A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Phase: PHASE3
Conditions: HIV-1 Infection
Sponsor: Gilead Sciences

CLINICAL STUDY PROTOCOL
Study Title:
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in 
HIV-1 Infected, Antiretroviral Treatment-Naïve Adults
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125,589 
2015-003988-10
NCT02607956
Indication:
HIV-1 Infection
Protocol ID:
GS-US-380-1490
Gilead Study Clinical 
Program Manager:
Name:
Telephone:
Fax:
Gilead Medical 
Monitor:
Name:
Telephone:
Fax:
Gilead Study Director:
Name:
Telephone:
Fax:
Protocol Version/Date:
Original:
21 October 2015
Amendment 1:
19 February 2016
Amendment 2:
19 October 2016
Amendment 3:
06 May 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The information contained in this document, particularly unpublished data, is the property or 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.
PPD
PPD
PPD
PPD
PPD
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PPD
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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....................................................................12
1.
INTRODUCTION ..............................................................................................................................................15
1.1.
Background ............................................................................................................................................15
1.2.
GS-9883 .................................................................................................................................................16
1.2.1.
General Information .............................................................................................................16
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................16
1.2.3.
Clinical Trials of GS-9883 ...................................................................................................18
1.3.
Information about Emtricitabine (Emtriva®, FTC).................................................................................28
1.4.
Information about Tenofovir Alafenamide (TAF, GS-7340).................................................................28
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) 
or Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide 
(FTC/TAF)...........................................................................................................................28
1.4.2.
Clinical Trials of FTC/TAF as part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF).........................................................................................................................30
1.5.
Information about GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) ........................32
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883,
FTC, and TAF between GS-9883/F/TAF and GS-9883 + F/TAF........................................32
1.6.
Information about Dolutegravir (DTG, Tivicay®)..................................................................................33
1.7.
Rationale for this Study..........................................................................................................................33
1.8.
Risk/Benefit Assessment for the Study..................................................................................................34
1.9.
Rationale for Dose Selection..................................................................................................................35
1.10.
Compliance ............................................................................................................................................36
2.
OBJECTIVES.....................................................................................................................................................37
3.
STUDY DESIGN................................................................................................................................................38
3.1.
Endpoints ...............................................................................................................................................38
3.2.
Study Design..........................................................................................................................................38
3.3.
Study Treatments ...................................................................................................................................38
3.4.
Duration of Treatment............................................................................................................................39
3.5.
Biomarker Testing..................................................................................................................................40
3.5.1.
40
3.5.2.
Additional Sample Storage...................................................................................................41
4.
SUBJECT POPULATION..................................................................................................................................42
4.1.
Number of Subjects and Subject Selection ............................................................................................42
4.2.
Inclusion Criteria....................................................................................................................................42
4.3.
Exclusion Criteria...................................................................................................................................43
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................45
5.1.
Randomization, Blinding and Treatment Codes ....................................................................................45
5.1.1.
Procedures for Breaking Treatment Codes...........................................................................45
5.2.
Description and Handling.......................................................................................................................46
5.2.1.
Formulation..........................................................................................................................46
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5.2.2.
Packaging and Labeling .......................................................................................................47
5.2.3.
Storage and Handling...........................................................................................................48
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide and 
Dolutegravir + Emtricitabine/Tenofovir alafenamide............................................................................48
5.4.
Prior and Concomitant Medications.......................................................................................................49
5.4.1.
Prior and Concomitant Medications (Blinded Phase through End of 
Blinded Treatment Visit)......................................................................................................49
5.4.2.
Prior and Concomitant Medications (Open-Label Rollover Extension 
Phase)...................................................................................................................................50
5.5.
Accountability for Investigational Medicinal Product (IMP).................................................................51
5.5.1.
Investigational Medicinal Product Return or Disposal.........................................................51
6.
STUDY PROCEDURES ....................................................................................................................................52
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................52
6.2.
Pretreatment Assessments......................................................................................................................52
6.2.1.
Screening Visit .....................................................................................................................52
6.2.2.
Day 1 Assessments...............................................................................................................54
6.3.
Randomization .......................................................................................................................................56
6.4.
Treatment Assessments (Week 4 -144)..................................................................................................56
6.5.
Treatment Assessments (Post Week 144 until the Open Label Rollover Extension).............................59
6.5.1.
Post Week 144 Assessments ................................................................................................59
6.5.2.
End of Blinded Treatment Visit ...........................................................................................61
6.5.3.
Treatment Assessments (Open-Label Rollover Extension)..................................................63
6.6.
Post-treatment Assessments ...................................................................................................................65
6.6.1.
Early Study Drugs Discontinuation Assessments.................................................................65
6.6.2.
30 Day Follow Up................................................................................................................66
6.7.
Criteria for Discontinuation of Study Treatment....................................................................................67
6.8.
Blood and Urine Storage........................................................................................................................68
6.9.
Assessments for Premature Discontinuation from Study.......................................................................68
6.10.
End of Study...........................................................................................................................................68
6.11.
Post Study Care......................................................................................................................................68
6.12.
Virologic Failure....................................................................................................................................68
6.12.1.
Management of Virologic Rebound .....................................................................................69
6.12.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48, 96, 144, Week 48 OL or Week 96 OL .................................................................70
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT...............................................................................71
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events.................................71
7.1.1.
Adverse Events.....................................................................................................................71
7.1.2.
Serious Adverse Events........................................................................................................71
7.1.3.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events .........................................................................72
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................72
7.2.1.
Assessment of Causality for Study Drugs and Procedures...................................................72
7.2.2.
Assessment of Severity ........................................................................................................73
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead.......................................................................................................................73
7.3.1.
Adverse Events.....................................................................................................................73
7.3.2.
Serious Adverse Events........................................................................................................74
7.4.
Gilead Reporting Requirements.............................................................................................................75
7.5.
Toxicity Management ............................................................................................................................75
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event..................................................75
7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event.............................................................76
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................76

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7.5.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B 
Management.........................................................................................................................76
7.5.5.
Management of Potential Hepatobiliary Toxicity ................................................................78
7.5.6.
On-Treatment Hepatitis C Management...............................................................................78
7.6.
Special Situations Reports......................................................................................................................79
7.6.1.
Definitions of Special Situations..........................................................................................79
7.6.2.
Instructions for Reporting Special Situations.......................................................................79
8.
STATISTICAL CONSIDERATIONS................................................................................................................81
8.1.
Analysis Objectives and Endpoints........................................................................................................81
8.1.1.
Analysis Objectives..............................................................................................................81
8.1.2.
Primary Endpoint .................................................................................................................81
8.1.3.
Secondary Endpoint .............................................................................................................81
8.2.
Analysis Conventions.............................................................................................................................81
8.2.1.
Analysis Sets ........................................................................................................................81
8.3.
Data Handling Conventions ...................................................................................................................83
8.4.
Demographic Data and Baseline Characteristics ...................................................................................84
8.5.
Efficacy Analysis ...................................................................................................................................84
8.5.1.
Primary Analysis..................................................................................................................84
8.5.2.
Secondary Analyses .............................................................................................................85
8.5.3.
Efficacy Analyses for All GS-9883/F/TAF Analysis...........................................................86
8.6.
Safety Analysis.......................................................................................................................................86
8.6.1.
Extent of Exposure...............................................................................................................86
8.6.2.
Adverse Events.....................................................................................................................87
8.6.3.
Laboratory Evaluations ........................................................................................................87
8.6.4.
Other Safety Evaluations......................................................................................................87
8.7.
Pharmacokinetic Analysis......................................................................................................................88
8.8.
Patient Reported Outcomes (PRO).........................................................................................................88
8.9.
Sample Size............................................................................................................................................88
8.10.
Data Monitoring Committee ..................................................................................................................88
8.11.
Analysis Schedule ..................................................................................................................................89
9.
RESPONSIBILITIES..........................................................................................................................................90
9.1.
Investigator Responsibilities ..................................................................................................................90
9.1.1.
Good Clinical Practice..........................................................................................................90
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................90
9.1.3.
Informed Consent.................................................................................................................90
9.1.4.
Confidentiality......................................................................................................................91
9.1.5.
Study Files and Retention of Records ..................................................................................91
9.1.6.
Case Report Forms...............................................................................................................92
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................93
9.1.8.
Inspections............................................................................................................................93
9.1.9.
Protocol Compliance............................................................................................................93
9.2.
Sponsor Responsibilities ........................................................................................................................94
9.2.1.
Protocol Modifications.........................................................................................................94
9.2.2.
Study Report and Publications .............................................................................................94
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................94
9.3.1.
Payment Reporting...............................................................................................................94
9.3.2.
Access to Information for Monitoring..................................................................................95
9.3.3.
Access to Information for Auditing or Inspections ..............................................................95
9.3.4.
Study Discontinuation..........................................................................................................95
10.
REFERENCES ...................................................................................................................................................96

