Clinical trial NCT03060447
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences
Start date: 2017-05-09; Completion date: 2020-02-13
Enrollment: 25 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the safety and tolerability of a 10-dose regimen of vesatolimod in HIV-1 infected controllers on antiretroviral treatment (ART) and during analytical treatment interruption (ATI) following vesatolimod dosing.

Detailed description:

Arms: arm 1: Participants in Period 1 will receive 10 doses of vesatolimod (4 mg to 8 mg) once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and vesatolimod and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months. arm 2: Participants in Period 1 will receive 10 doses of placebo matched to vesatolimod once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and placebo and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
Interventions: intervention 1: Vesatolimod intervention 2: Placebo intervention 3: ART
Intervention descriptions: intervention 1: Tablets Administered orally intervention 2: Tablets Administered orally intervention 3: ART regimens administered in accordance with their prescribing information. The following agents are allowed as part of the ART regimen: nucleoside reverse transcriptase inhibitors, raltegravir, dolutegravir (DTG), rilpivirine, and maraviroc.

Protocol documents:
Prot_001.pdf: 
Study Title: 
Sponsor: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Indication: 
Protocol ID: 
GILEAU 
CLINICAL STUDY PROTOCOL 
A Phase lb, Randomized, Double-Blind, Placebo-controlled Study to Evaluate the 
Safety and Efficacy of GS-9620 in Antiretroviral Treated HIV-1 Infected 
Controllers 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
122452 
Not Applicable 
NCT03060447 
HIV-1 Infection 
GS-US-382-3961 
Clinical Program Managft": 
Name: 
PPD 
PPD 
PPD 
Telephone: 
Fax: 
Gilead Medical Monitor: 
Name: 
Telephone: 
Fax: 
Gilead Study Director: 
Name: 
Telephone: 
Fax: 
Mobile: 
Protocol Version/Date: 
Original: 
Amendment 1: 
Amendment 2: 
Amendment 3: 
Amendment 4: 
PPD 
PPD 
PPD 
PPD 
PPD 
PPD 
PPD 
11 July 2016 
2 September 2016 
6 September 2017 
08 June 2018 
05 February 2019 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Institutional 
Review Board or Independent Ethics Committee. The information is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol. 
You will not disclose any of the information to others without written authorization :from 
Gilead Sciences, Inc., except to the extent necessary to obtain informed consent :from those 
persons to whom the drug may be administered. 


GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
Final 
Amendment4 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ 5 
LIST OF IN-TEXT FIGURES ...................................................................................................................................... 5 
PROTOCOL SYNOPSIS .............................................................................................................................................. 6 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 20 
1. 
INTRODUCTION .............................................................................................................................................. 24 
1.1. 
Backgrowid ............................................................................................................................................ 24 
1.2. 
GS-9620 ................................................................................................................................................. 25 
1.2.1. 
General Infonnation ............................................................................................................. 25 
1.2.2. 
Preclinical Pharmacology and Toxicology ........................................................................... 26 
1.2.3. 
Clinical Trials ofGS-9620 ................................................................................................... 29 
1.3. 
Rationale for This Study ........................................................................................................................ 34 
1.4. 
Rationale for Dose Selection/Dosing Interval ........................................................................................ 35 
1.5. 
Rationale for Biomarker Testing ............................................................................................................ 36 
1.6. 
Risk/Benefit Assessment for the Study .................................................................................................. 36 
1.7. 
Compliance ............................................................................................................................................ 37 
2. 
OBJECTIVES ..................................................................................................................................................... 38 
3. 
STUDYDESIGN ................................................................................................................................................ 40 
3 .1. 
Endpoints ............................................................................................................................................... 40 
3.2. 
Study Design .......................................................................................................................................... 41 
3.3. 
Study Treatments ................................................................................................................................... 43 
3.4. 
Duration ofTreatment ............................................................................................................................ 43 
3.5. 
Discontinuation Criteria ......................................................................................................................... 43 
3.6. 
End ofStudy ........................................................................................................................................... 44 
3.7. 
Post Study Care ...................................................................................................................................... 44 
3.8. 
Source Data ............................................................................................................................................ 44 
3.9. 
Biomarker Testing .................................................................................................................................. 44 
3.9.1. 
Biomarker Samples to Address the Study Objectives .......................................................... 44 
4. 
SUBJECT POPULATION .................................................................................................................................. 46 
4.1. 
Number of Subjects and Subject Selection ............................................................................................ 46 
4.2. 
Inclusion Criteria .................................................................................................................................... 46 
4.3. 
Exclusion Criteria ................................................................................................................................... 47 
4.4. 
Other Protocol Restrictions .................................................................................................................... 49 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS ........................................................................................... 50 
5.1. 
Randomization, Blinding and Treatment Codes .................................................................................... 50 
5.1.1. 
Procedures for Breaking Treatment Codes ........................................................................... 50 
5.2. 
Description and Handling of GS-9620 and Placebo-to-match GS-9620 ................................................ 51 
5.2.1. 
Foimulation .......................................................................................................................... 51 
5.2.2. 
Packaging and Labeling ....................................................................................................... 51 
5.2.3. 
Storage and Handling ........................................................................................................... 51 
5.3. 
Dosage and Ad1ninistration of GS-9620 ................................................................................................ 52 
5.4. 
Prior and Conco1nitant Medications ....................................................................................................... 52 
5.5. 
Accountability for GS-9620 ................................................................................................................... 54 
CONFIDENTIAL 
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Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
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05 February 2019 
5.5.1. 
Investigational Medicinal Product Return or Disposal ......................................................... 54 
6. 
STUDY PROCEDURES .................................................................................................................................... 55 
6.1. 
Subject Enrollment and Treatment Assignment ..................................................................................... 55 
6.2. 
Pretreatment Assessments (Period 1) ..................................................................................................... 55 
6.2.1. 
Screening Visit ..................................................................................................................... 55 
6.2.2. 
Pre-Baseline/Day -13 Assessments ...................................................................................... 57 
6.2.3. 
Randomization ..................................................................................................................... 58 
6.2.4. 
Dose 1-Day 1 Assessments .................................................................................................. 58 
6.3. 
Treatment Assessments (Period 1) ......................................................................................................... 59 
6.3.1. 
Treatment Assessments on Dosing Visits Dose 2- Dose 10 ................................................. 59 
6.3.2. 
Treatment Assessments on Non Dosing Days ...................................................................... 62 
6.4. 
Post-treatment Assessments (Period 2) .................................................................................................. 64 
6.4.1. 
Analytical treatment interruption Visit 1 .............................................................................. 64 
6.4.2. 
ATI visits 2-24 (once/week) beginning at ATI Visit 1 ......................................................... 65 
6.4.3. 
ATI Remission Visit ............................................................................................................. 66 
6.5. 
Post-treatment Extension Assessments (Period 3) ................................................................................. 67 
 
 
6.5.2. 
End of Study Visit for subjects who have not re-initiated ART anytime 
through Period 2 and 3 ......................................................................................................... 68 
6.6. 
ART Re-initiation and Post Re-Suppression Visits (may occur in Period 2 or Period 3) ...................... 69 
6.6.1. 
ART Re-initiation Visits ...................................................................................................... 69 
6.6.2. 
Post-ART Re-suppression Visits 1-6 .................................................................................... 70 
6.6.3. 
Assessments for Premature Discontinuation from Study ..................................................... 71 
6.7. 
Criteria for Discontinuation of Study Treatment .................................................................................... 73 
 
 
6.9. 
Prolonged Viremia During GS-9620 Dosing Phase ............................................................................... 73 
6.9.1. 
Management of Prolonged Viremia During GS-9620 Dosing Phase ................................... 73 
6.9.2. 
Management of Subjects during ATI 
 .................................................... 74 
6.9.3. 
Management of Virologic Failure post ART Restart ........................................................... 75 
6.10. 
Management of HIV-1 Seronegative Study Subject Sexual Partners .................................................... 75 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ............................................................................... 76 
7.1. 
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events ................................. 76 
7.1.1. 
Adverse Events ..................................................................................................................... 76 
7.1.2. 
Serious Adverse Events ........................................................................................................ 76 
7.1.3. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events ......................................................................... 77 
7.2. 
Assessment of Adverse Events and Serious Adverse Events ................................................................. 77 
7.2.1. 
Assessment of Causality for Study Drugs and Procedures ................................................... 77 
7.2.2. 
Assessment of Severity ........................................................................................................ 78 
7.3. 
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead ....................................................................................................................... 78 
7.4. 
Gilead Reporting Requirements ............................................................................................................. 79 
7.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events .......................................................................................................................... 80 
7.6. 
Toxicity Management ............................................................................................................................ 80 
7.6.1. 
Management of Dose-Limiting Toxicities (DLTs)............................................................... 80 
7.6.2. 
Management of Other Toxicities .......................................................................................... 81 
7.7. 
Special Situations Reports ...................................................................................................................... 82 
7.7.1. 
Definitions of Special Situations .......................................................................................... 82 
7.7.2. 
Instructions for Reporting Special Situations ....................................................................... 83 
8. 
STATISTICAL CONSIDERATIONS ................................................................................................................ 85 
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Amendment 4 
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8.1. 
Analysis Objectives and Endpoints ........................................................................................................ 85 
8.1.1. 
Analysis Objectives .............................................................................................................. 85 
8.1.2. 
Primary Endpoint ................................................................................................................. 86 
8.1.3. 
Secondary Endpoint ............................................................................................................. 86 
 
 
8.2. 
Analysis Conventions ............................................................................................................................. 87 
8.2.1. 
Analysis Sets ........................................................................................................................ 87 
8.3. 
Data Handling Conventions ................................................................................................................... 88 
8.4. 
Demographic Data and Baseline Characteristics ................................................................................... 88 
8.5. 
Efficacy Analysis ................................................................................................................................... 88 
8.5.1. 
Virology Analysis ................................................................................................................ 88 
8.5.2. 
Immunology/Pharmacodynamics Analysis .......................................................................... 89 
8.6. 
Safety Analysis....................................................................................................................................... 89 
8.6.1. 
Extent of Exposure ............................................................................................................... 89 
8.6.2. 
Adverse Events ..................................................................................................................... 89 
8.6.3. 
Laboratory Evaluations ........................................................................................................ 90 
8.7. 
Pharmacokinetic Analysis ...................................................................................................................... 90 
8.8. 
Sample Size ............................................................................................................................................ 90 
8.9. 
Safety Evaluation Committee ................................................................................................................. 91 
8.10. 
Analysis Schedule .................................................................................................................................. 91 
8.10.1. 
Interim Unblinded Analyses ................................................................................................. 91 
8.10.2. 
Final Analyses ...................................................................................................................... 91 
9. 
RESPONSIBILITIES.......................................................................................................................................... 92 
9.1. 
Investigator Responsibilities .................................................................................................................. 92 
9.1.1. 
Good Clinical Practice.......................................................................................................... 92 
9.1.2. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval ........................................................................................................... 92 
9.1.3. 
Informed Consent ................................................................................................................. 93 
9.1.4. 
Confidentiality ...................................................................................................................... 93 
9.1.5. 
Study Files and Retention of Records .................................................................................. 93 
9.1.6. 
Case Report Forms ............................................................................................................... 95 
9.1.7. 
Investigational Medicinal Product Accountability and Return............................................. 95 
9.1.8. 
Inspections ............................................................................................................................ 95 
9.1.9. 
Protocol Compliance ............................................................................................................ 96 
9.2. 
Sponsor Responsibilities ........................................................................................................................ 96 
9.2.1. 
Protocol Modifications ......................................................................................................... 96 
9.2.2. 
Study Report and Publications ............................................................................................. 96 
9.3. 
Joint Investigator/Sponsor Responsibilities ........................................................................................... 97 
9.3.1. 
Payment Reporting ............................................................................................................... 97 
9.3.2. 
Access to Information for Monitoring .................................................................................. 97 
9.3.3. 
Access to Information for Auditing or Inspections .............................................................. 97 
9.3.4. 
Study Discontinuation .......................................................................................................... 97 
10. REFERENCES ................................................................................................................................................... 98 
11. APPENDICES .................................................................................................................................................. 100 
 
Appendix 1. 
Investigator Signature Page .................................................................................................. 101 
Appendix 2. 
Study Procedures Table ........................................................................................................ 102 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events .................................................... 108 
Appendix 4. 
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities ............. 109 
Appendix 5. 
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements................................................................................................. 131 
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Protocol GS-US-382-3961 
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Gilead Sciences, Inc. 
Amendment 4 
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Appendix 6. 
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ........................... 134 
 
 
LIST OF IN-TEXT TABLES 
Table 1-1. 
Estimated Margins of GS-9620 Following Oral Administration at the Highest 
Anticipated Human Dose ....................................................................................................... 28 
Table 5-1. 
Prohibited Concomitant Medications ..................................................................................... 53 
 
 
LIST OF IN-TEXT FIGURES 
Figure 3-1. 
Study Schema ......................................................................................................................... 42 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 6 
05 February 2019 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
 
 
Study Title: 
A Phase 1b, Randomized, Double-Blind, Placebo-controlled Study 
to Evaluate the Safety and Efficacy of GS-9620 in Antiretroviral 
Treated HIV-1 Infected Controllers  
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
122452 
Not Applicable 
NCT03060447 
Study Centers Planned: 
Multiple centers in North America 
Objectives: 
The primary objective of this study is: 
• To evaluate the safety and tolerability of a 10-dose regimen of 
GS-9620 in HIV-1 infected controllers on antiretroviral 
treatment (ART) and during analytical treatment interruption 
(ATI) following GS-9620 dosing 
The secondary objectives of this study are: 
Virology 
• To evaluate the effect of GS-9620 in reactivating the HIV-1 
reservoir, as measured by changes in plasma HIV-1 RNA by 
Taqman 2.0  
• To evaluate the effect of GS-9620 in modulating time to 
virologic rebound and plasma viral load set-point following ATI 
Immunology/Pharmacodynamics 
• To evaluate the pharmacodynamics (PD) of GS-9620 as 
measured by changes in serum/plasma cytokines, and mRNA of 
interferon-stimulated genes (ISGs) in whole blood 
• To evaluate effects of GS-9620 on immune cell activation in 
whole blood 
Pharmacokinetics 
• To evaluate the plasma pharmacokinetics (PK) of GS-9620 


GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
Study Design: 
CONFIDENTIAL 
-
I 
I 
I 
I 
I 
I 
I 
Final 
Amendment4 
This is a randomized, double-blind study with a single coho1i of 
HN -1 infected controllers on ART with a histo1y of pre-ART 
plasma HN -1 RNA between 50 and :S5,000 copies/mL. 
Randomization will be stratified by pre-ART viral load 
(~50 to < 2,000 copies/mL or ~2,000 to :S5,000 copies/mL) 
at screening. 
The study will be conducted in three periods. fu Period 1, up to 
30 subjects will be randomized 2:1 to receive GS-9620 or 
placebo-to-match. All subjects will receive a total of 10 doses of 
their assigned study treatment administered orally once every 
14 days. Subjects will continue to take their ART. 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
Number of Subjects 
Planned: 
CONFIDENTIAL 
Final 
Amendment4 
In Period 2, all subjects will discontinue ART and be monitored for 
rebound in HIV-1 plasma viremia for 24 weeks of close observation 
and follow up. 
For the 24 weeks of ATI, subjects will be seen weekly (ATI Visits 
1-24). 
Subjects who resta1i ART during Period 2 will complete ART 
Re-Initiation Visits, and then Post ART Re-Suppression Visits 
monthly for 6 additional months (Post ART Re-Suppression Visits 
1-6). For these subjects, the last study visit will be the Post ART 
Re-Suppression Visit 6. 
Subjects who complete 24 weeks of A TI without restaiiin 
will move onto Period 3. 
-
B) If subjects restaii ART at the strut of Period 3, subjects will 
complete ART Re-Initiation Visits, and then Post ART 
Re-Suppression Visits monthly for 6 additional months 
(Post ART Re-Suppression Visits 1-6). For these subjects, the 
last study visit will be the Post ART Re-Suppression Visit 6. 
Up to 30 subjects in total; randomized 2: 1 to receive GS-9620 
or placebo-to-match. 
Subjects who discontinue study paiiicipation before completion of 
dosing for reasons other than study treatment-related adverse events 
(AEs) may be replaced. 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
Target Population: 
Duration of 
Treatment: 
Diagnosis and Main 
Eligibility Criteria: 
CONFIDENTIAL 
Final 
Amendment4 
HN-1 infected male and non-pregnant, non-lactating female adults 
who have a documented histo1y of controlling plasma HN-1 RNA 
between 50 and :::;5,000 copies/mL prior to ART initiation and who 
have been virologically suppressed (HN-1 RNA <50 copies/mL) 
on ART for at least 6 months prior to screening. 
Subjects will receive up to 10 doses of GS-9620 or placebo-to-match 
over a minimum of a 20-week period (Period 1), followed by 
24 weeks of close observation post ATI stmi (Period 2). 
For subjects who re-initiate ART during Period 2, duration of study 
will extend for 6 months following virologic re-suppression on ART 
(Post ART Re-suppression Visits 1-6). 
After 24 weeks of A TI, subjects will- resta1i ART-
-
(Period 3). Subjects who restmi ART will complete ART 
Re-lmbation Visits and then will complete Post ART 
Re-Suppression Visits monthly for 6 additional months. For these 
sub'ects, the last stud visit will be Post ART Re-Su ression Visit 
6. 
The End of Study visit will occur one week after the last 
ATI visit. 
HN-1 infected subjects who meet the following criteria: 
• 
Age 
18 years of age 
• 
Plasma HN-1 RNA levels <50 copies/mL at Screening 
• 
Chronic HN -1 infection (for ~6 months) prior to ART initiation 
• 
Pre-ART Plasma HN-1 RNA set point between 50 and 
:::;5,000 copies/mL measured within two years prior to ART 
initiation calculated as below: 
-
At least one plasma HN -1 RNA level, while off ART, above 
the level of detection using standard assays ( <40 copies/mL 
Abbott, <50 copies/mL Roche, <75 copies/mL bDNA) and 
:::;5,000 copies/mL prior to ART initiation. 
-
Using all available viral load detenninations during the 
two years prior to ART, the mean HN-1 RNA viral load 
( defined as viral load set point) must be above the limit of 
detection and :::;5,000 copies/mL (those determinations below 
the level of quantification will be considered as detectable at 
this threshold level). Two years of prior data are not required 
but up to two years of data will be evaluated. 
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Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 10 
05 February 2019 
• On ART for ≥6 months prior to screening 
 The following agents are allowed as part of the current ART 
regimen: NRTIs, raltegravir, dolutegravir, rilpivirine, 
and maraviroc 
 A change in ART regimen ≥45 days prior to 
Pre-baseline/Day -13 for reasons other than virologic failure 
(e.g., tolerability, simplification, drug-drug interaction 
profile) is allowed 
 
• Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months 
preceding the Screening visit (or undetectable HIV-1 RNA level 
according to the local assay being used if the limit of detection 
is ≥ 50 copies/mL). 
• Unconfirmed virologic elevations of ≥ 50 copies/mL 
(transient detectable viremia, or “blip”) prior to screening are 
acceptable. (If the lower limit of detection of the local HIV-1 
RNA assay is < 50 copies/mL, the plasma HIV-1 RNA level 
cannot exceed 50 copies/mL on two consecutive HIV-1 RNA 
tests) 
• If ART regimen is changed ≥ 45 days prior to Pre-baseline/ 
Day -13, plasma HIV-1 RNA <50 copies/mL at Pre-baseline/ 
Day -13 visit is required 
• No documented history of resistance to any components of the 
current ART regimen 
• Availability of a fully active alternative ART regimen, in the 
opinion of the Investigator, in the event of discontinuation of the 
current ART regimen with development of resistance. 
• Hemoglobin ≥ 11.5 g/dL (males) or ≥ 11 g/dL (females) 
• White Blood Cells ≥ 2,500 cells/μL 
• Platelets ≥ 125,000/mL 
• Absolute Neutrophil Counts ≥ 1,000 cells/μL 
• CD4+ count ≥ 500 cells/μL 
• Alanine aminotransferase (ALT), aspartate aminotransferase 
(AST) or bilirubin ≤ 2 × upper limit of normal (ULN) 
• Estimated glomerular filtration rate ≥ 60 mL/min 
• No autoimmune disease requiring on-going immunosuppression 
• No evidence of current HBV infection 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 11 
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• No evidence of current HCV infection (positive anti-HCV 
antibody and negative HCV PCR results are acceptable) 
• No documented history of pre-ART CD4 nadir < 200 cells/μL 
(unknown pre-ART CD4 nadir is acceptable) 
• No history of opportunistic illness indicative of stage 3 HIV 
• No acute febrile illness within 35 days prior to Pre-Baseline/ 
Day -13 
Study Procedures/ 
Frequency: 
The main study phase (Period 1 and Period 2) consists of a screening 
period of up to 35 days, a pre-treatment period of 14 days 
(from Day -13 to Day 1), a treatment period of up to 10 doses 
(from Dose 1-Day 1 to Dose 10-Day 1) administered orally every 
14 days, a period of 24 weeks of close observation post ATI start 
beginning on Dose 10-Day 28, additional follow up visits 
(either ART Re-Initiation Visits with Post ART Re-Suppression 
Visits 
), and an End of Study Visit 
(if applicable). Enrolled subjects will undergo the following 
scheduled study visits. 
Period 1: 
Pre-Baseline/Day -13, may include tissue sampling 
Baseline/Dose 1-Day 1, Dose 1-Day 2, Dose 1-Day 8 
Dose 2-Day 1, Dose-2-Day 8 
Dose 3-Day 1, Dose 3-Day 8 
Dose 4-Day 1, Dose 4-Day 2, Dose 4-Day 4, Dose 4-Day 8 
Dose 5-Day 1, Dose 5-Day 8 
Dose 6-Day 1, Dose 6-Day 4, Dose 6-Day 8 
Dose 7-Day 1, Dose 7-Day 8 
Dose 8-Day 1, Dose 8-Day 8 
Dose 9-Day 1, Dose 9-Day 8 
Dose 10-Day 1, Dose 10-Day 2, Dose 10-Day 4, Dose 10-Day 8, 
Dose 10-Day 14 (may include tissue sampling) 
If HIV-1 RNA viral load is >5,000 copies/mL at any visit post Dose, 
viral load will be observed at next scheduled visit or retested within 
4 days. The next dose will be withheld and only given if a viral load 
of ≤5,000 copies/mL is achieved. The study procedure schedule will 
be reset relative to the next dose of GS-9620. 
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GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 12 
05 February 2019 
 
Subjects who prematurely discontinue study drug prior to 
completing Dose 10 will be required to complete an Early Study 
Drug Discontinuation Visit within 30 days after their last dose. 
Period 2: 
ATI Visit 1 (Beginning of analytical treatment interruption, 
28 days after Dose 10) subjects will discontinue ART. 
Subjects will be closely observed for a 24 week ATI period during 
which plasma HIV-1 RNA values, CD4+ cell count, CD8+ cell 
count, CD4/CD8 ratio and CD4 % will be measured once a week. 
Viral Remission 
After the first 12 weeks of ATI are complete, an additional ATI 
Remission Visit (may include tissue sampling) may be scheduled. 
This visit will be completed once HIV-1 RNA is <50 copies/mL. 
Viral Rebound 
During the 24 week ATI period, if plasma HIV-1 RNA becomes 
> 50 copies/mL, the visit schedule for HIV-1 RNA measurements 
may be adjusted per Investigator’s discretion. 
ART Restart Criteria 
During 24-week ATI period 
, 
ART will be re-initiated if any of the criteria below are met: 
• if HIV-1 RNA is >10,000 copies/mL on four consecutive weekly 
measurements OR 
• if HIV-1 RNA does not decrease to <1,000 copies/mL within 
6 weeks of virologic rebound OR 
• if CD4+ cell count is confirmed to decrease by >30% from 
pre-ATI levels OR 
• if CD4+ cell count is confirmed<350 cells/µL OR 
• Per Investigator or Sponsor’s discretion due to other clinical 
criteria 
ART Restart Measurements 
Following ART re-initiation, weekly visits measuring plasma HIV-1 
RNA, CD4+ cell count, CD8+ cell count, CD4/CD8 ratio and CD4% 
will be conducted. 
If plasma viral load becomes undetectable (<50 copies/mL); then 
monitoring measurements will be every other week for 
two consecutive measures then once a month for 6 months. 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
CONFIDENTIAL 
Final 
Amendment4 
At Post-ART Re-suppression Visit 6, HIV-1 reservoir will be 
measured by plasma SCA, CA VR, CA VD 
-
· The subject will end the study at this visit. 
If plasma viral load is ~200 copies/mL for four weeks then 
resistance testing will be perfonned at the next visit per 
Management ofVirologic Failure post ART Restaii (Section 6.9.3). 
Period 3: 
After 24 weeks of A TI, subjects will- resta1i 
ART. 
Subjects who resta1i ART will complete ART Re-Initiation Visits 
and then will complete Post ART Re-Suppression Visits monthly for 
6 additional months. For these subjects, the last study visit will be 
Post ART Re-Suppression Visit 6. 
Screening Procedures: 
Screening procedures include: complete physical examination, vital 
signs, height, weight, medical histo1y (including route and estimated 
duration of HIV infection, pre-ART viral load set point, and 
complete ART histo1y), HIV-1 RNA, hematology, sernm chemistiy, 
CD4+ cell count, CD8+ cell count, CD4/CD8 ratio, CD4%, sernm 
pregnancy test (for females of childbea1ing potential), 
HBV and HCV serologies, eGFR, urinalysis, plasma ART trough 
PK collection, and electi·ocardiogram (ECG). Screening procedures 
also include collection of HLA class I and II type if not available 
through historical repo1is. Pre-ART CD4 nadir, and historical 
genotype will be collected, if available. 
In order to establish eligibility, Investigators may repeat screening 
procedures or laboratory assessments for subjects who have an acute 
illness or abnonnal laborato1y value that is expected to resolve 
without sequelae within the screening window. 
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Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 14 
05 February 2019 
 
On-Study Procedures: 
Dosing: 
Dosing will occur 14 days apart starting at Dose 1-Day 1, 
Dose 2-Day 1, Dose 3-Day 1, Dose 4-Day 1, Dose 5-Day 1, 
Dose 6-Day 1, Dose 7-Day 1, Dose 8-Day 1, Dose 9-Day 1 and 
Dose 10-Day 1 visits respectively. Subjects will fast for at 
least 2 hours (preferably overnight) before dosing. Subjects will 
also be asked to provide information on food consumption and 
total fasting time prior to dosing. 
 
