventricular pause 
3.0 sec
Complete AV block 
Pediatric 16 Years
1st degree AV block
(PR > normal for age and 
rate)
Type I 2nd degree AV block 
Type II 2nd degree AV 
block 
Complete AV block
Prolonged QTc
Asymptomatic, QTc interval 
0.45 to 0.47 sec OR Increase 
interval 0.03 sec above 
baseline
Asymptomatic, QTc interval 
0.48 to 0.49 sec OR Increase 
in interval 0.03 to 0.05 sec 
above baseline
Asymptomatic, QTc interval 
0.50 sec OR Increase in 
interval 0.06 sec above 
baseline
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Pediatric 16 Years
Asymptomatic, QTc interval 
0.450 to 0.464 sec 
Asymptomatic, QTc interval 
0.465 to 0.479 sec 
Asymptomatic, QTc interval 
0.480 sec 
Life-threatening 
consequences, eg, Torsade de 
pointes or other associated 
serious ventricular 
dysrhythmia
Thrombosis/Embolism
NA
Deep vein thrombosis AND 
No intervention indicated 
(eg, anticoagulation, lysis 
filter, invasive procedure) 
Deep vein thrombosis AND 
Intervention indicated 
(eg, anticoagulation, lysis
filter, invasive procedure) 
Embolic event (eg, pulmonary 
embolism, life-threatening 
thrombus) 
Vasovagal Episode (associated 
with a procedure of any kind)
Present without loss of 
consciousness 
Present with transient loss of 
consciousness
NA 
NA
Ventricular Dysfunction 
(congestive heart failure, 
CHF)
NA
Asymptomatic diagnostic 
finding AND intervention 
indicated
New onset with symptoms 
OR Worsening symptomatic 
CHF
Life-threatening CHF


GS-6207 and TAF
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Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Bronchospasm (acute)
FEV1 or peak flow reduced to 
70% to 80%
FEV1 or peak flow 50% to 69%
FEV1 or peak flow 25% 
to 49% 
Cyanosis OR FEV1 or peak flow 
25% OR Intubation
Dyspnea or Respiratory 
Distress
Dyspnea on exertion with no 
or minimal interference with 
usual social & functional 
activities 
Dyspnea on exertion causing 
greater than minimal 
interference with usual social & 
functional activities 
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities 
Respiratory failure with 
ventilatory support indicated
Pediatric 14 Years
Wheezing OR minimal 
increase in respiratory rate for 
age
Nasal flaring OR Intercostal 
retractions OR Pulse oximetry 
90% to 95%
Dyspnea at rest causing 
inability to perform usual 
social & functional 
activities OR Pulse 
oximetry 90%
Respiratory failure with 
ventilatory support indicated
OCULAR/VISUAL
Grade 1
Grade 2
Grade 3
Grade 4
Uveitis
Asymptomatic but detectable 
on exam
Symptomatic anterior uveitis OR 
Medical intervention indicated
Posterior or pan-uveitis OR 
Operative intervention 
indicated
Disabling visual loss in affected 
eye(s) 
Visual Changes (from 
baseline)
Visual changes causing no or 
minimal interference with 
usual social & functional 
activities
Visual changes causing greater 
than minimal interference with 
usual social & functional 
activities
Visual changes causing 
inability to perform usual 
social & functional 
activities
Disabling visual loss in affected 
eye(s)


GS-6207 and TAF
Protocol GS–US-200-4072
Final
Gilead Sciences, Inc. 
Amendment 4
CONFIDENTIAL
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SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Alopecia
Thinning detectable by 
study participant or 
caregiver (for disabled 
adults)
Thinning or patchy hair loss 
detectable by health care 
provider
Complete hair loss
NA
Cutaneous Reaction – Rash
Localized macular rash 
Diffuse macular, 
maculopapular, or 
morbilliform rash OR Target 
lesions 
Diffuse macular, 
maculopapular, or morbilliform 
rash with vesicles or limited 
number of bullae OR 
Superficial ulcerations of 
mucous membrane limited to 
one site
Extensive or generalized 
bullous lesions OR 
Stevens-Johnson syndrome 
OR Ulceration of mucous 
membrane involving 
two or more distinct 
mucosal sites OR Toxic 
epidermal necrolysis 
(TEN)
Hyperpigmentation
Slight or localized
Marked or generalized
NA
NA
Hypopigmentation
Slight or localized 
Marked or generalized
NA
NA
Pruritis (itching – no skin 
lesions) 
(See also Injection Site 
Reactions: Pruritis associated 
with injection)
Itching causing no or 
minimal interference with 
usual social & functional 
activities
Itching causing greater than 
minimal interference with 
usual social & functional 
activities
Itching causing inability to 
perform usual social & 
functional activities 
NA


GS-6207 and TAF
Protocol GS–US-200-4072
Final
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Amendment 4
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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Anorexia
Loss of appetite without 
decreased oral intake
Loss of appetite associated with 
decreased oral intake without 
significant weight loss 
Loss of appetite associated 
with significant weight loss 
Life-threatening 
consequences OR Aggressive 
intervention indicated 
[eg, tube feeding or total 
parenteral nutrition]
Ascites
Asymptomatic
Symptomatic AND Intervention 
indicated (eg, diuretics or 
therapeutic paracentesis)
Symptomatic despite 
intervention
Life-threatening 
consequences
Cholecystitis
NA
Symptomatic AND Medical 
intervention indicated
Radiologic, endoscopic, or 
operative intervention 
indicated
Life-threatening 
consequences (eg, sepsis or 
perforation) 
Constipation 
NA
Persistent constipation requiring 
regular use of dietary 
modifications, laxatives, or 
enemas 
Obstipation with manual 
evacuation indicated
Life-threatening 
consequences 
(eg, obstruction)
Diarrhea 
Adult and Pediatric 
1 Year
Transient or intermittent 
episodes of unformed 
stools OR Increase of 
3 stools over 
baseline/24 hr
Persistent episodes of unformed 
to watery stools OR Increase of 
4–6 stools over baseline per 
24 hrs. 
Bloody diarrhea OR Increase 
of 7 stools per 24-hour 
period OR IV fluid 
replacement indicated
Life-threatening 
consequences 
(eg, hypotensive shock)
Pediatric 1 Year
Liquid stools (more 
unformed than usual) but 
usual number of stools
Liquid stools with increased 
number of stools OR Mild 
dehydration
Liquid stools with moderate 
dehydration
Liquid stools resulting in 
severe dehydration with 
aggressive rehydration 
indicated OR Hypotensive 
shock
Dysphagia-Odynophagia 
Symptomatic but able to 
eat usual diet
Symptoms causing altered 
dietary intake without medical 
intervention indicated
Symptoms causing severely 
altered dietary intake with 
medical intervention 
indicated
Life-threatening reduction in 
oral intake


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GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Mucositis/Stomatitis 
(clinical exam)
See also Proctitis, 
Dysphagia-Odynophagia
Erythema of the mucosa
Patchy pseudomembranes or 
ulcerations 
Confluent pseudomembranes
or ulcerations OR Mucosal 
bleeding with minor trauma
Tissue necrosis OR Diffuse 
spontaneous mucosal 
bleeding OR Life-threatening 
consequences (eg, aspiration, 
choking)
Nausea 
Transient (24 hours) or 
intermittent nausea with no 
or minimal interference 
with oral intake
Persistent nausea resulting in 
decreased oral intake for 
24-48 hours
Persistent nausea resulting in 
minimal oral intake for 
48 hours OR Aggressive 
rehydration indicated 
(eg, IV fluids)
Life-threatening 
consequences 
(eg, hypotensive shock)
Pancreatitis
NA
Symptomatic AND 
Hospitalization not indicated 
(other than ER visit)
Symptomatic AND 
Hospitalization indicated 
(other than ER visit)
Life-threatening 
consequences (eg, sepsis, 
circulatory failure, 
hemorrhage)
Proctitis 
(functional-symptomatic)
Also see Mucositis/ 
Stomatitis for Clinical Exam
Rectal discomfort AND No 
intervention indicated
Symptoms causing greater than 
minimal interference with usual 
social & functional activities 
OR Medical intervention 
indicated 
Symptoms causing inability 
to perform usual social/ 
functional activities OR 
Operative intervention 
indicated 
Life-threatening 
consequences 
(eg, perforation)
Vomiting
Transient or intermittent 
vomiting with no or 
minimal interference with 
oral intake
Frequent episodes of vomiting 
with no or mild dehydration
Persistent vomiting resulting 
in orthostatic hypotension OR 
Aggressive rehydration 
indicated
Life-threatening 
consequences 
(eg, hypotensive shock)


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Alteration in 
Personality-Behavior or in 
Mood (eg, agitation, 
anxiety, depression, mania, 
psychosis)
Alteration causing no or 
minimal interference with 
usual social & functional 
activities 
Alteration causing greater than 
minimal interference with 
usual social & functional 
activities 
Alteration causing inability to 
perform usual social & 
functional activities 
Behavior potentially harmful 
to self or others 
(eg, suicidal/homicidal 
ideation or attempt, acute 
psychosis) OR Causing 
inability to perform basic 
self-care functions
Altered Mental Status 
For Dementia, see Cognitive 
and Behavioral/Attentional 
Disturbance (including 
dementia and ADD)
Changes causing no or 
minimal interference with 
usual social & functional 
activities
Mild lethargy or somnolence 
causing greater than minimal 
interference with usual social 
& functional activities
Confusion, memory 
impairment, lethargy, or 
somnolence causing inability 
to perform usual social & 
functional activities
Delirium OR obtundation, OR 
coma
Ataxia 
Asymptomatic ataxia 
detectable on exam OR 
Minimal ataxia causing no 
or minimal interference with 
usual social & functional 
activities
Symptomatic ataxia causing 
greater than minimal 
interference with usual social 
& functional activities
Symptomatic ataxia causing 
inability to perform usual 
social & functional activities 
Disabling ataxia causing 
inability to perform basic 
self-care functions
Cognitive and 
Behavioral/Attentional 
Disturbance (including 
dementia and Attention 
Deficit Disorder) 
Disability causing no or 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources not indicated
Disability causing greater than 
minimal interference with 
usual social & functional 
activities OR Specialized 
resources on part-time basis 
indicated
Disability causing inability to 
perform usual social & 
functional activities OR 
Specialized resources on a 
full-time basis indicated
Disability causing inability to 
perform basic self-care 
functions OR 
Institutionalization indicated
CNS Ischemia
(acute)
NA
NA
Transient ischemic attack
Cerebral vascular accident 
(CVA, stroke) with 
neurological deficit 