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11.
APPENDICES ....................................................................................................................................................97
Appendix 1.
Investigator Signature Page....................................................................................................98
Appendix 2.
Study Procedures Table (Blinded Phase) ...............................................................................99
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)..................................................102
Appendix 4.
Management of Clinical and Laboratory Adverse Events....................................................104
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.............105
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines) ...........................127
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements.................................................................................................129
LIST OF IN-TEXT TABLES
Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following Single Doses 
of GS-9883 in Healthy Subjects (GS-9883 PK Analysis Set; Part A: Single Dosing) ...........21
Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by GS-9883 Dose 
Following Multiple-Dose Administration of GS-9883 (Analysis Set: GS-9883 PK 
Part B: Multiple-Dose) ...........................................................................................................22
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic Parameters 
Following Single-Dose Administration of GS-9883 in the Fasted and Fed States 
(GS-9883 PK Analysis Set)....................................................................................................22
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following GS-9883 
Administration Under Fasting Conditions and Corresponding Protein-Adjusted 
IQ95 Values (GS-9883 PK Analysis Set)...............................................................................23
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady State 
Following GS-9883 Administration Under Fasting Conditions and Corresponding 
Protein-Adjusted IQ95 Values.................................................................................................35
Table 5-1.
Prior and Concomitant Medications (Blinded Phase through End of Blinded 
Treatment Visit) .....................................................................................................................49
Table 5-2.
Prior and Concomitant Medications (Open-Label Rollover Extension Phase) ......................50
LIST OF IN-TEXT FIGURES
Figure 1-1.
GS-US-141-1219: Mean and 95% CIs of Change from Baseline in HIV-1 RNA 
(log10 copies/mL) (PP Analysis Set).......................................................................................24
Figure 3-1.
Study Schema.........................................................................................................................40
Figure 6-1.
Virologic Rebound Schema....................................................................................................70

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety 
and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in 
HIV-1 Infected, Antiretroviral Treatment-Naïve Adults
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
125,589
2015-003988-10
NCT02607956
Study Centers 
Planned:
Approximately 150 centers in North America, Europe, Latin America 
and Asia Pacific
Objectives:
The primary objective of this study is as follows:

To evaluate the efficacy of a fixed dose combination (FDC) 
containing GS-9883/emtricitabine/tenofovir alafenamide 
(GS-9883/F/TAF) versus dolutegravir (DTG) + a FDC containing 
emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, 
antiretroviral treatment-naïve adult subjects as determined by the 
achievement of HIV-1 RNA 50 copies/mL at Week 48
The secondary objective of this study is as follows: 

To evaluate the efficacy, safety and tolerability of the 
two treatment groups through Weeks 48, 96, and 144

To evaluate the long term efficacy and safety of FDC 
GS-9883/F/TAF through open-label (OL) Weeks 48 and 96
Study Design:
Randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus DTG 
+ F/TAF FDC in HIV-1 infected, antiretroviral treatment-naïve adult 
subjects. Subjects who provide written consent and meet all eligibility 
criteria will be randomized in a 1:1 ratio to one of the following 
two treatment groups:

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Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 
200 mg/ tenofovir alafenamide 25 mg (GS-9883/F/TAF) + Placebo to 
match dolutegravir 50 mg and Placebo to match FDC of emtricitabine 
200 mg/tenofovir alafenamide 25 mg (F/TAF) administered orally, 
once daily, without regard to food (n=300)
Treatment Group 2: Dolutegravir 50 mg + FDC of emtricitabine 
200 mg/tenofovir alafenamide 25 mg (F/TAF) + Placebo to match 
FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without 
regard to food (n=300)
Randomization will be stratified by HIV-1 RNA level 
(≤100,000 copies/mL, > 100,000 to ≤ 400,000 copies/mL, or 
> 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening, and region 
(US vs. Ex-US) at randomization.
Number of Subjects 
Planned:
Approximately 600 subjects in total.
300 subjects in each Treatment Group 1 and Treatment Group 2
Target Population:
Antiretroviral treatment-naïve (except the use for pre-exposure 
prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to 
one month prior to screening), HIV-1 infected adults with plasma 
HIV-1 RNA levels ≥ 500 copies/mL and a screening genotype 
showing sensitivity to FTC and tenofovir (TFV).
Duration of 
Treatment:
Subjects will be treated for at least 144 weeks during the blinded 
treatment phase.  After Week 144, all subjects will continue to take 
their blinded study drug and attend visits every 12 weeks until the 
End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all 
subjects will return to the clinic (preferably within 30 days) for an
End of Blinded Treatment Visit. At the End of Blinded Treatment 
Visit, subjects will be given GS-9883/F/TAF FDC in an open label 
(OL) extension phase for 96 weeks (Week 96 OL). After Week 96 
OL, subjects will discontinue the study drug, transition onto
commercially available treatment and complete a 30-Day Follow-up 
Visit. In a country where GS-9883/F/TAF is not available, subjects
will be given the option to continue OL GS-9883/F/TAF until the 
product becomes accessible to subjects through an access program, or 
until Gilead Sciences elects to discontinue the study in that country, 
whichever occurs first.

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All subjects participating in the open label extension phase, without 
regard to their blinded treatment regimen, will return for study visits 
at Week 12 OL and every 12 weeks thereafter for at least 96 weeks.
Subjects who complete the study through the End of Blinded 
Treatment Visit and do not continue on the open-label 
GS-9883/F/TAF FDC extension phase, will be required to return to 
the clinic after End of Blinded Treatment Visit for a 30-Day 
Follow-Up Visit.
Treatment assignments will be provided to the investigators within 
30 days of the last subject completing the End of Blinded Treatment 
Visit.
Diagnosis and Main 
Eligibility Criteria:
Medically stable HIV-1 infected subjects who meet the following 
criteria:

Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening

Antiretroviral treatment naïve (≤ 10 days of prior therapy with 
any antiretroviral agent following a diagnosis of HIV-1 infection) 
except the use for PrEP or PEP, up to one month prior to 
screening.

Screening genotype report must show sensitivity to FTC and TFV

Estimated GFR ≥ 30 mL/min according to the Cockcroft-Gault 
formula for creatinine clearance
Study Procedures/
Frequency:
After screening procedures, eligible subjects will be randomized 1:1 
to Treatment Group 1 or Treatment Group 2 and treated for 
144 weeks. Following the Day 1 visit, subjects will be required to 
return for study visits at Weeks 4, 8, and 12, and then every 12 weeks 
from Week 12 through Week 144.  After 144 weeks, all subjects will 
continue to take their blinded study drugs and attend study visits 
every 12 weeks until the End of Blinded Treatment Visit. All subjects 
participating in the open label extension phase, without regard to their 
blinded treatment regimen, will return for study visits at Week 12 OL 
and every 12 weeks thereafter for at least 96 weeks
For all eligible subjects, blood will be collected at Day 1,Weeks 4, 8, 
12, and then every 12 weeks through the End of Blinded Treatment 
Visit. Blood will also be collected at Week 12 OL and every 12 
weeks thereafter for at least 96 weeks during open label extension 
phase Laboratory analyses (hematology, chemistry, and urinalysis), 
HIV-1 RNA, CD4+ cell count, and complete or symptom-directed 
physical examinations will be performed at the Screening, Day 1 and 
all subsequent study visits.
Adverse events and concomitant medications will be assessed at each 
visit.

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Test Product, Dose, 
and Mode of 
Administration:
FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir alafenamide 
25 mg (GS-9883/F/TAF) administered orally, once daily, without 
regard to food.
Reference Therapy, 
Dose, and Mode of 
Administration:
Dolutegravir 50 mg + FDC of emtricitabine 200 mg/tenofovir 
alafenamide 25 mg (F/TAF) administered orally, once daily, without 
regard to food.
Criteria for 
Evaluation:
Safety:
Adverse events and clinical laboratory tests to evaluate the safety and 
tolerability of the treatment regimens.
Efficacy:
The primary efficacy endpoint is:

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Week 48 as defined by the United States (US) 
Food and Drug Administration (FDA)-defined snapshot algorithm
The secondary efficacy endpoints include:

The proportion of subjects who achieve HIV-1 RNA 
50 copies/mL at Week 96 and 144 as defined by the US 
FDA-defined snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA 
< 20 copies/mL at Weeks 48, 96, and 144 as defined by the 
US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and in CD4+ cell 
count at Weeks 48, 96, and 144

The proportion of subjects who achieve HIV-1 RNA 
< 50 copies/mL at Weeks 48 OL and 96 OL as defined by 
Missing = Excluded and Missing = Failure algorithm

The change from baseline in CD4+ cell count at Weeks 48 OL 
and 96 OL.
Pharmacokinetics:
 
For all subjects on study drug, a single anytime pre or post-dose PK 
blood sample will be collected at Weeks 8, 24, and 36. 
For all subjects on study drug, a trough PK blood sample will be 
obtained 20-28 hours following the last dose at Weeks 4 and 12. 
Following an observed dose, one post-dose PK blood sample will be 
collected between 1 and 4 hours post-dose.
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The concentration of GS-9883 may be summarized using descriptive 
statistics. The pharmacokinetics of GS-9883 may be evaluated using 
population approaches. TAF and FTC concentrations may be 
analyzed and PK may be summarized as applicable.
 