The Investigator will verify the subject’s continued eligibility for 
dosing at post Baseline/Dose 1-Day 1 dosing visits, including the 
absence of dose-limiting toxicities (DLTs) and a negative urine 
pregnancy test (for females of childbearing potential), 
prior to dosing. All doses will be directly administered by blinded 
site staff. Subjects will fast for 2 hours after dosing. 
After Dose 1 on Day 1, subjects will remain on site for 10 hours 
after dosing for safety assessment and phlebotomy. 
Safety: 
Solicitation of AEs and concomitant medications at every visit. 
Symptom-directed physical examination at every visit during 
Period 1. Complete physical examination once a month and 
symptom directed physical examination on other visits to occur 
every two weeks during Period 2 
 
 
Hematology, serum chemistry, and urinalysis at all dosing visits, 
monthly during Period 2 
, post ART 
Re-suppression Visits and Early Study Drug Discontinuation Visit. 
Urine pregnancy test (for females of childbearing potential) prior to 
each dose, at ATI visit 1 (ATI start visit), at every other visit 
thereafter during Period 2, 
, at first ART 
Re-initiation visit and monthly thereafter until Post ART 
Re-Suppression Visit 1, post ART Re-suppression Visits and End of 
Study Visit. 
Vital signs (blood pressure, pulse, respiration rate and temperature) 
at all dosing visits and every other week during Period 2 
 
. 
Subjects will be instructed to contact the site immediately if any 
flu-like symptoms are noted (e.g., fatigue, pyrexia, chills, myalgia, 
joint pain or headache). 
CCI
CCI
CCI
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
CONFIDENTIAL 
Pharmacokinetics: 
Final 
Amendment4 
Plasma GS-9620 concentrations: blood collection at Pre-dose 
(~ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10 and 24 hours 
post dose at Dose I-Day 1 visit. 
Plasma ART concentrntions: a single trough PK sample will be 
collected at Screening. The timing of the ART trnugh collection is to 
be 20-24 hours following the subject's previous QD regimen dose 
(and, for any subject on a regimen containing a BID component, the 
trnugh collection must also occur 8-12 hours following the subject's 
previous dose of that BID component). Another single trough PK 
sample will be collected at Dose 6 Day 4. These samples may be 
analyzed to assess ART adherence. 
Additional PK samples may be drawn to verify that subject 
continues to be off-ART during the ATI phase (Period 
). Samples will be drawn upon Sponsor 
request depending on the subject's HN -1 RNA levels. 
Pharmacodynamics: 
Whole blood ISG mRNA panel: within 1 hour before and 1 day after 
Doses 1, 4, 10 of study dmg. 
TLR7 genotyping: at Pre-Baseline/Day -13 
Changes in the levels of sernm/plasma cytokines/chemokines by 
immunoassays: within 1 hour before and 1 and 7 days after Doses 1, 
4, and 10, and ATI Remission Visit. 
Virology: 
Plasma HN -1 RNA: at every visit. 
CA VR and CA VD from PBMCs: at Pre-baseline/Day -13 and 
within 1 hour before and 1 and 3 days after Doses 4 and 10, 
within 1 hour before and 3 days after Dose 6, Dose 10-Day 14, 
ATI Remission Visit and at Post-ART re-suppression Visit 6 
(6 months post-ART virologic re-suppression). 
Plasma HN -1 RNA Single Copy Assay (SCA) from plasma: 
at Pre-Baseline/Day -13, within 1 hour before, and 1 and 3 days after 
Doses 4 and 10, within 1 hour before and 3 days after Dose 6, 
Dose 10-Day 14, ATI Remission Visit and Post-ART re-suppression 
Visit 6 (6 months post-ART virologic re-suppression). 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
CONFIDENTIAL 
Immunology: 
Final 
Amendment4 
RN -specific T-cell responses from PBMC by intracellular cytokine 
staining (ICS): at Pre-Baseline/Day -13, Dose 10-Day 14, and ATI 
Remission Visit. 
RN -specific antibody profiling from sernm: at 
Pre-Baseline/Day -13, Dose 10-Day 14, and ATI Remission Visit. 
Additional End of Study Procedures: 
Symptom-directed physical examination, review of AEs and 
concomitant medications, vital signs, weight, eGFR, hematology, 
sernm chemistry , mine pregnancy test and minalysis 
Early Study Drug Discontinuation Visit Procedures: 
Symptom-directed physical examination, review of AEs and 
concomitant medications, vital signs, weight, eGFR, RN-1 RNA, 
hematology, sernm chemistry, whole blood ISG mRNA panel, 
sernm cytokine/soluble biomarker studies, minalysis, urine 
pregnancy test. 
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Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 17 
05 February 2019 
 
Procedure Definitions and Specifications: 
HIV-1 RNA will be performed by a validated assay with a lower 
limit of quantitation of at least 50 copies/mL. 
Hematology panel includes: complete blood count (CBC) with 
differential and platelets, CD4+ cell count, CD8 cell count, 
CD4/CD8 ratio and CD4%. 
Serum chemistry panel includes: alkaline phosphatase, AST, ALT, 
total and direct bilirubin, total protein, albumin, bicarbonate, BUN, 
calcium, chloride, creatinine, glucose, phosphate, magnesium, 
potassium, sodium, CPK, and uric acid. 
Urinalysis includes dipstick. 
 
Serum and urine pregnancy tests are performed only on female 
subjects of childbearing potential. 
Phlebotomy volume limits will be maintained in accordance with 
American Red Cross blood donation guidelines, which limit blood 
donation to 473 mL every 56 days. Subjects will undergo periodic 
phlebotomy over study period and will provide no more than 
473 mL every 56 days. Subjects will be prohibited from blood 
donation in excess of that required for clinical care within 30 days 
prior to screening and 30 days after study ends. 
HIV-1 seronegative sexual partners of enrolled study subjects may 
be referred to a local HIV Pre-Exposure Prophylaxis (PrEP) clinic 
for HIV risk assessment evaluation. 
Test Product, Dose, and 
Mode of 
Administration: 
GS-9620 8 mg dose, administered as four 2 mg tablets orally every 
14 days (window of ± 1 day). 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Placebo-to-match GS-9620, administered orally every 14 days 
(window of ± 1 day). 
Duration of Treatment: 
Subjects will be treated to receive up to 10 doses of GS-9620 or 
placebo-to-match. 
Other Treatment: 
Subjects will continue their existing ART regimen (as currently 
prescribed and supplied) for the duration of study Period 1 and then 
undergo ATI four weeks after the final (tenth) dose of GS-9620 or 
placebo-to-match. 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
Criteria for Evaluation: 
Safety: 
Virology: 
Phaimacodynamics: 
Immunology: 
Statistical Methods: 
Safety: 
Virology: 
CONFIDENTIAL 
Adverse events and clinical laborato1y tests 
Plasma log10 HIV-I RNA 
Plasma HIV-I RNA by SCA 
PBMC, 
PBMC associated viral reservoir measurements 
Time to HIV-I viral rebound during ATI 
Peak HIV-I viral load during A TI 
Plasma HIV-I viral set point during A TI 
Senun/plasma cytokines/ chemokines 
Whole blood ISG mRNAs 
Immune cell frequency, 
-
Final 
Amendment4 
The incidences of treatment-emergent AEs and treatment-emergent 
laborato1y abno1malities will be summai·ized by treatment group. 
The propoition of subjects in each treatment group with an AE 
leading to premature discontinuation of study diug and propo1iion of 
subjects with serious adverse events (SAEs) will be summarized by 
treatment group. 
The change in plasma HIV-I RNA and the incidence of detectable 
plasma HIV-I RNA by Taqman 2.0 at each visit will be smnmai·ized 
by treatment group. 
Time to viral rebound during ATI will be smnmarized by treatment 
group. 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
Phaimacodynamics: 
Immunology: 
Phaimacokinetics: 
Sainple Size: 
Final 
Amendment4 
The difference in plasma viral set point between pre-ART values 
and given time points (including but not limited to): prior to ART 
restait in Period 2 and 3, and ATI Remission Visit will be 
sUIIllnai·ized by treatment group. 
The peak HIV-1 viral load during Period 2 or 3 will be summai·ized 
by treatment group. 
The change in plasma HIV-1 RNA by SCA may be explored. 
The changes in sennn/plasma cytokines and mRNA of ISGs in 
whole blood will be summai·ized using descriptive statistics by 
ti·eatment group. 
The type ofTLR7 genotype may be repo1ted and its association with 
key pai·aineters may be explored. 
The changes in immune cell activation in whole blood will be 
sUIIllnai·ized using descriptive statistics by treatinent group. 
The change in immune cell frequency and phenotyping may be 
explored. 
The change in magnitude and 
T cell immune res ons 
The plasma pha1macokinetics (PK) of GS-9620 will be evaluated. 
This is an exploratory study to characterize the safety and efficacy of 
GS-9620; therefore, no power calculation was perfo1med. 
Up to 20 subjects receiving GS-9620 will provide a preliminaiy 
assessment of safety and efficacy. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including ai·chiving of essential documents. 
CONFIDENTIAL 
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GS-9620 
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Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 20 
05 February 2019 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS 
°C 
degree(s) Celsius 
°F 
degree(s) Fahrenheit 
Ab 
Antibody 
ACAT 
Acetyl-coenzyme A acetyltransferase 
ACE 
Angiotensin Converting Enzyme 
ACTG 
AIDS Clinical Trials Group 
ADCC 
Antibody dependent T cell-mediated cytotoxicity 
ADCP 
Antibody dependent T cellular phagocytosis 
AE 
adverse event 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
alanine aminotransferase (SGPT) 
ANOVA 
analysis of variance 
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase (SGOT) 
ATI 
analytical treatment interruption 
AUC0-t 
area under the plasma concentration-time curve from zero 
AUC24h 
area under the plasma concentration-time curve in 24 hours 
AUCtau 
area under the plasma concentration versus time curve over the dosing interval (tau) 
BID 
bis in die ( two-or twice-a-day) 
BLQ 
below the limit of quantitation 
BUN 
blood urea nitrogen 
CAVD 
cell-associated viral DNA 
CAVR 
cell associated viral RNA 
CBC 
complete blood count 
CD 
Cluster of Differentiation  
CDC 
Center for Disease Control and Prevention 
CFR 
Code of Federal Regulations (United States) 
CHB 
Chronic hepatitis B 
Clast 
last observed quantifiable concentration of the drug 
CLcr 
creatinine clearance 
Cmax 
maximum observed concentration of drug 
CNS 
central nervous system 
CPK 
creatine phosphokinase (= creatine kinase, CK) 
CSR 
clinical study report 
Ctau 
observed drug concentration at the end of the dosing interval (tau) 
CYP3A 
cytochrome P450  
DHHS 
Department of Health and Human Services 
dL 
deciliter(s) 
DLT 
dose-limiting toxicities 
DNA 
deoxyribonucleic acid 
PVE 
Pharmacovigilance and Epidemiology (PVE), Gilead Sciences 


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DTG 
Dolutegravir 
EC 
ethics committee 
EC50 
50% effective inhibitory concentration 
ECG 
Electrocardiogram 
eCRF 
electronic case report form(s)  
EDC 
Electronic data capture 
eGFR 
estimated glomerular filtration rate 
ESDD 
Early Study Drug Discontinuation 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
ET 
Early termination 
FAS 
Full analysis set 
FDA 
Food and Drug Administration (United States) 
FSH 
Follicle stimulating hormone 
FTC 
Emtricitabine 
g 
Gram 
GALT 
gut associated lymphoid tissue 
GCP 
Good Clinical Practice (Guidelines) 
GSI 
Gilead Sciences, Inc. 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HBcAb 
hepatitis B virus core antibody 
HBsAb 
hepatitis B virus surface antibody 
HBsAg 
hepatitis B virus surface antigen 
HDACi 
histone deacetylase inhibitors 
hERG 
human ether-à-go-go-related gene 
HLA 
Human Leucocyte Antigen 
HLT 
high level term 
HLGT 
high level group term 
HMG-Coa 
3-hydroxy-3-methylglutaryl-coenzyme 
HPF 
high-power field 
HIV 
human immunodeficiency virus 
hr 
Hour 
hsCRP 
High sensitivity C-Reactive Protein 
ICH 
International Conference on Harmonization 
ICS 
intracellular cytokine staining 
IC50 
50% inhibitory concentration 
IEC 
Institutional Ethics Committee 
IFN 
Interferon 
IFN-α 
interferon-alpha 
IMP 
Investigational Medicinal Product 
IND 
Investigational New Drug (Application) 
IP-10 
interferon γ–inducible protein-10  
IRB 
Institutional Review Board 


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ISGs 
interferon-stimulated genes 
IUD 
intrauterine device 
IU 
international unit 
 
 
Kg 
Kilogram 
LAM 
Lactational amenorrhea method 
LRA 
latency reversal agent 
LLN 
lower limit of the normal range 
LLOD 
lower limit of detection 
LLOQ 
lower limit of quantitation 
LLT 
lower level term 
LN 
lymph node 
MAD 
multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities; MedDRA® 
mg 
milligram 
µg 
microgram 
µL 
microliter 
min 
minute 
mDC 
conventional (myeloid) dendritic cell 
mL 
milliliter 
mRNA 
messenger ribonucleic acid 
NDA 
New Drug Application 
NK 
natural killer (cell) 
NRTI 
Nucleoside Reverse-Transcriptase Inhibitors 
NOAEL 
no observed adverse effect level 
OAV 
oral antivirals 
PCR 
Polymerase Chain Reaction 
PEG 
pegylated interferon 
PBMC 
peripheral blood mononuclear cell 
PD 
pharmacodynamics(s) 
pDC 
plasmacytoid dendritic cell 
PK 
pharmacokinetic(s) 
POC 
Proof of concept 
PrEP 
Pre-Exposure Prophylaxis 
PT 
prothrombin time 
PT 
preferred term 
pVL 
plasma viral load 
PXR 
pregnane X receptor 
Q1 
First quartile 
Q3 
Third quartile 
QD 
quaque die (one- or once-a-day) 
QOD 
every other day (dosing) 
qPCR 
quantitative PCR 
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QVOA 
Quantitative viral outgrowth Assay 
RBC 
red blood cell (count) 
RNA 
ribonucleic acid 
sCD 
Soluble CD 
SAD 
single ascending dose 
SADR 
serious adverse drug reaction 
SAE 
serious adverse event 
SCA 
single copy assay 
SD 
standard deviation 
SEC 
Safety Evaluation Committee 
SIV 
Simian immunodeficiency virus 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
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 (λz) 
Th1/Th2/Th17 
T helper cells (1, 2, 17) 
Tr1 
Type 1 T regulatory cells 
Tlast 
time (observed time point) of Clast 
Tmax 
time (observed time point) of Cmax 
Treg 
T regulatory (cells) 
TBD 
to be determined 
TFV 
tenofovir 
TLR 
toll-like receptor 
ULN 
upper limit of the normal range 
US 
United States 
USA 
United States of America 
vs 
versus 
WHO 
World Health Organization 
wt 
weight 
λz 
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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Gilead Sciences, Inc. 
Amendment 4 
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1. 
INTRODUCTION 
1.1. 
Background 
Human immunodeficiency virus type-1 (HIV-1) infection is a life-threatening and serious 
disease that is of major public health interest around the world. There are approximately 
2.4 million people in North America and Western and Central Europe living with HIV-1 and 
36 million people worldwide {Joint United Nations Programme on HIV/AIDS (UNAIDS) 
2016}. Untreated infection leads to deterioration in immune function and death. The availability 
of antiretroviral therapy (ART) has been associated with a dramatic decrease in acquired immune 
deficiency syndrome (AIDS)-related morbidity and mortality {Palella 1998}, {Mocroft 1998}, 
{Sterne 2005}. 
While ART effectively suppresses HIV replication, HIV infection remains incurable. 
Persistent viral reservoirs fuel rebound viremia when treatment ceases. Despite the availability of 
chronic treatment, morbidity, and mortality due to HIV infection remain high due to the latent 
HIV reservoir, which may contribute to ongoing inflammation-driven disease. Current therapy is 
associated with challenges with tolerability, long-term adherence and safety, drug-drug 
interactions, and expense. Persistent HIV infection may also be associated with psychosocial 
stigma. Thus, the discovery and development of therapeutic interventions that can eradicate or 
control HIV reservoirs, leading to long-term ART-free remission or HIV cure, is a major 
priority. 
Following entry into a target cell, HIV-1 stably integrates into the host genome, thus establishing 
the basis for latent infection and the main barrier to HIV cure. Neither the host immune system 
nor ART can eliminate transcriptionally inactive virus. Therefore, adjunctive therapies that 
efficiently reactivate (“kick”) virus out of this latent reservoir to enable its destruction (“kill”) 
may be required for viral eradication. This “kick and kill” strategy to cure or induce long-term 
HIV remission has been tested in clinical trials of latency reversal agents (LRA) such as histone 
deacetylase inhibitors (HDACi). While short-term treatment with HDACi such as romidepsin 
appears to be safe and may activate viral transcription in individuals virologically suppressed on 
ART, the size of the latent viral reservoir as measured by total peripheral blood mononuclear cell 
(PBMC)-associated HIV-1 DNA or quantitative viral outgrowth assay (QVOA) appears to be 
unchanged {Sogaard 2015}. However, a TLR9 agonist has been dosed in HIV-1 positive 
participants on ART in a single-arm open-label study demonstrating increases in plasma IFN-α 
levels, transcriptional (messenger ribonucleic acid [mRNA]) induction of interferon stimulated 
genes (ISGs), activation of pDCs, activation of cytotoxic natural killer (NK) and CD8+ T cells 
with transient increases in plasma HIV-1 RNA in a subset of individuals {Vibholm 2017}. It is 
postulated that a combination of therapies exerting viral latency reversing activity and 
engagement of the host immune system will be necessary to have a demonstrable effect on 
reducing the HIV-1 reservoir. To date there is no fully validated biomarker for the latent HIV-1 
reservoir. Therefore, measurement of the time to viral rebound and/or new viral load set-points 
following analytical treatment interruption (ATI) is the most accurate endpoint to evaluate the 
efficacy of “kick and kill” interventions. The AIDS Clinical Trials Group (ACTG) has reported 
that ATI can be conducted safely in patients {Bar 2016, Li 2016} and that certain measures of 
the HIV reservoir may be correlated with time to viral rebound {Li 2016}. 


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While previous ATI trials have included standard cohorts of chronically HIV-infected 
participants, a subset of infected individuals known as HIV controllers offers a unique 
opportunity to evaluate novel HIV cure interventions. These patients are defined by a history of 
maintaining undetectable or low HIV viral loads in the absence of ART, with the mechanism of 
control likely being a robust adaptive immune response {Walker 2013}. However, while 
controllers may be able to suppress HIV replication without treatment for extended periods, 
recent evidence supports initiating ART to minimize the pathologic immune activation and 
inflammation associated with chronic HIV infection {Hatano 2013}. Therefore, studying “kick 
and kill” interventions in the setting of an ATI in treated HIV controllers could potentially 
provide useful information while minimizing the risk of high peak viral load rebound in the 
absence of ART. 
GS-9620 is an orally-administered toll-like receptor (TLR) 7 agonist currently in clinical 
development for the treatment of HIV. In vitro, GS-9620 appears to mediate both HIV-1 “kick” 
and “kill” activity. In a rhesus macaque model of chronic SIV infection, treatment with GS-9620 
or its close analog GS-436986 has also demonstrated the ability to both “kick” and “kill”: 
treatment resulted in transient detection of plasma viremia within 24-72 hours of dosing, 
decreases in ex vivo SIV production from T-cell receptor stimulated PBMC cultures or immune 
cell isolates of peripheral lymph nodes comparing pre-treatment to post-dosing samples and 
a ~0.5 log10 lower viral load set-point after discontinuation of ART {Lim 2018}. Most 
importantly, in a subset of animals, there was a lack of detectable plasma virus (< 50 SIV 
RNA copies/mL) for at least 2 years after discontinuation of ART. During the off ART, 
phase two animals from one of the studies had no viral rebound after administration of antibodies 
depleting NK and CD8+ lymphocytes or transfer of viral infection after infusion of mononuclear 
immune cells from lymph node and peripheral blood into naïve animals; implying a substantial 
reduction in viral reservoir. The administration of multiple doses of GS-9620 has been shown to 
be safe in clinical studies of healthy subjects (single doses up to 12 mg), hepatitis B virus (HBV) 
infected subjects (multiple doses up to 4 mg), and subjects with chronic HIV-1-infection on ART 
(multiple doses up to 8 mg). This study will therefore investigate the safety and efficacy of 
GS-9620 in a cohort of HIV controllers on ART who undergo ATI following treatment with 
GS-9620. 
1.2. 
GS-9620 
1.2.1. 
General Information 
GS-9620 is an orally-administered TLR7 agonist in development for the treatment of HIV 
infection. 
Data in-vitro have shown that GS-9620 is a potent and selective TLR7 receptor agonist with 
a > 30-fold selectivity for TLR7 (32-fold based on EC50 and 81-fold based on minimum 
effective concentration) over toll-like receptor 8 (TLR8), with no detectable stimulation of other 
human TLRs at concentrations up to 100 μM (PC-243-2031). 


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Nonclinical data in mice and in chimpanzees chronically infected with HBV demonstrated that 
oral administration of GS-9620 induce a type I IFN dependent innate response in the liver, 
as measured by induction of interferon-stimulated genes (ISGs), in the absence of concomitant 
serum detectable levels of IFN-α (i.e. a pre-systemic response) {Fosdick 2013}, {Lanford 2013}. 
The induction of type I IFN-dependent innate immune responses without the induction of 
detectable systemic IFN-α has been confirmed in healthy human subjects (GS-US-320-0101) and 
patients affected by chronic hepatitis C (GS-US-243-0102) or by chronic hepatitis B 
(GS-US-283-0102, GS-US-283-0106, GS-US-283-1059, and GS-US-283-1062). 
For further information on GS-9620, refer to the investigator’s brochure for GS-9620. 
1.2.2. 
Preclinical Pharmacology and Toxicology 
Preclinical in vivo pharmacology studies in different non-human primate species have 
consistently demonstrated that GS-9620 induces IFN-α, multiple cytokines, chemokines, 
peripheral blood mononuclear cell (PBMC) derived ISG mRNAs and peripheral immune cell 
activation in a dose-dependent manner. Of note, with escalating doses of GS-9620 cynomolgus 
monkeys were shown to have an exaggerated IFN-α response both in vitro and in vivo compared 
to other species (mice, chimpanzees, and humans). 
In in vitro PBMC cultures, GS-9620 stimulated markedly higher maximal levels of secreted 
IFN-α in cynomolgus monkey PBMC compared to human PBMC cultures; the in vitro mean 
peak IFN-α was 9105 pg/mL and 1552 pg/mL in cynomolgus monkey and human PBMCs, 
respectively. 
Similarly, the mean peak IFN-α concentration in serum following a single oral dose in vivo was 
notably higher in cynomolgus monkeys than healthy human volunteers at an equivalent dose; 
at 0.5 mg/kg (human equivalent dose 9.6 mg) the mean peak of serum IFN-α was 4859 pg/mL in 
cynomolgus monkey versus 93.7 pg/mL in human healthy volunteers receiving 12 mg dose 
[study GS-US-243-0101] (human equivalent dose was calculated using a conversion factor 
of 0.32 for cynomolgus monkey and assuming a human body weight of 60 kg {U. S. Department 
of Health and Human Services (DHHS) 2005}). 
Single oral doses of GS-9620 given in preclinical studies in cynomolgus monkeys 
(0.05 to 0.5 mg/kg; human equivalent dose 1 – 9.6 mg) and mice (0.3 mg/kg; 
human equivalent dose 1.4 mg) human equivalent dose was calculated using a conversion factor 
of 0.08 for mice and assuming a human body weight of 60 kg {U. S. Department of Health and 
Human Services (DHHS) 2005} have shown that GS-9620 can induce an innate immunity gene 
expression signature, e.g. up-regulation of interferon-stimulated genes (ISG) in the absence of 
detectable serum IFN-α concentrations. These observations are consistent with the concept of 
a pre-systemic response elicited by oral GS-9620. 


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Body temperature increases were noted in the cardiovascular/respiratory safety pharmacology 
study in cynomolgus monkeys (≥ 0.5 mg/kg) at Cmax exposures that were approximately 
equivalent to the Cmax at the highest dose tested in HBV infected patients 
(4 mg; study GS-US-283-0102). Increases in heart rate were observed concurrently with the 
increases in body temperature and with the peak of IFN-α levels. Of note, body temperature and 
heart rate increase were not seen at the 4-mg dose in the human clinical studies. Increases in 
body temperature and heart rate are well-described side effects of exogenous IFN-α 
administration in humans {Vial 1994} and in nonhuman primates {Kubicek 1958}, {Vial 1994} 
and may reflect the sequelae of elevated IFN-α in the cynomolgus monkeys. 
In an in vitro electrophysiology assay GS-9620 inhibited the human ether-à-go-go-related gene 
(hERG)-mediated current at an IC50 (50% inhibitory concentration) value that was 
150-fold higher than the Cmax at the highest dose used in HBV infected patients 
(4 mg; study GS-US-283-0102). These margins are likely even higher once adjusted for protein 
binding. 
No adverse cardiovascular effects were noted in cynomolgus monkeys at Cmax exposures up to 
5-fold higher than the projected Cmax (4.19 ng/mL) for an 8 mg dose of GS-9620. No notable 
effects on the central nervous or respiratory systems were seen in the safety pharmacology 
studies. Safety pharmacology studies did not identify any major effects that would impede the 
use of GS-9620 in human subjects. 
Preclinical toxicology studies were conducted in single dose and multiple dose settings in 
different animal species. 
Single Dose Toxicology Studies 
Single oral doses of GS-9620 were well tolerated at up to 30 mg/kg and up to 2 mg/kg in mice 
and cynomolgus monkeys, respectively. At higher doses, mortality was noted in single dose oral 
studies in mice at 100 mg/kg (TX-243-2008) or greater (AD-243-2017) and in a single 
woodchuck administered 10 mg/kg orally (AD-243-2014). Additionally, mortality was observed 
following intravenous administration of 3 mg/kg to rhesus monkeys (AD-243-2034). 
These deaths were attributed to high systemic exposure to GS-9620 (≥ 21-fold higher than the 
AUC0-24 in HBV infected patients [study GS-US-283-0102]; 44.3 pg•h/mL at 4 mg). 
Multiple Dose Toxicology Studies 
Oral administration of GS-9620 every-other-day (QOD) was well tolerated in the 
4-week and 6-week studies in mice, with the highest doses of 5 and 3 mg/kg QOD, respectively, 
being the no observed adverse effect levels (NOAELs) (Table 1-1). 
In cynomolgus monkeys, GS-9620 was well tolerated in the 4-week study with the highest dose 
of 1.5 mg/kg QOD being the NOAEL (Table 1-1). 