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Developmental delay –
Pediatric 16 Years
Mild developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate 
for the setting 
Moderate developmental 
delay, either motor or 
cognitive, as determined by 
comparison with a 
developmental screening tool 
appropriate for the setting 
Severe developmental delay, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting 
Developmental regression, 
either motor or cognitive, as 
determined by comparison 
with a developmental 
screening tool appropriate for 
the setting
Headache 
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater 
than minimal interference with 
usual social & functional 
activities
Symptoms causing inability to 
perform usual social & 
functional activities
Symptoms causing inability to 
perform basic self-care 
functions OR Hospitalization 
indicated (other than ER visit) 
OR Headache with significant 
impairment of alertness or
other neurologic function 
Insomnia
NA
Difficulty sleeping causing 
greater than minimal 
interference with usual 
social/functional activities
Difficulty sleeping causing 
inability to perform usual 
social & functional activities
Disabling insomnia causing 
inability to perform basic 
self-care functions
Neuromuscular Weakness 
(including myopathy & 
neuropathy) 
Asymptomatic with 
decreased strength on exam 
OR Minimal muscle 
weak-ness causing no or 
minimal interference with 
usual social & functional 
activities
Muscle weakness causing 
greater than minimal 
interference with usual social 
& functional activities
Muscle weakness causing 
inability to perform usual 
social & functional activities 
Disabling muscle weakness 
causing inability to perform 
basic self-care functions OR 
Respiratory muscle weakness 
impairing ventilation
Neurosensory Alteration 
(including paresthesia and 
painful neuropathy)
Asymptomatic with sensory 
alteration on exam or 
minimal paresthesia causing 
no or minimal interference 
with usual social &
functional activities 
Sensory alteration or 
paresthesia causing greater 
than minimal interference with 
usual social & functional 
activities 
Sensory alteration or 
paresthesia causing inability to 
perform usual social & 
functional activities
Disabling sensory alteration or 
paresthesia causing inability to 
perform basic self-care 
functions


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Seizure: (new onset) 
NA
1 seizure 
2–4 seizures 
Seizures of any kind that are 
prolonged, repetitive 
(eg, status epilepticus), or 
difficult to control 
(eg, refractory epilepsy)
Seizure: (pre-existing) 
For Worsening of Existing 
Epilepsy the Grades Should 
Be Based on an Increase 
from Previous Level of 
Control to Any of These 
Levels
NA
Increased frequency of 
pre-existing seizures 
(non-repetitive) without 
change in seizure character 
OR infrequent breakthrough 
seizures while on stable meds 
in a previously controlled 
seizure disorder
Change in seizure character 
from baseline either in 
duration or quality 
(eg, severity or focality) 
Seizures of any kind that are 
prolonged, repetitive 
(eg, status epilepticus), or 
difficult to control 
(eg, refractory epilepsy)
Seizure 
– Pediatric 18 Years
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
< 5 minutes with < 24 hours 
post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
5-20 minutes with 
< 24 hours post ictal state
Seizure, generalized onset 
with or without secondary 
generalization, lasting 
> 20 minutes 
Seizure, generalized onset 
with or without secondary 
generalization, requiring 
intubation and sedation
Syncope (not associated 
with a procedure)
NA
Present
NA
NA
Vertigo
Vertigo causing no or 
minimal interference with 
usual social & functional 
activities
Vertigo causing greater than 
minimal interference with 
usual social & functional 
activities 
Vertigo causing inability to 
perform usual social & 
functional activities
Disabling vertigo causing 
inability to perform basic 
self-care functions


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MUSCULOSKELETAL
Grade 1
Grade 2
Grade 3
Grade 4
Arthralgia
See also Arthritis
Joint pain causing no or 
minimal interference with 
usual social & functional 
activities
Joint pain causing greater than 
minimal interference with usual 
social & functional activities
Joint pain causing inability 
to perform usual social & 
functional activities
Disabling joint pain causing 
inability to perform basic 
self-care functions
Arthritis
See also Arthralgia
Stiffness or joint swelling 
causing no or minimal 
interference with usual 
social & functional 
activities
Stiffness or joint swelling causing 
greater than minimal interference 
with usual social & functional 
activities
Stiffness or joint swelling 
causing inability to perform 
usual social & functional 
activities
Disabling joint stiffness or 
swelling causing inability to 
perform basic self-care 
functions
Bone Mineral Loss
BMD t-score or z-score
–2.5 to –1.0 
BMD t-score or z-score –2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening consequences 
Pediatric 21 Years
BMD z-score 
–2.5 to –1.0
BMD z-score < –2.5
Pathological fracture 
(including loss of vertebral 
height)
Pathologic fracture causing 
life-threatening consequences 
Myalgia
(non-injection site)
Muscle pain causing no or 
minimal interference with 
usual social & functional 
activities
Muscle pain causing greater than 
minimal interference with usual 
social & functional activities
Muscle pain causing 
inability to perform usual 
social & functional 
activities
Disabling muscle pain causing 
inability to perform basic 
self-care functions
Osteonecrosis
NA
Asymptomatic with radiographic 
findings AND No operative 
intervention indicated
Symptomatic bone pain 
with radiographic findings 
OR Operative intervention 
indicated
Disabling bone pain with 
radiographic findings causing 
inability to perform basic 
self-care functions


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SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Acute Systemic Allergic 
Reaction 
Localized urticaria
(wheals) with no medical 
intervention indicated
Localized urticaria with medical 
intervention indicated OR Mild 
angioedema with no medical 
intervention indicated
Generalized urticaria OR 
Angioedema with medical 
intervention indicated OR 
Symptomatic mild 
bronchospasm
Acute anaphylaxis OR 
Life-threatening 
bronchospasm OR laryngeal 
edema
Chills
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities 
Symptoms causing inability to 
perform usual social & 
functional activities
NA
Fatigue
Malaise
Symptoms causing no or 
minimal interference with 
usual social & functional 
activities
Symptoms causing greater than 
minimal interference with usual 
social & functional activities
Symptoms causing inability to 
perform usual social & 
functional activities
Incapacitating fatigue/malaise 
symptoms causing inability to 
perform basic self-care 
functions
Fever (nonaxillary)
37.7C to 38.6C
99.8F to 101.5F
38.7C to 39.3C
101.6F to 102.8F
39.4C to 40.5C
102.9F to 104.9F
40.5C 
104.9F
Pain- Indicate Body Site
See also Injection Site 
Pain, Headache, 
Arthralgia, and Myalgia
Pain causing no or 
minimal interference with 
usual social & functional 
activities
Pain causing greater than minimal 
interference with usual social & 
functional activities
Pain causing inability to 
perform usual social & 
functional activities
Disabling pain causing 
inability to perform basic 
self-care functions OR 
Hospitalization (other than ER 
visit) indicated
Unintentional Weight 
Loss
NA
5% to 9% loss in body weight from 
baseline
10% to 19% loss in body 
weight from baseline
20% loss in body weight 
from baseline OR Aggressive 
intervention indicated 
[eg, tube feeding or total 
parenteral nutrition]


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INJECTION SITE REACTION
Grade 1
Grade 2
Grade 3
Grade 4
Injection Site Pain (pain 
without touching)
Or Tenderness (pain when 
area is touched) 
Pain/tenderness causing no 
or minimal limitation of use 
of limb
Pain/tenderness limiting use of 
limb OR Pain/tenderness 
causing greater than minimal 
interference with usual social 
& functional activities
Pain/tenderness causing 
inability to perform usual 
social & functional 
activities
Pain/tenderness causing inability 
to perform basic self-care 
function OR Hospitalization 
(other than ER visit) indicated 
for management of 
pain/tenderness
Injection Site Reaction 
(Localized), 15 Years
Erythema OR Induration
of 5 5 cm to 9 9 cm 
(or 2581 cm2)
Erythema OR Induration OR 
Edema 9 cm any diameter 
(or 81 cm2)
Ulceration OR Secondary 
infection OR Phlebitis OR 
Sterile abscess OR Drainage
Necrosis (involving dermis and 
deeper tissue)
Pediatric 15 Years
Erythema OR Induration 
OR Edema present but 
2.5 cm diameter
Erythema OR Induration 
OR Edema > 2.5 cm 
diameter but < 50% surface 
area of the extremity 
segment (eg, upper 
arm/thigh)
Erythema OR Induration 
OR Edema involving 
50% surface area of the 
extremity segment 
(eg, upper arm/thigh) OR 
Ulceration OR Secondary 
infection OR Phlebitis OR 
Sterile abscess OR 
Drainage
Necrosis (involving dermis and 
deeper tissue)
Pruritis Associated with 
Injection 
See also Skin: Pruritis 
(itching—no skin lesions)
Itching localized to injection 
site AND Relieved 
spontaneously or with 
48 h treatment 
Itching beyond the injection 
site but not generalized OR 
Itching localized to injection 
site requiring 48 h treatment 
Generalized itching causing 
inability to perform usual 
social & functional 
activities
NA


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ENDOCRINE/METABOLIC
Grade 1
Grade 2
Grade 3
Grade 4
Lipodystrophy (eg, back 
of neck, breasts, 
abdomen)
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious 
changes on casual visual 
inspection
NA
Diabetes Mellitus
NA
New onset without need to initiate 
medication OR Modification of 
current meds to regain glucose 
control
New onset with initiation of 
indicated med OR Diabetes 
uncontrolled despite treatment 
modification
Life-threatening consequences 
(eg, ketoacidosis, 
hyperosmolar non-ketotic 
coma) 
Gynecomastia
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on 
casual visual inspection
NA
Hyperthyroidism 
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid suppression therapy 
indicated
Symptoms causing inability to 
perform usual social & 
functional activities OR 
Uncontrolled despite treatment 
modification 
Life-threatening consequences 
(eg, thyroid storm)
Hypothyroidism
Asymptomatic
Symptomatic causing greater than 
minimal interference with usual 
social & functional activities OR 
Thyroid replacement therapy 
indicated
Symptoms causing inability to 
perform usual social & 
functional activities OR 
Uncontrolled despite treatment 
modification 
Life-threatening consequences
(eg, myxedema coma)
Lipoatrophy (eg, fat loss 
from the face, extremities, 
buttocks)
Detectable by study 
participant or caregiver 
(for young children and 
disabled adults)
Detectable on physical exam by 
health care provider
Disfiguring OR Obvious on 
casual visual inspection
NA


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GENITOURINARY
Grade 1
Grade 2
Grade 3
Grade 4
Intermenstrual Bleeding 
(IMB)
Spotting observed by participant 
OR Minimal blood observed 
during clinical or colposcopic 
exam
Intermenstrual bleeding not 
greater in duration or amount 
than usual menstrual cycle
Intermenstrual bleeding greater 
in duration or amount than usual 
menstrual cycle
Hemorrhage with 
life-threatening hypotension 
OR Operative intervention 
indicated
Urinary Tract 
obstruction (eg, stone)
NA
Signs or symptoms of urinary 
tract obstruction without 
hydronephrosis or renal 
dysfunction
Signs or symptoms of urinary 
tract obstruction with 
hydronephrosis or renal 
dysfunction
Obstruction causing 
life-threatening 
consequences
INFECTION
Grade 1
Grade 2
Grade 3
Grade 4
Infection (any other 
than HIV infection)
Localized, no systemic antiμbial 
treatment indicated AND 
Symptoms causing no or 
minimal interference with usual 
social & functional activities
Systemic antiμbial treatment 
indicated OR Symptoms 
causing greater than minimal 
interference with usual social 
& functional activities
Systemic antiμbial treatment 
indicated AND Symptoms 
causing inability to perform 
usual social & functional 
activities OR Operative 
intervention (other than simple 
incision and drainage) indicated
Life-threatening 
consequences (eg, septic 
shock)
Basic Self-care Functions: Activities such as bathing, dressing, toileting, transfer/movement, continence, and feeding.
Usual Social & Functional Activities: Adaptive tasks and desirable activities, such as going to work, shopping, cooking, use of transportation, pursuing a hobby, etc