 
 
 
 
 
 
 
 
 
 
Patient Reported 
Outcomes:
Short Form 36 Health Survey (SF-36), HIV Symptoms Distress 
Module, Work Productivity and Activity Impairment Questionnaire 
(WPAI) and Pittsburgh Sleep Quality Index (PSQI) will be 
administered at Day 1, Weeks 4, 12 and 48.
Statistical Methods:
The primary analysis will consist of a non-inferiority test of 
GS-9883/F/TAF versus DTG + F/TAF, with respect to the proportion 
of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 as 
defined by the US FDA-defined snapshot algorithm. 
It will be concluded that GS-9883/F/TAF is non-inferior to 
DTG + F/TAF if the lower bound of the 2-sided 95% confidence 
interval (CI) of the difference (GS-9883/F/TAF – DTG + F/TAF) in 
the response rate (HIV-1 RNA < 50 copies/mL as defined by the 
CCI
CCI
CCI

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US FDA-defined snapshot algorithm) is greater than -12%; i.e., a 
margin of 12% is applied to non-inferiority assessment. The 95% CI 
will be constructed using a normal approximation method based on 
stratified Mantel-Haenszel proportions, where stratification factors 
include baseline HIV-1 RNA level (≤ 100,000 copies/mL, vs.
> 100,000 copies/mL) and region (US vs. Ex-US).
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL 
at Weeks 96 and 144 and the proportion of subjects who achieve 
HIV-1 RNA < 20 copies/mL at Weeks 48, 96, and 144 as defined by 
the US FDA-defined snapshot algorithm will also be summarized. 
The 95% CIs will be constructed in the same manner as described for 
the primary efficacy endpoint. 
The change from baseline in log10 HIV-1 RNA and CD4+ cell count 
at Weeks 48, 96, and 144 will be summarized using descriptive 
statistics. The differences and the associated 2-sided 95% CIs will be 
constructed using an Analysis of Variance (ANOVA) model, 
including treatment (GS-9883/F/TAF vs. DTG + F/TAF), baseline 
HIV-1 RNA level (100,000 copies/mL vs. 100,000 copies/mL), 
and region (US vs. Ex-US) as fixed effects in the model.
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL 
at Weeks 48 OL and 96 OL will be summarized, where missing 
HIV-1 RNA will be excluded and treated as failure, respectively. The 
changes from baseline in CD4+ cell count and percentage at 
Weeks 48 OL and 96 OL will be summarized using descriptive 
statistics.
Adverse events, clinical laboratory assessments, and pharmacokinetic 
parameters will be summarized using descriptive statistics.  
A total of approximately 600 HIV-1 infected subjects, randomized in 
a 1:1 ratio to 2 treatment groups (300 subjects per treatment group), 
achieves at least 95% power to detect a non-inferiority margin of 
12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as 
defined by the US FDA-defined snapshot algorithm) difference 
between the 2 treatment groups. For the sample size and power 
computation, it is assumed that both treatment groups have a response 
rate of 91% (based on Gilead Studies GS-US-292-0104 and 
GS-US-292-0111), that the non-inferiority margin is 12%, and that 
the significance level of the test is at a one-sided 0.025 level.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.

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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C 
degrees Celsius
F
degrees Fahrenheit
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil counts
ARV
antiretroviral
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration versus time 
curve
BID
twice a day 
BUN
blood urea nitrogen
CBC
complete blood count
CI
confidence interval
CLcr
creatinine clearance
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMH
Cochran-Mantel-Haenszel
CNS
central nervous system
COBI, /co
cobicistat (GS-9350)
Ctau
the observed drug concentration at the end of the dosing interval
CPK
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CYP
cytochrome P450
DHHS
Department of Health and Human Services
DNA
deoxyribonucleic acid
DTG
dolutegravir, Tivicay
ECG
electrocardiogram
eCRF
electronic case report form(s)
eGFR
estimated glomerular filtration rate
FAS
full analysis set
EVG
elvitegravir
E/C/F/TAF
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Stribild
FAS
full analysis set
FDA
(United States) Food and Drug Administration
FDC
fixed dose combination
FTC/TAF 
emtricitabine/tenofovir alafenamide 

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FSH
follicle-stimulating hormone
FTC, F
emtricitabine, Emtriva
GCP
Good Clinical Practice (Guidelines)
GGT
gamma glutamyl transferase
GLSM
geometric least squares mean
GSI
Gilead Sciences, Inc.
GS-9883/F/TAF
GS-9883/emtricitabine/tenofovir alafenamide
HAART
highly active antiretroviral therapy
HBV
hepatitis B virus
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HDPE
high-density polyethylene
hERG
human Ether-à-go-go-Related Gene
HIV
human immunodeficiency virus
HIV Sx
HIV Symptoms  Distress Module
HLA
human leukocyte antigen
IB
investigator’s brochure
ICH
International Conference on Harmonisation
IDMC
Independent Data Monitoring Committee
IND
Investigational New Drug (Application)
INSTI
integrase strand-transfer inhibitors
IRB
institutional review board
IWRS
interactive web response system
KS
Kaposi’s sarcoma
LDH
lactate dehydrogenase
LLN
lower limit of the normal range
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
MH
Mantel-Haenszel
min
minute
mmHg
millimeters mercury
nM
nanoMolar
NNRTI
non-nucleoside reverse transcriptase inhibitor
OL
Open Label
NOAEL
no observed adverse effect level
NRTI
nucleoside/nucleotide reverse transcriptase inhibitor
PEP
post-exposure prophxylaxis
P-gp
P-glycoprotein

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PI
protease inhibitor
PK
pharmacokinetic
PSQI
Pittsburgh Sleep Quality Index
PT
preferred term 
PT
prothrombin time 
PVE
Pharmacovigilance and Epidemiology
PTM
placebo-to-match
QD
once daily 
RAL
raltegravir
RNA
ribonucleic acid
SA
single agent
SAE
serious adverse event
SF-36
Short Form 36 Health Survey
SmPC
Summary of Product Characteristics
SUSAR
Suspected Unexpected Serious Adverse Reaction
TAF
tenofovir alafenamide 
TDF
tenofovir disoproxil fumarate, Viread
TFV-DP
tenofovir diphosphate (TFVpp)
tmax
the time (observed time point) of Cmax
TSH
thyroid stimulating hormone
UGT1A1
uridine 5'-diphospho-glucuronosyltransferase 
UGT
uridine glucuronosyltransferase
ULN
upper limit of the normal range
US
United States
WPAI
Work Productivity and Activity Impairment Questionnaire

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1.
INTRODUCTION
1.1.
Background
Human immunodeficiency virus-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. The Joint United Nations Programme on HIV/AIDS (UNAIDS) 2014. The infection, 
if left untreated or suboptimally treated, is characterized by deterioration in immune function, 
ultimately resulting in death. Therapeutic strategies for the treatment of HIV-1 disease have been 
significantly advanced by the availability of highly active antiretroviral therapy (HAART); the 
introduction of HAART was associated with a dramatic decrease in acquired immune deficiency 
syndrome (AIDS)-related morbidity and mortality {Mocroft 1998, Palella 1998, Sterne 2005}.
The success of potent and well-tolerated ART means that morbidity and mortality in the 
HIV-infected population is increasingly driven by non-AIDS–associated comorbidities. Clinical 
attention has become more focused on the optimization of tolerability, long-term safety, and 
adherence of potent ART regimens {Costagliola 2014}. In addition, there remains a significant 
medical need for new, effective therapies that take into consideration HIV genetic variability, the 
aging HIV-infected population, ARV resistance, non-HIV comorbidities, and regimen 
simplification.
For ART-naive HIV-infected patients, current treatment guidelines suggest that initial therapy 
consist of 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTI) and either an integrase 
strand-transfer inhibitor (INSTI) or the boosted protease inhibitor darunavir {Department for 
Health and Human Services (DHHS) 2015}. Virologically suppressed, HIV-infected patients 
may switch from their current regimen because of safety or tolerability concerns or for regimen 
simplification. All patient populations may benefit from once-daily fixed-dose combination 
(FDC) regimens as these have been shown to provide increased adherence and improved clinical 
and virologic outcomes {Aldir 2014, Sterrantino 2012}
Tenofovir (TFV) is a nucleotide analog that inhibits HIV-1 reverse transcription. While tenofovir 
disoproxil fumarate (TDF), an oral prodrug of TFV, is a preferred NtRTI for initial therapy, 
nephrotoxicity is an identified risk, and reductions in bone mineral density (BMD) have been 
shown that are larger than those seen with other NRTIs. Tenofovir alafenamide (TAF) is also an 
oral prodrug of TFV. TAF is more stable in plasma than TDF, provides higher intracellular 
levels of the active phosphorylated metabolite tenofovir diphosphate (TFV-DP), and 
approximately 90% lower circulating levels of TFV relative to TDF at the clinical doses. 
The distinct metabolism of TAF offers the potential for an improved clinical profile compared 
with TDF.

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GS-9883 is a potent inhibitor of HIV-1 integrase that is being evaluated for the treatment of 
HIV-1 infection.  Antiviral testing has shown that GS-9883 is active against a broad panel of 
HIV-1 viral lab strains and clinical isolates.  GS-9883 is fully active against a panel of mutant 
viruses with resistance to NRTIs, non-nucleoside reverse-transcriptase inhibitors (NNRTIs), and 
protease inhibitors (PIs).  Integrase mutant viruses that are resistant to the INSTIs raltegravir 
(RAL) and elvitegravir (EVG) remain largely sensitive to GS-9883.
Gilead Sciences (Gilead) has coformulated GS-9883 with the NRTI emtricitabine (FTC; F) and 
the NtRTI tenofovir alafenamide (TAF) into an FDC tablet that is suitable for once-daily use. 
This GS-9883/F/TAF FDC may provide a potent, convenient, tolerable, and practical regimen 
for the long-term treatment of patients with HIV infection.
1.2.
GS-9883
1.2.1.
General Information
GS-9883, a potent inhibitor of HIV-1 integrase is being evaluated for the treatment of HIV 
infection. Antiviral testing has shown that GS-9883 is active against a broad panel of HIV-1 viral 
lab strains and clinical isolates. GS-9883 is fully active against a panel of mutant viruses with 
resistance to NRTIs, NNRTIs, and PIs. Integrase mutant viruses that are resistant to the INSTIs
RAL and EVG remain largely sensitive to GS-9883.
1.2.2.
Preclinical Pharmacology and Toxicology
A core battery of safety pharmacology studies have been conducted with GS-9883. These 
include assessments of cytotoxicity, off-target receptor and ion-channel binding, effects on 
human Ether-à-go-go-Related Gene (hERG) potassium current and papillary muscle action 
potential, and in vivo studies in rats and dogs that evaluated effects of GS-9883 on all major 
organ systems. The volume of distribution of GS-9883 ranged between 0.09 and 0.22 L/kg in the 
preclinical species, which indicates that the distribution of GS-9883 is limited to the extracellular 
compartment due to its high binding to plasma proteins. The projected half-life of GS-9883 in 
humans is approximately 20 hours based upon the estimates of clearance and volume of 
distribution.
1.2.2.1.
Pharmacology
GS-9883 has IC50 values ranging from 1.5 to 2.4 nM, similar to the inhibitory effect of DTG and 
EVG. GS-9883 is highly potent against HIV replication in MT4 cells with an EC50 (50% 
effective inhibitory concentration) value of 1.9 nM and a protein adjusted EC95 value of 361 nM. 
GS-9883 does not show significant cytotoxicity against dividing and non-dividing human 
PBMCs, primary human hepatocytes and various non-target human cell lines.
GS-9883 is mainly metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT1A1) and 
CYP3A. GS-9883 does not inhibit major human CYP isoforms or UGT1A1 at concentrations up 
to 25 M. Consequently, GS-9883 is unlikely to be a clinically relevant inhibitor of these
enzymes, and is not expected to inhibit the metabolic clearance of drugs metabolized by these 
enzymes. GS-9883 only modestly inhibits renal transporter OCT2 (IC50 = 0.42 M). As a result, 