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In the 26-week cynomolgus monkey toxicity study, GS-9620 administration at 
≤ 0.15 mg/kg/dose was well tolerated. Administration of 0.50 mg/kg every other day 
(reduced to 0.3 mg/kg every other day at Week 11) resulted in morbidity/mortality of 3 animals 
beyond 8 weeks of QOD dosing. In this study the pharmacodynamic effects appeared to increase 
over time and were associated with high levels of circulating IFN-α. Cynomolgus monkeys were 
the most sensitive toxicology species and have an apparent exaggerated IFN-α response to 
GS-9620 (Table 1-1). The observed mortalities in cynomolgus monkeys are consistent with data 
obtained from the New Drug Application (NDA) approvals of peginterferon alpha 2a (Pegasys®) 
and peginterferon alpha 2b (Peg-Intron®) showing that repeated high doses of IFN-α or PEG 
cause a similar spectrum of effects in cynomolgus monkeys as those observed in the 26-week 
toxicology study with GS-9620 {European Medicines Agency (EMA) 2006}, {Pilaro 2000}. The 
margins of exposure in the preclinical species, based on IFN-α stimulation, range from 0.33 to 
122-fold depending on the duration of exposure due to GS-9620 dosing every other day. Less 
frequent administration, once every other week, in the clinical setting would be expected to 
minimize chronic IFN-α exposure side effects. 
Table 1-1. 
Estimated Margins of GS-9620 Following Oral Administration at the 
Highest Anticipated Human Dose 
Species 
Duration 
Dose 
(mg/kg/dose) 
AUC0-tau
a 
ng•h/mL 
Cmax
a 
ng/mL 
Mean 
Peak 
IFN-α 
pg/mL 
Margin of Exposure 
AUCinf
b 
Cmax
b 
IFN-αc 
Mouse 
QOD x 4 weeks 
5 
(NOAEL) 
43.5 
13.4 
237 
0.3x 
1.1x 
2.4x 
QOD x 26 weeks 
3 
(NOAEL) 
15.8 
6.64 
60.7 
0.1x 
0.6x 
0.6x 
Cynomolgus 
Monkey 
QOD x 4 weeks 
1.5 
(NOAEL) 
73.8 
86.7 
11900 
0.5x 
7.2x 
122x 
QOD x 26 weeks 
0.15 
(NOAEL) 
0.171 
0.077 
32 
0.001x 
0.006x 
0.33x 
0.5/0.3 
1.82d 
0.504d 
23085d 
0.013x 
0.04x 
21x 
a 
Males and females combined, Week 4 or Week 26 as applicable 
b 
Margins of exposure were calculated using clinical GS-9620 Cmax and AUCinf at 12 mg of 12.0 ng/mL and 140 ng•h/mL, 
respectively (GS-US-243-0101) 
c 
Margins of exposure were calculated using the mean peak for IFN-α (97.3 pg/mL) from healthy subjects dosed with 12 mg 
GS-9620 (GS-US-243-0101) 
d 
Week 17 at 0.3 mg/kg 
Source: Studies TX-243-2005, TX-243-2011, TX-243-2004, TX-243-2012 


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Monotherapy Proof-of-Concept Studies in Monkeys 
In a rhesus macaque model of chronic SIV infection, treatment with GS-9620 or its close analog 
GS-436986 has also demonstrated the ability to both “kick” and “kill.” Treatment resulted in 
transient detection of plasma viremia within 24-72 hours of dosing, decreases in ex vivo SIV 
production from T-cell receptor stimulated PBMC cultures or immune cell isolates of peripheral 
lymph nodes comparing pre-treatment to post-dosing samples and a ~0.5 log10 lower viral load 
set-point after discontinuation of ART {Lim 2018}. Most importantly, in a subset of animals, 
there was a lack of detectable plasma virus (< 50 SIV RNA copies/mL) for > 2 years after 
discontinuation of ART. During the off ART phase, two animals from one of the studies had no 
viral rebound after administration of antibodies depleting NK and CD8+ lymphocytes or transfer 
of viral infection after infusion of mononuclear immune cells from lymph node and peripheral 
blood into naïve animals; implying a substantial reduction in viral reservoir. 
1.2.3. 
Clinical Trials of GS-9620 
As of 27 March 2018, 4 Phase 1 clinical studies, 1 Phase 2 clinical study, and 1 registry study 
have been completed in which 55 healthy subjects, 42 HCV infected subjects, and 230 subjects 
with chronic hepatitis B (CHB) (189 virologically suppressed and 41 treatment naive subjects) 
were dosed with GS-9620. In addition, a Phase 2 clinical trial (283-1059) in virologically 
suppressed CHB subjects has completed dosing and a Phase 1 clinical trial (382-1450) in 
HIV-1-infected subjects on ART is currently on-going. In these studies, single doses ranged from 
0.3 mg to 12 mg in healthy volunteers, and from 0.3 mg to 4 mg in HCV- and HBV-infected 
subjects. Multiple doses (two doses one week apart and up to 12 doses one week apart) were 
assessed in HCV-infected and HBV-infected subjects and ranged from 0.3 mg to 4 mg. 
In HIV-infected subjects, multiple doses of GS-9620 ranging from 1 mg to 6 mg were assessed, 
with the 8 mg dosing cohort currently in progress. 
1.2.3.1. 
GS-US-243-0101 
Study GS-US-243-0101 was a first-in-human, randomized, double-blind, placebo-controlled, 
single ascending dose (SAD) study of GS-9620 in 75 healthy male and female subjects. 
The primary objective of the study was to evaluate the safety and tolerability of GS-9620 and the 
secondary objectives were to characterize the plasma PK/PD profile of GS-9620. Doses used 
were: 0.3, 1, 2, 4, 6, 8, and 12 mg.  
The treatment was generally well tolerated. There were no Grade 4 AEs or serious adverse 
events (SAEs) reported, and most AEs were mild. No individual subject discontinued due to AEs 
or laboratory abnormalities. Treatment-emergent Grade 3 AEs included pyrexia in 2 subjects 
who received GS-9620 12 mg. A higher incidence of flu-like symptoms was also reported in 
subjects administered the higher doses (8 and 12 mg). 
Plasma concentrations of GS-9620 peaked between 1.5 and 6 hours after dosing and declined 
gradually over 48 hours. The mean maximum plasma concentration (Cmax) ranged from 
184.2 pg/mL at the 0.3 mg dose to 11.97 ng/mL at the 12 mg dose. Exposures were higher in the 
fasted state than in the fed state. After the 1 mg, 2 mg, and 4 mg doses, GS-9620 was detectable 
at 48 hours after dosing and had a median terminal half-life between 17.16 and 26.96 hours. 


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Three ISGs were analyzed: ISG15, MX-1 and OAS-1. Significant ISG induction was observed at 
the 2-mg dose and above. ISG15 mRNA expression showed the highest induction compared to 
MX-1 and OAS-1. Serum IFN-α was detected only in subjects who received the 8 or 12 mg 
doses. A dose-dependent induction was observed for serum IP-10 but not for TNF-α. 
Dose-dependent T cell activation was also observed at the 2 mg dose and above. 
In summary, single doses of GS-9620 up to 12 mg were well tolerated, with significant ISG 
induction at doses of 2, 4, and 6 mg in the absence of detectable serum IFN-α or systemic AEs. 
1.2.3.2. 
Other Phase 1 studies 
The following studies have also demonstrated good tolerability of GS-9620 (see IB for details): 
• GS-US-243-0102: A Phase 1b ascending, single and multiple-dose study evaluating the 
safety, PK, PD, and antiviral activity in treatment-naive HCV subjects. 
• GS-US-283-0102: A Phase 1b ascending, single and multiple-dose study evaluating the 
safety, PK/PD, and antiviral activity in virologically-suppressed HBV subjects. 
• GS-US-283-0106: A Phase 1b ascending, single and multiple-dose study evaluating the 
safety, PK/PD, and antiviral activity in treatment-naive HBV subjects. 
• GS-US-283-0110: An observational registry study of subjects who did not achieve loss of 
HBsAg and sustained HBV viral load reduction below the level of quantitation in 
Gilead-Sponsored trials of GS-9620 in subjects with chronic HBV infection. 
1.2.3.3. 
GS-US-283-1059 
GS-US-283-1059 was a Phase 2, randomized, double-blind, placebo-controlled multi-center 
study to evaluate the safety and efficacy of GS-9620 in HBV-infected subjects who are 
virologically suppressed. In this study, 162 subjects received weekly dosing with GS-9620 
(1, 2 or 4 mg) or placebo for a total of 4 (Cohort A), 8 (Cohort B) or 12 (Cohort C) weeks. The 
efficacy of GS-9620 was evaluated by assessing the change from baseline to Week 24 in HBsAg 
levels. 
Overall, once-weekly dosing of GS-9620 1, 2, or 4 mg for 4, 8, or 12 weeks was generally well 
tolerated in virologically-suppressed subjects with CHB on OAV. Most subjects had Grade 1 
(mild) AEs and, except for the Cohort C 4-mg group in which a higher proportion of subjects had 
Grade 2 (moderate) and 3 (severe) AEs compared with Cohorts A and B. No other dose-related 
or treatment duration-related safety findings were observed. No Grade 4 (life threatening) AEs 
were reported in any of the cohorts. Four subjects had SAEs, 3 of these subjects had AEs that led 
to discontinuation of study drug, and 3 of the 4 subjects had study drug interrupted due to AEs. 
No deaths occurred in any study participant. 


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Two subjects interrupted study treatment after having experienced SAEs due to an overdose 
caused by a dispensing error at the study site. One of these subjects randomized to 2 mg 
GS-9620 mistakenly received 10 mg and one subject randomized to 4mg mistakenly received 
20 mg. These 2 subjects experienced transient Grade 3 AEs of flu-like symptoms and decline in 
lymphocytes count. The subject who received 10 mg experienced Grade 3 AEs of pyrexia, chills 
and hot flush, all SAEs that were assessed as related to study drug by the investigator. The 
subject who received 20 mg experienced SAEs of Grade 3 AE of tremor and Grade 2 
hypotension requiring hospitalization. This subject also experienced additional Grade 2 AEs of 
abdominal pain, diarrhea, and vomiting, and an increase in ALT value. For both subjects, each of 
the AEs resolved within 24 hours after overdose. A meeting of the Data Monitoring Committee 
reviewed these events and determined them to be due to the overdose of GS-9620 with expected 
effects of interferon-alpha induction and cytokine release and allowed for the study to proceed as 
planned. The other two subjects with SAEs were in Cohort C (cataract, which was reported in 
one subject with a medical history of cataract, and cholecystitis, which was reported in the other 
subject). The subject who experienced cholecystitis also withdrew from study drug and the 
study. 
Most AEs reported were Grade 1 or Grade 2 in severity. No Grade 4 (life threatening) AEs 
occurred in any of the cohorts. For Cohort A, 1 subject in each group had Grade 3 AEs. None of 
the Grade 3 AEs led to withdrawal from study drug and none occurred in more than 1 subject. 
All of the Grade 3 AEs resolved. Excluding the 2 overdosed subjects discussed above, 2 subjects 
(placebo and GS-9620 1 mg) experienced transient Grade 3 AE of anxiety and diarrhea, 
respectively, during the treatment period with GS-9620/placebo; both AEs resolved within 
24 hours. For Cohort B, no subjects had Grade 3 AEs. For Cohort C, 6 subjects had Grade 3 
AEs: 2 subjects in the GS-9620 1-mg group, 1 subject in the GS-9620 2-mg group, 2 subjects in 
the GS-9620 4-mg group, and 1 subject in the placebo group. Two subjects, both in the GS-9620 
4-mg group, with Grade 3 AEs (cholecystitis [discussed above] and panic attack) withdrew from 
the study and study drug. 
Overall, patients from both the GS-9620-treated and placebo groups experienced a similar 
number of treatment emergent AEs (TEAEs) (68% study drug vs. 70% placebo). Upon 
assessment of relation to study drug, 37% of patients treated with GS-9620 reported at least one 
AE compared to 50% of placebo patients, all of which were mild to moderate in severity. No 
dose-dependency for AEs was observed across cohorts. The most commonly reported related 
AEs (for ≥2 or more patients) in Cohort A were fatigue (4 of 16 [25.0%] subjects) and diarrhea, 
headache, oropharyngeal pain, pruritus, and pyrexia (each of which occurred in 2 of 16 patients 
[12.5%]) (1-mg group); headache (4 of 15 [26.7%] subjects), fatigue (3 of 15 [20.0%] patients) 
and chills (2 of 15 [13.3%] patients) (2-mg group); and fatigue and pyrexia (each in 3 of 16 
[18.8%] patients) and headache (2 of 16 [12.5%] patients) (4-mg group). In Cohort B, headache 
(6 of 18 [33.3%] patients), nausea (3 of 18 [16.7%] patients) and acne, dizziness, fatigue, 
insomnia, and oropharyngeal pain (each in 2 of 18 [11.1%] patients) (1-mg group); headache and 
dizziness (each in 2 of 17 [11.8%] patients) (2-mg group); and headache (4 of 17 [23.5%] 
patients) and fatigue, influenza-like illness, and rhinorrhea (each in 2 of 17 [11.8%] patients) 
(4-mg group) were most common. In Cohort C, headache, fatigue, influenza-like illness (each in 
4 of 16 [25.0%] patients) and asthenia, pyrexia and somnolence (each in 2 of 16 [12.5%] 


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patients) (1-mg group); abdominal pain upper and headache (each in 3 of 17 [17.6%] patients) 
and fatigue (2 of 17 [11.8%] patients) (2-mg group); and asthenia (5 of 14 [35.7%] patients), 
headache, influenza-like illness, and pyrexia (each in 3 of 14 [21.4%] patients) and myalgia (2 of 
14 [14.3%] patients) (4-mg group). Headache was the most commonly reported placebo group 
AE (40-50% of patients). 
Among the patients dosed with GS-9620, treatment-emergent graded ALT elevations were seen 
in 5 subjects (4 subjects with Grade 1 and one subject with Grade 2). All grade 1 elevations were 
transient (1 placebo, 1 GS-9620 2 mg, and 2 GS-9620 4 mg) and the grade 2 elevation occurred 
22 days after the last dose of GS-9620 4 mg and reduced to grade 1 elevation 3 days later. 
Please refer to the current GS-9620 Investigator’s Brochure for the treatment of chronic 
hepatitis B virus infection for additional information regarding the above studies. 
1.2.3.4. 
GS-US-283-1062 
This Phase 2, randomized, double-blind, placebo-controlled study was conducted to evaluate the 
safety and efficacy of administering either 1 mg, 2 mg or 4 mg of GS-9620 orally once a week 
(every 7 days) for 12 doses (Weeks 0-11) in adult subjects with CHB who were not currently on 
treatment for CHB. 192 subjects were randomized in a 1:2:2:2 ratio to 1 of the 4 treatment arms 
(placebo, GS-9620 1 mg, 2 mg, or 4 mg) for weekly dosing for a total of 12 doses and stratified 
by HBeAg status (positive versus negative) and ALT (> versus ≤ 19 IU/mL for female; > versus 
≤ 30 IU/mL for male). All subjects were also treated with TDF 300 mg oral daily for 48 weeks.  
Preliminary interim safety results from Week 48 show that overall, once-weekly dosing of 
GS-9620 1, 2, or 4 mg was generally well tolerated. 65% of subjects overall had at least 1 AE 
during the study and most of the reported AEs were Grade 1 (mild) or 2 (moderate) in severity. 
Overall, the majority of subjects had Grade 1 (mild) or moderate (Grade 2) AEs. Six subjects 
experienced Grade 3 (severe) AEs. No Grade 4 (life threatening) AEs were reported in any of the 
treatment groups.  
Four subjects had treatment-emergent SAEs: an SAE of laceration (deep laceration on the right 
foot) on Day 133 which resolved on Day 252, an SAE of asthma (worsening of asthma) on 
Day 257 which resolved on Day 288, an SAE of breast cancer on Day 422 continuing at the time 
of the interim data cut, and an SAE of abdominal pain (exacerbation of chronic generalized 
abdominal pain) on Day 71 which resolved on Day 85. All SAEs were considered by the 
investigator to be unrelated to study drugs or to study procedures. No action was taken with 
study drugs, with the exception of TDF dose interruption for the abdominal pain case and dose 
withdrawn for the breast cancer case. No deaths occurred. 
Six subjects overall (3.1%) discontinued study drug due to an AE, all of which were considered 
related to study drugs by the investigator. 
Across the treatment groups, most laboratory abnormalities were Grade 1 or 2 in severity. 
Five subjects had ALT ≥ 10x ULN and thirty had ALT between 3x ULN and < 10x ULN and 
> 2x nadir. 


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1.2.3.5. 
GS-US-382-1450 
GS-US-382-1450 is a Phase 1b, single/multiple ascending dose, randomized, double-blind, 
placebo-controlled multi-center study to evaluate the safety of GS-9620 in HIV-infected subjects 
who are virologically suppressed. In this study, approximately 32 subjects received biweekly 
dosing with GS-9620 (1, 2 or 4 mg) or placebo for a total of 6 doses, or 6 mg for a total of 
10 doses. The 1 mg, 2 mg, 4 mg and 6 mg dosing cohorts have now completed dosing. 
Enrollment of the 8 mg cohort is complete and dosing is ongoing. 
In the 1 mg dose cohort (Cohort 1) a total of 8 subjects were enrolled. There were no deaths, 
SAEs, Grade 3 or 4 AEs or AEs leading to discontinuation. There were no study drug-related 
AEs. 6 subjects experienced a treatment-emergent AE. These included fatigue (4), 
nasal congestion (3), cough (2), oropharyngeal pain (2), and nausea (2). There were no Grade 3 
or 4 lab abnormalities. There was one case of post-dose increase in plasma HIV-1 RNA that 
failed to resolve to <50 copies/mL within 10 days. In this subject the HIV-1 RNA rose to 
1040 copies/mL at day 7 post-dose 3, was 629 copies/mL at day 10 and returned to undetectable 
at day 17. There were no other significant lab changes and the only concomitant AE was “vessel 
site puncture pain”. The safety evaluation committee (SEC) recommended proceeding with 
enrollment of Cohort 2. 
In the 2 mg dose cohort (Cohort 2) a total of 8 subjects were enrolled. There was one loss to 
follow-up after dose 2, no deaths and no AEs leading to discontinuation. There was one SAE 
(diverticulitis considered unrelated to study drug) and 1 Grade 3 or 4 AE. There was one 
drug-related AE of headache. There were no treatment-emergent AEs occurring in 2 or more 
subjects. There were no Grade 3 or 4 lab abnormalities and no dose-limiting toxicities. The SEC 
recommended proceeding with Cohort 3 (4 mg), which is now complete. 
In the 4 mg dose cohort (Cohort 3) a total of 8 subjects were enrolled. There were no AEs 
leading to study drug discontinuation, no Grade 3 or 4 AEs and no SAEs. One subject 
experienced AEs of sluggishness and dysgeusia which were considered related to study drug by 
the investigator. Six subjects experienced treatment-emergent laboratory abnormalities, all of 
which were Grade 1 or 2. 
In the 6 mg dose cohort (Cohort 4) of this study, 6 subjects experienced treatment-emergent AEs. 
Three of these subjects had AEs which were considered to be related to study drug by the 
investigator: one subject had decreased concentration, vivid dreams, sweats, and fatigue; another 
subject had headache and increased peripheral neuropathy; the third subject had fatigue, myalgia, 
and nasal congestion. All of these AEs were grade 1 or 2 and all resolved during the dosing 
period. There have been no grade 3 or 4 AEs, AEs leading to study drug discontinuation, SAEs, 
or deaths. The protocol-defined SEC reviewed blinded safety data from the 6 mg cohort on 
25 September 2017 and recommended proceeding with the addition of the 8 mg cohort 
(Cohort 5).  


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In the 8 mg dose cohort (Cohort 5) of this study, a total of 8 subjects have been enrolled and are 
currently being dosed with study drug. At the time of the interim safety data cut (30 April 2018), 
all subjects have completed 5 out of 10 doses, and 3 subjects have completed 6 doses. There 
have been no grade 3 or 4 AEs, AEs leading to study drug discontinuation, SAEs, or deaths. 
Three subjects have had mild AEs considered related to study drug by the investigator. These 
AEs include chills and malaise in one subject, pyrexia and myalgia in another subject, and 
headache in the last subject. All AEs resolved within one day and have not recurred after Dose 3, 
thus far. 
1.3. 
Rationale for This Study 
Despite the extensive advances made in the treatment of chronic HIV-1 infection, control and/or 
eradication of the latent HIV-1 reservoir is still needed to achieve a remission or cure that 
abrogates the requirement for lifelong ART. To this end, “kick and kill” strategies to reactivate 
and target latent virus have been tested in a number of clinical trials, but none have resulted in 
lasting virologic remission. GS-9620 is a promising candidate for this approach given the 
demonstration of both SIV reactivation (as measured by transient plasma viremia in the presence 
of ART), decrease in SIV reservoir (as measured by proviral DNA in PBMCs, lymph node and 
colon), and ~0.5 log reduction in SIV set point relative to pre-ART plasma viral load set point 
following ART interruption in studies of SIV-infected rhesus macaques treated with GS-436986, 
a close analog of GS-9620. In a second study in SIV-infected rhesus on ART the TLR7 agonists 
GS-9620 or GS-436986 administered for 10 or 19 doses produced transient plasma viremia 
within 24-72 hours after dosing. Sampling PBMCs and immune cell isolates from lymph node 
biopsies prior to TLR7 agonist administration and after completing all doses demonstrated a 
decrease in the amount of SIV production following T-cell receptor stimulation. Interestingly, 
two of these animals, one from the GS-9620 dosing group and one from the GS-436986 dosing 
group had no detectable ex vivo SIV production from both PBMCs and isolated immune cells 
from lymph node biopsies. Most importantly, after ART discontinuation these same two animals 
had no detectable plasma virus (< 50 SIV RNA copies/mL) rebound which has been sustained 
for at least twelve months. These results suggest the possible use of TLR7 agonists in 
combination with ART toward reduction of HIV reservoirs and ultimately finite therapies for 
HIV-1 infection. In addition, GS-9620 appears to be safe in healthy, HBV-infected, and 
HIV-infected subjects on ART. 
The next goal is to measure the efficacy of GS-9620 in reducing and/or controlling the HIV-1 
reservoir. Measurement of the time to viral rebound and/or new viral set-point following ATI is 
the most definitive method for evaluating HIV-1 cure interventions. The ACTG and other groups 
have demonstrated the safety of ATI in chronically HIV-infected individuals, despite the risk 
associated with viral rebound to high levels. Recent evidence supporting the initiation of ART in 
HIV-1 controllers (individuals defined as having a history of maintaining low plasma HIV-1 
RNA copies/mL prior to ART) has resulted in the establishment of limited cohorts of treated 
controllers. Therefore, studying “kick and kill” interventions in the setting of an ATI in these 
subjects could potentially provide useful information while minimizing the risk of high peak 
viral load rebound in the absence of ART. The ability to delay plasma viral rebound and/or 
decrease viral load set point to less than pre-ART levels would suggest potential clinical benefit 
of GS-9620 in HIV-1-infected individuals for the first time. 


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The primary objective of study GS-US-382-3961 is to evaluate the safety and tolerability of 
a 10-dose regimen of GS-9620 in HIV-1 infected controllers on antiretroviral treatment (ART) 
and during analytical treatment interruption (ATI) following GS-9620 dosing. Secondary 
objectives include assessing virologic effects (HIV-1 reactivation, reservoir reduction, plasma 
viral load during ATI), pharmacokinetics, pharmacodynamics (cytokines and ISG), 
and immunologic effects (immune cell profile, function and inflammation). 
1.4. 
Rationale for Dose Selection/Dosing Interval 
An adaptive dose selection is being utilized in this study. The current dose of 8 mg is selected 
based on the safety and tolerability results from the ongoing blinded study GS-US-382-1450 in 
HIV-infected ART suppressed subjects. In the GS-US-382-1450 study, multiple doses of 1 mg, 
2 mg, 4 mg and 6 mg every other week have been well-tolerated. A cohort of subjects receiving 
8 mg or placebo every other week for 10 doses is ongoing, with all 8 subjects having received 
5 out of 10 doses at the time of an interim safety data cut on April 30th, 2018. This dose level was 
deemed safe by the SEC on June 4, 2018, with no dose-limiting toxicities, no grade 3 or 4 AEs, 
no AEs leading to study drug discontinuation, no SAEs, or deaths. 
Initial doses of GS-9620 have been selected based on the results from the study in healthy 
volunteers (GS-US-243-0101) that showed a dose dependent ISG mRNA induction from 0.3 mg 
up to 12 mg, with detectable serum IFN-α levels (lower limit of detection (LLOD) 15.6 pg/mL) 
only at the highest dose of 8 and 12 mg. 
Initial dose selection was also supported by the results from studies in 50 HCV and in 100 HBV 
infected patients, in which doses up to 4 mg of GS-9620 were evaluated, either as a single dose 
or two doses one week apart. Safety data from these studies demonstrated that GS-9620 at doses 
up to 4 mg are well-tolerated with no evidence of dose dependent adverse events or laboratory 
abnormalities that are consistent with systemic immune activation such as flu-like symptoms, 
hematologic reductions or increases in liver enzymes including transaminases. In the majority of 
patients there was no detectable IFN-α in serum, consistent with the mechanism of action of 
pre-systemic innate immune system activation in the GALT and/or in the liver. Evidence of 
biological activity was observed in a dose dependent manner in all 3 studies, with maximal 
induction of ISG15 occurring within 48 hours and return to baseline levels of expression within 
168 hours (7 days). In addition, the safety of a weekly dosing interval was supported by the 
observed elimination half-life (median range ∼ 8 to 25 hours for 1, 2, or 4 mg doses in HBV- or 
HCV-infected subjects) and that no accumulation of GS-9620 occurred following once-weekly 
dosing. 
A dosing schedule of once every 2 weeks is planned for this protocol in order to verify the 
resolution of GS-9620-induced viremia (>5000 copies/mL) prior to additional dosing. This 
schedule is more conservative than the weekly administrations used in the Phase 1 evaluations 
across the above-referenced studies in chronic hepatitis B and C patients. GS-9620 will be 
administered under fasted conditions to ensure maximal absorption. 


GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
1.5. 
Rationale for Biomarker Testing 
Final 
Amendment4 
It is hypothesized that the mechanism of action of GS-9620 is paiily due to the initial activation 
of innate immunity via TLR7 positive pDCs, promoting the maturation of the pDCs and the 
release of antiviral cytokines and chemokines including IFN-a. The matured pDCs present HIV 
antigens to HIV-specific CD4 and CD8 T cells, thereby enhancing the HIV-specific adaptive 
response (cytotoxic CD8 T cells). In addition, the release ofIFN-a could lead to activation of 
NK cells, and to activation of innate immunity. These multifaceted effector mechanisms 
(cytotoxic CD8 T cells, NK cells and antiviral cytokines) together strengthen the anti-HIV 
immune response and may lead to lowering the viral set point. 
To provide proof of concept on the mechanism of action of GS-9620 in HIV-I infected patients, 
several immunological biomarkers will be examined and are listed below. The testin outlined 
below is based u on the cmTent state of scientific knowled e. 
examined, depending on number of viable cells and blood volume obtained: 
• 
Whole blood samples will be collected for interferon stimulated gene (ISG) mRNA 
measurements 
• 
Levels of cytokines/chemokines 
nnmunoassays. 
I 
I 
I 
1.6. 
Risk/Benefit Assessment for the Study 
will be quantified by 
Potential risks associated with GS-9620 include transient flu-like symptoms (such as chills, 
pyrexia, aches and headache) and transient increases in plasma HIV-I viral load that ai·e 
expected to resolve by the end of the dosing period. Potential risks of A TI include rebound of 
plasma HIV-I viremia to >50 copies/mL, development of HIV-I resistance mutations, decrease 
in CD4+ T cell count, symptoms ofretroviral syndrome and ti·ansmission of vims to other 
individuals. 
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To mitigate these risks, plasma viral load and CD4+ T cell count will be measured frequently 
during ATI and ART will be promptly reinitiated according to the protocol-defined algorithm. 
Subjects will also be monitored for adverse events, and ART will be reinitiated if these are 
judged (by the investigator and/or sponsor) to be related to the ATI. In addition, subjects will be 
required to agree to the use of barrier prophylaxis for the duration of the study. The initial 
selection of subjects who have a history of a low pre-ART viral set point ≤5000 copies/mL and 
the availability of a fully active alternative ART regimen, in the event of discontinuation of the 
current ART regimen with development of resistance, will further minimize the risks of ATI. 
Potential benefits include reduction of the latent HIV-1 viral reservoir, enhanced immune control 
of virus producing cells, and finally the combination of these effects on HIV-1 viral control 
(measured as plasma virus rebound and viral load set point) in the absence of ART. There are no 
direct benefits to subjects participating in this study. 
1.7. 
Compliance 
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements. 


GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
2. 
OBJECTIVES 
The primary objective of this study is: 
Final 
Amendment4 
• 
To evaluate the safety and tolerability of a 10-dose regimen of GS-9620 in HIV-1 infected 
controllers on antiretroviral treatment (ART) and during analytical treatment intenuption 
(A TI) following GS-9620 dosing 
The secondary objectives of this study are: 
Virology 
• 
To evaluate the effect of GS-9620 in reactivating the HIV-1 reservoir, as measured by 
changes in plasma HIV-1 RNA by Taqman 2.0 
• 
To evaluate the effect of GS-9620 in modulating time to virologic rebound and plasma viral 
set-point following ATI 
Immunology/Pha1macodynamics 
• 
To evaluate the phannacodynamics (PD) of GS-9620 as measured by changes in 
sernm/plasma cytokines, and mRNA of interferon-stimulated genes (ISGs) in whole blood 
• 
To evaluate effects of GS-9620 on immune cell activation in whole blood 
Phaimacokinetics 
• 
To evaluate the plasma phaimacokinetics (PK) of GS-9620 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
3. 
STUDY DESIGN 
3.1. 
Endpoints 
The primary endpoint of this study is: 
• 
fucidence of treatment-emergent SAEs and all ti·eatment-emergent adverse events 
The secondary endpoints of this study are: 
Virology 
• 
Changes in plasma HIV-1 RNA by Taqman 2.0 
• 
Time to virologic rebound and change in plasma viral set-point following ATI 
• 
Peak HIV-1 viral load during ATI 
Immunology/Phannacodynamics 
• 
Changes in semm/plasma cytokines, and mRNA of IS Gs in whole blood 
• 
Changes in immune cell activation in whole blood 
Phaimacokinetics 
• 
PK paraineters of GS-9620 in plasma 
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3.2. 
Study Design 
Final 
Amendment4 
This is a randomized, double-blind, two period, single cohort study involving HIV-I infected 
controllers on ART with a histo1y of pre-ART plasma HIV-I RNA between 50 and 
:S5000 copies/mL. 
The study will be conducted in three periods. In Period 1, up to 30 subjects will be 
randomized 2:1 to receive GS-9620 or placebo-to-match. All subjects will receive up to 10 doses 
of their assigned study treatment administered orally eve1y 14 days. Subjects will continue to 
take their prescribed ART during Period 1. 
In Period 2, all subjects will discontinue ART and be monitored for rebound in HIV-I plasma 
viremia. 
B) If subjects restait ART at the strut of Period 3, subjects will complete ART Re-Initiation 
Visits, and then Post ART Re-Suppression Visits monthly for 6 additional months (Post ART 
Re-Suppression Visits 1-6). For these subjects, the last study visit will be the Post ART 
Re-Suppression Visit 6. 
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GS-9620 
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Gilead Sciences, Inc. 
Amendment 4 
Figure 3-1. 
Study Schema 
Screening 
<=35 days 
Pre-
Baseline 
(Day -13)~• 
Dose 1-Day 1 to 
Dose 10-Day 8 visits••• 
Period 1 
Weekly visits until 
' Re-initiate ART'•• 
HIV-1 RNA<50 
copies/ml 
Dose 
10-
Day 
14' 
All 
ATI 
Visit 
Remission 
1• 
Visitf,c 
Visits 2-12•· 
Visits 13.24•• 
End of 
study 
VisitS 
Period 2 
Period 3 
Visits every other 
week until HIV-1 
ART Re-Suppression 
RNA< 50 copies/ml at H 
Visits 1-6' 
two consecutive visits 
a 
Subjects w-ill be randomized at Pre-Baseline/Day -13 
b 
Subject dosing to occur eve,y 14 days on Dose 1-Day 1, Dose 2-Day 1, Dose 3-Day 1, Dose 4-Day 1, Dose 5-Day 1, 
r 
Dose 6-Day 1, Dose 7-Day 1, Dose 8-Day 1, Dose 9-Day 1 and Dose 10-Day 1. Subjects to be monitored on Dose I-Days 2 
and 8, Dose 2-Day 8, Dose 3-Day 8, Dose 4-Days 2,4 and 8, Dose 5-Day 8, Dose 6-Day 8, Dose 7-Day 8, Dose 9-Day 8, 
Dose 10-Da s 2,4, 8 and 14. 
d 
ATI V1s1t 1 to occtu· at Dose 10-Day 28 for subjects w-ith HIV-1 RNA <50 co ies/mL at Dose 10-Day 14 visit. Subjects to 
discontinue ART from ATI Visit 1 through ATI Visit 24 
. For subjects with viral load 
>50 copies/nll, at Dose 10-Day 14, the ATI Visit 1 w-ill on y occur 1 
e Vll'a oa 1s achieved w-ithin two re-test 
measurements. 
e 
Weekly visits 2-24 
f 
ATI Remission Visit w-ill be planned aHer completion of 12 weeks of ATI for subjects with plasma HIV-1 RNA 
<50 copies/nu, in the absence of ART re initiation. If subjects have HIV-1 viral load <50 copies/nu, at A TI Visit 12, the 
visit should occtu· w-ithin a week of A TI Visit 12. However, if the sub· ect does not have HIV-1 viral load <50 co ies/nll, at 
ATI Visit 12, 
g 
En o stu y VISlt may occtu· or subjects who have not re-initiated ART through Period 2 and 3 
h 
IfHIV-1 RNA viral load is >5000 copies/ml, at any visit post Dose, viral load will be observed at next scheduled visit or 
retested within 4 days. TI1e next dose w-ill be w-ithheld and only given if a viral load of ::;5000 copies/ml, is achieved. 
The study procedure schedule will be reset relative to the next dose of GS-9620. 
During 24-week A TI period 
, ART w-ill be re initiated if any of the criteria below are met: 
ifHIV-1 RNA is >10,000 copies/ml, on four consecutive weekly measurements OR 
if HIV-1 RNA does not decrease to <1,000 copies/nll, 1,vithin 6 weeks of virologic rebound OR 
if CD4+ cell count is confinued to decrease by >30% from pre ATI levels OR 
if CD4+ cell count is confinued <350 cells/~tL OR 
Per Investigator or Sponsor's discretion due to other clinical criteria 
J 
ART may also be re-initiated dlll-ing ATI period per investigator or sponsor discretion due to other clinical criteria 
k 
Visits to occtu· monthly 
I 
If subjects restait ART at the strut of Period 3, subjects will go straight into ART Re-Initiation Visits, and then Post ART 
Re-Su ression Visits month! for 6 additional months 
ost ART Re-Su ression Visits 1-6 . 
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Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
3.3. 
Study Treatments 
Final 
Amendment4 
Subjects will be randomized in a 2: 1 ratio to receive GS-9620 or Placebo-to-match. All subjects 
will receive up to 10 doses of their assigned study ti·eatment administered orally eve1y 14 days. 
Subjects will continue their prescribed ART regimen during ti·eatment phase (Period 1). 
Single coho1i (n=30): GS-9620 8 mg or Placebo-to-match . 
3.4. 
Duration of Treatment 
Subjects will receive up to 10 doses of GS-9620 or placebo-to-match over a minimum of a 
20- week period (Period 1), followed by 24 weeks of close observation post ATI staii (Period 2), 
and additional follow u visits in Period 3 either ART Re-Initiation Visits with Post ART 
Re-Suppression Visits 
), and an End of Study Visit, if applicable. 
For subjects who re-initiate ART during first 24 weeks of ATI, duration of study will extend for 
6 months following virologic re-suppression on ART (Post ART Re-suppression Visits 1-6). 
After 24 weeks of ATI, subjects may either restaii ART or remain off ART. Subjects who restaii 
ART will complete ART Re-Initiation Visits and then will complete Post ART Re-Suppression 
Visits monthly for 6 additional months. For these sub'ects, the last stud visit will be Post ART 
Re-Su ression Visit 6. 
The End of study visit may occur for subjects who have not re initiated ART through Period 2 
and 3. 
3.5. 
Discontinuation Criteria 
Study medication 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 intercmTent 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 receives GS-9620 and experiences one or more DLTs (at discretion of SEC) 
• 
Subject requests to discontinue for any reason 
• 
Subject noncompliance 
• 
Pregnancy during the study; refer to Appendix 5 
• 
Discontinuation of the study at the request of Gilead, a regulato1y agency or an institutional 
review board or independent ethics committee (IRB/IEC) 
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Gilead Sciences, Inc. 
3.6. 
End of Study 
The end of study will be the last patient's last observation ( or visit). 
3.7. 
Post Study Care 
Final 
Amendment4 
After a subject has completed/tenninated their paiiicipation in the study, long-te1m cai·e for the 
subject will remain the responsibility of their primaiy treating physician. 
3.8. 
Source Data 
Source data will be collected using the system established by the Investigator. 
3.9. 
3.9.1. 
Bio marker Tes ting 
Biomarker Samples to Address the Study Objectives 
Biological specimens will be collected in this study as described in Section 6. The specimens 
will be used to evaluate the association of explorato1y , systemic and/or tissue specific biomarkers 
with the study drng response, including efficacy and/or adverse events and to increase 
knowledge and understanding of the biology of HIV and related diseases and/or the validation of 
a companion diagnostic for HIV cure. The specific biomai·kers will include, but will not be 
limited to lasma and sennn proteins, immunophenotyping, gene expression, 
, and genotyping. 
Because biomarker science is a rapidly evolving area of investigation, and adverse events in 
paiiiculai· ai·e difficult to predict, it is not possible to specify prospectively all tests that will be 
done on the specimens provided. Biomai·kers may be modified during or after the end of the 
study to remove tests no Ion er indicated and/or to add new tests based u on the ·owin state of 
aii knowled e. 
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4. 
SUBJECT POPULATION 
4.1. 
Number of Subjects and Subject Selection 
Approximately thirty (30) subjects who meet the inclusion/exclusion criteria will be enrolled. 
Subjects who discontinue study participation before completion of all doses for reasons other 
than study treatment related adverse events may be replaced. Eligible subjects may roll over 
from study GS-US-382-1450 and continue onto the ATI phase of GS-US-382-3961. Sponsor and 
Investigator will determine GS-US-382-1450 subject’s eligibility to enter the ATI phase in the 
GS-US-382-3961 study based criteria including on their pre-ART CD4 and HIV-1 RNA values, 
documentation of <50 copies/mL at the End of Study Visit and safety profile in 
GS-US-382-1450. 
4.2. 
Inclusion Criteria 
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) HIV-1 infected subjects of ≥ 18 years at Pre-Baseline/Day -13 
3) Chronic HIV-1 infection (for ≥6 months) prior to ART initiation 
4) Pre-ART Plasma HIV-1 RNA set point between 50 and ≤5,000 copies/mL measured within 
two years prior to ART initiation calculated as below: 
• At least one plasma HIV-1 RNA level, while off ART, above the level of detection using 
standard assays (<40 copies/mL Abbott, <50 copies/mL Roche, < 75 copies/mL bDNA) 
and ≤5000 copies/mL prior to ART initiation. 
• Using all available viral load determinations during the two years prior to ART, the mean 
HIV-1 RNA viral load (defined as viral load set point) must be above the limit of 
detection and ≤5000 copies/mL (those determinations below the level of quantification 
will be considered as detectable at this threshold level). Two years of prior data are not 
required but up to two years of data will be evaluated. 
5) On ART regimen for ≥ 6 consecutive months prior to screening 
• The following agents are allowed as part of the current ART regimen: NRTIs, raltegravir, 
dolutegravir, rilpivirine, and maraviroc 
• A change in ART regimen ≥45 days prior to Pre-Baseline/ Day -13 for reasons other than 
virologic failure (eg, tolerability, simplification, drug-drug interaction profile) is allowed. 
6) Plasma HIV-1 RNA levels <50 copies/mL at screening 


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7) Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months preceding the Screening 
visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of 
detection is ≥ 50 copies/mL). 
• Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or 
“blip”) prior to screening are acceptable. (If the lower limit of detection of the local 
HIV-1 RNA assay is < 50 copies/mL, the plasma HIV-1 RNA level cannot exceed 
50 copies/mL on two consecutive HIV-1 RNA tests) 
• If ART regimen is changed ≥ 45 days prior to Pre-Baseline/Day -13, plasma HIV-1 
RNA <50 copies/mL at Pre-baseline/Day -13 visit is required. 
8) Availability of a fully active alternative ART regimen, in the opinion of the Investigator, 
in the event of discontinuation of the current ART regimen with development of resistance. 
9) All subjects must agree to utilize male or female condoms during sexual activity, or practice 
sexual abstinence for the duration of the study. 
10) Females of childbearing potential must agree to utilize highly effective contraception 
methods (as described in Appendix 5) or be non-heterosexually active or practice sexual 
abstinence from screening through the duration of study treatment and for 36 days following 
the last dose of study drug. 
• Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least three months prior to study dosing 
• Female subjects who have stopped menstruating for ≥ 12 months but do not have 
documentation of ovarian hormonal failure must have a serum follicle stimulating 
hormone (FSH) level at screening within the post-menopausal range based on the 
Central Laboratory reference 
11) Male subjects must agree to utilize a highly effective method of contraception during 
heterosexual intercourse (as described in Appendix 5) or practice sexual abstinence from 
screening throughout the study period and for 90 days following discontinuation of 
investigational medicinal product. 
4.3. 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. 
1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 90 days prior to 
screening (refer to Appendix 6) 
2) Chronic hepatitis B 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 


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3) Hepatitis C antibody (HCVAb) positive 
• Positive anti-HCV antibody and negative HCV PCR results are acceptable 
4) Hemoglobin < 11.5 g/dL (males) or < 11 g/dL (females) 
5) White blood cells <2,500 cells/μL 
6) Platelets < 125,000/mL 
7) Absolute Neutrophil Count < 1000 cells/μL 
8) CD4 count < 500 cells/μL 
9) Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or bilirubin > 2 × upper 
limit of normal (ULN) 
10) Estimated glomerular filtration rate < 60 mL/min to the Cockcroft-Gault formula for 
creatinine clearance {Cockcroft 1976}: 
i) Male: (140 – age in years) × (wt in kg) = CLcr (mL/min) 
 
 
72 × (serum creatinine in mg/dL) 
ii) Female: 
(140 – age in years) × (wt in kg) × 0.85 = CLcr (mL/min) 
 
 
72 × (serum creatinine in mg/dL) 
11) Documented history of pre-ART CD4 nadir < 200 cells/µL 
• Unknown pre-ART CD4 nadir is acceptable 
12) Females who are pregnant (as confirmed by positive serum pregnancy test) 
13) Females who are breastfeeding 
14) Autoimmune disease requiring on-going immunosuppression 
15) Acute febrile illness within 35 days prior to Pre-Baseline/Day -13 
16) Participation in any other clinical trial (including observational trials) without prior approval 
from the sponsor is prohibited while participating in this trial 
17) Current alcohol or substance use judged by the Investigator to potentially interfere with 
subject study compliance 
18) History or presence of allergy or intolerance to the study drug, the metabolites or formulation 
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19) Documented history of resistance to any components of the current ART regimen 
20) Any vaccination or immunomodulatory concomitant medication within 30 days prior to 
Pre-Baseline/Day -13. Elective vaccination (eg flu shot, hepatitis A or B vaccine) during the 
course of the study will require prior approval from Sponsor. 
21) Subjects receiving ongoing therapy with any of the medications listed in Section 5.4. 
Administration of any disallowed medications must be discontinued at least 14 days prior to 
Pre-Baseline/Day -13 visit. Refer to the current Prescribing Information for the medications 
that are contraindicated with the current ART regimen 
22) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would 
make the subject unsuitable for the study or unable to comply with dosing requirements. 
23) History of autoimmune disease (e.g. lupus erythematosus, rheumatoid arthritis, inflammatory 
bowel disease, sarcoidosis, moderate or severe psoriasis) 
4.4. 
Other Protocol Restrictions 
Subjects will be encouraged to avoid strenuous or prolonged exercise, as well as saunas, 
steam baths, and sunbathing or other prolonged UV exposure, (eg in a tanning salon) from the 
screening evaluation until completion of end of study procedures, as these activities are known to 
affect certain clinical laboratory test parameters, (eg CPK) and may provide false indicators of a 
potentially treatment-related toxicity.  
Subjects will also be prohibited from blood donation (in excess of that required for clinical care) 
within 30 days prior to Screening and 30 days after end of study. 
Smokers and other current tobacco users should keep their tobacco use relatively consistent 
while enrolled in the study. Non-smokers or ex-smokers should not start or resume smoking. 
Other restrictions include all illegal or illicit drug use and use of prescription drugs outside the 
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5. 
INVESTIGATIONAL MEDICINAL PRODUCTS 
5.1. 
Randomization, Blinding and Treatment Codes 
It is the responsibility of the investigator to ensure that the subject is eligible for the study prior 
to enrollment. Subjects will be assigned a screening number at the time of consent. 
The subject number assignment may be performed ± 3 days of the in-clinic Pre-Baseline/Day -13 
visit, provided that all other screening procedures have been completed and subject eligibility has 
been confirmed. Once a subject number has been assigned, it will not be reassigned to any other 
subject. 
Eligible subjects (n= 30) will be randomized in a 2:1 ratio to receive GS-9620 8 mg or 
placebo-to-match. 
Randomization will be stratified by pre-ART viral load (≥50 to < 2000 copies/mL 
or ≥2000 to ≤5000 copies/mL) at screening. 
Subjects will be responsible to continue to source their anti-retroviral medications. 
Investigator must provide the prescription to the subject for their anti-retroviral medications. 
Clinical Packaging & Labeling for purposes of managing blinded labeling and Clinical Supply 
Management for purposes of inventory management will remain unblinded throughout the study 
to prepare and manage the study drug. The Pharmacokinetics File Administrator, or designee, 
who facilitates data transfer of PK files between Gilead and vendors, will remain unblinded. 
5.1.1. 
Procedures for Breaking Treatment Codes 
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 for that subject. 
Detailed instructions for study treatment assignment unblinding will be provided to the 
investigator by the Sponsor. Gilead recommends but does not require that the investigator 
contact the Gilead medical monitor before breaking the blind. Treatment assignment should 
remain blinded unless that knowledge is necessary to determine subject’s emergency medical 
care. The rationale for unblinding must be clearly explained in source documentation and on the 
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. 
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, 
if a subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject. 
Gilead Drug Safety and Public Health (PVE) may independently unblind cases for expedited 
reporting of suspected unexpected serious adverse reactions (SUSARs). 


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5.2. 
Description and Handling of GS-9620 and Placebo-to-match GS-9620 
5.2.1. 
Formulation 
An 8 mg dose of GS-9620 will be administered as four 2 mg strength tablets. The tablets are 
round, biconvex, plain-faced, and film-coated white. 
GS-9620 tablets contain the following inactive ingredients: lactose anhydrous, microcrystalline 
cellulose, croscarmellose sodium, magnesium stearate, polyethylene glycol, polyvinyl alcohol, 
talc, and titanium dioxide. 
Placebo-to-match GS-9620 tablets are round, biconvex, plain-faced, and film-coated white. 
Placebo tablets contain lactose anhydrous, microcrystalline cellulose, croscarmellose sodium, 
magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. 
5.2.2. 
Packaging and Labeling 
GS-9620 tablets and placebo-to-match tablets are packaged in white, high density polyethylene 
bottles. Each bottle contains up to 5 tablets, silica gel desiccant, and polyester packing material. 
Each bottle is capped with a child-resistant polypropylene screw cap fitted with an induction 
sealed, aluminum-faced liner. 
Study drug(s) to be distributed to centers in the US shall be labeled to meet applicable 
requirements of the United States Food and Drug Administration (FDA) and/or other local 
regulations. 
5.2.3. 
Storage and Handling 
GS-9620 and placebo-to-match 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, bottles of GS-9620 and placebo-to-match should be stored in 
a securely locked area, accessible only to authorized site personnel. To ensure the stability of the 
tablets and proper product identification, the drug products should be stored in the containers in 
which they are supplied. Keep the bottles tightly closed. 
Consideration should be given to handling, preparation, and disposal through measures that 
minimize drug contact with the body. Appropriate precautions should be followed to avoid direct 
eye contact or exposure when handling GS-9620. 


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5.3. 
Dosage and Administration of GS-9620 
On dosing days, GS-9620 or placebo-to-match should be taken by subject with 
approximately 240 mL of water on an empty stomach (i.e. no food or liquids, except water for at 
least 2 hours prior to dosing; overnight fasting is preferable). If subjects eat prior to the 2 hour 
fasting period before GS-9620 dosing, no more than a light meal should be eaten. Subjects will 
not be allowed to consume water 1 hour before and 2 hours after dosing, except for the 240 mL 
with the study treatment. Subjects should remain fasting without food until 2 hours after dosing. 
Subjects will be asked to provide information on food consumption and total fasting time prior to 
dosing. 
5.4. 
Prior and Concomitant Medications 
No clinical drug-drug interaction studies have been conducted with GS-9620. 
GS-9620 is predominantly metabolized by CYP3A with minor contribution of CYP2C8 and 
CYP2D6 in vitro, and was shown to be a substrate of P-gp and BCRP in vitro. GS-9620 plasma 
exposures may increase or decrease on co-administration with CYP3A/P-gp/BCRP inhibitors or 
inducers.  
ART agents known to inhibit or induce CYP3A/P-gp/BCRP are excluded from use in this 
protocol. The following agents are NOT allowed as part of the current ART regimen: HIV 
protease inhibitors (including low dose ritonavir), cobicistat-containing regimens, elvitegravir, 
efavirenz, etravirine and nevirapine. 
Concomitant use of herbal/natural supplements with GS-9620 may result in pharmacokinetic 
interactions resulting in alterations in exposure of GS-9620. Administration of GS-9620 with 
grapefruit juice or Seville orange juice may result in higher exposures to GS-9620. Subjects will 
refrain from consumption of grapefruit juice, grapefruits, and Seville orange juice throughout 
participation in the study. 
Subjects are restricted from receiving therapy with any medication listed in Table 5-1. 
Administration of any of the disallowed medications listed in Table 5-1 must be discontinued at 
least 14 days prior to the Pre-Baseline/Day -13 and through completion of treatment or the 
Early Study Drug Discontinuation Visit. Any medications not on the list must be reviewed 
with the Sponsor prior to randomization and during the study treatment period. 
Vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications are 
exceptions and are allowed during the study period. No immunomodulatory concomitant 
medications are allowed for at least 30 days prior to Pre-Baseline/Day -13. 
Subjects’ ART regimens must be used in accordance with their Prescribing Information. 
At clinically achieved plasma concentrations, GS-9620 is not expected to be a perpetrator of 
systemic drug-drug interactions. GS-9620 concentrations estimated to be achieved in the gut at 
the ≥10 mg GS-9620 doses may transiently inhibit intestinal P-gp and increase systemic 
exposures of the drugs that are known P-gp substrates. It is recommended that oral P-gp 
substrates are administered with caution in combination with GS-9620 ≥10 mg doses. 


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Table 5-1. 
Prohibited Concomitant Medications 
Drug Class 
Agents Disallowed 
Use Discouraged and To be Used 
with Caution 
Acid Reducing Agents 
Proton Pump Inhibitors 
H2-receptor antagonistsa 
ACAT inhibitor 
Avasimibe 
 
ACE Inhibitors 
Captopril 
 
Analeptic 
Modafinil 
 
Angiotensin II inhibitors 
Telmisartan 
 
Anti-anginals 
Ranolazine 
 
Anti-arrhythmics 
Amiodarone, Dronedarone, Quinidine 
 
Antibiotics 
Azithromycin, Clarithromycin, Erythromycin, Nafcillin, 
Telithromycin 
Ciprofloxacin, Trimethoprim 
Anticonvulsants 
Carbamazepine, Phenytoin, Phenobarbital, 
Oxcarbazepine 
 
Antidepressants 
Nefazodone, Venlafaxine, Ziprasidone, Paroxetine 
 
Antidiabetics 
Pioglitazone 
 
Anti-epileptics 
Divalproex 
 
Antiemetics 
 
Aprepitant, Casopitant 
Antifungals 
Caspofungin, Ketoconazole, Itraconazole, Voriconazole, 
Posaconazole, Fluconazole 
 
Antimycobacterials 
Rifampin, Rifampentine, Rifabutin, Isoniazid 
 
Antiretroviral Agents 
HIV Protease Inhibitors (including low dose Ritonavir), 
Cobicistat-containing regimens, Elvitegravir, Efavirenz, 
Etravirine and Nevirapine 
 
Beta-Blockers 
Carvedilol, Talinolol 
 
Calcium Channel Blockers 
Diltiazem, Felodipine Mibefradil, Nicardipine, 
Nifedipine, Nitrendipine, Verapamil 
 
Diuretics 
Conivaptan 
 
Endothelin Receptor 
Antagonists 
Bosentan 
 
 
 
 
Herbal/Natural Supplements* 
St. John’s Wort, Echinacea, Gingko, Milk thistle, 
Chinese herb shosaiko-to (or Xiao-Shai-Hu-Tang) 
 
HMG-Coa Reductase 
Inhibitors 
Atorvastatin, 
Pitavastatin, Pravastatin, 
Rosuvastatin, Lovastatin, 
Fluvastatin, Simvastatin 
Immunosuppressants 
Cyclosporine, Rapamycin, Sirolimus, Tacrolimus 
 
Systemic Corticosteroids 
All agents, including dexamethasone 
Use of Prednisone as a steroid burst 
(≤ 1 week of use) should be 
monitored appropriately 
Systemic Chemotherapeutic 
(antineoplastic) Agents 
All agents 
 
a 
Dose not to exceed 20 mg famotidine or equivalent and dose should be administered not less than 24 hours prior to dosing 
with GS-9620 and not less than 12 hours after dosing with GS-9620. 
* 
Use of complementary or alternative medicines is prohibited at least 14 days prior to Dose 1-Day 1 through the end of the 
follow-up 


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Should subjects have a need to initiate treatment with any concomitant medication, the 
Gilead Medical Monitor must be consulted prior to initiation of the new medication. In instances 
where a medication is initiated prior to discussion with the Sponsor, the Investigator must notify 
Gilead as soon as he/she is aware of the use of the medication. 
5.5. 
Accountability for GS-9620 
The investigator is responsible for ensuring adequate accountability of all used and unused IMP 
(Investigational Medicinal Product). This includes acknowledgement of receipt of each shipment 
of IMP (quantity and condition). All used and unused IMP dispensed to subjects must be 
returned to the site. 
GS-9620 accountability records will be provided to each study site to: 
• Record the date received and quantity of IMP kits 
• Record the date, subject number, subject initials, the IMP kit number dispensed 
• Record the date, quantity of used and unused IMP returned, along with the initials of the 
person recording the information. 
5.5.1. 
Investigational Medicinal Product Return or Disposal 
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. 
If return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP 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 is destroyed on site, the investigator must maintain accurate records for all IMP 
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 drug is destroyed on site, the investigator must maintain accurate records for all study drug 
bottles destroyed. Records must show the identification and quantity of each unit destroyed, 
the method of destruction, and person who disposed of the drug. All study drug records must be 
maintained at the site and copies must be submitted to Gilead Sciences at the end of the study. 
The study monitor will review IMP 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. 
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 
It is the responsibility of the Investigator to ensure that subjects are eligible for study prior to 
enrollment. Please refer to Section 6.2 for details about randomization and treatment assignment. 
6.2. 
Pretreatment Assessments (Period 1) 
6.2.1. 
Screening Visit 
Subjects will be screened within 35 days before Pre-Baseline/Day -13 to determine eligibility for 
participation in the study. The following will be performed and documented at screening after 
obtaining written informed consent: 
• Obtain medical history including route and estimated duration of HIV-1 infection, history of 
HIV-1 disease-related events, anti-retroviral treatment (ART) history for at least 6 months 
and prior medications within 35 days of the screening visit 
• Obtain pre-ART viral load set point 
• Collect pre-ART CD4 nadir, and historical genotype(s), if available 
• Obtain HLA class I and II type through available records, if available or obtain blood sample 
for testing 
• Complete physical examination. Urogenital/anorectal exams will be performed at the 
discretion of the Investigator 
• Vital signs (blood pressure, pulse, respiration rate and temperature) 
• Body weight, and height 
• 12-lead ECG performed supine 
• Obtain urine for urinalysis 


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• Obtain blood samples for: 
 Serum pregnancy test (females of childbearing potential only). If the test is positive, 
the subject will not be enrolled 
 Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid 
 Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, 
and triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, 
but the subject must return within 72 hours in a fasted state to draw blood for the 
metabolic assessments. 
 Estimated GFR according to the Cockcroft-Gault formula for creatinine clearance: 
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 
 CD4+ cell count, CD8 cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 Hepatitis B virus serology 
 Hepatitis C virus serology 
 Plasma ART trough PK  
Record any serious adverse events and all adverse events related to protocol mandated 
procedures occurring after signing of the consent form. 
In order to establish eligibility, Investigators may repeat screening procedures or laboratory 
assessments for subjects who have an acute illness or abnormal laboratory value that is expected 
to resolve without sequelae within the screening window. 
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 35 days after screening for Pre-Baseline/Day -13 and randomization into the study. 