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Appendix 5.
Definitions of Stage 3 Opportunistic Illnesses in HIV 
(CDC Guidelines)
1) Candidiasis of bronchi, trachea, or lungs
2) Candidiasis of esophagus
3) Cervical cancer, invasive
4) Coccidioidomycosis, disseminated or extrapulmonary
5) Cryptococcosis, extrapulmonary
6) Cryptosporidiosis, chronic intestinal (1 month duration)
7) Cytomegalovirus disease (other than liver, spleen or nodes)
8) Cytomegalovirus retinitis (with loss of vision)
9) Encephalopathy, HIV-related
10) Herpes simplex: chronic ulcer(s) (1 month duration); or bronchitis, pneumonitis or 
esophagitis
11) Histoplasmosis, disseminated or extrapulmonary
12) Isosporiasis, chronic intestinal (1 month duration)
13) Kaposi’s sarcoma
14) Lymphoma, Burkitt’s (or equivalent term)
15) Lymphoma, immunoblastic (or equivalent term)
16) Lymphoma, primary, of brain
17) Mycobacterium avium complex or Myobacterium kansasii, disseminated or extrapulmonary
18) Mycobacterium tuberculosis, of any site, pulmonary, disseminated or extrapulmonary
19) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
20) Pneumocystis jirovecii (previously known as “Pneumocystis carinii) pneumonia
21) Pneumonia, recurrent
22) Progressive multifocal leukoencephalopathy
23) Salmonella septicemia, recurrent
24) Toxoplasmosis of brain
25) Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {Schneider 2008}


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Appendix 6.
GS-6207 Pregnancy Precautions (Part A), Definition for Female of 
Childbearing Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) 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 subject of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
a. Study Drug Effects on Pregnancy and Hormonal Contraception
GS-6207 is contraindicated in pregnancy as a malformation effect has been 
demonstrated/suspected or is unknown, taking into consideration class effects, genotoxic 
potential, or a strong suspicion of human teratogenicity/fetotoxicity in early pregnancy based on 
non-clinical data. GS-6207 has demonstrated/suspected or has insufficient data to exclude the 
possibility of a clinically relevant interaction with hormonal contraception that results in reduced 
contraception efficacy. Therefore, contraceptive steroids are not recommended as a contraceptive 
method either solely or as a part of a contraceptive regimen. Please refer to the latest version of 
the investigator’s brochure for additional information.
b. Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. Women 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 negative urine pregnancy test at Day 1 prior to first dose of study drug. Pregnancy 
tests will be performed as defined by the schedule of assessments in Appendix 2. In the event of 
a delayed menstrual period (over one month between menstruations), a pregnancy test must be 
performed to rule out pregnancy. This is even true for women of childbearing potential with 
infrequent or irregular periods. Female subjects of childbearing potential must agree to one of the 
following from Screening until 300 days following the administration of study drug.


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
Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle.
Or

Consistent and correct use of 1 of the following methods of birth control listed below. 
Intrauterine device (IUD) with a failure rate of <1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 300 days after the administration of study drug.
3) Contraception Requirements for Male Subjects
It is theoretically possible that a relevant systemic concentration may be achieved in a female 
partner from exposure of the male subject’s seminal fluid. Therefore, male subjects with female 
partners must use condoms during treatment and until 360 days after the administration of study 
drug. Additional contraception recommendations should also be considered if the female partner 
is not pregnant.
Male subjects must also refrain from sperm donation during treatment and until at least 360 days 
after the administration of study drug.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM). Female condom and male condom should not 
be used together.
5) Procedures to be Followed in the Event of Pregnancy
Female subjects will be instructed to notify the investigator if they become pregnant or suspect 
that they are pregnant at any time during the study or if they become pregnant within 300 days
after the administration of study drug. A male subject whose partner has become pregnant or 
suspects she is pregnant during the study or within 360 days of the male subject’s administration 
of study drug must report the information to the investigator. Instructions for reporting 
pregnancy, partner pregnancy, and pregnancy outcome are outlined in Section 7.7.2.1.


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Appendix 7.
TAF Pregnancy Precautions (Part B), Definition for Female of 
Childbearing Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) 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 subject of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born subject is considered fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
a. Study Drug Effects on Pregnancy and Hormonal Contraception
Data from clinical pharmacokinetic interaction studies of TAF have demonstrated that there is no 
reduction in the clinical efficacy of hormonal contraception. Non-clinical toxicity studies of TAF 
have demonstrated no adverse effect on fertility or embryo-fetal development. However, the data 
on TAF in pregnant women is limited or not available. Please refer to the latest version of the 
investigator’s brochure for additional information.
b. Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires using at least an acceptable 
effective contraceptive measure. They must have a negative serum pregnancy test at Screening 
and a negative urine pregnancy test at Day 1 prior to first dose of study drug. Pregnancy tests 
will be performed as defined by the schedule of assessments in Appendix 2. In the event of a 
delayed menstrual period (over one month between menstruations), a pregnancy test must be 
performed to rule out pregnancy. This is even true for women of childbearing potential with 
infrequent or irregular periods. They must also agree to one of the following from Screening 
until 7 days after the last dose of Biktarvy during the study. If Biktarvy is not initiated, one of the 
following contraception requirements should be followed until 10 days after the dose of TAF. 


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Amendment 4
CONFIDENTIAL
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
Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle.
Or

Consistent and correct use of 1 of the following methods of birth control listed below. 
Intrauterine device (IUD) with a failure rate of <1% per year
Intrauterine hormone-releasing system (IUS) with a failure rate of <1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Barrier methods (one female barrier and one male barrier must be used in combination)
■
Female barriers: Diaphragm with spermicide or Cervical cap with spermicide
■
Male barriers: Male condom (with or without spermicide)
Hormonal methods (Female subjects who utilize a hormonal contraceptive as one of their 
birth control methods must have used the same method for at least 3 months prior to 
study drug dosing.)
■
Oral contraceptives (either combined or progesterone only)
■
Injectable progesterone
■
Implants of levonorgestrel
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 7 days after the last dose of Biktarvy on the study. If Biktarvy is not initiated, 
female subjects must also refrain from egg donation and in vitro fertilization after TAF 
administration and until at least 10 days after the dose of TAF.


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Amendment 4
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3) Contraception Requirements for Male Subjects
During treatment on the study, male subjects with female partners of childbearing potential 
should use condoms when engaging in intercourse of reproductive potential, and male subjects 
must also refrain from sperm donation.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method (LAM). Female condom and male condom should not 
be used together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 7 days of the last dose of Biktarvy on the study. 
Subjects who become pregnant or who suspect that they are pregnant during the study must 
report the information to the investigator and discuss with the investigator whether to continue 
Biktarvy. Subjects whose partner has become pregnant or suspects she is pregnant during the 
study must report the information to the investigator. Instructions for reporting pregnancy and 
pregnancy outcome are outlined in Section 7.7.2.1.

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 1b Randomized, Double-Blinded, Placebo Controlled, 
Multi-Cohort Study of the Safety, Pharmacokinetics, and 
Antiviral Activity of GS-6207 administered subcutaneously in 
HIV-1 Infected Subjects
Name of Test Drug:
Lenacapavir (LEN; GS-6207)
Study Number:
GS-US-200-4072
Protocol Version (Date):
Original:
14 September 2018
Amendment 1:
20 December 2018
Amendment 2:
13 March 2019
Amendment 3:
21 May 2019
Amendment 4:
13 June 2019
Analysis Type:
Final Analysis 
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
14 September 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................3
LIST OF ABBREVIATIONS........................................................................................................................................4
PHARMACOKINETIC ABBREVIATIONS................................................................................................................6
1.
INTRODUCTION ................................................................................................................................................7
1.1.
Study Objectives ......................................................................................................................................7
1.2.
Study Design............................................................................................................................................8
1.3.
Sample Size and Power..........................................................................................................................11
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................12
2.1.
Interim Analyses ....................................................................................................................................12
2.2.
Final Analysis ........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................13
3.1.
Analysis Sets..........................................................................................................................................13
3.1.1.
All Enrolled Analysis Sets ...................................................................................................13
3.1.2.
Full Analysis Set ..................................................................................................................13
3.1.3.
Safety Analysis Set...............................................................................................................14
3.1.4.
Pharmacokinetic Analysis Set..............................................................................................14
3.1.5.
Peripheral Blood Mononuclear Cell Pharmacokinetic Analysis Set ....................................14
3.2.
Subject Grouping ...................................................................................................................................14
3.3.
Strata and Covariates..............................................................................................................................14
3.4.
Examination of Subject Subgroups........................................................................................................14
3.5.
Multiple Comparisons............................................................................................................................14
3.6.
Missing Data and Outliers......................................................................................................................15
3.6.1.
Missing Data ........................................................................................................................15
3.6.2.
Outliers.................................................................................................................................15
3.7.
Data Handling Conventions and Transformations .................................................................................15
3.8.
Analysis Visit Windows.........................................................................................................................16
3.8.1.
Definition of Study Day, Baseline, and Postbaseline...........................................................16
3.8.2.
Analysis Visit Windows.......................................................................................................17
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window................................................................................................................................19
4.
SUBJECT DISPOSITION ..................................................................................................................................21
4.1.
Subject Enrollment and Disposition.......................................................................................................21
4.2.
Extent of Study Duration........................................................................................................................22
4.3.
Protocol Deviations................................................................................................................................22
4.4.
Missing Protocol-Specified Information due to COVID-19 ..................................................................22
5.
BASELINE CHARACTERISTICS....................................................................................................................23
5.1.
Demographics and Baseline Characteristics ..........................................................................................23
5.2.
Other Baseline Characteristics ...............................................................................................................23
5.3.
Medical History......................................................................................................................................23
6.
EFFICACY ANALYSES ...................................................................................................................................24
6.1.
Primary Efficacy Endpoint.....................................................................................................................24
6.2.
Secondary Efficacy Endpoint.................................................................................................................24


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6.2.1.
Number and Percentage of Subjects Ever Achieving HIV-1 RNA 
< 50 copies/mL by Day 10 (Part A) .....................................................................................24
6.3.
Other Efficacy Endpoints.......................................................................................................................24
6.3.1.
Definition of Other Efficacy Endpoints................................................................................24
6.3.2.
Analysis of Other Efficacy Endpoints..................................................................................24
6.4.
Changes from Protocol-Specified Efficacy Analyses ............................................................................25
7.
SAFETY ANALYSES........................................................................................................................................26
7.1.
Adverse Events and Deaths....................................................................................................................26
7.1.1.
Adverse Event Dictionary ....................................................................................................26
7.1.2.
Adverse Event Severity........................................................................................................26
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................26
7.1.4.
Serious Adverse Events........................................................................................................26
7.1.5.
Treatment-Emergent Adverse Events...................................................................................26
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................27
7.2.
Laboratory Evaluations ..........................................................................................................................28
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................29
7.2.2.
Graded Laboratory Values ...................................................................................................29
7.3.
Body Weight and Vital Signs.................................................................................................................30
7.4.
Prior and Concomitant Medications and Disease-Specific Medications................................................30
7.4.1.
Prior and Disease-Specific Prior Medications......................................................................30
7.4.2.
Concomitant Medications.....................................................................................................31
7.5.
Electrocardiogram Results .....................................................................................................................31
7.5.1.
Investigator Electrocardiogram Assessment ........................................................................31
7.6.
Other Safety Measures ...........................................................................................................................32
7.7.
Changes from Protocol-Specified Safety Analyses................................................................................32
8.
PHARMACOKINETIC (PK) ANALYSES........................................................................................................33
8.1.
PK Sample Collection............................................................................................................................33
8.2.
PK Analyses Related to PK Sampling ...................................................................................................33
8.2.1.
Estimation of PK Parameters ...............................................................................................33
8.2.2.
PK Parameters......................................................................................................................34
8.3.
Statistical Analysis Methods ..................................................................................................................35
8.3.1.
General Considerations ........................................................................................................35
8.3.2.
Sensitivity Analyses .............................................................................................................36
8.3.3.
Changes from Protocol-Specified PK Analyses...................................................................36
9.
REFERENCES ...................................................................................................................................................37
10.
SOFTWARE.......................................................................................................................................................38
11.
SAP REVISION..................................................................................................................................................39
12.
APPENDICES ....................................................................................................................................................40
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Windows for HIV-1 RNAa and Vital Signs.............................................................17
Table 3-2.
Analysis Windows for CD4+ and CD4%...............................................................................18
Table 3-3.
Analysis Windows for Hematology, Chemistry, Urinalysis, and eGFRCG.............................18
Table 3-4.
Analysis Windows for ECG ...................................................................................................19
Table 8-1.
Study Treatments and Associated Analytes ...........................................................................34
Table 8-2.
PK Parameters for Each Analyte............................................................................................34