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GS-9883 is not expected to significantly interfere with the key transporter responsible for 
creatinine tubular elimination at the clinically projected Cmax. Additionally, the risk that GS-9883 
will affect the OCT2-mediated excretion of co-administered drugs is considered to be low.
GS-9883 does not activate AhR and only weakly activates PXR at concentrations up to 50 M 
(less than 5% and 40% of activation, respectively, compared to positive control compound). 
Therefore, GS-9883 is not expected to act as an inducer through PXR- or AhR-mediated 
pathways at the doses and exposure levels projected in clinical use.
1.2.2.2.
Toxicology
Single oral doses of GS-9883 up to 1000 mg/kg were well-tolerated in rats (AD-141-2286). The 
increase in exposure was limited (< 2-fold) between 100 and 300 mg/kg and similar exposure 
was observed between 300 and 1000 mg/kg suggesting saturation of absorption at 300 mg/kg 
(AUC0-24 2205 gh/mL and 1931 gh/mL, respectively). In monkeys, single oral doses of 
GS-9883 up to 1000 mg/kg were well-tolerated (AD-141-2284). The increase in exposure was 
limited (< 2-fold) between 300 to 1000 mg/kg (AUC0-24 803 gh/mL and 1078 g h/mL, 
respectively).
In 2-week (TX-141-2029) and 26-week (TX-141-2031) oral toxicity studies in rats at doses up to 
300 mg/kg/day, GS-9883 was well-tolerated with no GS-9883-related effects on clinical 
observations, body weight, food consumption, ophthalmic examinations, and anatomic 
pathology.  The high dose of 300 mg/kg/day was considered the maximum feasible dose based 
upon saturation of absorption. The no observed effect level (NOEL) in the 26-week study was 
considered to be the high dose of 300 mg/kg/day.  At the NOEL, GS-9883 exposures in the rat 
were considered to be approximately 12-/31-fold higher (males/females) than the projected 
steady state human exposure of GS-9883 following administration of GS-9883/F/TAF 
(50/200/25 mg) QD under fed conditions.
In a 39-week study in monkeys (TX-141-2032), following administration of 1000 mg/kg/day 
(high dose) of GS-9883 for 39 weeks, pathology data indicated minimal to marked bile duct 
hyperplasia and minimal or moderate hepatocyte hypertrophy in both sexes, and minimal 
regenerative hyperplasia and minimal or slight neutrophil infiltrate in males.  The macroscopic 
finding of rough surface on the liver in one male administered 1000 mg/kg/day correlated with 
moderate hepatocyte hypertrophy and marked bile duct hyperplasia. After a 4-week recovery 
period, GS-9883-related microscopic liver findings included marked bile duct hyperplasia, slight 
hepatocyte hypertrophy, minimal regenerative hyperplasia, and slight lymphocyte infiltrate in 
one male and slight bile duct hyperplasia in one female administered 1000 mg/kg/day, while the 
other two animals in the high dose group had no hepatobiliary findings. Minimally to mildly 
increased ALT activities (≤3.5-fold versus baseline values), likely associated with liver findings, 
exhibited reversibility. There were no other adverse findings in the study, including clinical 
observations, or effects on body weight, body weight change, food consumption, ECGs, 
hematology, coagulation, clinical chemistry, urinalysis, and ophthalmoscopy. 

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No GS-9883-related effects were observed in the mid-dose group (200 mg/kg/day) which was 
considered the no-observed-effect-level (NOEL).  The estimated margin of exposure at the 
NOEL was approximately 5.1-fold based on expected human exposure with the once daily 
dosing of the GS-9883/F/TAF (50/200/25 mg) tablet.
A standard battery of in vitro and in vivo studies was performed to assess the genotoxic potential 
of GS-9883. There was no evidence of mutagenic or clastogenic activity in an in vitro bacterial 
reverse mutation assay (Study TX-141-2026), a chromosomal aberration assay in human 
lymphocytes (Study TX-141-2027), or in a rat micronucleus test (Study TX-141-2029).
1.2.3.
Clinical Trials of GS-9883
Clinical trials entailing the use of GS-9883 include:

GS-US-141-1218, a Phase 1 double blind, randomized, placebo-controlled, first-in-human, 
single- and multiple-ascending dose study evaluating the safety, tolerability, and PK of oral 
GS-9883 in healthy subjects and a randomized, open-label, 2-cohort, 3-period, crossover, PK 
study evaluating the drug interaction potential between F/TAF FDC tablet and GS-9883 in 
healthy subjects (completed)

GS-US-141-1219, a Phase 1b randomized, double-blinded, sequential cohort
placebo-controlled study of the safety, PK, and antiviral activity of GS-9883 in HIV-1 
infected subjects (5 mg, 25 mg, 50 mg, 100 mg) (completed)

GS-US-141-1233, a Phase 1,Open-label, Two-Cohort, Multiple-Period, Fixed-Sequence, 
Crossover Study to Evaluate 1) the Relative Bioavailability of Two GS-
9883/Emtricitabine/Tenofovir Alafenamide (75/200/25 mg and 50/200/25 mg) Fixed-Dose 
Combination Tablets Versus a GS-9883 (75 mg) Tablet and a Emtricitabine/Tenofovir 
Alafenamide (200/25 mg) Fixed-Dose Combination Tablet Administered Simultaneously and 
2) the Effect of Food on the Pharmacokinetics of GS-9883, Emtricitabine and Tenofovir 
Alafenamide When Administered as GS-9883/Emtricitabine/Tenofovir Alafenamide 
(75/200/25 mg and 50/200/25 mg) Fixed-Dose Combination Tablets (completed)

GS-US-141-1478, a Phase 1, Open Label, Parallel Group, Adaptive, Single-Dose Study to 
Evaluate the Pharmacokinetics of GS-9883 in Subjects with Normal and Impaired Hepatic 
Function (in life portion completed)

GS-US-141-1479, a Phase 1, open-label, parallel-group, adaptive single-dose study to 
evaluate the PK of GS-9883 in subjects with normal and impaired renal function (completed)

GS-US-141-1480, a Phase 1 partially-blinded, randomized, placebo- and positive-controlled 
study to evaluate the effect of GS-9883 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-141-1481, a Phase 1 study to evaluate the pharmacokinetics, metabolism, and 
excretion of GS-9883 in healthy subjects (completed)

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
GS-US-141-1485, a Phase 1 adaptive study to evaluate transporter, CYP-mediated and 
UGT1A1 drug-drug interactions between GS-9883 and probe drugs (completed)

GS-US-141-1487, a Phase 1 randomized, Blinded, Placebo-Controlled Phase 1 Study 
Evaluating the Effect of GS-9883 on Renal Function as Assessed by Markers of Glomerular 
Filtration Rate (completed)

GS-US-311-1790, a Phase 1Randomized, Open Label, Drug Interaction Study Evaluating the 
Effect of F/TAF FDC Tablet or GS-9883 on the Pharmacokinetics of a Representative 
Hormonal Contraceptive Medication, Norgestimate/Ethinyl Estradiol (completed)

GS-US-380-1761, a Phase 1 Study to Evaluate Pharmacokinetic Drug-Drug Interaction 
Potential between GS-9883/Emtricitabine/Tenofovir Alafenamide Fumarate 
(GS-9883/F/TAF) and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-Dose Combination (FDC) 
Tablets (completed)

GS-US-380-1991, a Phase I Single and Multiple Dose Study Evaluating the 
Pharmacokinetics, Safety, and Tolerability of GS-9883/Emtricitabine/Tenofovir Alafenamide 
Fumarate (GS-9883/FTC/TAF) in Healthy Japanese and Caucasian Subjects (ongoing)

GS-US-380-1999, a Phase 1 Multiple Dose Study to Evaluate the Pharmacokinetic 
Drug-Drug Interaction Potential between GS-9883/Emtricitabine/Tenofovir Alafenamide 
Fumarate and Sofosbuvir/Velpatasvir/GS-9857 in Healthy Subjects (completed)

GS-US-380-3908, a Phase 1, Blinded, Placebo-controlled, Two-period Crossover Drug 
Interaction Study to Assess the Effect of GS-9883/F/TAF on Metformin Pharmacokinetics in 
Healthy Subjects (completed)

GS-US-380-3909, a Phase 1, Open Label, Multiple-Cohort, Multiple-Period, 
Fixed-Sequence, Drug Interaction Study to Evaluate the Effect of Antacid and Mineral 
Supplements on GS-9883 Pharmacokinetics (completed)

GS-US-141-1475, a Phase 2 Randomized, Double-Blinded Study of the Safety and Efficacy 
of GS-9883 + Emtricitabine/Tenofovir Alafenamide Versus 
Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral 
Treatment-Naive Adults (ongoing)
Please refer to the GS-9883/F/TAF Investigators’ Brochure for further information about these 
studies.