GS-9620 
Protocol GS-US-382-3961 
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Gilead Sciences, Inc. 
Amendment 4 
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05 February 2019 
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. 
6.2.2. 
Pre-Baseline/Day -13 Assessments 
The following evaluations are to be completed at the Pre-Baseline/Day -13 visit. 
The Pre-Baseline/Day -13 visit is to be completed within 35 days of Screening. 
• Review of Inclusion/Exclusion criteria to confirm subject eligibility 
• Review of AEs and changes in concomitant medications 
• Review medical history 
• Symptom-directed physical examination as needed 
• Blood sample collection for the following laboratory analyses: 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 Plasma HIV-1 RNA by SCA 
 TLR7 genotyping 
 PBMC associated viral RNA and DNA by CAVR and CAVD 
 
 
 T cell ICS 
 Immune cell activation and phenotyping 
 Serum antibody profiling assays 
 
 
 
 
 
 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
I 
I 
I 
6.2.3. 
Randomization 
Final 
Amendment4 
Obtain subject number and randomize the subject. The subject number assignment and 
randomization may be perfo1med ±3 days of the in-clinic Pre-Baseline/Day -13 visit provided 
that all screening procedures have been completed and subject eligibility has been confmned. 
If subject's ART regimen is changed~ 45 days prior to Pre-Baseline/Day -13, plasma HIV-1 
RNA <50 copies/mL at Pre-Baseline/Day -13 visit is required to confnm eligibility. 
6.2.4. 
Dose 1-Day 1 Assessments 
Subjects are to arrive in a fasting state for the Dose 1-Day 1 visit. Food will not be pennitted 
between at least 2 hours prior to and until 2 hours after dosing. Overnight fasting is preferred. 
Aside from the 240 mL of water provided at dosing, water/liquids will not be pe1mitted from 
1 hour prior to until 2 hours after dosing. If subjects eat prior to the 2 hour fasting period before 
study drng dosing, no more than a light meal should be eaten. 
The subject must complete all Dose 1-Day 1 procedures ( except for post-dose PK collection) 
before being dispensed the study drng. Initiation of the treatment with the study drng must take 
place in the clinic and will be administered by blinded study staff. Subjects will remain on-site 
for 10 hours after the first dose for safety assessments and phlebotomy. The visit should 
occur within 13 day±l day from Pre-Baseline/Day -13. The following evaluations are to be 
completed at the Dose 1-Day 1 Visit: 
• 
Review medical histo1y 
• 
Review of AEs and changes in concomitant medication 
• 
Symptom-directed physical examination as needed 
• 
Vital signs (blood pressure, pulse, respiration rate and temperature) 
• 
Weight 
• 
VAS Adherence Questionnaire to be completed by the subject. Subject is to read 
questionnaire by himsel£'herself and write/mark answers directly onto questionnaires. 
CONFIDENTIAL 
Page 58 
05 Februa1y2019 


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• Urine collection for the following laboratory procedures: 
 Urine pregnancy test (females of childbearing potential only). If the urine pregnancy test 
is positive at Dose 1-Day 1, study drug will not be dispensed. The positive result will be 
confirmed with a serum pregnancy test. If the serum pregnancy test is positive, the 
subject will not be able to participate. 
 Urinalysis 
• Blood sample collection for the following laboratory analyses: 
 Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid 
 Hematology profile: complete blood count (CBC) with differential and platelet count 
 Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance 
 CD4+ cell count, CD8 cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 Whole blood ISG mRNA panel  
 Cytokine, chemokines  
 GS-9620 Pharmacokinetic assessments - Intensive PK samples will be collected at 
Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post dose at 
Dose 1-Day 1 visit. 
 
 
•  In-Clinic Dosing 
• Collect information on food consumption and total fasting time prior to fasting 
• Provide instructions to contact the clinic immediately if any flu-like symptoms are noted 
(eg: fatigue, pyrexia, chills, myalgia, joint pain or headache) 
6.3. 
Treatment Assessments (Period 1) 
6.3.1. 
Treatment Assessments on Dosing Visits Dose 2- Dose 10 
These study visits are to be scheduled at an interval of 14 days with visit window of ± 1 day 
relative to the previous dosing visit if next dose is uninterrupted. The following procedures will 
be performed. The procedures are to be completed prior to dosing at each visit. 
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Study Procedure/Visit 
Dose 2- 
Day 1 
Dose 3- 
Day 1 
Dose 4- 
Day 1 
Dose 5- 
Day 1 
Dose 6- 
Day 1 
Dose 7- 
Day 1 
Dose 8- 
Day 1 
Dose 9- 
Day 1 
Dose 10- 
Day 1 
Review of AEs and 
changes in concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Symptom Directed 
Physical Examination as 
needed 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood collection for 
CD4+ cell count, CD8 
cell count, CD4/CD8 
ratio and CD4 % 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry Profile 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology Profile 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma HIV-1 RNA by 
Taqman® 2.0 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma HIV-1 RNA by 
SCA 
 
 
X 
 
X 
 
 
 
X 
PBMC associated viral 
RNA and DNA by 
CAVR and CAVD 
 
 
X 
 
X 
 
 
 
X 
Whole blood ISG 
mRNA panel 
 
 
X 
 
 
 
 
 
X 
Cytokine, chemokines 
X 
X 
Immune cell activation 
and phenotyping  
 
 
X 
 
 
 
 
 
 
VAS Questionnaire 
 
 
X 
 
 
 
X 
 
 
Urine collection for: 
Urine Pregnancy Test 
(females of childbearing 
potential only) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Review DLTs to 
confirm dosing can 
proceeda 
X 
X 
X 
X 
X 
X 
X 
X 
X 
In-Clinic Dosingb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a 
Prior to the subject being administered the in-clinic dose, the Investigator must verify the subject’s continued eligibility for 
in-clinic dosing, including the absence of Dose Limiting Toxicities (DLTs) described in Section 7.6.1. 
b 
All doses will be directly administered to the study subject by blinded site staff. 
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Gilead Sciences, Inc. 
Amendment 4 
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If the urine pregnancy test is positive at a dosing visit, study drug will not be dispensed. 
The positive result will be confirmed with a serum pregnancy test. If the serum pregnancy test is 
positive, the subject will be discontinued from the study. 
Chemistry profile includes alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, glucose, 
phosphorus, magnesium, potassium, sodium, uric acid. 
Hematology profile includes complete blood count (CBC) with differential and platelet count. 
If HIV-1 RNA viral load will be >5,000 copies/mL at any visit post Dose, viral load will be 
observed at next scheduled visit or retested within 4 days. The next dose will be withheld and 
only be given if viral load of ≤5,000 copies/mL is achieved. The study procedure schedule will 
be reset relative to the next dose of GS-9620. 
On dosing days, GS-9620 or placebo-to-match should be taken by subject with approximately 
240 mL of water on an empty stomach. Food will not be permitted between at least 2 hours prior 
to and until 2 hours after dosing. Aside from the 240 mL of water provided at dosing, 
water/liquids will not be permitted from 1 hour prior to until 2 hours after dosing. If subjects eat 
prior to the 2 hour fasting period before study drug dosing, no more than a light meal should be 
eaten. Subjects will be asked to provide information on food consumption and total fasting time 
prior to dosing. 
These fasting guidelines should be followed by subjects on all dosing days. 
At each visit, instructions will be provided to subjects to contact the clinic immediately if any 
flu-like symptoms are noted (e.g.: fatigue, pyrexia, chills, myalgia, joint pain or headache) 


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6.3.2. 
Treatment Assessments on Non Dosing Days 
All study visits are to be scheduled relative to each dosing day visit. All study visits listed above 
except for Dose 1-Day 2 allow a visit window of ± 1 day of the protocol specified visit. 
These visits may occur at the investigator site or at other location agreed by subject by mobile 
nurse vendor. The following procedures will be performed: 
Study 
Procedure/ 
Visit 
Dose 1-Day 2 
Dose 1-Day 8 
Dose 2-Day 8 
Dose 3-Day 8 
Dose 4-Day 2 
Dose 4-Day 4 
Dose 4-Day 8 
Dose 5-Day 8 
Dose 6-Day 4 
Dose 6-Day 8 
Dose 7-Day 8 
Dose 8-Day 8 
Dose 9-Day 8 
Dose 10-Day 2 
Dose 10-Day 4 
Dose 10-Day 8 
Dose 10-Day 14 
Review of 
AEs and 
changes in 
concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Symptom 
Directed 
Physical 
Examination 
as needed 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
 
 
X 
Weight 
 
 
X 
Blood collection for 
CD4+ cell 
count, CD8 
cell count, 
CD4/CD8 
ratio and 
CD4 % 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Plasma 
GS-9620 
Intensive 
PK 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasma ART 
Trough PK 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Plasma 
HIV-1 RNA 
by 
Taqman® 
2.0 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma 
HIV-1 RNA 
by SCA 
 
 
 
 
X 
X 
 
 
X 
 
 
 
 
X 
X 
 
X 
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Study 
Procedure/ 
Visit 
Dose 1-Day 2 
Dose 1-Day 8 
Dose 2-Day 8 
Dose 3-Day 8 
Dose 4-Day 2 
Dose 4-Day 4 
Dose 4-Day 8 
Dose 5-Day 8 
Dose 6-Day 4 
Dose 6-Day 8 
Dose 7-Day 8 
Dose 8-Day 8 
Dose 9-Day 8 
Dose 10-Day 2 
Dose 10-Day 4 
Dose 10-Day 8 
Dose 10-Day 14 
PBMC 
associated 
viral RNA 
by CAVR 
and CAVD 
X 
X 
X 
X 
X 
X 
Whole 
blood ISG 
mRNA 
X 
X 
X 
Cytokine, 
chemokines 
X 
X 
X 
X 
X 
X 
T cell ICS 
X 
Immune cell 
activation, 
phenotyping 
X 
X 
Serum for 
antibody 
profiling 
assays 
X 
Inflammator
y 
biomarkers 
X 
Urine 
collection 
for urine 
pregnancy 
test 
X 
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Amendment 4 
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Study 
Procedure/ 
Visit 
Dose 1-Day 2 
Dose 1-Day 8 
Dose 2-Day 8 
Dose 3-Day 8 
Dose 4-Day 2 
Dose 4-Day 4 
Dose 4-Day 8 
Dose 5-Day 8 
Dose 6-Day 4 
Dose 6-Day 8 
Dose 7-Day 8 
Dose 8-Day 8 
Dose 9-Day 8 
Dose 10-Day 2 
Dose 10-Day 4 
Dose 10-Day 8 
Dose 10-Day 14 
 
If the urine pregnancy test is positive at a dosing visit, study drug will not be dispensed. 
The positive result will be confirmed with a serum pregnancy test. If the serum pregnancy test is 
positive, the subject will be discontinued from the study. 
Subject will be reminded to contact the clinic immediately if any flu-like symptoms are noted 
(eg: fatigue, pyrexia, chills, myalgia, joint pain or headache). 
6.4. 
Post-treatment Assessments (Period 2) 
6.4.1. 
Analytical treatment interruption Visit 1 
This visit will occur 28 days (± 3 days) after Dose 10-Day 1 Visit provided plasma HIV-1 RNA 
viral load is <50 copies/mL at Dose 10-Day 14. For subjects with HIV-1 RNA viral load 
>50 copies/mL at Dose 10-Day 14, the ATI Visit 1 will only occur if undetectable viral load is 
achieved within two re-test measurements. Subjects will take their last dose of ART on the day 
prior to ATI Visit 1. 
Eligible subjects may roll over from study GS-US-382-1450 and continue onto the ATI phase of 
GS-US-382-3961. Sponsor and Investigator will determine GS-US-382-1450 subject’s eligibility 
to enter the ATI phase in the GS-US-382-3961 study based on criteria including their pre-ART 
CD4 and HIV-1 RNA values, documentation of <50 copies/mL at the End of Study Visit and 
safety profile in GS-US-382-1450. For these subjects, ATI Visit 1 will occur approximately 
within 2 weeks of completing End of Study visit on GS-US-382-1450. 
The following evaluations and/or procedures will be performed: 
• Review of AEs and changes in concomitant medications 
• Complete physical examination 
• Vital signs (blood pressure, pulse, respiration rate and temperature) 
• Weight 
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Amendment 4 
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• Blood sample collection for the following laboratory analyses: 
 CD4+ cell count, CD8 cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 Chemistry profile : alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid 
 Hematology profile: complete blood count (CBC) with differential and platelet count 
 Estimated glomerular filtration ate according to the Cockcroft-Gault formula for 
creatinine clearance  
• Urine collection for the following laboratory procedures: 
 Urine pregnancy test (females of childbearing potential only). If the urine pregnancy test 
is positive, the positive result will be confirmed with a serum pregnancy test. If the serum 
pregnancy test is positive, the subject will be discontinued from the study 
 Urinalysis 
6.4.2. 
ATI visits 2-24 (once/week) beginning at ATI Visit 1  
The visits will occur weekly and should be scheduled at least 5 days apart. The first visit should 
occur at least 5 days after ATI Visit 1. The following procedures will be conducted at all visits 
unless otherwise stated. The visits may occur at investigator site or at agreed upon location by 
subject by mobile nurse vendor. 
• Review of AEs and changes in concomitant medications 
• Symptom directed physical examination as needed (Visits 3, 7, 11, 15, 19, 23) 
• Complete physical examination. Urogenital/anorectal exams will be performed at the 
discretion of the Investigator (Visits 5, 9, 13, 17, 21) 
• Vital signs (blood pressure, pulse, respiration rate and temperature) (Visits 3, 5, 7, 9, 11, 13, 
15, 17, 19, 21, 23) 
• Weight (Visits 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23) 
• Blood sample collection for the following laboratory analyses: 
 Chemistry profile : alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid (Visits 5, 9, 13, 17, 21) 


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Gilead Sciences, Inc. 
Amendment 4 
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 Hematology profile: complete blood count (CBC) with differential and platelet count 
(Visits 5, 9, 13, 17, 21) 
 Estimated glomerular filtration ate according to the Cockcroft-Gault formula for 
creatinine clearance (Visits 5, 9, 13, 17, 21) 
 CD4+ cell count, CD8+ cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
• Urine collection for the following laboratory procedures: 
 Urine pregnancy test (females of childbearing potential only). If the urine pregnancy test 
is positive, the positive result will be confirmed with a serum pregnancy test. If the serum 
pregnancy test is positive, the subject will be discontinued from the study (Visits 3, 5, 7, 
9, 11, 13, 15, 17, 19, 21, 23) 
 Urinalysis (Visits 5, 9, 13, 17, 21) 
During the ATI period, if HIV-1 RNA becomes > 50 copies/mL, the visit schedule for HIV-1 
RNA values may be adjusted per Investigator discretion. 
ART should also be re-initiated if subject meets the criteria defined in Section 6.6.1 
6.4.3. 
ATI Remission Visit  
This visit will be planned after completion of 12 weeks of ATI for subjects with plasma HIV-1 
RNA <50 copies/mL in the absence of ART re-initiation. The visit will occur approximately 
within 2 weeks of subjects achieving HIV-1 viral load <50 copies/mL at or after ATI Visit 12 
. The following procedure will be followed: 
• 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 (blood pressure, pulse, respiration rate and temperature) 
• Weight 
• Blood sample collection for the following laboratory analyses: 
 CD4+ cell count, CD8 cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 Plasma HIV-1 RNA by SCA 
 PBMC associated viral RNA and DNA by CAVR and CAVD 
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Cytokines, chemokines 
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T cell ICS 
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Immune cell activation and phenotyping 
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Sernm for antibody profiling assays 
• 
Urine collection for the following laboratory procedures: 
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Urine pregnancy test (females of childbearing potential only). If the urine pregnancy test 
is positive, the positive result will be confnmed with a sernm pregnancy test. If the sernm 
pregnancy test is positive, the subject will be discontinued from the study. 
6.5. 
Post-treatment Extension Assessments (Period 3) 
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6.5.2. 
End of Study Visit for subjects who have not re-initiated ART anytime 
through Period 2 and 3 
End of Study Visit will occur for subjects who have continued the study through Period 2 and 3 
and have not re-initiated ART. The Visit will occur 1 week after completion of the last ATI visit. 
For the pmpose of scheduling the end of study visit, a± 1 days window may be used. 
ART Re-initiation post the End of Study Visit will be up to the subject's health care provider 
discretion. 
The following evaluations and/or procedures will be perfo1med at the end of study visit: 
• 
Review of AEs and changes in concomitant medications 
• 
Symptom directed physical examination as needed 
• 
Vital signs (blood pressure, pulse, respiration rate and temperature) 
• 
Weight 
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• Blood sample collection for the following laboratory analyses: 
 Chemistry profile : alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid 
 Hematology profile: complete blood count (CBC) with differential and platelet count 
 Metabolic assessments: Fasting (no food or drinks, except water, at least 8 hours prior to 
blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, 
and triglycerides). If the subject has not fasted prior to the visit, the visit may proceed, 
but the subject must return within 72 hours in a fasted state to draw blood for the 
metabolic assessments. 
 CD4+ cell count, CD8 cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance 
• Urine collection for 
 Urinalysis 
 Urine pregnancy test (females of childbearing potential only). Positive urine pregnancy 
test will be confirmed with serum test 
6.6. 
ART Re-initiation and Post Re-Suppression Visits (may occur in Period 2 or 
Period 3)  
6.6.1. 
ART Re-initiation Visits 
During the 24 week ATI period (Visits 2-24) 
 
, ART will be re-initiated if any of the criteria below are met: 
• if HIV-1 RNA is >10,000 copies/mL on four consecutive weekly measurements OR 
• if HIV-1 RNA does not decrease to <1,000 copies/mL within 6 weeks of virologic rebound 
OR 
• if CD4+ cell count is confirmed to decrease by >30% from pre-ATI levels OR 
• if CD4+ cell count is confirmed <350 cells/µL OR 
• Per Investigator or Sponsor’s discretion due to other clinical criteria 
Principal investigator will construct the regimen per his/her discretion. The visits will occur 
weekly until plasma viral load is <50 copies/mL and then every other week until two consecutive 
measures are undetectable. 
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If/when HIV-1 RNA is > 1,000 copies/mL during the ATI
 or undetectable viral 
load is not achieved within 4 weeks of ART re-initiation (and if viral load is ≥200 copies/mL), 
resistance testing will be performed at the next visit. 
Once the initial 24 weeks of ATI are completed, subjects who restart ART will complete ART 
Re-Initiation Visits per frequency stated above. A window of ±3 days may be used to schedule 
these visits. 
The following procedures will be performed at these visits: 
• Review of AEs and changes in concomitant medications 
• Vital signs (blood pressure, pulse, respiration rate and temperature) 
• Blood sample collection for the following laboratory analyses: 
 CD4+ cell count, CD8+ cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
• Urine collection for following analyses at the first ART re-initiation visit and then once a 
month until Post ART Re-suppression Visits 
 Urine pregnancy test (females of childbearing potential only). Positive urine pregnancy 
test will be confirmed with serum test 
6.6.2. 
Post-ART Re-suppression Visits 1-6 
These visits will occur monthly for 6 months after the subject has completed necessary ART 
Re-Initiation Visits.A window of ± 6 days may be used to schedule this visit. 
The following procedures will be followed at Visits 1-5: 
• Review of AEs and changes in concomitant medications 
• Vital signs (blood pressure, pulse, respiration rate and temperature) 
• Blood sample collection for the following laboratory analyses: 
 Chemistry profile : alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid 
 Hematology profile: complete blood count (CBC) with differential and platelet count 
 CD4+ cell count, CD8+ cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
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• Urine collection for 
 Urinalysis 
 Urine pregnancy test (females of childbearing potential only). Positive urine pregnancy 
test will be confirmed with serum test. 
The following procedure will be followed at Post-ART Re-suppression Visit 6: 
• Review of AEs and changes in concomitant medications 
• Symptom-directed physical examination as needed 
• Vital signs (blood pressure, pulse, respiration rate and temperature) 
• Weight 
• Blood sample collection for the following laboratory analyses: 
 Chemistry profile : alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid 
 Hematology profile: complete blood count (CBC) with differential and platelet count 
 CD4+ cell count, CD8 cell count, CD4/CD8 ratio and CD4 % 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 HIV-1 reservoir measurements using plasma SCA, CAVR, CAVD  
 
 
• Urine collection for 
 Urinalysis 
 Urine pregnancy test (females of childbearing potential only). Positive urine pregnancy 
test will be confirmed with serum test. 
6.6.3. 
Assessments for Premature Discontinuation from Study 
Subjects who prematurely discontinue study drug prior to completing Dose 10 will be required to 
complete an Early Study Drug Discontinuation Visit (ESDD) within 30 days after their last dose 
of study treatment. 
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If a subject discontinues study dosing (for example, as a result of an AE), every attempt should 
be made to keep the subject in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.7, Criteria for Discontinuation of Study Treatment). 
If this is not possible or acceptable to the subject or investigator, the subject may be withdrawn 
from the study. 
At the ESDD Visit, any evaluations showing abnormal results indicating that there is a 
possible or probable causal relationship with the study drug, should be repeated weekly 
(or as often as deemed prudent by the Investigator) until the abnormality is resolved, 
returns to baseline, or is otherwise explained. 
The following evaluations are to be completed at the Early Study Drug Discontinuation Visit: 
• Review of AEs and changes in concomitant medication 
• Symptom-directed physical examination as needed 
• Vital signs (blood pressure, pulse, respiration rate and temperature) 
• Weight 
• Blood sample collection for the following laboratory analyses: 
 Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, direct and indirect 
bilirubin, total protein, albumin, CPK, bicarbonate, BUN, calcium, chloride, creatinine, 
glucose, phosphorus, magnesium, potassium, sodium, uric acid 
 Estimated glomerular filtration rate according to the Cockcroft-Gault formula for 
creatinine clearance 
 Hematology profile: complete blood count (CBC) with differential and platelet count 
 Plasma HIV-1 RNA by TaqMan® v2.0 
 CD4+ cell count, CD8+ cell count, CD4/CD8 ratio and CD4 % 
 Cytokine, chemokines 
 Whole blood ISG mRNA panel 
• Urine collection for the following laboratory procedures: 
 Urinalysis 
 Urine pregnancy test (females of childbearing potential only). Positive urine pregnancy 
test will be confirmed with serum test 


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Criteria for Discontinuation of Study Treatment 
Study medication may be discontinued in the following instances: 
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• 
futercmrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercmTent 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 receives GS-9620 and experiences one or more DLTs (at discretion of SEC) 
• 
Subject request to discontinue for any reason 
• 
Subject noncompliance 
• 
Pregnancy during the study; refer to Appendix 5 
• 
Discontinuation of the study at the request of Gilead, a regulato1y agency or an institutional 
review board or independent ethics committee (IRB/IEC) 
6.9. 
Prolonged Viremia During GS-9620 Dosing Phase 
Subjects will be considered to have prolonged viremia if they have at least two consecutive 
plasma HIV-1 RNA levels 
5000 copies/mL during a single dosing period. 
6.9.1. 
Management of Prolonged Viremia During GS-9620 Dosing Phase 
If HIV-1 RNA viral load is >5000 copies/mL at any visit post Dose, viral load will be tested at 
next scheduled visit or retested within 4 days. The next dose will be withheld and only given 
after viral load of ~5000 copies/mL is achieved. The study procedure schedule will be reset 
relative to the next dose of GS-9620. 
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If HIV-1 RNA viral load >5000 copies/mL is confnmed during a single dosing period, then this 
subject will be considered to have prolonged viremia and blood samples from this visit will be 
used for HIV-1 genotype/phenotype testing with assays conesponding to the antiretroviral 
medications the subject is taking. 
If primaiy resistance mutations to the subject's existing ART regimen ai·e identified, a new ART 
regimen will be configured at the discretion of the Investigator and the subject will be 
discontinued from the study. If the genotyping/phenotyping assay fails to provide results or no 
dmg resistance mutations ai·e identified, a new ART regimen may be configured at the discretion 
of the Investigator. Subjects who strut a new ART regimen will not be allowed to receive fmther 
doses of study drng, but can be monitored for the study duration at the discretion of the study 
Investigator. Subjects who remain on their cunent ART regimen must show confnmed HIV-1 
RNA levels ::::;5000 copies/mL before resuming study drng dosing at the discretion of the 
Investigator. 
6.9.2. 
Management of Subjects during ATI 
Subjects will discontinue ART on ATI Visit 1 
throu 
ATI Visit 24. 
Subjects will be closely obse1ved for the initial 24 week ATI period during which plasma HIV-1 
RNA values, CD4+ count, CD8 cell count, CD4/CD8 ratio and CD4 % will be measured 
once a week. 
During the 24 week ATI period (ATI Visits 1-24) 
ART will be re-initiated if subject meets the criteria as defined in Section 6.6.1. 
If/when HIV-1 RNA is > 1,000 copies/mL during the ATI 
, resistance 
testing will be perfonned at the next visit. Subject will be monitored and HIV-1 RNA viral load 
will be measured at subsequent visits. 
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6.9.3. 
Management of Virologic Failure post ART Restart 
If a subject’s ART has to be re-initiated, subject’s viral load will be checked on weekly basis. 
If after 4 weeks post ART re-initiation, HIV-1 viral load remains ≥ 200 copies/mL, resistance 
testing will be performed. If primary resistance mutations to the subject’s existing ART regimen 
are identified, a new ART regimen will be configured at the discretion of the Investigator. 
If the genotyping/phenotyping assay fails to provide results or no drug resistance mutations are 
identified, a new ART regimen may be configured at the discretion of the Investigator. 
6.10. 
Management of HIV-1 Seronegative Study Subject Sexual Partners 
In addition to requiring utilization of barrier prophylaxis by all study subjects, HIV-1 
seronegative sexual partners of enrolled study subjects may be referred to a local HIV 
Pre-Exposure Prophylaxis (PrEP) clinic for HIV risk assessment evaluation. 


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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 7.7.1) 
• 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 
CRF. 
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. 
7.1.3. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events 
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and urinalysis) 
that require medical or surgical intervention or lead to IMP interruption, modification, 
or discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, 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 laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (ie, decreased hemoglobin). 
For specific information on handling of clinical laboratory abnormalities in this study, 
please refer to Section 7.5. 
7.2. 
Assessment of Adverse Events and Serious Adverse Events 
The investigator or qualified sub-investigator 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 sub-investigator is responsible for assessing the relationship to IMP 
or current ART using clinical judgment and the following considerations: 
• No: Evidence exists that the adverse event has an etiology other than the IMP or current 
ART. 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 IMP or 
current ART. 


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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) 
7.2.2. 
Assessment of Severity 
The severity grading of AEs will be assessed as Grade 1, 2, 3, or 4 using 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. 
7.3. 
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 initiation of study medication, the following types of events 
should be reported on the case report form (CRF/eCRF): all SAEs and adverse events related to 
protocol-mandated procedures. 
Adverse Events 
Following initiation of study medication, all AEs, regardless of cause or relationship, and 
throughout the duration of the study, including the protocol-required post-treatment follow-up 
period 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 
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fuvestigators 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 paiticipation has concluded 
and the event is deemed relevant to the use of IMP, he/she should promptly document and repo1t 
the event to Gilead PVE. 
Electronic Serious Adverse Event (eSAE) Repo1ting 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 for any reason it is not possible to record the SAE infonnation electr·onically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event repo1ting 
fo1m and submit within 24 hours to Gilead PVE: 
Gilead Sciences PVE Representative: 
Fax: 
E-mail: 
IPIPD 
PPU 
• 
As soon as it is possible to do so, any SAE repo1ted via paper must be h'anscribed into the 
eCRF Database according to instrnctions in the eCRF completion guidelines. 
• If an SAE has been repo1ted via a paper f 01m because the eCRF database has been locked, 
no fmther action is necessary. 
• 
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
• 
For fatal or life-threatening events, copies of hospital case repo1ts, autopsy repo1ts, 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 h'aceability of a document to the subject identifiers. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
reports. 
• 
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 fo1m. 
7.4. 
Gilead Reporting Requirements 
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 country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse dmg reactions (SAD Rs), 
or suspected unexpected serious adverse reactions (SUSARs). fu accordance with the 
EU Clinical Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide 
regulatory agencies and the relevant IEC in concerned Member States of applicable SUSARs as 
outlined in cmTent regulations. 
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Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
7.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events 
Laboratory abnormalities are usually not recorded as AEs or SAEs. However, laboratory 
abnormalities (eg, clinical chemistry, hematology, urinalysis) independent of the 
underlying medical condition that require medical or surgical intervention or lead to 
investigational medicinal product interruption or discontinuation must be recorded as an AE, 
as well as an SAE, if applicable. In addition, laboratory or other abnormal assessments 
(eg, electrocardiogram, 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 laboratory abnormality is part of a syndrome, record the 
syndrome or diagnosis (ie, anemia) not the laboratory result (ie, decreased hemoglobin). 
Severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 4) For adverse events 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 
7.6.1. 
Management of Dose-Limiting Toxicities (DLTs) 
Prior to the subject being administered the in-clinic dose the Investigator will verify the subjects 
continued eligibility for dosing, including the absence of DLTs listed below: 
• ALT elevation as defined as: 
 ALT ≥ 10 × ULN OR 
 Confirmed ALT elevation (ie. Grade shift or 2× previous value) with evidence of 
worsened hepatic function (e.g. total bilirubin > 2mg/dL above Baseline, 
serum albumin > 1 g/dL decrease from Baseline) 
• A confirmed ≥ Grade 3 AE considered drug related by the Investigator 
• A confirmed, clinically significant ≥ Grade 3 laboratory abnormality considered study 
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• A persistent (≥ 72 hours) ≥ Grade 2 flu-like symptom (pyrexia, fatigue, myalgia, arthralgia, 
headache, chills) considered study drug-related by the investigator 
• A post-dose increase in plasma HIV-1 RNA that fails to resolve to < 5000 copies/mL within 
two re-test measurements 
The designated Safety Evaluation Committee contact will be notified within 24 hours of the 
Investigator’s knowledge of a subject having any of the above DLTs. Dosing must be withheld 
until the Safety Evaluation Committee determines the appropriate next steps, including but not 
limited to additional safety, pharmacokinetic and pharmacodynamic assessments. 
The SEC may hold or discontinue study drug dosing for a subject if they receive GS-9620 and 
experience one or more DLTs. The SEC may also suspend dosing in additional subjects. 
7.6.2. 
Management of Other Toxicities 
Unless otherwise specified in Section 7.6.1, toxicities will be managed according to the 
guidelines below. 
• All clinical and clinically significant laboratory toxicities will be managed according to 
uniform guidelines detailed in Appendix 3. 
• Grade 3 and 4 clinically significant laboratory abnormalities should be confirmed by repeat 
testing within 3 calendar days of receipt of results and before investigational medicinal 
product (IMP) discontinuation, unless such a delay is not consistent with good medical 
practice. 
• Clinical events and clinically significant laboratory abnormalities will be graded according to 
the Table for GSI Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities (Appendix 4). 
• When restarting IMP following resolution of the adverse event, the investigational medicinal 
product should be restarted at full dose or modified dose that is dependent upon discussion 
with the Gilead Sciences Medical Monitor. 
• Any recurrence of the Grade 3 or 4 clinical or clinically significant laboratory adverse event 
following dose interruption mandates permanent discontinuation of IMP. 
• Any questions regarding toxicity management should be directed to the 
Gilead Sciences Medical Monitor. 
7.6.2.1. 
Grades 1 and 2 Laboratory Abnormality or Clinical Event 
Continue investigational medicinal product at the discretion of the Investigator. 