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
ANOVA
analysis of variance 
ART
antiretroviral treatment
ARV
antiretroviral 
AST
aspartate aminotransferase
AUC
area under the curve
B/F/TAF
bictegravir/emtricitabine/tenofovir alafenamide
BLQ
below the limit of quantitation
BMI
body mass index
BUN
blood urea nitrogen
CAI
capsid inhibitor
CBC
complete blood count
CCG
CRF Completion Guidelines
CI
confidence interval
COVID-19
coronavirus disease 2019
CPK
creatine phosphokinase
CRF
case report form
CSR
clinical study report
CV
coefficient of variation
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
ET
early termination
FAS
Full Analysis Set
FSH
follicle stimulating hormone
GLPS
Global Patient Safety - previously Pharmacovigilance & Epidemiology (PVE)
GLSM
geometric least-squares means
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HLGT
high-level group term
HLT
high-level term
ID
identification
INSTI
integrase strand transfer inhibitor
LEN
lenacapavir; previously referred to as GS-6207
LOQ
limit of quantitation


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LTT
lower-level term
MedDRA
Medical Dictionary for Regulatory Activities
NLP
Natural Language Processing
NNRTI
non-nucleoside reverse transcriptase inhibitor
PBMC
peripheral blood mononuclear concentration
PD
pharmacodynamics
PI
protease inhibitor
PK
pharmacokinetics
PT
preferred term
Q1, Q3
first quartile, third quartile
RNA
ribonucleic acid
RT
reverse transcriptase
SAE
serious adverse event 
SAP
statistical analysis plan
SC
subcutaneous
SD
standard deviation 
SE
standard error
SOC
system organ class
TAF
tenofovir alafenamide
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
TFV
tenofovir
TFV-DP
tenofovir diphosphate
ULN
upper limit of normal
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUC0-t
area under the concentration versus time curve from time zero to time t  
AUCinf
area under the concentration versus time curve from time zero to infinity 
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCtau
area under the concentration versus time curve over the dosing interval
Ct
observed drug concentration at time t 
Clast
last observed quantifiable concentration of the drug 
Cmax
maximum observed concentration of drug 
Ctau
observed drug concentration at the end of the dosing interval
CL/F
apparent oral clearance after administration of the drug:
at steady state: CL/F = Dose/AUCinf, where “Dose” is the dose of the drug
Vz/F
apparent volume of distribution of the drug
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log 
of 2 by the terminal elimination rate constant (z)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination 
phase of the concentration of drug versus time curve


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-200-4072. This SAP is based on the study protocol amendment 4 dated 
13 June 2019 and the electronic case report form (eCRF). The SAP will be finalized before 
database finalization. Any changes made after the finalization of the SAP will be documented in 
the CSR. Throughout the text of this SAP, the study treatment for Part A is referred to as 
lenacapavir (LEN; previously referred to as GS-6207); the designation GS-6207 is used in 
preprogrammed tables, figures, and listings (ie, for treatment groups and PK analytes.)
1.1.
Study Objectives
Part A (LEN Cohorts 1-5)
The primary objective of this study is as follows:

To evaluate the short-term antiviral activity of LEN compared to placebo LEN, with respect 
to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through 
Day 10 in HIV-1 infected adult subjects who are antiretroviral treatment (ART) naïve or are 
experienced but capsid inhibitor (CAI) naïve
The secondary objectives of this study are as follows:

To investigate the safety and tolerability of LEN as compared to placebo LEN in HIV-1 
infected subjects

To characterize the plasma pharmacokinetics (PK) of LEN in HIV-1 infected subjects

To characterize the PK/pharmacodynamics (PK/PD) relationship between LEN concentration 
and the viral dynamics of HIV-1

To determine the number and percentage of subjects ever achieving HIV-1 RNA 
< 50 copies/mL by Day 10 at each dose level

To examine any emergence of CAI resistance
Part B (TAF Cohorts 6-8)
The primary objective of this study is as follows: 

To evaluate the short-term antiviral activity of tenofovir alafenamide (TAF) with respect to 
the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through 
Day 10 in HIV-1 infected adult subjects who are ART naïve or are experienced but without 
resistance to TAF. 


LEN and TAF 
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Statistical Analysis Plan - Final Analysis 
The secondary objectives of this study are as follows: 
• 
To investigate the safety and tolerability of TAF in HIV-1 infected subjects 
• 
To characterize the PK of T AF and its metabolites in HIV-1 infected subjects 
• 
To examine any emergence of TAF resistance 
I 
1.2. 
Study Design 
Version 1.0 
This is a Phase 1 b study with 2 parts. Part A (LEN Cohorts 1-5) is a randomized, double-blind, 
and placebo-controlled study of LEN. Part B (T AF Cohorts 6-8) is a single-ann study of T AF. 
Up to approximately 64 subjects (Part A: up to 5 cohorts of 8 subjects; Part B: up to 3 cohorts of 
8 subjects) will be randomized/enrolled. 
Treatment Groups and Dosing 
Part A: 
Subjects will be randomized centrally within a cohort in a 3:1 ratio to receive active LEN (n 6) 
or placebo (n 2). A single dose of LEN or placebo will be administered as a subcutaneous (SC) 
injectable free acid suspension in the morning without regard to food. LEN doses may be 
administered as multiple SC injections at different abdominal sites. The doses to be evaluated in 
Cohorts 2 through 5 will be detennined based on cumulative safety (through at least Day 14), 
available PK, and viral kinetic data from previous cohorts, as well as available safety (through at 
least Day 14) and PK data from Study GS-US-200-4070 (Phase 1, first-in-human, single 
ascending dose study of GS-6207 SC suspension fonnulation, in which GS-6207 30 to 450 mg 
was administered subcutaneously). As such, Cohorts 2-5 may be initiated in parallel. Selected 
doses will be either lower than, or no more than 3-fold higher than, previously evaluated doses 
either in this study or in Study GS-US-200-4070. The Sponsor may elect to hold dosing or stop 
study enrollment at any time based on review of preliminary safety and PK data. The protocol 
prespecified doses and the corresponding nmn ber of injections for each cohort are provided 
below. 
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Cohort
Protocol Prespecified Dose of LEN or Placebo 
Number of Injections 
1
150 mg
1
2
50 mg
1
3
450 mg
3
4
20 mg
1
5
750 mg
5
Part B: 
A single dose of TAF will be administered orally in the morning under fasted conditions on 
Day 1. The doses to be evaluated in Cohorts 7-8 will be determined based on cumulative safety 
(through at least Day 14), available PK, and viral kinetic data from previous cohorts. Selected 
doses will be either lower than, or no more than 3-fold higher than, previously evaluated doses in 
this study. Cohorts 7 and 8 may be run in parallel.
The protocol prespecified dose and actual dose used for each cohort are provided below.
Cohort 8 was not initiated due to observed antiretroviral activity from Cohorts 6 and 7 which did 
not demonstrate durable activity over 10 days.
Cohort
Protocol Prespecified Dose of TAF
Actual Dose of TAF
6
200 mg
200 mg1
7
Up to 600 mg
600 mg1
8
Up to 600 mg
Did not enroll
1
Subjects enrolled in Cohort 6 (200 mg) and Cohort 7 (600 mg) will be given 8 and 24 tablets of TAF 25 mg tablet, 
respectively.  
All subjects in Part A and Part B will initiate once-daily bictegravir/emtricitabine/tenofovir 
alafenamide (B/F/TAF, 50/200/25 mg) on Day 10 and be treated to Day 225.  
Key Eligibility Criteria
Subjects with chronic HIV-1 infection who meet the following criteria: 

Plasma HIV-1 RNA ≥5,000 copies/mL but ≤400,000 copies/mL and CD4 cell count 
> 200 cells/mm3

Treatment naïve or experienced but integrase strand transfer inhibitor (INSTI) naïve and CAI
naive (Part A only), and have not received any ART within 12 weeks of screening

Screening genotype report must show sensitivity to B/F/TAF to allow TAF monotherapy 
(Part B) and initiation of B/F/TAF on Day 10 (Part A and Part B)


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
Screening genotype report must show sensitivity to at least one agent in either 
non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) class to 
allow its use as part of standard of care oral ART in the future

Have adequate renal function (estimated glomerular filtration rate [eGFR] ≥70 mL/min)

No clinically significant abnormalities in electrocardiogram (ECG) at Screening 

Not pregnant or lactating 

Willing to initiate B/F/TAF on Day 10 after completion of all assessments
Schedule of Assessments 
In Part A, following screening and Day 1 visits, subjects will be required to visit the clinic on 
Days 2, 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197, and 225. 
In Part B, following screening and Day 1 visits, subjects will be required to visit the clinic on 
Days 2, 3, 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197, and 
225.
For both Part A and Part B, adverse events (AEs), concomitant medications, complete or 
symptom-directed physical examinations, and HIV-1 RNA will be performed at Screening, 
Day 1, and all subsequent study visits. CD4 cell count will be performed at Screening, Day 1, 
Day 10, Day 29, and all subsequent study visits. Other laboratory analyses (hematology, 
chemistry, and urine chemistry) will be performed at Screening, Days 1, 3, 7, 10, 14, and all 
subsequent study visits. Fasting is required for laboratory analyses at Days 1, 3, 7, 10, 85, 169,
and 225. ECGs will be performed at Screening, Days 1 (predose), 2, 10, 29, 57, 85, 169, and 225.
Additionally, in Part A, blood samples will be collected for genotypic and phenotypic testing of 
HIV-1 capsid and for determining PK of LEN. In Part B, blood samples will be collected for 
genotypic and phenotypic testing of HIV-1 reverse transcriptase (RT) and for determining PK of 
TAF and tenofovir (TFV). In Part B, the peripheral blood mononuclear concentration (PBMC)
PK samples will be collected to determine PK of tenofovir diphosphate (TFV-DP). 
Details regarding study procedures could be found in Appendix 1.