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1.2.3.1.
Phase 1 Safety and Pharmacokinetics
Study GS-US-141-1218 was a four part, first-in-human study.  Parts A and B were randomized, 
double-blind, placebo-controlled, single and multiple ascending dose studies of GS-9883 in 
healthy male and female subjects.  Part C was an open label, fixed sequence food effect study 
evaluating the effect of food on the PK of GS-9883.  Part D was a randomized, open-label, 
2-cohort, 3-period, crossover PK study evaluating the drug interaction potential between 
FTC/TAF FDC tablet and GS-9883 in healthy subjects.
There was no difference in the overall incidence or type of AEs when GS-9883 was administered 
in the fasted and fed states. There was no difference in the overall incidence of AEs when 
GS-9883 or FTC/TAF was each administered alone or in combination.
No deaths or pregnancies were reported. No Grade 3 or 4 AEs or SAEs, were reported in any 
cohort.
Changes in serum creatinine were observed in this study, presumably via inhibition of the renal 
transporter OCT2.  In the MAD cohorts (fasted), serum creatinine change at Day 14 ranged from 
0.05 mg/dL for the 5 mg cohort to 0.18 mg/dL for the 300 mg/dL cohort.  In Part D (DDI), 
conducted in the fed state (regular meal), subjects received 100 mg GS-9883 monotherapy for 
7 days and 100 mg GS-9883 with FTC/TAF for 7 days, the mean serum creatinine change at 
Day 7 was 0.14 mg/dL following GS-9883 and 0.17 mg/dL following GS-9883 + FTC/TAF.  All 
changes returned to baseline after discontinuation of GS-9883.
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. Grade 3 laboratory 
abnormalities included 10 subjects with Grade 3 urine dipstick tests for blood.  All of these 
subjects were female, none of the labs were considered by the Investigator to be clinically 
significant, and all were associated with menstruation. No other Grade 3 or 4 laboratory 
abnormalities were observed.
Based on results in study GS-US-141-1218, pharmacokinetic profile of GS-9883 was 
characterized by rapid absorption with time to peak plasma concentrations (median Tmax of 
cohorts) ranging between 1 and 4 hours following administration under fasted conditions. 
GS-9883 exposures were appropriately dose proportional following single dose 25-100 mg dose 
administration, with decreasing dose proportional at higher doses.  The half-life of GS-9883 was 
approximately 18 hours, with no changes observed across studied dose range as evidenced by 
parallel terminal phase slopes. A high-fat meal increased AUCinf and Cmax (geometric mean, 
84% and 101%, respectively) following 100 mg single dose administration. Steady state was 
achieved after 4-6 days of once daily dosing of GS-9883 with average accumulation ratios for 
AUC24hr of 1.6.

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Table 1-1.
GS-US-141-1218: GS-9883 Mean (%CV) PK Parameters Following 
Single Doses of GS-9883 in Healthy Subjects (GS-9883 PK Analysis 
Set; Part A: Single Dosing)
GS-9883 PK 
Parameter
Mean 
(%CV)
5mg
(N=6)
25 mg
(N=6)
50 mg
(N=6)
100 mg
(N=6)
300 mg
(N=6)
600 mg
(N=6)
Cmax (ng/mL)
691.2
(22.1)
1618.3
(26.7)
3965.0
(40.1)
6998.3
(36.1)
14605.0 
(27.1)
20050.0
(7.5)
Tmax (hr)
1.25 
(1.00-1.50)
2.00
(1.00-3.00)
3.00
(1.50-4.00)
2.25
(1.50-3.00)
3.50
(2.00-6.00)
3.5
(2.00-4.00)
AUCinf 
(ng.hr/mL)
13059.7
(25.1)
35718.2 
(21.3)
78399.5 
(29.7)
163028.2 
(24.3)
355917.3 
(32.9)
454446.8 
(19.9)
T1/2 (hr)
18.51
(16.81-19.99)
18.08
(16.63-19.64)
16.72
(15.77-17.11)
18.90
(17.96-20.05)
18.14
(17.86-20.53)
17.89
(16.38-19.52)
T1/2 and Tmax: Median (Q1, Q3)
Table 1-2 presents GS-9883 plasma PK parameters following administration of GS-9883 
(5, 25, 50, 100, and 300 mg) once daily for 7 days. Following administration of either GS-9883 
(5, 25, 50, 100, or 300 mg) once daily for 7 days, the PK absorption profile observed on Days 1 
and 7 was similar to that observed in Part A (SAD). The median Tmax values ranged from 1.5 to 
2.5 hours on Day 1 and 1.5 to 4.0 hours on Day 7. Linearity was observed comparing GS-9883 
AUC and Cmax on Days 1 and 7 over the dose range of 25 to 50 mg. Steady state levels of 
GS-9883 were achieved between Study Days 4 to 6 of dosing and maintained through Day 14. 
Accumulation is approximately 1.6-fold, which is consistent with the observed half-life of the 
GS-9883 (approximately 18 hours).

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Table 1-2.
GS-US-141-1218: GS-9883 Plasma Pharmacokinetic Parameters by 
GS-9883 Dose Following Multiple-Dose Administration of GS-9883
(Analysis Set: GS-9883 PK Part B: Multiple-Dose)
GS-9883 PK Parameter Mean
(%CV)a
Multiple-Dose GS-9883
5 mg
(N = 6)
25 mg
(N = 6)
50 mg
(N = 6)
100 mg
(N = 6)
300 mg
(N = 6)
Day 1
AUC0-24 (hr*ng/mL)
9033.6
(8.2)
27,775.1
(28.3)
58,371.4
(18.9)
79,773.8
(18.9)
180,714.3
(17.6)
Cmax (ng/mL)
709.7
(9.5)
2220.0
(35.6)
4648.3
(18.7)
6248.3
(26.8)
13,716.7
(19.1)
Tmax (hr)
1.50
(1.50, 1.50)
1.75
(1.00, 3.00)
1.50
(1.00, 2.00)
2.50
(2.00, 3.00)
2.50
(2.00, 4.00)
Day 7
AUCtau (hr*ng/mL)
14,392.0
(16.7)
50,008.2
(26.6)
89,710.1
(22.7)
126,785.8 
(23.7)
277,200.2 
(16.7)
Cmax (ng/mL)
982.5
(7.9)
3455.0
(24.1)
6538.3
(17.6)
9396.7
(20.8)
19,900.0 
(21.2)
Ctau (ng/mL)
400.83
(26.9)
1322.00
(27.8)
2241.67
(28.2)
3145.00 
(26.1)
6758.33 
(21.6)
Tmax (hr)
1.50
(1.00, 2.00)
3.00
(2.00, 3.00)
1.75
(1.50, 2.00)
1.75
(1.50, 3.00)
4.00
(2.00, 4.00)
Accumulation Ratio of AUC (%)
160.5
(19.0)
182.2
(17.1)
154.0
(15.9)
158.5
(12.1)
157.5
(22.6)
a
Data are presented as mean (%CV), except for Tmax, and t½, which are presented as median (Q1, Q3)
Table 1-3 presents the GLSM ratios and associated 90% CIs for the test (fed) versus reference 
(fasted) treatments for the primary plasma PK parameters of GS-9883. Administration of a single 
dose of GS-9883 100 mg with food (high-calorie/high-fat breakfast) increased the GLSM values 
of Cmax and AUCinf 101% (90% CI of GLSM ratio 165.93% to 242.74%) and 84% (90% CI of
GLSM ratio 152.05% to 222.59%), respectively. There were no apparent changes in clearance 
and T1/2 following administration with food, indicating that food enhanced the bioavailability of 
GS-9883 by improving its solubility and/or absorption.
Table 1-3.
GS-US-141-1218: Statistical Comparison of GS-9883 Pharmacokinetic 
Parameters Following Single-Dose Administration of GS-9883 in the 
Fasted and Fed States (GS-9883 PK Analysis Set)
GS-9883 PK Parameter 
Mean (%CV)
% GLSM Ratio 
(90% CI)
Test
GS-9883 100 mg Fed
(n=8)
Reference
GS-9883 100 mg Fasted
(n=8)
AUCinf (hr*ng/mL)
214,146.3 (15.9)
117,777.1 (23.3)
183.97 (152.05, 222.59)
AUClast (hr*ng/mL)
209,259.9 (15.1)
115,681.7 (24.0)
183.58 (151.91, 221.86)
Cmax (ng/mL)
11,268.8 (15.1)
5885.0 (34.9)
200.69 (165.93, 242.74)
CI = confidence interval; GLSM = geometric least squares mean