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7.6.2.2. 
Grade 3 Laboratory Abnormality or Clinical Event 
• For a Grade 3 clinical event or clinically significant Grade 3 laboratory abnormality 
confirmed by repeat testing, IMP should be withheld until the toxicity returns to ≤ Grade 2. 
• If a laboratory abnormality recurs to ≥ Grade 3 following rechallenge with IMP, then IMP 
should be permanently discontinued and the subject managed according to local practice. 
7.6.2.3. 
Grade 4 Laboratory Abnormality or Clinical Event 
• For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing, IMP should be withheld until the toxicity returns to ≤ Grade 2. 
• For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to IMP, IMP should be permanently 
discontinued and the subject managed according to local practice. The subject should be 
followed as clinically indicated until the laboratory abnormality returns to baseline or is 
otherwise explained, whichever occurs first. A clinically significant Grade 4 laboratory 
abnormality that is not confirmed by repeat testing should be managed according to the 
algorithm for the new toxicity grade. 
Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant (and therefore not an AE), Grade 4 laboratory abnormality (eg, Grade 4 CK after 
strenuous exercise, or triglyceride elevation that is non-fasting or that can be medically 
managed). 
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 occupational exposure and product complaints as well as 
adverse events in an infant following exposure from breastfeeding, 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 
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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 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 
initiation of study medication and throughout the study, including the post study drug follow-up 
period, to Gilead PVE using the pregnancy report form within 24 hours of becoming aware of 
the pregnancy. 
Refer to below 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 
Sections 7.1.1 and 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 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
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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 or 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 5 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 does 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. 
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8. 
STATISTICAL CONSIDERATIONS 
8.1. 
Analysis Objectives and Endpoints 
8.1.1. 
Analysis Objectives 
The primary objective of this study is: 
Final 
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• 
To evaluate the safety and tolerability of a 10-dose regimen of GS-9620 in HIV-1 infected 
controllers on ART and during ATI following GS-9620 dosing 
The secondary objectives of this study are: 
Virology 
• 
To evaluate the effect of GS-9620 in reactivating the HIV-1 reservoir, as measured by 
changes in plasma HIV-1 RNA by Taqman 2.0 
• 
To evaluate the effect of GS-9620 in modulating time to virologic rebound and plasma viral 
set-point following ATI 
Immunology/Phannacodynamics 
• 
To evaluate the PD of GS-9620 as measured by changes in semm/plasma cytokines, and 
mRNA of ISGs in whole blood 
• 
To evaluate effects of GS-9620 on immune cell activation in whole blood 
Phaimacokinetics 
• 
To evaluate the plasma PK of GS-9620 
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Primary Endpoint 
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The primary endpoint is incidence ofti·eatment-emergent SAEs and all h'eatment-emergent 
adverse events. 
8.1.3. 
Secondary Endpoint 
The secondary endpoints of this study are: 
Virology 
• 
Changes in plasma HIV-1 RNA by Taqman 2.0 
• 
Time to virologic rebound and change in plasma viral load set-point following ATI 
• 
Peak HIV-1 viral load during ATI 
Immunology/Phannacodynamics 
• 
Changes in semm/plasma cytokines and mRNA of IS Gs in whole blood 
• 
Changes in immune cell activation in whole blood 
Phaim acokinetics 
• 
PK paraineters of GS-9620 in plasma 
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8.2. 
8.2.1. 
8.2.1.1. 
Analysis Conventions 
Analysis Sets 
All Randomized 
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The randomized analysis set includes all subjects who are randomized into the study. This is the 
primaiy analysis set for by-subject listings. 
8.2.1.2. 
8.2.1.2.1. 
Efficacy 
Full Analysis Set 
The full analysis set (FAS) will include all subjects who (1) ai·e randomized into the study and 
(2) have received at least one dose of study chug. Subjects with major eligibility violations that 
ai·e identifiable based on pre-randomization chai·acteristics will be excluded. 
Subjects will be grouped according to the ti·eatment to which they were randomized. 
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8.2.1.3. 
Safety 
The safety analysis set will include all randomized subjects who received at least one dose of 
study drug. All the data collected up to 30 days after subjects permanently discontinue their 
study drug will be included in the safety summaries. Subjects will be grouped according to the 
treatment they actually received. 
8.2.1.4. 
Phamacokinetics 
The GS-9620 PK analysis set will include all subjects who are randomized and have received at 
least one dose of study drug and for whom PK parameters of analyte GS-9620 are available. 
8.3. 
Data Handling Conventions 
Natural logarithm transformation for key PK parameters, such as Cmax, Ctau and AUCtau, will be 
applied for pharmacokinetic analysis, as appropriate. 
For summary statistics, PK concentration values below the limit of quantitation (BLQ) will be 
imputed as zero at predose and one-half the lower limit of quantitation (LLOQ) at post dose, 
where LLOQ is corrected for the dilution factor (ie, reported dilution/dilution factor). 
Individual values that are BLQ will be presented as “BLQ” in the concentration data listing and 
will be imputed as specified above for summary purpose. 
8.4. 
Demographic Data and Baseline Characteristics 
Demographic and baseline measurements will be summarized using standard descriptive 
methods by treatment group. 
Demographic summaries will include sex, race/ethnicity, and age. 
Baseline data including body weight, height, body mass index, HIV-1 infection will be 
summarized. 
8.5. 
Efficacy Analysis 
The efficacy analysis will be based on the full analysis set (FAS). 
8.5.1. 
Virology Analysis 
The change in plasma HIV-1 RNA by Taqman 2.0 will be summarized by treatment group. 
The incidence of detectable plasma HIV-1 RNA by Taqman 2.0 at each visit will be summarized 
by treatment group. 
Time to viral rebound will be summarized by treatment group. 


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The difference in plasma viral set point between pre-ART value and prior to ART re-initiation 
will be summarized by treatment group. 
The peak HIV-1 viral load during ATI will also be summarized by treatment group. 
8.5.2. 
Immunology/Pharmacodynamics Analysis 
The changes in serum/plasma cytokines, mRNA of ISGs in whole blood, and cell activation in 
whole blood will be summarized using descriptive statistics by treatment group. 
8.6. 
Safety Analysis 
All safety analyses will be performed using the safety analysis set. 
All safety data collected on or after the date that study drug was first taken up to the date of 
last dose of study drug plus 30 days will be summarized by treatment group according to the 
study drug received. Data for the pretreatment period and the period post the date of last dose of 
study drug plus 30 days will be included in data listings. 
8.6.1. 
Extent of Exposure 
A subject’s extent of exposure to study drug will be generated from the study drug 
administration data. Exposure data will be summarized by treatment group. 
Duration of exposure to study drug will be expressed as the number of weeks between the 
first and last dose of the study drug, inclusive, regardless of temporary interruptions in study 
drug administration and summarized by treatment. 
Dosing information for individual subjects 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 with onset date on or after the study drug start 
date and no later than 30 days after the study drug stop date; or any adverse event leading to 
study drug discontinuation. 
Summaries (number and percentage of subjects) of treatment-emergent adverse events (by SOC, 
HLT [if applicable], and PT) will be provided by treatment. Additional summaries will include 
summaries for adverse events by grade, Investigator’s assessment of relationship to study drug, 
and effect on study drug dosing. 


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On an ongoing basis adverse events will be reviewed for events that might meet the definition of 
Stage 3 Opportunistic Illnesses in HIV are indicative of an AIDS-Defining Diagnoses. 
The Gilead medical personnel will review the possible Stage 3 events and approve the events 
that meet the definition. Those events that do meet the Stage 3 Opportunistic Illness definition of 
an AIDS-Defining Diagnosis will be listed. 
A listing of Stage 3 Opportunistic Illnesses in HIV can be found in Appendix 6. 
8.6.3. 
Laboratory Evaluations 
Selected laboratory data will be summarized using only observed data. Absolute values and 
changes from baseline at all scheduled visits will be summarized. 
Graded laboratory abnormalities will be defined using the grading scheme defined in Grading of 
laboratory abnormalities provided in Appendix 4. 
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
one toxicity grade from baseline at any time post baseline up to and including the date of 
last dose of study drug plus 30 days, will be summarized by treatment group. If baseline data are 
missing, any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. 
The maximum toxicity grade will be summarized by laboratory parameter. 
Laboratory abnormalities that occur before the first dose of study drug or after the subject has 
been discontinued from treatment plus 30 days will be included in a data listing. 
8.7. 
Pharmacokinetic Analysis 
The concentration data of GS-9620 will be summarized by nominal sampling time using 
descriptive statistics. For GS-9620, pharmacokinetic parameters (Cmax, Tmax, Clast, Tlast, λz, 
AUCinf, AUClast, and t½) will be listed and summarized using descriptive statistics (e.g., sample 
size, arithmetic mean, geometric mean, coefficient of variation (%), standard deviation, median, 
minimum, and maximum). Plasma concentrations over time will be plotted in semi-logarithmic 
and linear formats as mean ± standard deviation, and median (Q1, Q3). 
8.8. 
Sample Size 
This is an exploratory study to characterize the safety and efficacy of GS-9620; therefore, no 
power calculation was performed. Sample size is determined based on empirical considerations. 
A total of up to 20 subjects receiving GS-9620 will provide a preliminary assessment of safety 
and efficacy. 


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8.9. 
Safety Evaluation Committee 
A Safety Evaluation Committee (SEC) will review study progress, virology and safety of 
enrolled subjects. The SEC will consist of members not directly involved with the conduct of the 
study. After half of the subjects have received four doses of GS-9620 or placebo-to-match, 
the SEC will review safety data, including adverse events, clinical laboratory results, and plasma 
HIV-1 RNA. Please refer to the SEC Charter for additional details.  
8.10. 
Analysis Schedule 
8.10.1. 
Interim Unblinded Analyses 
Prior to the final analysis, a few selected individuals from Gilead will be unblinded to assess the 
interim safety and virology data of GS-9620. The immunology/pharmacodynamics and PK data 
of GS-9620 may also be part of the unblinded assessment. This group may consist of at least one 
representative from Clinical Research, Biostatistics, Clinical Pharmacology, 
Pharmacovigilance/Epidemiology, Biomarkers, Clinical Virology and may include other 
personnel as necessary. Details of unblinding (eg, memberships, responsibilities, analysis 
schedules) will be defined in a charter. 
After at least 10 subjects complete ATI Week 24 or meet criteria to restart ARV, the Sponsor 
will conduct interim unblinded analyses to review the data as described above. The results from 
these analyses may be submitted to regulatory agencies to facilitate the clinical development 
program, presented externally or published to disseminate the findings.  
8.10.2. 
Final Analyses 
The Sponsor will conduct a final analysis of all data after the last subject in the study completes 
the last visit 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. These standards are consistent with the European Union Clinical 
Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC. 
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/IEC. The investigator will not begin any study subject activities 
until approval from the IRB/IEC 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/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects. 


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9.1.3. 
Informed Consent 
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The investigator is responsible for obtaining written info1m ed consent from each individual 
paiticipating in this study after adequate explanation of the aims, methods, objectives, 
and potential hazai·ds of the study and before unde1taking any study-related procedures. 
The investigator must use the most cunent IRB or IEC approved consent fonn for documenting 
written infonned consent. Each info1med 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 b an im a1t ial witness if re uired b IRB/IEC or 
local re uirements. 
9.1.4. 
Confidentiality 
The investigator must assure that subjects' anonymity will be strictly maintained and that their 
identities are protected from unauthorized paities. Only subject initials, date ofbiith, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
fo1m or biological sainple submitted to the Sponsor, IRB/IEC, or laborato1y. 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 laborato1y instructions. 
NOTE: The investigator must keep a screening log showing codes, naines, and addresses for all 
subjects screened and for all subjects emolled in the ti·ial. Subject data will be processed in 
accordance with all applicable regulations. 
The investigator agrees that all infonnation received from Gilead, including but not limited to the 
investigator brochure, this protocol, eCRF, the IMP, and any other study infonnation, remain the 
sole and exclusive property of Gilead during the conduct of the study and thereafter. 
This infonnation is not to be disclosed to any third paity ( except employees or agents dii·ectly 
involved in the conduct of the study or as required by law) without prior written consent from 
Gilead. The investigator farther agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study site to any third pa1ty or othe1wise 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/ainendments, CRF and que1y fo1ms, 
IRB/IEC and governmental approval with correspondence, info1med consent, dmg records, staff 
cmTiculum vitae and authorization fonns, and other appropriate documents and con espondence. 
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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; 
• 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. 


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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 
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. 
Investigational Medicinal Product Accountability and Return 
Gilead recommends that used and unused IMP supplies be returned to the shipping facility from 
which it came for eventual destruction. The study monitor will provide instructions for return. 
If return is not possible, the study monitor will evaluate each study center’s IMP disposal 
procedures and provide appropriate instruction for destruction of unused IMP supplies. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead QA, the site may destroy used (empty or partially empty) and unused IMP 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 is destroyed on site, the investigator must maintain accurate records for all IMP 
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. 
The study monitor will review IMP supplies and associated records at periodic intervals. 
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/IEC, or to regulatory authority or health authority 
inspectors. 


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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/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented. 
9.2.2. 
Study Report and Publications 
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). 
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. 


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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. 
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. 


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10. 
REFERENCES 
Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, et al. Effect of HIV 
Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med 
2016;375 (21):2037-50. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41. 
European Medicines Agency (EMA). Pegasys: EPAR – Scientific Discussion: 8 August 2006.  8 
Aug, 2006. 
Fosdick A, Zheng J, Pflanz S, Frey CR, Hesselgesser J, Halcomb RL, et al. Pharmacokinetic and 
Pharmacodynamic Properties of GS-9620, a Novel TLR7 Agonist, Demonstrates 
ISG Induction without Detectable Serum Interferon at Low Oral Doses. J 
Pharmacol Exp Ther 2013. 
Hatano H, Yukl SA, Ferre AL, Graf EH, Somsouk M, Sinclair E, et al. Prospective antiretroviral 
treatment of asymptomatic, HIV-1 infected controllers. PLoS pathogens 2013;9 
(10):e1003691. 
Joint United Nations Programme on HIV/AIDS (UNAIDS). Global Aids Update 2016. Available 
at: http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-
2016. 31 May.  2016. 
Kubicek WG, Anderson WD, Geber WF. Effects of hypoxia on the course of induced fever in 
dogs and monkeys. Am J Physiol 1958;195 (3):601-13. 
Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM, et al. GS-9620, an Oral 
Agonist of Toll-Like Receptor-7, Induces Prolonged Suppression of Hepatitis B 
Virus in Chronically Infected Chimpanzees. Gastroenterology 2013;144 (7):1508-
17 e10. 
Li JZ, Etemad B, Ahmed H, Aga E, Bosch RJ, Mellors JW, et al. The size of the expressed HIV 
reservoir predicts timing of viral rebound after treatment interruption. AIDS 
2016;30 (3):343-53. 
Lim SY, Osuna CE, Hraber PT, Hesselgesser J, Gerold JM, Barnes TL, et al. TLR7 agonists 
induce transient viremia and reduce the viral reservoir in SIV-infected rhesus 
macaques on antiretroviral therapy [Research Article]. Science translational 
medicine 2018;10:eaao452. 
Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of 
mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. 
Lancet 1998;352 (9142):1725-30. 


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Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 99 
05 February 2019 
Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining 
Morbidity and Mortality Among Patients With Advanced Human 
Immunodeficiency Virus Infection. N Eng J Med 1998;338 (13):853-60. 
Pilaro AM, Green MD. Toxicologist's Review: Pegylated interferon-a 2b for the Treatment of 
Chronic Hepatitis C Infection (Biologics License Application # 99-1488).  
Clinical Pharmacology/Toxicology Branch, Division of Clinical Trials Design 
and Analysis, Center for Biologics Evaluation and Research.  December 19.  
2000. 
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. 
Sogaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, et al. The 
Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS pathogens 
2015;11 (9):e1005142. 
Sterne J, Hernán M, Ledergerber B, Tilling K, Weber R, Sendi P, et al. Long-term effectiveness 
of potent antiretroviral therapy in preventing AIDS and death: a prospective 
cohort study. Lancet 2005;366 (9483):378-84. 
U. S. Department of Health and Human Services (DHHS), Food and Drug Administration 
(FDA), Center for Drug Evaluation and Research (CDER). Guidance for Industry. 
Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for 
Therapeutics in Adult Healthy Volunteers. Rockville, MD.  July, 2005. 
Vial T, Descotes J. Clinical toxicity of the interferons. Drug Saf 1994;10 (2):115-50. 
Vibholm L, Schleimann MH, Hojen JF, Benfield T, Offersen R, Rasmussen K, et al. Short-
Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and 
Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection. 
Clin Infect Dis 2017;64 (12):1686-95. 
Walker BD, Yu XG. Unravelling the mechanisms of durable control of HIV-1. Nature reviews 
2013;13 (7):487-98. 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 100 
05 February 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. 
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements 
Appendix 6. 
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 1 b, Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Safety and 
Efficacy of GS-9620 in Antiretroviral Treated HIV-I Infected Controllers 
GS-US-382-3961, Amendment 3, 05 February 2019 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PD 
Name (Printed) 
Author 
Date 
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, Jnc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 101 
05 February 2019 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 102 
05 February 2019 
Appendix 2. 
Study Procedures Table 
 
 
 
Period 1v,w 
P2 
P=Period 
P3 
P2 or 
P3 
 
Visit 
Screening a 
Day -13 
Dose 1 -Day 1 
Dose 1-Day 2 
Dose 1-Day 8 
Dose 2- Day 1 
Dose 2-Day 8 
Dose 3 Day 1 
Dose 3-Day 8 
Dose 4 Day 1 
Dose 4-Day 2 
Dose 4-Day 4 
Dose 4-Day 8 
Dose 5 Day 1 
Dose 5-Day 8 
Dose 6 Day 1 
Dose 6-Day 4 
Dose 6-Day 8 
Dose 7 Day 1 
Dose 7-Day 8 
Dose 8 Day 1 
Dose 8-Day 8 
Dose 9 Day 1 
Dose 9-Day 8 
Dose 10 Day 1 
Dose 10-Day 2 
Dose 10-Day 4 
Dose 10-Day 8 
Dose 10-Day 14 
ATI Visit 1p 
Visits 2-24q,x 
ATI Remission r 
End of Studyt 
ART Re-initiation Visitsx 
Post ART re-suppression 
Visits 1-6z 
ESDDu 
Informed Consent 
X 
 
 
 
 
 
 
Medical Historyb 
X X X 
 
 
 
 
 
 
Pre-ART viral 
load set point 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA Class I and II 
type , pre-ART 
CD4 Nadir, 
historical genotype 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE and Con 
Medso 
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
Complete Physical 
Exam 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X X
h 
X 
 
 
 
 
Symptom Directed 
Physical Exam 
 
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
i 
 
X 
 
X 
X
12-Lead ECG 
X 
 
 
 
 
 
 
Vital Signs 
X 
 
X 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X X X
j 
X 
X X 
X 
X
Weight 
X 
 
X 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X X X
j 
X 
X 
 
X 
X
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X 
 
 
 
 
 
 
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Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
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GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 104 
05 February 2019 
 
 
 
Period 1v,w 
P2 
P=Period 
P3 
P2 or 
P3 
 
Visit 
Screening a 
Day -13 
Dose 1 -Day 1 
Dose 1-Day 2 
Dose 1-Day 8 
Dose 2- Day 1 
Dose 2-Day 8 
Dose 3 Day 1 
Dose 3-Day 8 
Dose 4 Day 1 
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Dose 4-Day 8 
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Dose 5-Day 8 
Dose 6 Day 1 
Dose 6-Day 4 
Dose 6-Day 8 
Dose 7 Day 1 
Dose 7-Day 8 
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Dose 8-Day 8 
Dose 9 Day 1 
Dose 9-Day 8 
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Dose 10-Day 2 
Dose 10-Day 4 
Dose 10-Day 8 
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ATI Remission r 
End of Studyt 
ART Re-initiation Visitsx 
Post ART re-suppression 
Visits 1-6z 
ESDDu 
Serum Pregnancy 
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X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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CD8 + cell count, 
CD4/CD8 ratio 
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X 
 
X 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X X X 
X 
X X 
X 
X
HBV/HCV 
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X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GS-9620 Intensive 
PKg 
 
 
X X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X
cc 
 
 
 
 
 
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2.0  
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X X X 
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pebb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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X 
 
 
 
 
 
 
 
 
 
 
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X 
 
 
 
 
 
 
 
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X 
 
 
 
X 
X 
 
 
 
 
 
 
 
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Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
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CONFIDENTIAL 
Page 105 
05 Februa1y2019 
Q 
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GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
Final 
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In-Clinic DosingY -------------------------------
X 
X 
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a 
Evaluations to be completed within 35 days prior to Pre-Baseline/Day -13 
b 
Medical histo1y including route and estimated duration ofHIV-1 infection, histo1y ofHIV-1 disease-related events, anti-retroviral treatment (AR1) histo1y for at least 
6 months and prior medications within 35 days of the screening visit 
c 
If subject's ART regimen is changed :C:: 45 days prior to Baseline/Dose 1-Day 1, plasma HIV-1 RNA <50 copies/nll, at Pre-baseline/Day -13 visit is required to confirm 
eligibility. 
d 
Females of childbearing potential only. Positive urine pregnancy tests will be confitmed with a semm test. 
e 
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has 
not fasted prior to the visit, the visit may proceed, but the subject must retmn within 72 hom-s in a fasted state to draw blood for the metabolic assessments. 
f 
HBV blood panel will be pe1formed at Screening (Hepatitis B vims surface antigen (HBsAg), Hepatitis B vims smface antibody (HBsAb) and Hepatitis B vims core antibody 
(HBcAb)). Hepatitis C antibody(HCVAb) will be pe1fo1med. 
g 
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h 
Complete physical examination at visits 5, 9, 13,17, 21, 26, 28, 30, 32, 34, 36 
Symptom directed physical examination as needed at visits 3, 7, 11, 15, 19, 23, 25, 27, 29, 31, 33, 35 
Vital signs and weight at visits 3,5,7,9,11,13, 15,17,19,21,23. 
CONFIDENTIAL 
Page 106 
05 Februa1y 2019 
Q 
00 


GS-9620 
Protocol GS-US-382-3961 
Gilead Sciences, Inc. 
k 
Chemistry, Hematology, eGFR and Urinalysis at visits 5, 9, 13, 17, 21, 26, 28, 30, 32, 34, 36 
Final 
Amendment4 
1 
Urine pregnancy test at visits 3,5,7,9,11,13,15,17,19,21,23. Urine pregnancy test 1,vill also be done at first ART re-initiation visit and monthly thereafter until Post ART 
re-su ression Visits 
I 
I' 
o 
ya verse event or test s owmg a norma results t 1at 1s believed to have a possible or probable causal relationship with the study dmg will be repeated weekly (or as often 
as deemed pmdent by the Investigator) until the abnomiality is resolved, rettuns to baseline, or is othenvise explained. 
p 
A TI Visit 1 to occtu· at Dose 10-Day 28 for subjects with IDV-1 RNA <50 copies/nil, at Dose 10-Day 14 visit. For subjects with viral load >50 copies/ml, at Dose 10-Day 14, 
the ATI Visit 1 will only occur if undetectable viral load is achieved within two re-test measurements. Subjects to discontinue study medication and ART from A TI Visit 1 
through ATI Visit 24 
q 
Weekly visits 2-24 
r 
This visit will be planned after completion of 12 weeks of ATI for subjects with plasnia HIV-1 RNA <50 copies/nil, in the absence of ART re initiation. If subjects have 
IDV-1 viral load <50 copies/ml, at ATI Visit 12, the visit should occur 1,vithin a week of ATI Visit 12. However, if the subject does not have HIV-1 viral load <50 copies/ml, 
at A TI Visit 12, this visit niay still occur at a later tinie point between A TI Visit 13 
once the IDV-1 viral load <50 copies/mL. 
r End of study visit to occtu· 7 days (± 1 day) after the last ATI Visit if subject has not re-initiated ART during Period 2 and 3. 
u 
Early Study Dmgs Discontinuation visit is required if subject discontinues study medication prior to completion of Dose 10. Tue visit to occur within 30 days oflast dose of 
studydmg. 
v 
IfHIV-1 RNA viral load will be >5000 copies/ml, at any visit post Dose, viral load will be observed at next scheduled visit or retested within 4 days. Tue next dose will be 
withheld and only given if viral load of ~5000 copies/ml, is achieved. The study procedure schedule will be reset relative to the next dose of GS-9620. 
w 
If plasnia vims HIV-1 RNA levels are > 5000 copies/nil, at third retest visit during a single dosing period, then this subject will be considered to have confirmed virologic 
failm·e and blood samples from this visit will be used for IDV-1 !l;eno 
e/phenotype testing 1,vith assays con-esponding to the antiretroviral medications the subject is talcing. 
x 
Dtuing Visits 2-24 in Period 2 
, ART will be re-initiated if subject meets the criteria defined in Section 6.6.1. Once ART is 
re-initiated, weekly visits (ART Re-1111tiation VISlts w1 occur to meastu·e plasma viral load and CD4+ cotmt will be conducted tmtil plasnia viral load becomes undetectable 
(<50 copies/nu,), and then every other week until two consecutive measures are tmdetectable. 
y 
Dosing to occtu· in fasting state. Food not penuitted 2 hotu-s prior to and 2 hours after dosing. Ovemight fasting is preferable. Aside from 240 mL water provided at dosing, 
water/liquid not to be peimitted from 1 hotu· prior to until 2 hours after dosing. Subjects to provide infomiation on food constU11ptio11 and total fasting time prior to dosing. 
z 
Post ART Re-suppression visits is applicable for subject(s) who re-initiates ART during ATI. Tue visit to occtu· monthly for six months after subject has achieved IDV-1 
RNA of <50 copies/ml, at two consecutive visits. A window of ± 6 days may be used to schedule this visit 
aa To be pe1fo1med at Post ART Re-suppression Visit 6 only 
bb IDV-1 genotype and phenotype testing for subjects with prolonged Viremia. Refei· to Section 6.9 for retesting and su~ 
cc 
Additional PK samples niay be drawn to verify that subject continues being off-ART during the ATI phase (Period 2----). Saniples will be drawn 
upon Sponsor request depending on the subject's HIV-1 RNA levels 
CONFIDENTIAL 
Page 107 
05 Februa1y2019 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 108 
05 February 2019 
Appendix 3. 
Management of Clinical and Laboratory Adverse Events 
 
 
Grade 1 
Grade 4 
Grade 3 
Grade 2 
May continue 
dosing at the 
discretion of the 
investigator 
Repeat lab to 
confirm toxicity 
grade 
Repeat lab to 
confirm toxicity 
grade 
 
If confirmed and possibly or probably related to investigational 
medicinal products: 
1.
Withhold investigational medicinal products until ≤ Grade 2 
2.
Restart all investigational medicinal products at full dose 
If confirmed and 
possibly or probably 
related to 
investigational 
medicinal products, 
discontinue 
investigational 
medicinal products 
dosing permanently 
and follow at periodic 
intervals at least 
weekly until a return 
to baseline or is 
otherwise explained 
 
If Grade 3 or 4 recurrence is confirmed following rechallenge 
with investigational medicinal product, discontinue all 
investigational medicinal products dosing permanently 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 109 
05 February 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 
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 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 110 
05 February 2019 
HEMATOLOGY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
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-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 111 
05 February 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-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 112 
05 February 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 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 113 
05 February 2019 
CHEMISTRY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
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 
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 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 114 
05 February 2019 
CHEMISTRY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
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 
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-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 115 
05 February 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-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 116 
05 February 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 (e.g., the severity of an AE could be either Grade 2 or Grade 3), select the higher of the two grades for 
the AE. 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 117 
05 February 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 
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 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 118 
05 February 2019 
CARDIOVASCULAR 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
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-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 119 
05 February 2019 
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) 
 


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Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 120 
05 February 2019 
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-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 121 
05 February 2019 
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 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 122 
05 February 2019 
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) 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 123 
05 February 2019 
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 
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 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 124 
05 February 2019 
NEUROLOGICAL 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
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 
weakness causing no or 
minimal interference with 
usual social & functional 
activities 
Muscle weakness causing 
greater than minimal 
interference with usual social 
& functional activities 
Muscle weakness causing 
inability to perform usual 
social & functional activities 
Disabling muscle weakness 
causing inability to perform 
basic self-care functions OR 
Respiratory muscle weakness 
impairing ventilation 
Neurosensory Alteration 
(including paresthesia and 
painful neuropathy) 
Asymptomatic with sensory 
alteration on exam or 
minimal paresthesia causing 
no or minimal interference 
with usual social & functional 
activities 
Sensory alteration or 
paresthesia causing greater 
than minimal interference 
with usual social & functional 
activities 
Sensory alteration or 
paresthesia causing inability 
to perform usual social & 
functional activities 
Disabling sensory alteration 
or paresthesia causing 
inability to perform basic 
self-care functions 
Seizure: (new onset) 
NA 
1 seizure 
2–4 seizures 
Seizures of any kind that are 
prolonged, repetitive 
(eg, status epilepticus), or 
difficult to control 
(eg, refractory epilepsy) 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 125 
05 February 2019 
NEUROLOGICAL 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
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 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 126 
05 February 2019 
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 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 127 
05 February 2019 
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] 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 128 
05 February 2019 
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 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 129 
05 February 2019 
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 
 


GS-9620 
Protocol GS-US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 130 
05 February 2019 
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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Protocol GS–US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 131 
05 February 2019 
Appendix 5. 
Pregnancy Precautions, 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. 
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 of 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 
The risks of treatment with GS-9620 during pregnancy have not been evaluated in humans. 
A clinical pharmacokinetic study evaluating the drug interaction potential of GS-9620 has not 
been conducted, however, based on the non-overlapping metabolic pathways for GS-9620 and 
oral contraceptives, no clinically relevant drug interactions are expected upon co-administration 
of these agents. As such, the efficacy of oral contraceptives is not expected to be affected by 
GS-9620. 
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. They must have a negative serum pregnancy test at Screening and a 
negative pregnancy test on the Pre-Baseline/Day -13 visit prior to randomization. At minimum, 
a pregnancy test will be performed at each dosing visit. 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 must also agree to one of the following from Screening until 36 days 
following the last dose of study drug. 