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1.3.
Sample Size and Power
Part A
A sample size of 6 subjects in each LEN treatment group and a total of 10 placebo subjects from 
all cohorts combined will provide 99% power to detect a treatment difference of 
2.79 log10 copies/mL in maximum reduction of HIV-1 RNA between at least one of the LEN
treatment groups and the placebo group. In this power analysis, it is assumed that a common 
standard deviation (SD) for maximum reduction in HIV-1 RNA is 0.526 log10 copies/mL 
(based on Study GS-US-141-1219) and a 2-sided t-test is conducted at an alpha level of 0.05. 
Part B
A sample size of 8 subjects in each TAF treatment group and a total of 10 subjects in the placebo 
group will provide 99% power to detect a treatment difference of 1.43 log10 copies/mL in 
maximum reduction of HIV-1 RNA between at least one of the TAF treatment groups and 
the placebo group from Part A of the study. In this power analysis, it is assumed that a 
common SD for maximum reduction in HIV-1 RNA is 0.52 log10 copies/mL (based on 
Studies GS-US-120-0104 and GS-US-120-1101) and a 2-sided t-test is conducted at an alpha 
level of 0.05.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
For the purpose of dose selection(s), planned interim analyses were conducted by the Sponsor 
based on the analysis schedule defined in Section 8.9 of the protocol. A few individuals from the
Sponsor were unblinded to assess the interim safety, efficacy, and PK (if available) of study 
drug. Details are defined in a charter.  
2.2.
Final Analysis
After all subjects have completed the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized, the study blind will be 
broken and the final analysis of the data will be performed.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each category will be presented; for continuous variables, 
the number of subjects (n), mean, SD or standard error (SE), median, first quartile (Q1), 
third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
Data from Part A (LEN cohorts) and Part B (TAF cohorts) will be summarized and listed 
separately. 
By-subject listings will be presented for all subjects in the All Enrolled Analysis Set, and sorted 
by subject identification (ID) number, visit date, and time (if applicable) in ascending order, 
unless otherwise specified. Data collected on log forms, such as AEs, will be presented in 
chronological order within subject. The treatment group to which subjects were initially assigned 
will be used in the listings. Age, sex at birth, race, and ethnicity will be included in the listings, 
as space permits.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The assignment of subjects to analysis sets will be done before the 
study blind is broken for analysis. The analysis set will be identified and included as a subtitle of 
each table, figure, and listing.
For each analysis set, the number and percentage of subjects eligible for inclusion will be 
summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
All Enrolled Analysis Sets
All Enrolled Analysis Set includes all subjects who either (a) are randomized into Part A of the 
study after screening or (b) receive a study subject identification number in Part B of the study 
after screening.
All Enrolled Analysis Set is the primary analysis set for by-subject listings. 
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all subjects who are randomized/enrolled and receive at 
least 1 full dose of study drug. This is the primary analysis set for efficacy analyses. Subjects 
with major eligibility violations that are identifiable based on pre-randomization/enrollment 
characteristics may be excluded.


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3.1.3.
Safety Analysis Set
The Safety Analysis Set includes all subjects who are randomized/enrolled and receive at least 
1 dose of study drug. This is the primary analysis set for safety analyses.
3.1.4.
Pharmacokinetic Analysis Set
The PK Analysis Set will be defined separately for each analyte of interest (ie, LEN, TAF, and 
its metabolite TFV). Each PK Analysis Set will include all subjects who are 
randomized/enrolled, receive at least 1 dose of study drug, and have at least 1 nonmissing 
postdose concentration value reported by the PK laboratory for the respective analyte. This is the 
primary analysis set for all PK analyses.
3.1.5.
Peripheral Blood Mononuclear Cell Pharmacokinetic Analysis Set
The PBMC PK Analysis Set will include all subjects who are enrolled in Part B of the study, 
receive at least 1 dose of study drug, and have at least 1 nonmissing TFV-DP concentration. The 
PBMC PK Analysis Set will be used for PK analyses of TFV-DP.
3.2.
Subject Grouping
For analyses based on the FAS, subjects will be grouped according to the treatment to which 
they were randomized/enrolled. For all other analyses, subjects will be grouped according to the 
actual treatment received. Data from the placebo recipients in Part A of the study will be 
combined to form one placebo group for the purpose of analysis.
Subjects will be grouped by treatment dose and pooled treatments (all LEN for Part A and all 
TAF for Part B).
For Part A enrollment, disposition, protocol deviations, demographics, baseline disease 
characteristics, and HIV-1 RNA < 50 copies/mL by visit tables, an additional total column for all 
Part A subjects will be included.
For efficacy tables and PK tables, pooled treatment groups will not be included.  
3.3.
Strata and Covariates
This study does not use a stratified randomization schedule when enrolling subjects. 
No covariates will be included in the analyses. 
3.4.
Examination of Subject Subgroups
There are no prespecified subject subgroupings for analyses.
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be made in this proof-of-concept study.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document. The handling of missing or incomplete 
dates for AE onset is described in Section 7.1.5.2 and for prior (disease-specific prior) and 
concomitant medications in Section 7.4.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
Only year of birth is collected in this study. Therefore, the following conventions will be used for 
the imputation of full date of birth: 

If year of birth is collected, “01 July” will be imputed as the day and month of birth

If year of birth is missing, date of birth will not be imputed
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, age derived based on date of birth and the Day 1 visit 
date will be used instead. If a randomized/enrolled subject was not dosed with any study drug, 
the randomization/enrollment date will be used instead of the Day 1 visit date. For screen 
failures, the date the first informed consent was signed will be used for the age derivation. Age 
required for longitudinal and temporal calculations and analyses (eg, estimates of creatinine 
clearance) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ)
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “x” (where x is considered the LOQ). For example, if the 
values are reported as < 20 and < 2.0, values of 19 and 19.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).


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If methods based on the assumption that the data are normally distributed are not adequate, 
analyses may be performed on transformed data or nonparametric analysis methods may be used, 
as appropriate.
Natural logarithm transformation will be used for analyzing concentrations and PK parameters. 
Concentration values that are below the limit of quantitation (BLQ) will be presented as “BLQ” 
in the concentration data listing. Values that are BLQ will be treated as 0 at predose time points, 
and one-half the value of the LOQ at postdose time points for summary purposes.
The following conventions will be used for the presentation of summary and order statistics for 
PK concentrations:

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
PK parameters that are BLQ will be imputed as one-half LOQ before log transformation or 
statistical model fitting.
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day, Baseline, and Postbaseline
Study day will be calculated from the first dose date of study drug and derived as follows:

For postdose study days: Assessment Date First Dosing Date + 1

For days prior to the first dose: Assessment Date First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.
Baseline is defined as the last available off-treatment value collected on or prior to the first dose 
of study drug (ie, start time of injection). 
Postbaseline is defined as any value collected after the first dose of study drug (ie, start time of 
injection). 
Last Study Date is the latest clinic visit dates and the laboratory visit dates, including the 30-day 
follow-up visit date, for subjects who prematurely discontinued study or who completed study 
according to the Study Completion eCRF.


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3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
The analysis windows for HIV-1 RNA and vital signs are provided in Table 3-1.
Table 3-1.
Analysis Windows for HIV-1 RNAa and Vital Signs
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
(none)
≤ Dose time on Day 1
[1]b
Day 2
2
> Dose time on Day 1
[2]b
2
Day 3
3
3
3
Day 4
4
4
5
Day 7
7
6
7
Day 8
8
8
8
Day 9
9
9
9
Day 10
10
10
11
Day 14
14
12
21
Day 29
29
22
35
Day 43
43
36
49
Day 57
57
50
70
Day 85
85
71
98
Day 113
113
99
126
Day 141
141
127
154
Day 169
169
155
182
Day 197
197
183
210
Day 225
225
211
(none)
a 
The analysis window for HIV 1 RNA only applies to the change from baseline in HIV 1 RNA analysis. When defining the 
maximum reduction from baseline in HIV 1 RNA and percentage of subjects ever achieving HIV 1 RNA < 50 copies/mL by 
Day 10, all HIV 1 RNA data will be used ignoring the analysis window.
b 
For vital signs as no times (only dates) were collected, Day 1 vital signs considered completed prior to administration of the 
dose of study drug.
The analysis windows for CD4+ cell count and CD4% are provided in Table 3-2.


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Table 3-2.
Analysis Windows for CD4+ and CD4%
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
(none)
≤ Dose time on Day 1
Day 10
10
> Dose time on Day 1
19
Day 29
29
20
35
Day 43
43
36
49
Day 57
57
50
70
Day 85
85
71
98
Day 113
113
99
126
Day 141
141
127
154
Day 169
169
155
182
Day 197
197
183
210
Day 225
225
211
(none)
The analysis windows for hematology, chemistry (including estimated glomerular filtration rate
using Cockcroft-Gault formula [eGFRCG]), and urinalysis are provided in Table 3-3.
Table 3-3.
Analysis Windows for Hematology, Chemistry, Urinalysis, and
eGFRCG
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
(none)
≤ Dose time on Day 1
Day 3
3
> Dose time on Day 1
4
Day 7
7
5
8
Day 10
10
9
11
Day 14
14
12
21
Day 29
29
22
35
Day 43
43
36
49
Day 57
57
50
70
Day 85
85
71
98
Day 113
113
99
126
Day 141
141
127
154
Day 169
169
155
182
Day 197
197
183
210
Day 225
225
211
(none)


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The analysis windows for 12-lead ECG are provided in Table 3-4.
Table 3-4.
Analysis Windows for ECG
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
(none)
≤ Dose time on Day 1
Day 2
2
> Dose time on Day 1
5
Day 10
10
6
19
Day 29
29
20
42
Day 57
57
43
70
Day 85
85
71
126
Day 169
169
127
196
Day 225
225
197
(none)
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value. 
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dose of study drug will be 
selected, unless specified differently. If there are multiple records with the same time or no 
time recorded on the same day, the baseline value will be the average of the measurements 
for continuous data (except for HIV-1 RNA, see below), or the measurement with the lowest 
severity (eg, normal will be selected over abnormal for safety ECG findings) for categorical 
data.

For postbaseline values:
The record closest to the nominal day for that visit will be selected (with the exception of
CD4+ cell count and CD4% in which the latest record will be selected and HIV-1 RNA 
level [see below]).
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken for 
continuous data (except for HIV-1 RNA, see below) and the worst severity will be taken 
for categorical data, unless otherwise specified.


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
For baseline and postbaseline HIV-1 RNA, the latest (considering both date and time) 
record(s) in the window will be selected. If both “HIV RNA Taqman 2.0” and “HIV RNA 
Repeat” (ie, the HIV-1 RNA result obtained from an additional aliquot of the original sample) 
are available with the same collection time, the results from the “HIV RNA Repeat” will be 
selected for analysis purposes; otherwise, if there are multiple “HIV RNA Taqman 2.0” 
records with the same collection time, the geometric mean will be taken for analysis purposes. 