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1.2.3.2.
Phase 1b Proof of Concept
The first HIV-1 positive human subjects were dosed in the fasted state with 10 days of GS-9883 
in study (GS-US-141-1219).  Four cohorts of 5 subjects each were randomized 4:1 to receive 
GS-9883 or placebo to match at doses of 5 mg, 25 mg, 50 mg, and 100 mg once daily for 
10 days. 
GS-9883 was generally well tolerated at the doses evaluated. A total of 9 of 20 subjects had an 
AE in this study. The most frequently reported AEs across all subjects were diarrhea (2 subjects), 
and headache (3 subjects).  No other AE was reported in more than 1 subject. There was no 
increase in the incidence of AEs with increasing doses of GS-9883. 
The majority of AEs were considered by the investigator to be not related to study drug. A total 
of 2 subjects experienced mild diarrhea that was considered related to study drug (1 in the 5 mg 
cohort, 1 in the 100 mg cohort).   
No deaths or pregnancies were reported. No Grade 3 or 4 AEs, SAEs, or AEs leading to 
discontinuation of study drug were reported in any cohort. 
The majority of laboratory abnormalities were Grade 1 or Grade 2 in severity. No Grade 3 
treatment emergent laboratory abnormalities were observed.   Median serum creatinine changes 
at Day 10 were: 0.05 mg/dL (5 mg), 0.04 mg/dL (25 mg), 0.06 mg/dL (50 mg), and 0.15 mg/dL 
(100 mg).  These changes in serum creatinine appeared to be transient and returned close to 
baseline values on discontinuation of study drug. One Grade 4 new onset laboratory abnormality 
was seen in 1 subject who received 5 mg GS-9883.  This was a Grade 4 CPK seen on Day 17, 
7 days following his last dose of study medication.  The subject was asymptomatic.  The 
Investigator felt that this was unrelated to study medication and was due to resumption of crystal 
methamphetamine use by the subject. An adverse event of elevated CK was reported unrelated to
study medication.   
Based on PK information collected in study GS-US-141-1219, which was in line with PK 
observed in study GS-US-141-1218, the median IQ for each dose were calculated and are 
presented in Table 1-4 below. 
Table 1-4.
Trough GS-9883 Plasma Concentrations at Steady State Following 
GS-9883 Administration Under Fasting Conditions and 
Corresponding Protein-Adjusted IQ95 Values (GS-9883 PK Analysis 
Set)
GS-9883 dose
n
Median (range) Ctau, SS (ng/mL)
Median (range) paIQ95a
5 mg
4
206.5 (146.0 to 342.0)
1.3 (0.9 to 2.1)
25 mg
4
797.5 (714.0 to 1900.0)
4.9 (4.4 to 11.7)
50 mg
4
2170.0 (852.0 to 3020.0)
13.4 (5.3 to 18.6)
100 mg
4
4190.0 (3730.0 to 5970.0)
25.9 (23.0 to 36.9)
a
The protein adjusted IQ95 (paIQ95) value is estimated based on steady-state Ctau values and the in vitro paIC95 value for 
wild-type HIV-1 (162 ng/ml).

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Protocol GS-US-380-1490 
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Final 
Amendment 3 
The mean and 95% Cis of change from baseline in HIV -1 RNA (log10 copies/mL) are presented 
in Figure 1-1. 
Figure 1-1. 
BL 
2 
Gs-9883 5 mg 
3 
3 
GS-9883 25 mg 
4 
3 
G$-9883 50 mg 
4 
4 
G$-9883 100 mg 
4 
4 
Placebo 
): 
4 
4 
GS-US-141-1219: Mean and 95% Cis of Change from Baseline in 
HIV-1 RNA (log1o copies/mL) (PP Analysis Set) 
3 
4 
3 
3 
4 
3 
4 
4 
4 
3 
4 
4 
7 
3 
4 
4 
4 
4 
8 
9 
Day 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
10 
11 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
14 
3 
4 
4 
4 
4 
17 
3 
3 
4 
4 
4 
NOTE: Baseline value was the last available value collected prior to the time of the first dose of study dl'Ug. 
0 
-1 
-2 
-3 
4 
-5 
Mean viral load change on Day 11 was -2.08 log10 in the 25 mg cohort, -2.06 logto in the 50 mg 
coh01t, and -2.43 log10 in the 100 mg coh01t. Time weighted average change from baseline at 
Day 11 (DAVGll) was -0.92logto in the 5 mg coh01t, -1.33logto in the 25 mg 
coh01t, -1.37logtoin the 50 mg coh01t and -1.61logto in the 100 mg cohort. Viral suppression 
(HIV-1 RNA < 50 copies/mL) was ever achieved by the end of the study (Day 17) by 1 subject 
(25.0%) in the GS-9883 50 mg group and 2 subjects (50%) in the GS-9883 100 mg group. 
1.2.3.3. 
Summmy of Phase 2 Study (GS-US-141-1475) 
Study GS-US-141-1475 is an ongoing Phase 2, randomized, double-blind, multicenter, 
active-controlled study to assess the safety and efficacy of a regimen containing 
GS-9883+F/TAF versus dolutegravir (DTG)+F/TAF in HIV-infected, ART-naive adult subjects. 
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Eligible subjects were randomized in a 2:1 ratio to one of the following treatment groups, 
stratified by HIV-1 RNA level (≤ 100,000 copies/mL, 100,000 copies/mL to 
400,000 copies/mL, or > 400,000 copies/mL) at screening:

Treatment Group 1: GS-9883 75 mg + F/TAF (200/25 mg) + placebo-to-match DTG 50 mg 
once daily

Treatment Group 2: DTG 50 mg + F/TAF (200/25 mg) + placebo-to-match GS-9883 75 mg 
once daily
Week 24 interim data are summarized below. 
Subject Disposition and Baseline Characteristics
A total of 98 subjects were randomized and treated in the study: 65 subjects in the 
GS-9883+F/TAF group and 33 subjects in the DTG+F/TAF group. At the time of the Week 24 
data analysis, 2 subjects (2.0%) had prematurely discontinued from the study, 1 in each treatment 
group; both subjects were lost to follow-up.
Demographic and baseline characteristics were similar between the 2 treatment groups.
Key baseline disease characteristics (ie, viral load, CD4 cell count, and eGFRCG) were similar 
between the 2 treatment groups.
Median (first quartile [Q1], third quartile [Q3]) baseline HIV-1 RNA was 
4.45 (3.96, 4.79) log10 copies/mL, with 82.7% of subjects having ≤ 100,000 copies/mL at 
baseline; 5 subjects had > 400,000 copies/mL at baseline; 4 of these subjects were randomized to 
GS-9883+F/TAF and 1 subject was randomized to DTG+F/TAF.
Median (Q1, Q3) baseline CD4 cell count was 444 (316, 595) cells/μL, with 41.8% of subjects 
having ≥ 500 cells/μL at baseline. Median (Q1, Q3) baseline eGFRCG was 125.3 
(105.7, 147.0) mL/min.
Efficacy Results
Virologic success at Weeks 12 and 24 was assessed using the US FDA-defined snapshot 
algorithm, defined as plasma HIV-1 RNA < 50 copies/mL. At Weeks 12 and 24, virologic 
success was high and similar between the 2 treatment groups as follows: Week 12 
GS-9883+F/TAF 93.8%, DTG+F/TAF 93.9% (stratum-adjusted difference in percentages: 
−1.3%; 95% CI: −12.9% to 10.2%; p = 0.79); Week 24 GS-9883+F/TAF 95.4%, DTG+F/TAF 
93.9% (1.0%; 95% CI: −10.7% to 12.7%; p = 0.84).
Of the 5 subjects with baseline viral load > 400,000 copies/mL, 4 had HIV-1 RNA 
< 50 copies/mL at Week 24, and 1 had HIV-1 RNA of 60 copies/mL. 

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Following initiation of study drug, the increases from baseline in CD4 cell count were similar 
between treatment groups. Mean (SD) baseline CD4 cell counts were as follows: 
GS-9883+F/TAF 471 (190.9) cells/μL; DTG+F/TAF 507 (271.0) cells/μL; p = 0.35. The mean 
(SD) change in CD4 cell count from baseline to Week 12 was similar between the 2 treatment 
groups as follows: GS-9883+F/TAF, +170 (150.0) cells/μL; DTG+F/TAF, +173 (220.5) cells/μL 
(difference in least squares mean [LSM]: 0; 95% CI: −76 to 76; p = 1.00). There were similar 
increases in the mean (SD) CD4 cell count in both treatment groups Week 24: GS-9883+F/TAF, 
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).
Interim Virology Resistance Data
Through Week 24, no emergent drug resistance was detected.
Safety Results
Adverse Events
The overall incidence of treatment-emergent AEs was balanced between treatment groups as 
follows: GS-9883+F/TAF 66.2%, 43 subjects; DTG+F/TAF 57.6%, 19 subjects. The most 
common treatment-emergent AEs (occurring in > 2 subjects) by treatment group were as 
follows:

GS-9883+F/TAF: diarrhea and headache (7.7%, 5 subjects each); and nausea, decreased 
appetite, arthralgia, and cough (4.6%, 3 subjects each)

DTG+F/TAF: nausea (12.1%, 4 subjects); diarrhea (9.1%, 3 subjects)
Most treatment-emergent AEs were Grade 1 in severity. Grade 3 or 4 AEs were reported in only 
1 subject (Grade 3 diabetic ketoacidosis), in the GS-9883+F/TAF group; this event was also 
reported as an SAE. One other SAE (appendicitis), also in the GS-9883+F/TAF group, was 
reported. Neither SAE was considered related to study drug by the investigator or resulted in 
study drug discontinuation or interruption, and both SAEs resolved.
The overall incidence of study drug-related treatment-emergent AEs was balanced between 
treatment groups as follows: GS-9883+F/TAF 15.4%, 10 subjects; DTG+F/TAF 18.2%, 
6 subjects. Most study drug-related treatment-emergent AEs were Grade 1 in severity. Grade 2 
study drug-related treatment-emergent AEs were reported in 1 subject in the GS-9883+F/TAF 
group (somnolence and headache) and 1 subject in the DTG+F/TAF group (vomiting). There 
were no Grade 3 or 4 treatment-emergent AEs or SAEs reported that were considered related to 
study drug.
No Grade 4 AEs, deaths, pregnancies, or AEs leading to premature study drug discontinuation 
were reported in either treatment group.