GS-9620 
Protocol GS–US-382-3961 
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Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 132 
05 February 2019 
• 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 female or male condom without spermicide plus one 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) 
• 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 30 days after the end of relevant systemic exposure. 
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 of childbearing potential must use condoms during treatment and until 90 days after the 
last dose. 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 90 days 
after the last dose. 


GS-9620 
Protocol GS–US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 133 
05 February 2019 
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 30 days (or 90 days for female partners of male 
subjects) of last study drug dose. Subjects who become pregnant or who suspect that they are 
pregnant during the study must report the information to the investigator and discontinue study 
drug immediately. 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, partner pregnancy, and pregnancy outcome are outlined in Section 7.7.2.1. 


GS-9620 
Protocol GS–US-382-3961 
Final 
Gilead Sciences, Inc. 
Amendment 4 
CONFIDENTIAL 
Page 134 
05 February 2019 
Appendix 6. 
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} 

SAP_000.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 1b, Randomized, Double-Blind, Placebo-controlled 
Study to Evaluate the Safety and Efficacy of GS-9620 in 
Antiretroviral Treated HIV-1 Infected Controllers
Name of Test Drug:
Vesatolimod (VES; GS-9620)
Study Number:
GS-US-382-3961
Protocol Version (Date):
Amendment 4: 05 February 2019
Analysis Type:
Final Analysis
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
17 March 2020
Analysis Plan Author:
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(rJ GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
PHARMACOKINETIC ABBREVIATIONS................................................................................................................7
1.
INTRODUCTION ................................................................................................................................................8
1.1.
Study Objectives ......................................................................................................................................8
1.2.
Study Design..........................................................................................................................................10
1.3.
Sample Size and Power..........................................................................................................................12
2.
TYPE OF PLANNED ANALYSIS ....................................................................................................................13
2.1.
Interim Analyses ....................................................................................................................................13
2.1.1.
Interim Blinded Analyses.....................................................................................................13
2.1.2.
Interim Unblinded Analyses.................................................................................................13
2.2.
Final Analysis ........................................................................................................................................13
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................14
3.1.
Analysis Sets..........................................................................................................................................14
3.1.1.
All Randomized Analysis Set...............................................................................................14
3.1.2.
Full Analysis set...................................................................................................................14
3.1.3.
Safety Analysis Set...............................................................................................................14
3.1.4.
VES Pharmacokinetic Analysis Set......................................................................................15
3.2.
Subject Grouping ...................................................................................................................................15
3.3.
Strata and Covariates..............................................................................................................................15
3.4.
Examination of Subject Subgroups........................................................................................................15
3.5.
Multiple Comparisons............................................................................................................................15
3.6.
Missing Data and Outliers......................................................................................................................16
3.6.1.
Missing Data ........................................................................................................................16
3.6.2.
Outliers.................................................................................................................................16
3.7.
Data Handling Conventions and Transformations .................................................................................16
3.8.
Analysis Visit Windows.........................................................................................................................17
3.8.1.
Definition of Study Day .......................................................................................................17
3.8.2.
Analysis Visits......................................................................................................................18
3.8.3.
Selection of Data in the Event of Multiple Records for a Visit............................................18
4.
SUBJECT DISPOSITION ..................................................................................................................................19
4.1.
Subject Enrollment and Disposition.......................................................................................................19
4.1.1.
Subject Enrollment...............................................................................................................19
4.1.2.
Subject Disposition ..............................................................................................................19
4.2.
Extent of Exposure.................................................................................................................................19
4.3.
Protocol Deviations................................................................................................................................20
5.
BASELINE CHARACTERISTICS....................................................................................................................21
5.1.
Demographics and Baseline Characteristics ..........................................................................................21
5.2.
Baseline Disease Characteristics............................................................................................................21
5.3.
Medical History......................................................................................................................................21
6.
EFFICACY ANALYSES ...................................................................................................................................22
6.1.
Definition of Efficacy Endpoints ...........................................................................................................22
6.2.
Statistical Hypotheses for Efficacy Endpoints .......................................................................................22
6.3.
Analysis of Efficacy Endpoints..............................................................................................................22
7.
SAFETY ANALYSES........................................................................................................................................24


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7.1.
Adverse Events and Deaths....................................................................................................................24
7.1.1.
Adverse Event Dictionary ....................................................................................................24
7.1.2.
Adverse Event Severity........................................................................................................24
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................24
7.1.4.
Relationship of Adverse Events to Study Procedure............................................................24
7.1.5.
Serious Adverse Events........................................................................................................24
7.1.6.
Treatment-Emergent Adverse Events...................................................................................25
7.1.6.1.
Definition of Treatment-Emergent Adverse Events .......................................25
7.1.6.2.
Incomplete Dates ............................................................................................25
7.1.7.
Summaries of Adverse Events and Deaths...........................................................................25
7.1.8.
Additional Analysis of Adverse Events ...............................................................................26
7.2.
Laboratory Evaluations ..........................................................................................................................27
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................27
7.2.2.
Graded Laboratory Values ...................................................................................................27
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities.............................................28
7.2.2.2.
Summaries of Laboratory Abnormalities........................................................28
7.3.
Body Weight, Height, BMI and Vital Signs...........................................................................................28
7.4.
Prior and Concomitant Medications.......................................................................................................29
7.4.1.
Antiretroviral Medications ...................................................................................................29
7.4.2.
Prior Antiretroviral Medications ..........................................................................................29
7.4.3.
Concomitant Non-Antiretroviral Medications......................................................................29
7.5.
Electrocardiogram Results .....................................................................................................................30
7.6.
Other Safety Measures ...........................................................................................................................30
7.7.
Changes From Protocol-Specified Safety Analyses...............................................................................30
8.
PHARMACOKINETIC ANALYSES ................................................................................................................31
8.1.
PK Sample Collection............................................................................................................................31
8.2.
PK Analyses Related to Intensive PK Sampling....................................................................................31
8.2.1.
Estimation of Pharmacokinetic Parameters..........................................................................31
8.2.2.
PK Parameters......................................................................................................................31
8.3.
Statistical Analysis Methods ..................................................................................................................32
9.
PHARMACODYNAMIC (PD) ANALYSES.....................................................................................................33
9.1.
Definition of PD Endpoints....................................................................................................................33
9.2.
Analysis of PD Endpoints ......................................................................................................................33
10.
REFERENCES ...................................................................................................................................................34
11.
SOFTWARE.......................................................................................................................................................35
12.
SAP REVISION..................................................................................................................................................36
13.
APPENDICES ....................................................................................................................................................37
Appendix 1.
PK Parameters ........................................................................................................................37
Appendix 2.
Schedule of Assessments........................................................................................................38
Appendix 3.
Programming Specification....................................................................................................43


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LIST OF IN-TEXT TABLES
Table 8-1.
PK Parameters for VES..........................................................................................................31


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
ANOVA
analysis of variance
ART
antiretroviral therapy
ARV
antiretroviral
AST
aspartate aminotransferase
BL
baseline
BLQ
below the limit of quantification
BMI
body mass index
CAVR/CAVD
cell-associated HIV-1 RNA/DNA
CRF
case report form
CSR
clinical study report
DLTs
dose-limiting toxicities
DMC
data monitoring committee
ECG
electrocardiogram
ESDD
early study drug discontinuation
eCRF
electronic case report form 
FU
follow-up
GLSM
geometric least-squares means 
GSI
Gilead Sciences, Inc
HLT
high level term
HLGT
high level group term
ICS
intracellular cytokine staining 
ISGs
interferon-stimulated genes 
IVRS
interactive voice response system
IWRS
interactive web response system
LLOQ
lower limit of quantitation
LLT
lower level term
LOQ
limit of quantitation
MAD
multiple ascending dose
MedDRA
medical dictionary for regulatory activities
PBMC
peripheral blood mononuclear cell
PT
preferred term
PVE
Pharmacovigilance and Epidemiology
Q1
first quartile


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Q3
third quartile
SAE
serious adverse event
SAP
statistical analysis plan
SCA
single copy assay
SD
standard deviation
SEC
safety evaluation committee 
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
Upper limit of normal
ULOQ
upper limit of quantification
VES (GS-
9620)
Vesatolimod
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as 
AUC0-last (Clast/z)
%AUCexp
Percentage of AUC extrapolated between AUC0-last and AUCinf
Clast
last observed quantifiable concentration of the drug in plasma
Cmax
maximum observed concentration of drug in plasma
CL/F
apparent oral clearance after administration of the drug:
at single dose: CL/F = Dose/AUCinf , where “Dose” is the dose of the dru
T1/2
estimate of the terminal elimination half-life of the drug in plasma, 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
Vz/F
apparent volume of distribution of the drug
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-382-3961. This SAP is based on the study protocol Amendment 4 dated 
05 February 2019 and the electronic case report form (eCRF). The SAP will be finalized before 
database finalization for the final analysis. Any changes made after the finalization of the SAP 
will be documented in the CSR.
1.1.
Study Objectives
The primary objectives of this study are as follows:
To evaluate the safety and tolerability of a 10-dose regimen of vesatolimod (VES; previously 
referred to as GS-9620) in HIV-1 infected controllers on antiretroviral treatment (ART) and 
during analytical treatment interruption (ATI) following VES dosing
The secondary objectives of this study are as follows:
Virology
To evaluate the effect of VES in reactivating the HIV-1 reservoir, as measured by changes in 
plasma HIV-1 RNA by Taqman 2.0
To evaluate the effect of VES in modulating time to virologic rebound and plasma viral load 
set-point following ATI
Immunology/Pharmacodynamics

To evaluate the pharmacodynamics (PD) of VES as measured by changes in serum/plasma
cytokines, and mRNA of interferon-stimulated genes (ISGs) in whole blood

To evaluate effects of VES on immune cell activation in whole blood
Pharmacokinetics

To evaluate the plasma pharmacokinetics (PK) of VES
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1.2. 
Study Design 
Version 1.0 
This is a phase 1 b, randomized, double-blind, placebo-controlled study with a single cohort of 
HIV-1 infected controllers on ART with a history of pre-ART plasma HIV-1 RNA between 
50 and :S 5000 copies/mL. 
Randomization was stratified by pre-ART viral load (~ 50 to< 2000 copies/mL or~ 2000 to 
:S 5000 copies/mL) at screening. Subjects were randomized in a 2: 1 ratio to receive YES or 
placebo-to-match. 
The study was conducted in three periods. In Period 1, up to 30 subjects were randomized 2: 1 to 
receive YES or placebo-to-match. All subjects received up to 10 doses of their assigned study 
treatment administered orally every 14 days only in Period 1. Subjects continued to take their 
prescribed ART during Period 1. 
In Period 2, all subjects discontinued ART and were monitored for rebom1d in HIV-1 plasma 
viremia for 24 weeks of close observation and follow up. 
If subjects restarted ART at the start of Period 3, subjects completed ART Re-Initiation Visits, 
and then Post ART Re-Suppression Visits monthly for 6 additional months (Post ART 
Re-Suppression Visits 1-6). For these subjects, the last study visit was the Post ART 
Re-Suppression Visit 6. 
Dosing of YES occurred 14 days apart starting at Dose 1-Day 1, Dose 2-Day 1, Dose 3-Day 1, 
Dose 4-Day 1, Dose 5-Day 1, Dose 6-Day 1, Dose 7-Day 1, Dose 8-Day 1, Dose 9-Day 1 and 
Dose 10-Day 1 visits respectively. Subjects fasted for at least 2 hours (preferably overnight) 
before dosing. Subjects were also asked to provide infonnation on food consumption and total 
fasting time prior to dosing. 
Laboratory analyses (hematolo 
visits, monthly during Period 2 
, and urinalysis) were perfonned at all dosing 
, post ART Re-suppression Visits 
and Early Study Drug Discontinuation (ESDD) Visit. 
Urine pregnancy test (for females of childbearing potential) was perfonne~
t 
ATI visit 1 (ATI start visit), at every other visit thereafter during Period 2, _ 
_ 
, at first ART Re-initiation visit and monthly thereafter until Post ART Re-Suppression 
Visit 1, post ART Re-suppression Visits and End of Study Visit. 
Vital signs (blood pressure, pulse, respiration rate and tern erature 
visits and every other week during Period 2 
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Plasma HIV-1 RNA was measured at every visit. Cell-associated HIV-1 RNA/DNA 
Version 1.0 
(CA VR/CA VD) from PBMCs was measured at Pre-baseline/Day -13 and within 1 hour before 
and 1 and 3 days after Doses 4 and 10, within 1 hour before and 3 days after Dose 6, 
Dose 10-Day 14, ATI Remission Visit and at Post-ART re-suppression Visit 6 (6 months 
post-ART virologic re-suppression). Plasma HIV-1 RNA Single Copy Assay (SCA) was 
collected at Pre-Baseline/Day -13, within 1 hour before, and 1 and 3 days after Doses 4 and 10, 
within 1 hour before and 3 days after Dose 6, Dose 10-Day 14, ATI Remission Visit and 
Post-ART re-su ression Visit 6 6 months ost-ART virolo ic re-su ression . 
Changes in the levels of serum/plasma 
cyto mes c emo mes y nmnunoassays were measured within 1 hour before and 1 and 7 days 
after Doses 1, 4, and 10, and ATI Remission Visit. 
Assessments of adverse events and concomitant medications were perfonned at each visit. 
Symptom-directed physical examination was perfonned at every visit during Period 1. Complete 
physical examination was perfonned once a month and symptom directed h sical examination 
on other visits was perfonned every two weeks during Period 2 
-· 
Blood samples were collected to detennine plasma VES concentrations and plasma ART 
concentrations at the following time points relative to study drug dosing: 
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Plasma VES concentrations at the following time points:
Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at 
Dose 1-Day 1 visit.
Plasma ARV concentrations:
a single trough ARV PK sample was collected at Screening. Another single trough PK sample 
was collected at Dose 6 Day 4.
1.3.
Sample Size and Power
No power calculation was performed because this was an exploratory study to characterize the 
safety and efficacy of VES.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Interim Blinded Analyses
A Safety Evaluation Committee (SEC) reviewed the progress of the study and performed interim 
reviews of the safety data in order to protect subject welfare and preserve study integrity. To 
ensure the best interests of the participants, the SEC recommended to the sponsor if the nature, 
frequency, and severity of adverse effects associated with the study treatment warranted the early 
termination of the study, the continuation of the study, or the continuation of the study with 
modifications.
The initial meeting of the SEC occurred through email prior to the first dose of the study. This 
meeting formally established the SEC and thoroughly acquainted the SEC with the protocol and 
the SEC Charter. Subsequent SEC analysis was performed after half of the subjects had received 
four doses of VES or placebo-to-match.
The SEC’s role and responsibilities and the scope of analysis to be provided to the SEC were 
provided in a mutually agreed upon charter, which defined the SEC membership, meeting 
logistics, and meeting frequency.
2.1.2.
Interim Unblinded Analyses
Prior to the final analysis, a few selected individuals from Gilead were unblinded to assess the
interim safety and virology data of VES. This group may have consisted of at least one 
representative from Clinical Research, Biostatistics, Clinical Pharmacology, 
Pharmacovigilance/Epidemiology, Biomarkers, and Clinical Virology. Details of unblinding 
(eg, memberships, responsibilities, analysis schedules) were defined in an Internal Data Review 
Team Charter.
After at least 10 subjects completed ATI Week 24 or met criteria to restart ART, the Sponsor 
conducted interim unblinded analyses to review the data as described above. The results from 
these analyses were submitted to regulatory agencies to facilitate the clinical development 
program, presented externally or published to disseminate the findings.
2.2.
Final Analysis
After all subjects had completed the study, outstanding data queries resolved or adjudicated as 
unresolvable, and the data had 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, standard deviation (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.
By-subject listings will be presented for all subjects in the All Randomized Analysis Set and 
sorted by subject ID number, visit date, and time (if applicable), unless specified otherwise. Data 
collected on log forms, such as AEs, will be presented in chronological order within the subject. 
The treatment group to which subjects were randomized will be used in the listings. Age, sex at 
birth, race, and ethnicity will be included in the listings, as space permits. In addition, 3 subjects 
rolled over from Study GS-US-382-1450 to the ATI phase of Study GS-US-382-3961. They will 
be included in the listings.
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. Subjects included in each analysis set will be determined 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. A summary of the number and percentage of subjects in each 
analysis set will be provided by treatment group.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set includes all subjects who were randomized into the study.
This is the primary analysis set for by-subject listings.
3.1.2.
Full Analysis set
The Full Analysis Set (FAS) will include all subjects who (1) were randomized into the study 
and (2) received at least one dose of study drug. Subjects will be grouped according to the 
treatment to which they were randomized. For the FAS, all efficacy data, including data 
collected after the last dose of study drug, will be included, unless specified otherwise. This is 
the primary analysis set for efficacy analyses.
3.1.3.
Safety Analysis Set
The Safety Analysis Set will include all subjects who (1) were randomized into the study and 
(2) received at least 1 dose of study drug. For the safety analysis set, all safety data, including 
data collected after the last dose of study drug, will be included, unless specified otherwise.
Subjects will be grouped according to the treatment they actually received. This is the primary 
analysis set for safety analyses.


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3.1.4.
VES Pharmacokinetic Analysis Set
The VES PK Analysis Set will include all subjects who (1) were randomized into the study, 
(2) received at least 1 dose of active VES, and (3) have at least 1 nonmissing postbaseline 
concentration value for VES. This is the primary analysis set for detailed PK analysis of 
intensive PK sampling.
3.2.
Subject Grouping
For analyses based on the All Randomized Analysis Set or the FAS, subjects will be grouped by 
randomized treatment. For other analyses, subjects will be grouped by actual treatment received. 
The actual treatment received will differ from the randomized treatment only when the actual 
treatment received differs from randomized treatment for the entire treatment duration.
The treatment groups for analysis are defined as follows:

VES

Placebo
However, for the overall TEAE and lab abnormality summary, the following treatment groups 
will be used due to dose change in protocol amendments.

VES (4 mg)

VES (4/6 mg)

VES (6 mg)

VES (6/8 mg)

VES (8 mg)

Placebo
3.3.
Strata and Covariates
Randomization was stratified by pre-ART viral load (≥50 to < 2000 copies/mL or ≥2000 to 
≤5000 copies/mL) at screening. No covariates will be included in analyses.
3.4.
Examination of Subject Subgroups
There are no pre-specified subject subsets for efficacy or safety analyses.
3.5.
Multiple Comparisons
All endpoint tests will be done at the significance level of 0.05 with no multiplicity adjustment in 
this proof-of-concept study.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
A missing datum for a given study analysis window may be due to any of the following reasons:

A visit occurring in the window but data were not collected or were unusable 

A visit not occurring in the window

A subject prematurely discontinuing from the study before reaching the window
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.
The handling of missing or incomplete dates for AE onset is described in Section 7.1.6.2, and for 
concomitant medications in Section 7.4.3.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted to evaluate the impact of outliers on efficacy or safety 
outcomes, unless specified otherwise. All data will be included in the data analyses.
3.7.
Data Handling Conventions and Transformations
Laboratory data that are continuous in nature but are less than the lower limit of quantitation
(LLOQ) or above the upper limit of quantitation (ULOQ) will be imputed as follows except for 
urine creatinine:

A value that is 1 unit less than the limit of quantitation (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 < 50 and < 5.0, values of 49 and 4.9, 
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).
For urine creatinine, a value of “< 1” is handled as a missing value in its summary and the 
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Logarithmic (base 10) transformations will be applied to HIV-1 RNA data for efficacy analyses. 
HIV-1 RNA results of ‘No HIV-1 RNA detected’ and “< 20 copies/mL HIV-1 RNA Detected” 
will be imputed as 19 copies/mL for analysis purposes. 
Biomarker values that are below the limit of quantitation (BLQ) will be presented as “BLQ” in 
the data listing. Values that are BLQ will be treated as LLOQ at both predose and postbaseline 
time points.
Natural logarithm transformation will be used for plasma/blood concentrations and analysis of 
PK parameters. Plasma concentration values that are below BLQ will be presented as “BLQ” in 
the concentration data listing. Values that are BLQ will be treated as 0 at pre-dose time points, 
and one-half the value of the LLOQ at postbaseline time points.
The following conventions will be used for the presentation of summary and order statistics: 

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.”
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing 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.


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3.8.2.
Analysis Visits
The nominal visit as recorded on the CRF or lab date will be used when data are summarized by 
visit. Any data relating to unscheduled visits will not be assigned to a particular visit or time 
point and will not be included in the summary tables, but will be included in the listings.
However, the following exceptions will be made:

An unscheduled visit prior to the first dosing of study drug may be included in the calculation 
of the baseline value, if applicable.

Unscheduled visits after the first dose of study drug will be included in determining the 
maximum postbaseline toxicity grade.

For subjects who prematurely discontinue from the study, early termination (ET) data will be 
summarized as a separate visit, labeled as “Early Termination Visit”.

Data obtained after the follow-up visit or last dose date plus 30 days (whichever is later) will 
be excluded from the summaries, but will be included in the listings.
3.8.3.
Selection of Data in the Event of Multiple Records for a Visit
Depending on the statistical analysis method, single values may be required for each day. For 
example, change from baseline by visit usually requires a single value. 
If multiple valid, nonmissing, numeric measurements exist on the same nominal visit, records 
will be chosen based on the following rules if a single value is needed:
In general, the baseline value will be the last nonmissing value on or prior to the first dosing date 
of study drug, unless specified differently. If multiple measurements occur on the same day, the 
last nonmissing value prior to the time of first dosing of study drug will be considered as the 
baseline value. If these multiple measurements occur at the same time or the time is not 
available, the average (arithmetic or geometric mean, as appropriate) of these measurements 
(for continuous data) will be considered the baseline value.
For postbaseline values:

If there is more than one record on the selected day, the average will be taken 
(geometric mean for HIV-1 RNA and arithmetic mean for others), unless otherwise specified.
If multiple valid, nonmissing, categorical measurements exist on the same nominal visit, records 
will be chosen based on the following rule if a single value if needed:

For baseline, the last available record on or prior to the first dose of study drug will be 
selected. If there are multiple records with the same time or no time recorded on the same 
day, the value with the lowest severity will be selected (eg, normal will be selected over 
abnormal for safety ECG findings).

For postbaseline visits, the value for the scheduled visit only will be used. If multiple records 
are available for a scheduled visit, the most conservative value within that day will be 
selected (eg, abnormal will be selected over normal for safety ECGs).


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
4.1.1.
Subject Enrollment
A summary of subject enrollment will be provided by treatment group for each country, 
investigator within a country and overall. The summary will present the number and percentage 
of subjects enrolled. The denominator for the percentage calculation will be the total number of 
enrolled subjects for that column. 
The randomization schedule used for the study will be provided as an appendix to the clinical 
CSR.
4.1.2.
Subject Disposition
The summary of subject disposition will be provided by treatment group and overall for all 
screened subjects. This summary will include the number of subjects screened, screen failure 
subjects who were not randomized, subjects who met all eligibility criteria and were not 
randomized, subjects randomized, subjects randomized but never treated, subjects in the safety 
analysis set, and subjects in the FAS.
In addition, the number and percentage of the subjects in the following categories will be 
summarized:

Completed study drug

Prematurely discontinuing study drug (with summary of reasons for discontinuing study 
drug)

Completed the study

Prematurely discontinuing from study (with summary of reasons for discontinuing study).
The denominator for the percentages of subjects in each category will be the number of subjects 
in the safety analysis set. 
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
4.2.
Extent of Exposure
A subject’s extent of exposure to study drug data will be generated from the study drug 
administration page in the eCRF. The number of doses by VES dose level will be summarized 
using descriptive statistics.


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4.3.
Protocol Deviations 
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, nonadherence to study drug, violation of select inclusion/exclusion criteria) will be 
summarized by treatment group for the Full Analysis Set. A by-subject listing will be provided 
for those subjects with important protocol deviation.