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by country, investigator, treatment group, and 
overall within Part A (all LEN and all subjects) and Part B (all TAF). The summary will present 
the number and percentage of subjects enrolled. For each column, the denominator for the 
percentage calculation will be the total number of subjects analyzed for that column.
The randomization schedule used for Part A will be provided as an appendix to the CSR.
A summary of subject disposition will present the number of subjects screened and the number 
of subjects who met all eligibility criteria but were not enrolled with reasons subjects not 
enrolled. Additional summaries of subject disposition will be provided by treatment group and 
overall within Part A (all LEN and all subjects) and Part B (all TAF) as well as the number and 
percentage of subjects in each of the categories listed below: 

All Enrolled Analysis Set 

Safety Analysis Set

Full Analysis Set 

Completed study drug

Did not complete study drug with reasons for premature discontinuation of study drug

Completed study

Did not complete the study with reasons for premature discontinuation of study
For the status of study drug and study completion and reasons for premature discontinuation, the 
number and percentage of subjects in each category will be provided. The denominator for the 
percentage calculation will be the total number of subjects in the Safety Analysis Set 
corresponding to that column. In addition, a flowchart will be provided to depict the disposition.
The following by-subject listings will be provided by subject ID number in ascending order to 
support the above summary tables:

Reasons for premature study drug or study discontinuation (including those related to 
coronavirus disease 2019 [COVID-19])

Reasons for screen failure (will be provided by screening ID number in ascending order)

Analysis set status (indicating whether or not a subject is included in a given analysis set)


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4.2.
Extent of Study Duration
A subject’s extent of exposure to LEN or TAF will be generated from the Study Drug 
Administration eCRF. Exposure data of LEN and TAF will be listed.   
Due to the long-acting feature of the study drug, a summary of the extent of study duration
(defined as last study day minus first dose date of study drug plus 1) will be provided,
summarizing the number of subjects still in study up to each nominal visit. The total study 
duration will also be summarized using descriptive statistics.
B/F/TAF is provided by Sponsor with dispensing information recorded on the Accountability 
eCRF. Accountability data of B/F/TAF will be listed.   
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry but enrolled in the study will be 
summarized regardless of whether they were exempted by the sponsor or not. The summary will 
present the number and percentage of subjects who did not meet at least 1 eligibility criterion and 
the number of subjects who did not meet specific criteria based on the Safety Analysis Set. A 
by-subject listing will be provided for those subjects who did not meet at least 1 eligibility 
(inclusion or exclusion) criterion. The listing will present the eligibility criterion (or criteria if 
more than 1 deviation) that subjects did not meet.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason and the total number of important protocol deviations by deviation reason
(eg, violation of select inclusion/exclusion criteria) will be summarized by treatment group and 
overall for the All Enrolled Analysis Set. By-subject listings will be provided for those subjects 
with important protocol deviations and for those with either important protocol deviations or 
non-important protocol deviations related to COVID-19.
4.4.
Missing Protocol-Specified Information due to COVID-19
A by-subject listing of subjects affected by the COVID-19 pandemic will be provided by subject 
ID number and comment visit in ascending order along with determination of if the subject 
missed the visit due to COVID-19 or had a virtual visit due to COVID-19. 
The determination of missing or virtual visits due to COVID-19 was done using Natural 
Language Processing (NLP) to search the CRF comment fields. A detailed explanation of the 
algorithm is given in Appendix 2. 


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5.
BASELINE CHARACTERISTICS  
5.1.
Demographics and Baseline Characteristics
Subject demographic variables (ie, age, sex, race, and ethnicity) and baseline characteristics 
(body weight [in kg], height [in cm], body mass index [BMI; in kg/m2]) will be summarized by 
treatment group and overall using descriptive statistics for continuous variables and using 
number and percentage of subjects for categorical variables. The summary of demographic data 
will be provided for the Safety Analysis Set.
A by-subject demographic and baseline characteristics listing, including the informed consent 
date, will be provided by subject ID number in ascending order.
5.2.
Other Baseline Characteristics
Other baseline characteristics include HIV-1 RNA (log10 copies/mL), CD4 cell count (/μL), 
CD4 percentage (%), mode of infection (HIV risk factors), HIV disease status, ever participated 
in pre-exposure prophylaxis (Yes/No), ever participated in post-exposure prophylaxis (Yes/No), 
and ART status (experienced/naïve). These baseline characteristics will be summarized by 
treatment group and overall using descriptive statistics for continuous variables and using 
number and percentage of subjects for categorical variables. The summary of these baseline 
characteristics will be provided for the Safety Analysis Set. No formal statistical testing is 
planned.
A by-subject listing of other baseline characteristics will be provided by subject ID number in 
ascending order.
5.3.
Medical History
General medical history data will be collected at screening and coded using the current version 
of Medical Dictionary for Regulatory Activities (MedDRA). Data on general medical history 
will be listed.  


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is the maximum reduction of plasma HIV-1 RNA 
(log10 copies/mL) from Day 1 through Day 10. 
Data from the placebo recipients in Cohorts 1-5 will be combined to form one placebo group. 
Each of the LEN treatment groups will be compared to the pooled placebo group with respect to 
the primary efficacy endpoint using the 2-sided t-test conducted at an alpha level of 0.05.
Pairwise comparison of the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from 
Day 1 though Day 10 among all LEN treatment groups will also be performed. The analysis will 
be conducted using the FAS.
6.2.
Secondary Efficacy Endpoint
6.2.1.
Number and Percentage of Subjects Ever Achieving HIV-1 RNA
< 50 copies/mL by Day 10 (Part A)
The number and percentage of subjects ever achieving HIV-1 RNA < 50 copies/mL by Day 10 
will be summarized by treatment group for Part A using the FAS. Fisher exact test will be used 
for comparison between treatment groups.
6.3.
Other Efficacy Endpoints
6.3.1.
Definition of Other Efficacy Endpoints 
Other efficacy endpoints include:

Change from baseline in HIV-1 RNA (log10 copies/mL) by Day 10

Number and percentage of subjects with HIV-1 RNA < 50 copies/mL 

Change from baseline in CD4 cell count (/μL) 
6.3.2.
Analysis of Other Efficacy Endpoints 
Baseline values, values at each visit, and the change from baseline in HIV-1 RNA 
(log10 copies/mL) by visit will be summarized by treatment group. Pairwise comparison of the 
change from baseline in HIV-1 RNA (log10 copies/mL) among all treatment groups and placebo 
at each visit through Day 10 will be performed in the same manner as that of the primary 
efficacy endpoint. 
Mean ± 95% confidence interval (CI) and median (Q1, Q3) of the change from baseline in 
HIV-1 RNA (log10 copies/mL) will be plotted to Day 10 using a line plot by treatment group and 
visit. 


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Number and percentage of subjects with HIV-1 RNA < 50 copies/mL by visit will be analyzed 
using the missing  excluded method, where missing data will be excluded in the computation of 
the percentages (ie, missing data points will be excluded from both numerator and denominator 
in the computation). The denominator for percentages at a visit is the number of subjects in the 
FAS with nonmissing HIV-1 RNA value at that visit. No statistical testing is planned. The 
number and percentage of subjects with HIV-1 RNA in the following categories will be 
summarized:

< 50 copies/mL
< 20 copies/mL
■
< 20 copies/mL Not Detectable
■
< 20 copies/mL Detectable
20 to < 50 copies/mL 

50 to < 200 copies/mL 

200 to < 400 copies/mL 

400 to < 1000 copies/mL

≥ 1000 copies/mL 
Baseline values, values at each visit, and the change from baseline in CD4 cell count (/μL) by 
visit will be summarized by treatment group. No statistical testing is planned.
All efficacy endpoints will be conducted using the FAS.
6.4.
Changes from Protocol-Specified Efficacy Analyses
Due to differences in the treatment regimens in Part A (subcutaneous injection) and Part B 
(oral administration), the TAF (Part B) oral dose groups will not be compared to the placebo 
injection group in Part A with respect to the efficacy endpoints.


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of MedDRA. System organ 
class (SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and 
lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, or 4 according to toxicity criteria 
specified in the protocol. The severity grade of events for which the investigator did not record 
severity will be categorized as “missing” for tabular summaries and data listings. The missing 
category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s
choice, not that of the medical monitor. Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Global Patient Safety 
(GLPS) Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any AE with an onset date on or 
after the study drug start date. 
7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dose date of 
study drug, then the month and year (or year alone if month is not recorded) of onset determine 
whether an AE is treatment emergent. The event is considered treatment emergent if the AE 
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An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dose date of study drug, will be considered to be treatment emergent
(and included in both TEAE summaries up to Day 10 and throughout the study.) In addition, an 
AE with the onset date missing and incomplete stop date with the same or later month and year 
(or year alone if month is not recorded) as the first dose date of study drug will be considered 
treatment emergent (and included in both TEAE summaries up to Day 10 and throughout the 
study).
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE Incidence in Combined Severity Grade Subsets 
A brief, high-level summary of the number and percentage of subjects who experienced at least 
1 TEAE in the categories described below will be provided by treatment group for TEAEs with 
onset date reported up to Day 10 (prior to the B/F/TAF first dose date) and throughout the study, 
respectively. All deaths observed in the study will also be included in this summary.
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT (if applicable), PT, and treatment group. 

TEAEs
For the AE categories described below, summaries will be provided by SOC, PT, and treatment 
group:

TEAEs with Grade 3 or higher (by severity)

TE treatment-related AEs

TE treatment-related AEs with Grade 3 or higher (by severity)

TEAEs leading to death (ie, outcome of death)

TE SAEs

TE treatment-related SAEs 

TEAEs leading to premature discontinuation of study drug

TEAEs leading to premature discontinuation of study
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC (and HLT within each SOC if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study. 


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In addition to the above summary tables, for the AE categories described below, summaries will 
be provided by PT only in descending order of total frequency:

TEAEs

TE SAEs
In addition, data listings will be provided for the following:

All AEs

All SAEs

All Deaths

All AEs leading to death (ie, outcome of death)

All AEs with severity of Grade 3 or higher

All AEs leading to premature discontinuation of study drug 

All AEs leading to premature discontinuation of study 

All AEs for COVID-19 and Suspected COVID-19 infection, defined as AE preferred terms 
of “Suspected COVID-19”, “COVID-19”, “COVID-19 pneumonia”, or “Asymptomatic 
COVID-19”
For each listing, whether the event is treatment emergent will be indicated.
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected throughout the study. The analysis will be 
based on values reported in conventional units. When values are below the LOQ, they will be 
listed as such, and the closest imputed value will be used for the purpose of calculating summary 
statistics as specified in Section 3.7.
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
flagged in the data listings, as appropriate.
No formal statistical testing is planned.


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7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values 

Values at each postbaseline visit 

Change from baseline at each postbaseline visit 
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date/time of first dose of study drug. Change from baseline to a postbaseline visit will be defined 
as the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and maximum 
values will be displayed to the reported number of digits; SD values will be displayed to the 
reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
7.2.2.
Graded Laboratory Values
The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities will be 
used to assign toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all 
values that do not meet the criteria for an abnormality of at least Grade 1. For laboratory tests 
with criteria for both increased and decreased levels, analyses for each direction (ie, increased, 
decreased) will be presented separately. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline visit. If the relevant baseline laboratory value 
is missing, any abnormality of at least Grade 1 observed within the time frame specified above 
will be considered treatment emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
subjects in the study with the given response at baseline and each scheduled postbaseline visit.
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

Graded laboratory abnormalities (note: in addition to summarizing abnormalities throughout 
the study, a separate table will summarize abnormalities reported up to Day 10, collected on 
or prior to the B/F/TAF first dose date)

Grade 3 or 4 laboratory abnormalities


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For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values. 
A by-subject listing of treatment-emergent laboratory abnormalities and treatment-emergent 
Grade 3 or 4 laboratory abnormalities, respectively, will be provided by subject ID number and 
visit in chronological order. This listing will include all test results that were collected 
throughout the study for the lab test of interest, with all applicable severity grades and abnormal 
flags displayed.
7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight and vital signs as 
follows:

Baseline value

Values at each postbaseline visit 

Change from baseline at each postbaseline visit 
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. Body weight, height, and BMI will be included in the vital signs listing, if 
space permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications and Disease-Specific Medications
Prior and concomitant medications (ie, non-antiretroviral [non-ARV] medications) collected at 
screening and during the study will be coded using the current version of the World Health 
Organization (WHO) Drug Dictionary. 
Disease-specific medications (ie, nonstudy drug ARV) used prior to, during, or after the study 
(if collect) will be coded using the Gilead-modified WHO Drug Dictionary. 
7.4.1.
Prior and Disease-Specific Prior Medications
Prior and disease-specific prior medications are defined as any medications taken before a 
subject took the first study drug.
A summary of prior or disease-specific prior medications will not be provided. 