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Clinical Laboratory Evaluations
The percentage of subjects with at least 1 treatment-emergent laboratory abnormality 
(ie, at least 1 grade level increase from baseline in graded abnormality) was similar between 
treatment groups as follows: GS-9883+F/TAF 76.6%, 49 subjects; DTG+F/TAF 78.1%, 
25 subjects. The majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in 
severity. The percentage of subjects with at least 1 Grade 3 or 4 treatment-emergent laboratory 
abnormality was similar between treatment groups as follows: GS-9883+F/TAF 17.2%, 
11 subjects; DTG+F/TAF 12.5%, 4 subjects. Grade 3 or 4 laboratory abnormalities occurring in 
at least 2 subjects in either treatment group were as follows: creatine kinase (GS-9883+F/TAF, 
7.8% [5 subjects]), fasting serum glucose (DTG+F/TAF, 6.3% [2 subjects]), aspartate 
aminotransferase (AST) (GS-9883+F/TAF, 3.1% [2 subjects]), and fasting low-density 
lipoprotein (LDL) (GS-9883+F/TAF, 3.1% [2 subjects]). The only Grade 4 laboratory 
abnormalities were for creatine kinase, reported in 2 subjects (3.1%) in the GS-9883+F/TAF 
group. All increased creatine kinase values appeared to be transient, and none were associated 
with AEs. Of the 2 subjects with increased AST, 1 subject had Grade 3 AST and Grade 3 ALT at 
Week 24 in the setting of alcohol abuse; the other subject had Grade 3 AST at Week 8 that 
returned to normal by Week 24.
There were no clinically significant changes from baseline or differences between treatment 
groups in the median values for hematology, chemistry, or metabolic parameters. There were 
similar increases from baseline in median (Q1, Q3) serum creatinine in both treatment groups at 
Week 24: GS-9883+F/TAF 0.12 (0.06, 0.18) mg/dL; DTG+F/TAF 0.13 (0.05, 0.21) mg/dL. 
There were decreases in median (Q1, Q3) eGFRCG at Week 24, which were smaller in the 
GS-9883+F/TAF compared with the DTG+F/TAF group: GS-9883+F/TAF 
−13.3 (−19.9, −4.0) mL/min; DTG+F/TAF −17.2 (−25.7, −6.9) mL/min.
Conclusions
Key Week 24 conclusions from Study GS-US-141-1475 include the following:

Virologic success at Week 24 when assessed using the US FDA-defined snapshot algorithm, 
defined as plasma HIV-1 RNA < 50 copies/mL, was similar between the 2 treatment groups 
as follows: GS-9883+F/TAF 95.4%; DTG+F/TAF 93.9%; stratum-adjusted difference in 
percentages: 1.0%; 95% CI: −10.7% to 12.7%; p = 0.84. There was a similar increase in the 
mean (SD) CD4 cell count between the 2 treatment groups, GS-9883+F/TAF,
+189 (177.8) cells/μL; DTG+F/TAF, +157 (163.2) cells/μL (difference in LSM: 39; 95% CI: 
−35 to 113; p = 0.30).

No resistance to any INSTIs, NRTIs, NNRTIs, or PIs was detected through Week 24.

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
No AEs led to study drug discontinuation in either treatment group.

Both GS-9883+F/TAF and DTG+F/TAF were generally well tolerated through 24 weeks of 
treatment. The most commonly reported treatment-emergent AEs were diarrhea and 
headache (7.7% each) in the GS-9883+F/TAF group and nausea (12.1%) and diarrhea (9.1%) 
in the DTG+F/TAF group. There were 2 SAEs, 1 of which was also a Grade 3 AE; neither of 
these events was considered related to study drug by the investigator, or led to study drug 
discontinuation. There were no other Grade 3 or 4 AEs, and no deaths, pregnancies, or AEs 
leading to premature study drug discontinuation reported. The percentage of subjects with at 
least 1 treatment-emergent laboratory abnormality was similar between treatment groups. 
The majority of treatment-emergent laboratory abnormalities were Grade 1 or 2 in severity. 
There were similar increases from baseline in serum creatinine in both treatment groups at 
Week 24.
1.3.
Information about Emtricitabine (Emtriva®, FTC) 
Emtricitabine (5-fluoro-1-[(2R, 5S)-2-(hydroxymethyl)-[1, 3]-oxathiolan-5-yl] cytosine, FTC) is 
a NRTI that has demonstrated potent and selective inhibition of the HIV. In HIV-infected adults, 
FTC is administered as a 200 mg QD dose concurrently with other ARVdrugs. The 200 mg FTC 
capsule formulation was approved by the US FDA for marketing on 2 July 2003 and is available 
under the name Emtriva®. In the European Union (EU), marketing authorization was granted for 
both the 200 mg Emtrivacapsule formulation and a 10 mg/mL Emtrivaoral Solution 
formulation on 24 October 2003, with indications for the treatment of HIV infection concurrently 
with other antiretroviral drugs in both adult and pediatric patients. 
Further information is available in the current Prescribing Information for Emtriva®.
1.4.
Information about Tenofovir Alafenamide (TAF, GS-7340)
Tenofovir alafenamide (GS-7340, TAF) is a second generation oral prodrug of tenofovir (TFV), 
a nucleotide analog that inhibits HIV-1 reverse transcription. Tenofovir is metabolized 
intracellularly to the active metabolite, tenofovir diphosphate (TFV-DP), a competitive inhibitor 
of HIV-1 reverse transcriptase (RT) that terminates the elongation of the viral DNA chain.  The 
intracellular metabolism of TAF and TFV are consistent with the 600-fold enhancement in 
anti-HIV activity in cell culture of TAF over TFV.
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.4.1.
Clinical Trials of Single Agent Tenofovir Alafenamide (TAF, GS-7340) or 
Fixed Dose Combination Emtricitabine/Tenofovir Alafenamide (FTC/TAF)
Clinical trials entailing the use of tenofovir alafenamide include:

GS-US-120-1101, a Phase 1/2 study of the pharmacokinetics and antiviral activity of 
GS-7340 (50 mg and 150 mg) in HIV-infected subjects (completed)

GS-US-120-0104, a Phase 1b study of the pharmacokinetics and antiviral activity of 
GS-7340 (8 mg, 25 mg, 40 mg) in HIV infected subjects (completed)

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
GS-US-120-0107, a Phase 1, partially-blinded, randomized, placebo- and positive controlled 
study to evaluate the effect of GS-7340 on the QT/QTc interval in healthy subjects 
(completed)

GS-US-120-0108, a Phase 1, open-label, parallel-design study to evaluate the 
pharmacokinetics of GS-7340 in subjects with severe renal impairment (completed)

GS-US-120-0109, a Phase 1 study to evaluate the pharmacokinetics, metabolism and 
excretion of GS-7340 (completed)

GS-US-120-0114, a Phase 1, open-label, parallel-group, single dose study to evaluate the 
pharmacokinetics of tenofovir alafenamide in subjects with normal and impaired hepatic 
function (completed)

GS-US-120-0117, a Phase 1 single-dose study evaluating the pharmacokinetic drug 
interaction potential between rilpivirine and tenofovir alafenamide (completed)

GS-US-120-0118, a Pharmacokinetic study evaluating the drug interaction potential of
tenofovir alafenamide with a boosted protease inhibitor or unboosted integrase inhibitor in
healthy subjects (completed)

GS-US-120-1538, a Fixed-Sequence, Open-Label, Study Evaluating the Pharmacokinetics 
and Drug Interaction Potential between Tenofovir Alafenamide and Midazolam (Oral and 
Intravenous) in Healthy Volunteers (completed) 

GS-US-120-1554, a Fixed-Sequence, Randomized, Open-Label, 2-Cohort, 2-Period, 
Multiple-Dose Study Evaluating the Pharmacokinetics and Drug Interaction Potential 
between Tenofovir Alafenamide and Rilpivirine in Healthy Subjects (completed)

GS-US-311-1386, a Phase 1 study to determine the effect of food on the pharmacokinetics of 
tenofovir alafenamide when administered as F/TAF FDC in healthy volunteers (completed)

GS-US-311-0101, a Phase 1 healthy volunteer study evaluating the drug interaction potential
between once-daily FTC/GS-7340 fixed-dose combination and efavirenz (EFV) or
COBI-boosted darunavir (DRV) (completed)

GS-US-311-1088, a Phase 1, Relative Bioavailability Study of Emtricitabine/Tenofovir
Alafenamide Fixed Dose Combination Tablet to evaluate the formulation performance of
emtricitabine (FTC) and tenofovir alafenamide (TAF) fixed dose combination tablets relative
to co-administration of individual agents (completed).

GS-US-311-1089, a Phase 3 study of the safety and efficacy of FTC/TAF in HIV infected,
virologically suppressed patients (ongoing).