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5.
BASELINE CHARACTERISTICS 
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, age, sex at birth, race, and ethnicity) and baseline characteristics 
(eg, body weight, height, and body mass index [BMI]) will be summarized by treatment group 
and overall for all cohorts combined using descriptive statistics (n, mean, SD, median, Q1, Q3, 
minimum, and maximum) for continuous data and by the number and percentage of subjects for 
categorical data. The summaries of demographic data and baseline subject characteristics will be 
provided for the safety analysis set.
5.2.
Baseline Disease Characteristics
The following baseline disease characteristics will be summarized:

HIV-1 RNA (log10 copies/mL)

HIV-1 RNA categories (copies/mL) (a) < 50 and (b) ≥50 

CD4 cell count (/μL)

CD4+ cell count categories (/μL): (a) < 50, (b) ≥50 to < 200, (c) ≥200 to < 350, (d) ≥350 to 
< 500, and (e) ≥500

CD4 percentage (%)

eGFRCG (mL/min)

Mode of infection (HIV risk factors)

HIV disease status

Time from HIV diagnosis to ART initiation (in years)

Duration of ART prior to study (in years)

Pre-ART HIV-RNA viral set point (log10 copies/mL)

Pre-ART HIV-RNA categories (copies/mL): (a) ≥ 50 to < 2000, (b) ≥2000 to ≤5000, 
(c) > 5000

Pre-ART CD4 cell count (/μL)

Pre-ART CD4 cell count categories (/μL): (a) < 50, (b) ≥ 50 to < 200, (c) ≥200 to < 350, 
(d) ≥350 to < 500, and (e) ≥500
5.3.
Medical History
General medical history data will be collected at screening and listed only. General medical 
history data will be coded using the current version of Medical Dictionary for Regulatory 
Activities (MedDRA).


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6.
EFFICACY ANALYSES
As this study is still in phase 1 of the drug development, p-values from statistical comparisons 
will not be adjusted for multiplicity, so the results should be interpreted with caution. 
6.1.
Definition of Efficacy Endpoints
Efficacy endpoints include the following: 

Change from baseline in plasma log10 HIV-1 RNA by Taqman 2.0 at any postdose timepoint

Time to virologic rebound based on 2 different cutoff values:
1) ≥50 copies/mL
2) ≥200 copies/mL

Change in plasma viral load set-point following ATI

Peak HIV-1 viral load during ATI
6.2.
Statistical Hypotheses for Efficacy Endpoints
The analysis of the efficacy endpoints is exploratory in nature and no formal hypothesis testing 
was planned. 
6.3.
Analysis of Efficacy Endpoints
The full analysis set will be used for the efficacy endpoint analysis.
The change from baseline in plasma log10 HIV-1 RNA by Taqman 2.0 at any postdose timepoint 
will be calculated for all subjects in the full analysis set using available on-treatment HIV-1 
RNA data, and summarized by treatment group using descriptive statistics (n, mean, SD, 
95% CI, median, Q1, Q3, minimum, and maximum). It will also be compared between the VES 
group and the placebo group using a Wilcoxon rank sum test at a two-sided 0.05 significant 
level. 
Time to virologic rebound will be analyzed using the Kaplan-Meier method. The log rank test 
will be performed to compare the differences in the distribution of time to virologic rebound 
between the 2 treatment groups. Subjects who do not rebound will be censored at the last HIV-1 
RNA collection date during ATI period.
Change in plasma viral load set-point following ATI will be summarized and analyzed in the 
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Peak HIV-1 viral load during ATI and change from baseline will be summarized and analyzed in 
the same fashion as that of the change from baseline in plasma log10 HIV-1 RNA.


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (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 (mild), Grade 2 (moderate), Grade 3 
(severe), or Grade 4 (life threatening) 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
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.
Relationship of Adverse Events to Study Procedure
Study procedure related AEs are those for which the investigator selected “Yes” on the AE CRF 
to the question of “Related to Study Procedures.” Relatedness will always default to the 
investigator’s choice, not that of the medical monitor. Events for which the investigator did not 
record relationships to study procedure will be shown as missing from that captured on the CRF 
in by-subject data listings.
7.1.5.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE 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 Pharmacovigilance and 
Epidemiology (PVE) Department before database finalization.


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7.1.6.
Treatment-Emergent Adverse Events
7.1.6.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as one or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug
7.1.6.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing 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 
either of the following 2 criteria is met:

The AE onset and end dates are the same as or after the month and year (or year) of the 
first dosing date of study drug

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent.
7.1.7.
Summaries of Adverse Events and Deaths
A brief high-level summary of TEAEs will be provided by treatment for the number and 
percentage of subjects who had the following: any TEAE; any TEAE of Grade 3 or above; any 
serious TEAE; any study drug-related TEAE; any study drug-related serious TEAE; any TEAE 
that led to premature discontinuation of study drug. The treatment-emergent deaths observed 
during the study will also be summarized and included in this table. Treatment-emergent death 
refers to the death occurred between the first dose date and the last dose date plus 30 days, 
inclusive.
Adverse event summaries will provide the number and percentage of subjects with AEs by SOC 
and PT, by VES dose level based on the Safety Analysis Set as follows:

All AEs

All AEs by severity

AEs of Grade 3 or above

All study-drug related AEs


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
All SAEs

All study-drug related SAEs

All AEs leading to premature discontinuation of study drug
Multiple events will be counted only once per subject per treatment in each summary. An AE 
that starts in one treatment period and continues into the following treatment period(s) will be 
counted only in the period in which the AE began. Adverse events will be summarized and listed 
first in alphabetic order of SOC and then by PT in order of descending incidence of the pooled 
treatment groups within each SOC. For summaries by severity, the most severe grade will be 
used for those AEs that occurred more than once in an individual subject per treatment during the 
study. 
In addition to the by-dose summaries described above, data listings will be provided for the 
following:

All AEs (with a variable indicating whether the event is treatment emergent)

SAEs

Deaths

AEs leading to premature discontinuation of study drug
7.1.8.
Additional Analysis of Adverse Events
An analysis was performed to summarize flu-like adverse events. This was done by selecting a 
subset of PTs for flu-like symptoms, and this list of terms was reviewed by clinical. Please see 
below for the selected PTs:

Influenza

Influenza-like illness

Fatigue

Pyrexia

Chills

Myalgia

Joint pain

Headache
A summary (number and percentage of subjects) of flu-like AEs by PT will be provided by dose 
level based on the safety analysis set. A data listing of flu-like AEs will be provided.


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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 up to the last dose of study drug plus 30 days. 
The analysis will be based on values reported in conventional units. When values are BLQ, they 
will be listed as such, and the imputed value will be used for the purpose of calculating summary 
statistics. 
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 inferential statistics will be generated.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment for each laboratory test specified in the study 
protocol as follows:

Baseline values 

Values at each postbaseline time point

Change from baseline at each postbaseline time point
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. If there is any lab toxicity grading scale overlapping 
with normal reference ranges (eg, grade 1 scale overlaps with normal reference ranges), 
laboratory values within normal range will not be graded.


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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 time point, up to and including the date of 
last dose of study drug plus 30 days. 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 time 
point.
The following summary (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment; subjects will be categorized according 
to the most severe postdose abnormality grade for a given lab test within a treatment:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities

Treatment-emergent Grade 2, 3, and 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
non-missing postbaseline values up to 30 days after last dosing date.
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities 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 displayed.
7.3.
Body Weight, Height, BMI and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI and vital signs 
as follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
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.


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A by-subject listing of vital signs will be provided by subject ID number and visit in 
chronological order. In the same manner, a by-subject listing of body weight, height, and BMI
will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the Gilead-modified World Health Organization (WHO) Drug dictionary.
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order.
7.4.1.
Antiretroviral Medications
Any ARV medications used prior to, during, or after the study (if collected) are all recorded on 
the ARV eCRF. All ARV medications recorded on the ARV eCRF will be coded using the
Gilead-modified WHO Drug Dictionary for ARV medication. The WHO preferred name and 
drug code will be attached to the clinical database. All ARV medications recorded on the ARV 
eCRF will be listed. No inferential statistics will be provided.
7.4.2.
Prior Antiretroviral Medications
Prior ARV medications are defined as ARV medications taken on or up to 2 days prior to the 
first dose date of randomized study drug based on ARVs reported on ARV eCRF.
7.4.3.
Concomitant Non-Antiretroviral Medications
Concomitant non-ARV medications (ie, non-ARV medications other than study drug that are 
taken while receiving study drug) will be coded using the WHO Drug Dictionary. The WHO 
preferred name and drug code will be attached to the clinical database. Use of concomitant 
medications will be summarized (number and percentage of subjects) by treatment group, WHO 
drug class and preferred name. Multiple drug use (by preferred name) will be counted only once 
per subject. The summary will be sorted alphabetically by drug class and then by decreasing total 
frequency within a class.
If the start or stop date of non-ARV medications is incomplete, the month and year (or year 
alone, if month is not recorded) of the start or stop date will be used to determine whether the 
non-ARV medications are concomitant or not. The medication is concomitant if the month and 
year of the start or stop (or year of the start or stop, if month is not recorded) of the medication 
does not meet either of the following criteria:

The month and year of start of the medication is after the last dose date

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If the start and stop date of non-ARV medications are complete, the start date is not after the 
last dose date and the stop date is not before the first dose date, or the non-ARV medications are 
marked as ongoing and start date is on or before the last dose date, the non-ARV medications are 
concomitant for the study.
Summaries of non-ARV concomitant medications will be provided for the safety analysis set. 
Subjects with any non-ARV concomitant medications will be listed. No inferential statistics will 
be provided.
7.5.
Electrocardiogram Results
Electrocardiogram (ECG) data will not be presented in the CSR since ECGs were not assessed in 
this study other than as part of the screening process for potential new subjects.
7.6.
Other Safety Measures
A by-subject listing of subject pregnancies during the study will be provided by subject ID 
number. No additional safety measures are specified in the protocol.
Although not necessarily related to safety, a by-subject listing of all comments received during 
the study on the comments form will be provided by subject ID number, and form for which the 
comment applies.
7.7.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
PHARMACOKINETIC ANALYSES
8.1.
PK Sample Collection
Plasma VES concentrations will be collected at the following time points:

Pre-dose (≤5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 
1-Day 1 visit.
8.2.
PK Analyses Related to Intensive PK Sampling
VES PK parameters will be determined in subjects in the VES PK analysis set. Concentrations of 
VES in plasma will be determined using validated bioanalytical assays.
8.2.1.
Estimation of Pharmacokinetic 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. 
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 AUCinf, 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
Pharmacokinetic parameters will be generated for all subjects for whom parameters can be 
derived. The primary PK parameters are AUClast, AUCinf, and Cmax of VES.
Table 8-1.
PK Parameters for VES
Analyte
Parameters
VES
Cmax, Tmax, Clast, Tlast, AUClast, AUCinf, %AUCexp, T1/2, Vz/F, CL/F, and 


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8.3.
Statistical Analysis Methods
Individual subject concentration data and individual subject PK parameters of VES will be listed 
and summarized for subjects in the VES PK analysis set by treatment. Summary statistics 
(n, mean, SD, coefficient of variation [CV(%)], minimum, median, maximum, Q1, Q3) will be 
presented. The number of subjects with concentration values BLQ will be presented. The 
geometric mean, geometric mean 95% CI, and the mean and SD of the natural log-transformed 
values will be presented for all PK parameters in addition to the summaries mentioned above.
Plasma concentrations over time will be plotted in the semi-logarithmic and linear scale as mean 
± SD, and median (Q1, Q3) by treatment. In addition, individual subject plasma concentrations 
over time will be plotted by treatment group. 


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9.
PHARMACODYNAMIC (PD) ANALYSES
9.1.
Definition of PD Endpoints
PD endpoints include the following:

Change, percentage change and fold change from baseline in the levels of serum cytokines 
(including IFN-, IL-1RA, IP-10, and ITAC)

Fold change in mRNA for ISGs including MX1, OAS1 and ISG15
9.2.
Analysis of PD Endpoints
The full analysis set will be used for other efficacy endpoint analysis. 
Change, percentage change and fold change from baseline (postbaseline/baseline) in the levels of 
serum cytokines will be summarized by treatment group using descriptive statistics and 
compared between each active treatment group and the pooled placebo group using a Wilcoxon 
rank sum test at a two-sided 0.05 significant level.
Fold change from baseline (postbaseline/baseline) in mRNA for ISGs will be analyzed similarly 
as above.


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10.
REFERENCES
Smith BP, Vandenhende FR, DeSante KA, Farid NA, Welch PA, Callaghan JT, et al. Confidence 
interval criteria for assessment of dose proportionality. Pharm Res 2000;17 (10):1278-83.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER). Guidance for Industry. Statistical Approaches to 
Establishing Bioequivalence.  January, 2001.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug 
Evaluation and Research (CDER). Guidance for Industry. Bioavailability and 
Bioequivalence Studies for Orally Administered Drug Products - General Considerations 
(Revision 1).  March, 2003.


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11.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
Phoenix WinNonlin. Version 7.0 Certara. Princeton, NJ.


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12.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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13.
APPENDICES 
Appendix 1.
PK Parameters
PK parameters evaluated in this study are listed below.
Parameter
Description
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as AUC0-
last (Clast/z)
%AUCexp
Percentage of AUC extrapolated between AUC0-last and AUCinf
Clast
last observed quantifiable concentration of the drug in plasma
Cmax
maximum observed concentration of drug in plasma
CL/F
apparent oral clearance after administration of the drug: 
at single dose: CL/F = Dose/AUCinf , where “Dose” is the dose of the drug
at steady state: CL/F = Dose/AUCtau, where “Dose” is the dose of the drug
T1/2
estimate of the terminal elimination half-life of the drug in plasma, 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
Vz/F
apparent volume of distribution of the drug
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination 
phase of the plasma concentration of drug versus time curve
The following plasma PK parameters of VES will be calculated:
Cmax, Tmax, Clast, Tlast, z, T1/2, AUClast, AUCinf, %AUCexp, Vz/F, and CL/F.


VES
GS-US-382-1450
Statistical Analysis Plan (Final Analysis) 
Version 1.0
CONFIDENTIAL
Page 38
17 March 2020
Appendix 2.
Schedule of Assessments
Visit
Period 1v,w
P2
P Period
P3
P2 or P3
Screening a
Day -13
Dose 1 -Day 1
Dose 1-Day 2
Dose 1-Day 8
Dose 2- Day 1
Dose 2-Day 8
Dose 3 Day 1
Dose 3-Day 8
Dose 4 Day 1
Dose 4-Day 2
Dose 4-Day 4
Dose 4-Day 8
Dose 5 Day 1
Dose 5-Day 8
Dose 6 Day 1
Dose 6-Day 4
Dose 6-Day 8
Dose 7 Day 1
Dose 7-Day 8
Dose 8 Day 1
Dose 8-Day 8
Dose 9 Day 1
Dose 9-Day 8
Dose 10 Day 1
Dose 10-Day 2
Dose 10-Day 4
Dose 10-Day 8
Dose 10-Day 14
ATI Visit 1p
Visits 2-24q,x
ATI Remission r
End of Studyt
ART Re-initiation Visitsx
Post ART re-suppression Visits 
1-6z
ESDDu
Informed 
Consent
X
Medical 
Historyb
X
X
X
Pre-ART viral 
load set point
X
HLA Class I and 
II type , 
pre-ART CD4 
Nadir, historical 
genotype
X
AE and Con 
Medso
X
X
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X
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X
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X
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Weight
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Xj
X
X
X
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Height
X
Review of I/E 
criteriac
X
Randomization
X
CCI


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GS-US-382- 1450 
Statistical Analysis Plan (Final Analysis) 
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and CD4 % 
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X 
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Plasma ART PK 
X 
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CONFIDENTIAL 
Page 39 
Version 1.0 
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17 March 2020 


YES 
GS-US-382- 1450 
Statistical Analysis Plan (Final Analysis) 
Version 1.0 
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Page 40 
17 March 2020 


YES 
GS-US-382- 1450 
Statistical Analysis Plan (Final Analysis) 
Version 1.0 
P2 
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----------------
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In-Clinic 
DosingY 
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a 
Evaluations to be completed within 35 days prior to Pre Baseline/Day 13 
b 
Medical history including route and estimated duration of HIV I infection, history of HIV I disease related events, anti retroviral treatment (ART) history for at least 6 months and prior 
medications within 35 days of the screening visit 
c 
If subject's ART regimen is changed 2:: 45 days prior to Baseline/Dose I Day I, plasma HIV I RNA <50 copies/mL at Pre baseline/Day 13 visit is re.quired to confim1 eligibility. 
d 
Females of childbearing potential only. Positive urine pregnancy tests will be confim1ed with a serum test. 
e 
Fasting (no food or drinks, except water, at least 8 hours prior to blood collection) glucose and lipid panel (total cholesterol, HDL, direct LDL, triglycerides). If the subject has not fasted prior to 
the visit, the visit may proceed, but the subject must return within 72 hours in a fasted state to draw blood for the metabolic assessments. 
f 
HBV blood panel will be perfom1ed at Screening (Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody (HBcAb)). 
Hepatitis C antibody (HCVAb) will be perfom1ed. 
Q 
Q 
CONFIDENTIAL 
Page 41 
17 March 2020 


YES 
GS-US-382- 1450 
Statistical Analysis Plan (Final Analysis) 
g 
Intensive PK samples will be collected at Pre dose (::S 5 minutes prior to dosing), 0.5, I, 2, 4, 6, 8, IO and 24 hours post dose at Dose I Day I visit. 
h 
Complete physical examination at visits 5, 9, 13,17, 2 1, 26, 28, 30, 32, 34, 36 
Symptom directed physical examination as needed at visits 3, 7, 11, 15, 19, 23, 25, 27, 29, 3 1, 33, 35 
j 
Vital signs and weight at visits 3,5, 7,9, 11, 13, 15, 17, 19,2 1,23. 
k 
Chemistry, Hematology, eGFR and Urinalysis at visits 5, 9, 13, 17, 2 1, 26, 28, 30, 32, 34, 36 
Version 1.0 
I 
Urine pregnancy test at visits 3,5,7,9, 11, 13,15, 17,19,2 1,23. Urine pregnancy test will also be done at first ART re initiation visit and monthly thereafter until Post ART re suppression Visits 
m 
During the Pre Baseline/Day 13, Dose IO Day 14, and AT! Remission visits, 110 ml of blood will be drawn. At Dose 6 Day I and Post ART Re Suppression Visit 6, only 20 ml of blood will be 
drawn 
r 
o 
ya verse event or tests owing abnorn1al results that is believed to have a possible or probable causal relationship with the study dmg will be repeated weekly (or as often as deemed pmdent 
by the Investigator) until the abnorn1ality is resolved, returns to baseline, or is otherwise explained. 
p 
AT! Visit I to occur at Dose 10 Day 28 for subjects with HIV I RNA <50 copies/mL at Dose 10 Day 14 visit. For subjects with viral load >50 copies/mL at Dose 10 Day 14 
-
I 
load is achieved within two re test measurements. Subjects to discontinue study medication and ART from AT! Visit I 
through AT! Visit 24 
q 
Weekly v1s1ts 2 24 
r 
This visit will be planned after completion of 12 weeks of AT! for subjects with plasma HIV I RNA <50 copies/mL in the absence of ART re initiation. If subjects have HIV I viral load 
<50 copies/mL at AT! Visit 12, the visit should occur within a week of A TI Visit 12. However, if the subject does not have HIV I viral load <50 copies/mL at AT! Visit 12, this visit may still 
occur at a later time point between AT! Visit 13 
once the HIV I viral load <50 copies/mL. 
r 
• 
End of study visit to occur 7 days (± I day) after the last AT! Visit if subject has not re initiated ART during Period 2 and 3. 
u 
Early Study Dmgs Discontinuation visit is re.quired if subject discontinues study medication prior to completion of Dose I 0. The visit to occur within 30 days of last dose of study dmg. 
v 
If HIV I RNA viral load will be >5000 copies/mL at any visit post Dose, viral load will be observed at next scheduled visit or retested within 4 days. The next dose will be withheld and only 
given if viral load of:::; 5000 copies/mL is achieved. The study procedure schedule will be reset relative to the next dose of GS 9620. 
w 
If plasma vims HIV I RNA levels are > 5000 copies/mL at third retest visit during a single dosing period, then this subject will be considered to have confirnied virologic failure and blood 
samples from this visit will be used for HIV I enot e/ henot e testing with assays corresponding to the antiretroviral medications the subject is taking. 
x 
During Visits 2 24 in Period 2 
, ART will be re initiated if subject meets the criteria defined in the protocol. Once ART is re initiated, weekly visits 
(ART Re initiation visits) will occur to measure plasma viral load and CD4+ count will be conducted until plasma viral load becomes undetectable (<50 copies/mL), and then every other week 
until two consecutive measures are undetectable. 
y 
Dosing to occur in fasting state. Food not pern1itted 2 hours prior to and 2 hours after dosing. Overnight fasting is preferable. Aside from 240 mL water provided at dosing, water/liquid not to be 
pern1itted from I hour prior to until 2 hours after dosing. Subjects to provide inforn1ation on food consumption and total fasting time prior to dosing. 
z 
Post ART Re suppression visits is applicable for subject(s) who re initiates ART during AT!. The visit to occur monthly for six months after subject has achieved HIV I RNA of <50 copies/mL 
at two consecutive visits. A window of± 6 days may be used to schedule this visit 
aa 
To be perfornied at Post ART Re suppression Visit 6 only 
bb 
HIV I genotype and phenotype testing for subjects with prolonged Viremia. Refer to the protocol for retesting and st~ 
cc 
Additional PK samples may be drawn to verify that subject continues being off ART during the AT! phase (Period 2----)- Samples will be drawn upon Sponsor re.quest 
depending on the subject's HIV I RNA levels 
CONFIDENTIAL 
Page 42 
17 March 2020 


VES
GS-US-382-1450
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 43
17 March 2020
Appendix 3.
Programming Specification
1) AGE calculated as follows:
a) AGE (years) is calculated from the number of days between the date of birth (DOB) 
and Day 1 (first dose date),
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
d) AGE  the integer of the result in (c),
e) If the DOB and Day 1 have the month in common and the birthday is later in the 
month than the date of Study Day 1, then subtract one from the AGE result above.
For subjects randomized and never dosed with study drug, age will be calculated from the 
date of randomization.
2) All screened subjects refer to all subjects who are screened (ie, with nonmissing 
screening date) and have a screening number. For summaries, the same subject is counted 
only once. DOB and other demographic information such as sex, race, ethnicity, country, 
and initials will be used to identify unique screened subjects.
3) Screen failure subjects are the subjects who are screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of 
protocol the subject was consent to. 
4) Subjects in the randomized analysis set are defined as subjects randomized into the study. 
IXRSRAND is the source to determine whether the subject is randomized (ie, subject 
with nonmissing RGMNDTN in the IXRSRAND dataset) and confirmed by the eCRF 
ENROLL dataset (ie, ENROLLYN  “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) are derived from IXRSRAND, while 
actual treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment 
if subject took at least 1 dose of study drug and assigned as blank if subject never dosed.
6) In disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.


VES
GS-US-382-1450
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 44
17 March 2020
7) Body mass index (BMI) and Body Surface Area (BSA)
BMI and BSA will be calculated only at baseline as follows:
BMI
 (weight [kg]) / (height [meters]2)
BSA (m2)  SQRT( [Height(cm) × Weight(kg) ] / 3600 )
Baseline height and weight will be used for this calculation. 
8) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded for 
percentage calculation. Except 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 factors, therefore percentage may add to more than 100% and no p-value will 
be generated. 
Subjects with Race  “Not Permitted” will also be excluded to define Race subgroup 
(ie, black vs. nonblack) for efficacy subgroup analysis. 
9) Last Dose Date and Last Study Date
a) Last Dose Date (ie, TRTEDTC, TRTEDT, TR01EDT or TR01EDTC) in ADSL was 
defined in Section 3.8.1.
For subjects with a partial last dosing date (ie, month and year of last dose are 
known), the latest of the dispensing dates of study drug bottles, study drug start dates 
and end dates, and the imputed last dose date [day imputed as 15] will be used as the 
final imputed last dose date. However if dispensing date’s month is after last dose 
date’s month, data query is needed.
If subject died and the death date is complete (ie, not partial date) and before the 
imputed last dose date, the complete death date should be used as the imputed last 
dose date. 
b) Last Study Date is the latest of the study drug start dates and end dates, the 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. If study drug start dates or end date is partially missing 
(ie, only year and month are known), the day will be imputed as 15 for the purpose of 
this analysis.
If subject died and the death date is complete (ie, not partial date) and before the 
imputed last study date, the complete death date should be used as the imputed last 
study date. 


VES
GS-US-382-1450
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 45
17 March 2020
10) Toxicity Grades:
a) For toxicity grade summaries, include all postbaseline graded results up to 30 days 
after the last dose of study drug, not just those used in by-visit summaries.
b) For glucose grading,the treatment-emergent flag cannot be determined for nonfasting 
glucose (including glucose results without a known fasting status). As a result, these 
records will be excluded from the “Maximum Treatment-emergent Toxicity Grade” 
summary in the “Treatment-emergent Laboratory Abnormalities” or 
“Treatment-emergent Grade 3 or 4 Laboratory Abnormalities” summary tables. In 
addition, fasting glucose and nonfasting glucose will be listed as two separate 
laboratory tests in the “Laboratory Abnormalities” and “Grade 3 or 4 Laboratory 
Abnormalities” listings. Only a maximum postbaseline toxicity flag will be displayed 
and the treatment-emergent flag will not be displayed for nonfasting glucose as the 
treatment-emergent flag cannot be determined for nonfasting glucose. 
11) TEAE
Events with Missing Onset Day and/or Month
An AE is treatment emergent if the following 3 criteria are met:

The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and

The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and

End date is as follows: 
a.
The (complete) end date is on or after the first dose date, or
b. The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
c.
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of 
the criteria specified in 3) above.


VES
GS-US-382-1450
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 46
17 March 2020
12) PK parameters at the individual subject level should be displayed with the following 
reported number of decimal places:

LambdaZ, r2, r2 adj, and CORRXY: 3 decimal places

t1/2, Tlast, Tmax, BEGHOUR, and ENDHOUR: 2 decimal places

AUCtau, AUC0-last, AUCinf, %otAUCexp, Vz/F, CL/F, CLss/F, Cmax, Clast and 
Ctau: 1 decimal place

NPOINTS: 0 decimal place

PK concentration data will be reported with 1 decimal place. 
13) Concomitant nonstudy-drug ARV medications (ie, ARV medications other than study 
drug that are taken while receiving study drug) will be flagged in “Nonstudy-Drug 
Antiviral Medication” listing. The logic to define concomitant nonstudy-drug ARV is 
similar to concomitant non-ARV Medications (see details in Section 7.4.3)
14) For biomarker data, study day will be calculated from the first dosing date of study drug 
and derived as follows:
For postdose study days: Collection Date First Dosing Date + 1
For days prior to the first dose: Collection Date First Dosing Date
Therefore, study day 1 is the day of first dose of study drug administration.
15) Time from HIV diagnosis to ART initiation (in years) is calculated as (the date ART 
started - date subject was diagnosed with HIV disease)/365.25. 
The duration of ART prior to study (in years) is calculated as (first dose date - date 
subject first start ART)/365.25. 
For the date subject was diagnosed with HIV disease and date subject first start ART, 
missing dates will be imputed. If only the date is missing, it is imputed as 15. If both 
month and date are missing, it will be imputed as July 1st.
16) Virologic rebound

The virologic rebound ≥50 copies/mL is defined as two consecutive HIV-1 RNA 
measurement ≥50 copies/mL. The date of rebound is the first time HIV-1 RNA 
measurement ≥50 copies/mL. 

The virologic rebound ≥200 copies/mL is defined as two consecutive HIV-1 RNA 
measurement ≥200 copies/mL. The date of rebound is the first time HIV-1 RNA 
measurement ≥200 copies/mL. 
Time to virologic rebound (in weeks)  (date of rebound-date of first ATI visit +1)/7.


VES
GS-US-382-1450
Statistical Analysis Plan (Final Analysis)
Version 1.0
CONFIDENTIAL
Page 47
17 March 2020
17) Change in plasma viral load set-point following ATI  viral set-point following ATI 
pre-ART set point
The plasma viral set-point following ATI is calculated as the geometric mean of all the 
HIV-1 RNA measurements between a start date and an end date. The start date and end 
date will be provided by clinical based on blinded individual subject data review. For 
Pre-ART set point, we will use the value if only one value is recorded in the clinical 
database. If there are multiple values recorded, we will use the geometric mean.
18) Peak HIV-1 viral load during ATI

For subjects who did not restart ART, the maximum value of HIV-1 RNA 
measurements during ATI is used as the peak value.

For subjects who restarted ART, the maximum value of HIV-1 RNA measurements 
during ATI before the restart of ART is used as the peak value.


GS-382-3961 Final Analysis SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Research eSigned 17-Mar-2020
19:26:27
Biostatistics eSigned
17-Mar-2020
19:29:05
PPD
PPD