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7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken on or after first dose date of study 
drug. Use of concomitant medications will be summarized by preferred name using the number 
and percentage of subjects for each treatment group. A subject reporting the same medication 
more than once will be counted only once when calculating the number and percentage of 
subjects who received that medication. The summary will be ordered by preferred term in 
descending overall frequency. For drugs with the same frequency, sorting will be done 
alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date of study drug will be considered concomitant medications. Medications started and stopped 
on the same day as the first dosing date of study drug will also be considered concomitant. 
Medications with a stop date prior to the date of first dosing date of study drug will be excluded 
from the concomitant medication summary. If a partial stop date is entered, any medication with 
the month and year (if day is missing) or year (if day and month are missing) prior to the date of 
first study drug administration will be excluded from the concomitant medication summary. If a 
partial start date is entered, any medication with the month and year (if day is missing) or year 
(if day and month are missing) on or after the study drug start date will be included in the 
concomitant medication summary. Medications with completely missing start and stop dates will 
be included in the concomitant medication summary, unless otherwise specified. Summaries will 
be based on the Safety Analysis Set. No formal statistical testing is planned.
All prior and concomitant medications (other than per-protocol study drugs) and all nonstudy 
drug ARV medications will be provided in by-subject listings sorted by subject ID number and 
administration date in chronological order.
7.5.
Electrocardiogram Results
Summaries of investigator assessment of ECG readings will be provided for the Safety Analysis 
Set for each scheduled visit. No formal statistical testing is planned.
7.5.1.
Investigator Electrocardiogram Assessment
A shift table of the investigators’ assessment of ECG results at each visit compared with baseline 
values will be presented by treatment group using the following categories: normal; abnormal, 
not clinically significant; abnormal, clinically significant; or missing. The number and 
percentage of subjects in each cross-classification group of the shift table will be presented. 
Subjects with a missing value at baseline or postbaseline will not be included in the denominator 
for percentage calculation. No formal statistical testing is planned.
A by-subject listing for ECG assessment results will be provided by subject ID number and visit 
in chronological order.


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7.6.
Other Safety Measures
No additional safety measures are specified in the protocol.
7.7.
Changes from Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
PHARMACOKINETIC (PK) ANALYSES
8.1.
PK Sample Collection
Part A (Cohorts 1-5 LEN PK sampling)
Blood samples will be collected to determine LEN PK (and metabolites, if applicable) in plasma 
at the following time points relative to study drug dosing: 

Day 1: 0 (predose), 1, 2, 4, 8, 12, and 24 hours postdose 

Days 3, 4, 7, 8, 9, 10, 14, 29, 43, 57, 85, 113, 141, 169, 197, and 225 for a single anytime PK 
sample 
Part B (Cohorts 6-8 TAF PK sampling)
Plasma PK samples will be collected to determine PK of TAF and its metabolite, TFV, at the 
following time points relative to study drug dosing: 

Day 1: 0 (predose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours postdose

Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, and 10 at approximately the same time in the 
morning as predose on Day 1
PBMC PK samples will be collected to determine PK of TFV-DP at the following time points 
relative to study drug dosing: 

Day 1: 0 (predose), 1, 2, 4, 6, 8, 12, 24, and 48 hours postdose 

Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, and 10 at approximately the same time in the 
morning as predose on Day 1
8.2.
PK Analyses Related to PK Sampling
8.2.1.
Estimation of PK Parameters
PK parameters will be estimated using Phoenix WinNonlin® software using standard 
noncompartmental methods. The linear/log trapezoidal rule will be used in conjunction with the 
appropriate noncompartmental model, with input values for dose level, dosing time, plasma 
concentration, and corresponding real-time values, based on drug dosing times whenever 
possible.
All predose sample times before time-zero will be converted to 0.


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For area under the curve (AUC), samples BLQ of the bioanalytical assays occurring prior to the 
achievement of the first quantifiable concentration will be assigned a concentration value of 0 to 
prevent overestimation of the initial AUC. Samples that are BLQ at all other time points will be 
treated as missing data in WinNonlin. The nominal time point for a key event or dosing 
interval (τ) may be used to permit direct calculation of AUC over specific time intervals. The 
appropriateness of this approach will be assessed by the PK scientist on a profile-by-profile 
basis.
Pharmacokinetic parameters such as λz and t1/2 are dependent on an accurate estimation of the 
terminal elimination phase of drug. The appropriateness of calculating these parameters will be 
evaluated upon inspection of PK data on a profile-by-profile basis by the PK scientist.
8.2.2.
PK Parameters
PK parameters will be generated for all subjects for whom parameters can be derived. The 
analytes presented in Table 8-1 will be derived if data are available. 
Table 8-1.
Study Treatments and Associated Analytes
Cohort
Treatment
Analyte
1
LEN 150 mg SC
LEN
2
LEN 50 mg SC
LEN
3
LEN 450 mg SC
LEN
4
LEN 20 mg SC
LEN
5
LEN 750 mg SC
LEN
6
TAF 200 mg tablet
TAF, TFV, TFV-DP
7
TAF 600 mg tablet
TAF, TFV, TFV-DP
8
Not conducted
The analytes and parameters presented in Table 8-2 will be used to evaluate the PK objectives of 
the study. The PK parameters to be estimated in this study are listed and defined in the PK
Abbreviations section.
Table 8-2.
PK Parameters for Each Analyte
Analyte
Parameters
LEN
AUC0-t, AUCinf, AUClast, CL/F, t1/2, λz, Vz/F, Cmax, Tmax, Clast, CD10, Tlast
TAF
AUC0-t, AUCinf, AUClast, CL/F, t1/2, λz, Vz/F, Cmax, Tmax, Clast, Tlast
TFV
AUC0-t, AUCinf, AUClast, t1/2, λz, Cmax, Tmax, Clast, Tlast
TFV-DP
AUC0-t, AUCinf, AUClast, t1/2, λz, Cmax, Tmax, Clast, Tlast


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8.3.
Statistical Analysis Methods
8.3.1.
General Considerations
All PK analyses will be summarized based on the PK Analysis Set for the analyte of interest with 
the exception of the summary of TFV-DP which will be based on the PBMC PK Analysis set.  
Individual subject concentration data and applicable individual subject PK parameters will be 
listed and summarized using descriptive statistics by treatment. Summary statistics (n, mean, SD, 
coefficient of variation [%CV], median, min, max, Q1, and Q3) will be presented for both 
individual subject concentration data by time point and individual subject PK parameters by 
treatment. Moreover, the geometric mean, 95% CI, and the mean and SD of the natural 
log-transformed values will be presented for individual subject PK parameter data. 
Individual concentration data listings and summaries will include all subjects with concentration 
data. The sample size for each time point will be based on the number of subjects with 
nonmissing concentration data at that time point. The number of subjects with concentration 
BLQ will be presented for each time point. For summary statistics, BLQ values will be treated as 
0 at predose and one-half of the lower LOQ for postdose time points.
Individual PK parameter data listings and summaries will include all subjects for whom PK 
parameter(s) can be derived. The sample size for each PK parameter will be based on the number 
of subjects with nonmissing data for that PK parameter.
The following tables will be provided for each analyte by treatment:

Individual subject concentration data and summary statistics

Individual subject plasma PK parameters and summary statistics
The following figures may be provided for each analyte by treatment:

Mean (± SD) concentration data versus time (on linear and semilogarithmic scales)

Median (Q1, Q3) concentration data versus time (on linear and semilogarithmic scales)
Mean and median postdose concentration values that are ≤LLOQ will not be displayed in the 
figures and remaining points connected.
PK sampling details by subject, including procedures, differences in scheduled and actual draw 
times, and sample age will be provided in listings. Individual data on determination of plasma 
half-life and corresponding regression correlation coefficient will also be listed. 
The molecular weight of TFV-DP (447.17 g/mol) and the density of 5000 million cells/mL will 
be used in the conversion of concentration from ng/million cells to µmol/L; where the value in 
ng/million cells * (5000/447.17) results in the value in µmol/L or µM.  

	 
 ×
1 	
447.17  ×
1 μ
1000 	 × 5000 	 

1 
× 1000 

μ	

μ


LEN and TAF 
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Statistical Analysis Plan - Final Analysis 
8.3.2. 
Sensitivity Analyses 
Version 1.0 
Sensitivity analysis may be conducted for the key PK analyses if the PK scientist identifies PK 
data as questionable. The sensitivity analysis will exclude specific data from analyses, if 
appropriate. If a sensitivity analysis is deemed necessary, a listing of the PK parameter(s) data 
being excluded, with associated reason(s) provided by the PK scientist, will be generated. 
8.3.3. 
Changes from Protocol-Specified PK Analyses 
The secondary endpoint of the correlation between C1 ( concentration at Day 10) of LEN (Part A) 
and the maximum reduction of lasma HIV-1 RNA lo 10 co ies/mL from baseline throu h 
---ed 
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9.
REFERENCES
No references were used in this document. 


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
Phoenix WinNonlin® 7.0 Pharsight Corporation, Princeton, NJ, USA.


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11.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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12.
APPENDICES
Appendix 1.
Schedule of Assessments
Appendix 2.
Determining Missing and Virtual visits due to COVID-19
Appendix 3.
Programming Specifications


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Appendix 1.
Schedule of Assessments
Screeninga
Day 1b, h
Day 2
Day 3h
Day 4
Day 7 h
Day 8
Day 9
Day 10h
Day 14
Day 29
Day 43
Day 57
Day 85 h
Day 113
Day 141
Day 169 h
Day 197
Day 225 h
Early 
Terminatio
Written Informed 
Consent
X
Medical History 
X
Complete Physical 
Examination
X
X
X
Symptom Directed 
Physical 
Examination
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signsj
(including weight)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12 lead ECG
X
X
X
X
X
X
X
X
X
Height
X
Hematologyf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistryg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Estimated GFRc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis and Urine 
Chemistryk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Storage 
Sample
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy 
Teste
X
X
X
X
X
X
X
X
X
X
Serum FSHi
X
Urine Pregnancy test
X
HBV, HCV Testing
X
CD4+ Cell Count
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV 1 Genotyping/
Phenotyping
X
CCI


LEN and TAF 
GS-US-200-4072 
Statistical Analysis Plan - Final Analysis 
= 
... 
·= 
,s 
N 
;,., 
;,., 
... ., 
0: 
0: 
('1 
Q 
Q 
HIV I capsid 
X 
Genotype/Phenotype' 
HIV DNA 
genotyping 
Plasma HIV I RNA 
X 
X 
X 
Plasma Storage 
X 
X 
Sample 
Intensive PK Plasma 
X' 
Collection (Part A) 
Single Anytime PK 
Plasma Sample (Part 
A)" 
... 
... 
..., 
...,. 
r--
00 
0\ 
;,., 
;,., 
;,., 
;,., 
;,., 
0: 
0: 
0: 
0: 
0: 
Q 
Q 
Q 
Q 
Q 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Version 1.0 
... 
... 
... 
... 
..., 
0\ 
r--
"' 
0: 
0 
...,. 
0\ 
..., 
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"' 
...,. 
\D 
0\ 
N 
= 
N 
...,. 
"' 
00 
N 
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;,., 
;,., 
;,., 
;,., 
;,., 
;,., 
;,., 
;,., 
;,., 
;,., 
;,., 
...... 
0: 
0: 
0: 
0: 
0: 
0: 
0: 
0: 
0: 
0: 
0: 
0: 
Q 
Q 
Q 
Q 
Q 
Q 
Q 
Q 
Q 
Q 
Q 
"-lE--
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK Plasma Sample 
X 
X 
X 
X 
X 
X 
X 
X 
(Part 8 ) 0 
IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII 
X 
X 
X 
X 
X 
X 
.-. ~' -· 
.. ••---1 ---••········· 
X 
T AF Administration 
X 
(Part B) 
8/FtrAF 
X 
X 
X 
X 
X 
dispensation 
Adverse Events/ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Meds 
CONFIDENTIAL 
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14 September 2020 


LEN and TAF 
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Statistical Analysis Plan - Final Analysis 
a 
Screening evaluations must be completed within 42 days prior to Day I. 
b 
Day I tests and procedures must be completed prior to administration of the dose of study dmg 
c 
According to the Cockcroft Gault fornrnla 
Version 1.0 
d 
Within 72 hours of pern1anently discontinuing study. Counsel subject regarding the importance of continuing a complete ARV therapy in accordance to standard of care, and 
refer patient to an appropriate HIV treatment facility. 
e 
Females of childbearing potential only 
f 
Hematology: CBC with differential and platelet count 
g 
Chemistries: Alkaline phosphatase, AST, ALT, GGT, total bilimbin, direct and indirect bilimbin, total protein, albumin, LOI-I, CPK, bicarbonate, BUN, calcium, chloride, 
creatinine, glucose, phosphoms, magnesium, potassium, sodium, uric acid, and amylase (reflex lipase testing if total amylase > 1.5 >< ULN). 
h 
Fasting overnight (;,: 6 hours) required for Days I, 3, 7, 10, 85, 169 and 225 
FSJ-1 test is re.quired for female subjects who have stopped menstmating for 2:: 12 months but do not have documentation of ovarian horn1onal failure. 
j 
Vital signs 
blood pressure, pulse, respiration rate, and temperature, weight 
k 
Urinalysis and Urine Chemistry: including color & clarity, specific gravity, pl-I, glucose, ketones, bilimbin, urobilinogen, blood, nitrite, leukocyte esterase and microscopic 
(if microscopic elements are seen), urine protein, albumin, creatinine, phosphate, calcium, magnesium and uric acid 
I 
n 
0 
p 
r 
r 
Part A: Serial blood samples to detern1ine pharn1acokinetics (PK) in plasma will be collected at the following time points relative to study dmg dosing 0 (pre dose), I, 2,4, 8, 
12 and 24 hours ost dose. 
art : mg e 
nyttme 
samp e to e co ecte at t e ay , , an 
t roug 
v1S1ts. 
Part 8 : Plasma P-
sam les to be collected at the following time points relative to study dmg dosing: 0 (pre dose), 0.5, I, 2, 3, 4, 6, 8, I 0, 12, 24 and 48 hours post dose; as 
well as at Days 4, 
7, 8, 9 and IO at approximately the same time in the morning as pre dose on Day I. 
Part 8 : PBMC P 
sam es to e co ecte at t e following time points relative to study dmg dosing: 0 (pre dose), I, 2, 4, 6, 8, 12, 24 and 48 hours post dose, as well as at 
Da s 4 
7 8 9 and IO at a 
roximatel the same time in the morning as pre dose on Day I . 
1 1ty pn or to randomization. Part 8 : the capsid genotype/phenotype will be completed for 
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Appendix 2.
Determining Missing and Virtual visits due to COVID-19
This appendix describes the site collection of COVID-19 data as pertains to missed/virtual visits 
and the data processing algorithm used to determine which visits were missing and which visits 
were virtual.
Data collection
A COVID-19 supplement to the eCRF Completion Guidelines (CCG) was provided by data 
management to instruct clinical trial sites with respect to data entry expectations pertaining to 
scenarios related to the COVID-19 pandemic. If a visit was missed, sites should enter “Visit 
missed due to COVID-19.” If a visit which was to be conducted in-person was conducted 
virtually, sites should enter “Virtual visit due to COVID-19.”  
Determination of Missed and Virtual visits
Natural Language Processing (NLP) was used to search the CRF comment fields to identify 
instances of “COVID-19” (or synonyms, see Appendix Table 1) and “Virtual” (or synonyms, 
see Appendix Table 1). The search terms are maintained in a global lookup and can be modified 
and/or corrected to tune the NLP model. For each comment field the following algorithm was 
applied:
STEP 1: Eliminate extraneous text from each comment field, e.g. “and”, “or”, “for”, etc.  This is 
done using the list of extraneous terms given in Appendix Table 2.
STEP 2: Check each of the remaining comment text strings against the “COVID-19” terms and 
“Virtual” terms with the Levenshtein distance, using SAS function COMPGED (Computes a 
generalized edit distance using the Levenshtein operations to compute/summarize the degree of 
difference between two text strings): 
i.
If Levenshtein distance < 149 for any of the “COVID-19” terms then COVIDFL
 1, 
else COVIDFL
 0
ii.
If Levenshtein distance < 149 for any of the “Virtual” terms then VIRTFL
 1, else 
VIRTFL
 0
STEP 3: For any comments with COVIDFL
 1, assign “Missed visit” or “Virtual visit as 
follows
i.
IF COVIDFL 1 and the visit date is missing then result is ‘Missed Visit’
ii.
IF COVIDFL 1 and VIRTFL  1 then result is  ‘Virtual Visit’
iii.
Otherwise result is missing


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Appendix Table 1.
Examples of search terms for “COVID-19” and “Virtual” used to 
identify missed and virtual visits.
Search terms for “COVID-19”
Search terms for “Virtual”
COVID19
VIRTUAL
CORONA
TELEMED
CORONAVIRUS
TELEHEALTH
PANDEMIC
TELEPHONE
OUTBREAK
REMOTE
CRISIS
TELEMEDICINE
LOCKDOWN
TELECONSULTATION
QUARANTINE
TELEPHONICALLY
SHELTER
PHONE
HOME VISIT
ZOOM
SKYPE


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Appendix Table 2.
Examples of extraneous text terms to eliminate from the comment 
fields.
a
down
in
she'd
until
about
during
into
she'll
up
above
each
is
she's
very
after
few
it
should
was
again
for
its
so
we
against
from
it's
some
we'd
all
further
itself
such
we'll
am
had
i've
than
were
an
has
let's
that
we're
and
have
me
that's
we've
any
having
more
the
what
are
he
most
their
what's
as
he'd
my
theirs
when
at
he'll
myself
them
when's
be
her
nor
themselves
where
because
here
of
then
where's
been
here's
on
there
which
before
hers
once
there's
while
being
herself
only
these
who
below
he's
or
they
whom
between
him
other
they'd
who's
both
himself
ought
they'll
why
but
his
our
they're
why's
by
how
ours
they've
with
could
how's
ourselves
this
would
did
i
out
those
you
do
i'd
over
through
you'd
does
if
own
to
you'll
doing
i'll
same
too
your
down
i'm
she
under
you're
you've
yourself
yourselves
yours


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Appendix 3.
Programming Specifications
1) For subjects who have previously screen failed, rescreened then enrolled into the study, the 
later date of rescreening will be used as the screening date. For subjects who have screen 
failed twice, the first screening date will be used as the screening date.
2) For enrolled subjects who have previously screen failed then rescreened, only eligibility 
criteria deviations from the rescreening visit were summarized in table and listings.
3) Body mass index (BMI)
BMI will be calculated only at baseline as follows:
BMI  (weight [kg]) / (height [meters]2)
Baseline height and weight will be used for this calculation.
4) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded for 
percentage calculation. An exception is for Mode of infection (HIV Risk Factors), where 
“Unknown” will be included for percentage calculation, since a subject may fit more than 
1 HIV risk factor, therefore percentage may add to more than 100%.
5) Graded Laboratory Abnormalities Summary
The following labels will be used for treatment-emergent laboratory abnormalities and treatment-
emergent Grade 3 or 4 laboratory abnormalities summary tables and listings:
Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Hematology
Hemoglobin
Decrease
Hemoglobin (Decreased)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Chemistry
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
Amylase
Increase
Amylase (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
GGT
Increase
GGT (Increased)


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GS-US-200-4072
Statistical Analysis Plan – Final Analysis 
Version 1.0
CONFIDENTIAL
Page 48
14 September 2020
Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Fasting)
Decrease
Serum Glucose (Fasting, Hypoglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Decrease
Serum Glucose (Nonfasting, Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Urea Nitrogen (BUN)
Increase
Urea Nitrogen (Increased)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Uric Acid
Decrease
Uric Acid (Hypouricemia)
Urinalysis
Urine Glucose
Increase
Urine Glucose (Glycosuria)
Urine Protein
Increase
Urine Protein (Proteinuria)
Urine RBC (Quantitative)
Increase
Urine RBC (Hematuria, Quantitative)
6) PK concentration analysis visit names will follow day/hour labeling combinations defined in 
the protocol Section 6.6.1 (i.e. Day 1 48 hours post dose).
7) Clarification for “Pharmacokinetic Sampling Details and Concentrations” listings
“Sample age” will be added in this listing, defined as the duration in days between 
sample collection date and assay date, ie, sample age  assay date sample collection 
date + 1.
Scheduled PK sampling time for intensive PK samples at predose is 5 mins prior to 
dosing time. 
SAMTIME is calculated as the duration in hours between the dosing time before sample 
collected and sample collection time, except for intensive PK samples at predose. 
SAMTIME for intensive PK samples at predose is calculated as the duration in hours 
between the dose time on the same day (ie, right after the predose sample collection) and 
sample collection time.   


LEN and TAF
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Statistical Analysis Plan – Final Analysis 
Version 1.0
CONFIDENTIAL
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14 September 2020
8) PK parameters at the individual subject level should be displayed with the following reported 
decimal places
LambdaZ, r2, r2 adj, and CORRXY: 3 decimal places
t1/2, Tlast, Tmax, BEGHOUR and ENDHOUR: 2 decimal places
AUC0 D10, AUCtau, AUClast, AUCinf, %AUCexp, Vz/F, CL/F, CLss/F, Cmax, Clast, 
Ctau, AR_AUC, and AR_Cmax: 1 decimal place
NPOINTS: 0 decimal places
9) Concomitant nonstudy-drug ARV medications (ie, ARV medications other than study drug
that are taken on or after first dose date) will be flagged in “Antiviral Medication” listings. 


GS-US-200-4072 Final Analysis SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
15-Sep-2020
18:28:29
Clinical Research eSigned 16-Sep-2020
03:04:46
Clinical Pharmacology
eSigned
17-Sep-2020
16:17:12
PPD
PPD
PPD
-