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In Study GS-US-311-1386, the effect of food (high-calorie, high-fat meal) on the PK of the TAF 
component of the F/TAF FDC was evaluated. The GLSM ratio of the AUClast of TAF when 
administered with a high-fat meal was 177% (90% CI: 166% to 188%), and the TAF Cmax
GLSM ratio was 84.5% (90% CI: 74.9% to 95.4%). This ~75% increase in TAF plasma 
exposure and ~15% decrease in TAF plasma Cmax when administered with food was 
accompanied by a delay in Tmax (increase from 1.00 hour under fasted conditions to 2.00 hours 
under fed conditions). The exposures of TAF observed under fed or fasted conditions in this 
study are within the range of exposures observed in the E/C/F/TAF clinical development 
program and are commensurate with safe and effective plasma levels of TAF (see investigator 
brochure for further details). Therefore, the changes in TAF exposures when F/TAF is 
administered with food should not result in differences in efficacy and thus are not clinically 
relevant. TAF can be administered without regard for food and these findings can be 
extrapolated to F/TAF (as FTC can be taken without regard to food).
1.4.2.
Clinical Trials of FTC/TAF as part of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) 
Clinical trials using tenofovir alafenamide, coformulated into the E/C/F/TAF STR include: 

GS-US-292-0101, a Phase 1 healthy volunteer study evaluating the relative bioavailability of 
EVG, FTC, TFV, and COBI administered as E/C/F/TAF STR relative to E/C/F/TDF or TAF
(completed)

GS-US-292-0103, a Phase 1 healthy volunteer study to evaluate the pharmacokinetics and 
relative bioavailability of the E/C/F/TAF STR relative to the individual components at 
GS-7340 doses of 10 mg (STR) or 25 mg Single Agent (SA) (completed)

GS-US-292-0102, a Phase 2 randomized, double-blinded study of the safety and efficacy of 
E/C/F/TAF STR versus E/C/F/TDF STR in HIV-1 infected, antiretroviral treatment-naive 
adults (ongoing)

GS-US-292-0104 and GS-US-292-0111, Phase 3 randomized, double-blinded study of the 
safety and efficacy of E/C/F/TAF STR versus E/C/F/TDF STR in HIV-1 infected, 
antiretroviral treatment-naive adults (ongoing)

GS-US-292-0109, a Phase 3 open-label study to evaluate switching from a TDF-containing 
combination regimen to a TAF-containing combination single tablet regimen (STR) in 
virologically-suppressed, HIV-1 positive subjects (ongoing)

GS-US-292-0112, a Phase 3 Open-label Safety Study of 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide single-tablet Regimen in HIV-1 
positive patients with mild to moderate renal impairment (ongoing)

GS-US-292-0117, a Phase 3, two-part study to evaluate the efficacy of Tenofovir 
Alafenamide versus placebo added to a failing regimen followed by treatment with 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in HIV-1 positive, 
antiretroviral treatment-experienced adults (ongoing)

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
GS-US-292-0119, a Phase 3 open-label study to evaluate switching from optimized stable 
antiretroviral regimens containing darunavir to 
Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) single tablet 
regimen (STR) plus darunavir (DRV) in treatment experienced HIV-1 positive adults
(ongoing)

GS-US-292-0106, a Phase 2/3, open-label study of the pharmacokinetics, safety, and 
antiviral activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide 
(E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected antiretroviral treatment-naive 
adolescents (ongoing).
Study GS-US-292-0101 is a Phase 1 study of 40 subjects evaluating the relative bioavailability 
of two different formulations of E/C/F/TAF STR, each with TAF dose of 25 mg or 40 mg, versus 
E/C/F/TDF STR or TAF 25 mg alone. Exposures of EVG, COBI, and FTC were comparable 
between E/C/F/TAF vs E/C/F/TDF regardless of formulation (monolayer or bi-layer). In 
contrast, TAF exposures were ~2.2-fold higher (and corresponding tenofovir exposures ~ 3-fold 
higher) when administered as E/C/F/TAF (25 mg) vs TAF single agent (SA) 25 mg for both 
formulations of the E/C/F/TAF, likely mediated by inhibition of P-gp-mediated intestinal
secretion of TAF by COBI.
Study GS-US-292-0103 is a completed Phase 1 healthy volunteer study which evaluated the PK
and relative bioavailability of the E/C/F/TAF STR relative to the individual components at TAF
doses of 10 (STR) or 25 mg SA. Results indicate that when dosed as the E/C/F/TAF 10 mg STR, 
TAF and TFV exposures were comparable to those observed with TAF 25 mg dosed alone. 
Exposures of EVG, COBI, and FTC were also comparable between the STR and individually 
dosed formulations. 
Study GS-US-292-0102 is an ongoing, randomized, active-controlled Phase 2 study, compares 
E/C/F/TAF (10 mg) versus Stribild® (STB, E/C/F/TDF) in treatment-naïve, HIV-1 infected 
subjects. At Week 48, the E/C/F/TAF demonstrated potent antiviral efficacy (HIV-1 RNA 
< 50 copies/mL) similar to STB (88.4% [99/112] vs 87.9% [51/58] using the snapshot 
algorithm); in the E/C/F/TAF group, no patient had emergent resistance to 1 or more components 
of the E/C/F/TAF. Importantly, E/C/F/TAF demonstrated a potential benefit over E/C/F/TDF in 
terms of renal and bone safety: smaller median decreases in eGFR (mL/min) (at Week 48, 
E/C/F/TAF -5.5 vs E/C/F/TDF -10.0 [P<0.001) and smaller median percentage decreases in 
BMD (at Week 48, spine E/C/F/TAF -1.00 vs E/C/F/TDF -3.37 [p<0.001], hip -0.62 
vs -2.39 [p<0.001]).
Studies GS-US-292-0104 and GS-US-292-0111 are ongoing, Phase 3 randomized, 
double-blinded studies of the safety and efficacy of E/C/F/TAF versus E/C/F/TDF in HIV-1 
infected, antiretroviral treatment-naive adults. The interim Week 48 key conclusions from pooled 
data showed that E/C/F/TAF once daily was noninferior to STB once daily when administered 
for 48 weeks to HIV-infected, ART-naive adults, as assessed using the US FDA-defined 
snapshot algorithm with HIV-1 RNA < 50 copies/mL (E/C/F/TAF 92.4%; STB 90.4%; 
difference in percentages: 2.0%, 95% CI: -0.7% to 4.7%).  Administration of E/C/F/TAF resulted 

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in > 90% lower plasma TFV and higher intracellular TFV-DP relative to STB.  E/C/F/TAF 
showed an improved renal and bone safety profile with significantly less decline in hip and spine 
BMD, less increase in serum creatinine and reduction in estimated glomerular filtration rate 
(eGFR).
1.5.
Information about GS-9883/Emtricitabine/Tenofovir Alafenamide 
(GS-9883/F/TAF)
Please refer to the GS-9883/F/TAF Investigator’s Brochure for further information.
1.5.1.
GS-US-141-1233: Study of the Relative Bioavailability of GS-9883, FTC, and 
TAF between GS-9883/F/TAF and GS-9883 + F/TAF
Study GS-US-141-1233 is an ongoing Phase 1, open-label, 2-cohort, multiple-period,
fixed-sequence, crossover study conducted at a single center in the US to evaluate 1) the relative 
bioavailability (BA) of 2 GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets 
compared with the GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC tablet administered 
simultaneously and 2) the effect of food on the PK of GS-9883, FTC, and TAF when 
administered as GS-9883/F/TAF (75/200/25 mg and 50/200/25 mg) FDC tablets. 
Cohort 1 evaluated the relative BA and food effect of GS-9883/F/TAF (75/200/25 mg) FDC 
tablet in a 3-period sequence. Following review of preliminary data from Cohort 1, Cohort 2 was 
added to the study via protocol amendment. Cohort 2 evaluated the relative BA and food effect 
of GS-9883/F/TAF (50/200/25 mg) FDC tablet in a 4-period sequence. 
The in-life portion of Cohorts 1 and 2 are complete. Preliminary results are summarized below. 
Cohort 1 Results:

Pharmacokinetic Results Under fasted conditions, GS-9883 AUCinf and Cmax were 27% and 
31% higher, respectively, following GS-9883/F/TAF (75/200/25 mg) FDC administration 
than following administration of single-agent GS-9883 (75 mg ) with the F/TAF (200/25 mg) 
FDC. FTC and TAF exposure was similar following administration of GS-9883/F/TAF 
(75/200/25 mg) or single-agent GS-9883 (75 mg) with the F/TAF (200/25 mg) FDC. 
Compared with administration under fasted conditions, administration of the GS-9883/F/TAF 
(75/200/25 mg) FDC with a high-fat meal resulted in a 46% higher GS-9883 AUCinf and a 
27% higher GS-9883 Cmax. The impact of food on TAF and FTC exposure was similar to that 
previously observed for F/TAF (Study GS-US-311-1386). GS-9883/F/TAF may be taken 
without regard to food.  Based on these results, Cohort 2 was added to the study via protocol 
amendment to evaluate the relative BA of the GS-9883/F/TAF (50/200/25 mg) FDC tablet 
compared with the single-agent GS-9883 (75 mg) tablet and the F/TAF (200/25 mg) FDC 
tablet administered simultaneously.
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 1, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.

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Cohort 2 Results:
Pharmacokinetic Results
The PK results from Study GS-US-141-1233 demonstrated that the GS-9883 AUCinf and Cmax
following administration of the 50mg GS-9883 FDC tablets was 79% and 78%, respectively of 
those observed in the same study following co-administration of GS-9883 75 mg single agent 
with F/TAF (200/25 mg) under fasted conditions. The GS-9883 exposures of 50 and 75 mg fixed 
dose combination tablets were approximately dose proportional under fasted and fed conditions,
and a high fat and moderate fat meal had similar impact on GS-9883 with AUCinf increasing by 
24%. The steady state paIQ95 of GS-9883/F/TAF (50/200/25 mg) was predicted to be 
17 (fasted)-23 (fed). The exposures of TAF and FTC of the 50 mg GS-9883 FDC were similar 
to those of GS-9883 75 mg single agent with F/TAF FDC, and the food effect on TAF and FTC 
was similar to the historical results.  
Safety Results
Of the 28 subjects included in the Safety Analysis Set for Cohort 2, 12 subjects (43%) had at 
least 1 treatment-emergent AE. All treatment emergent AEs were assessed as Grade 1 or 2 in 
severity. No deaths or other SAEs occurred during this study, and no subject discontinued the 
study due to an AE.
1.6.
Information about Dolutegravir (DTG, Tivicay®)
For more detailed information, refer to the current Prescribing Information and local product 
labeling for dolutegravir.
1.7.
Rationale for this Study
HIV standard of care has relied upon nucleos(t)ide backbones for effective and durable virologic 
suppression, but nucleos(t)ide-associated toxicities are increasingly important as HIV-infected 
patients are often diagnosed earlier, initiate therapy earlier, and look toward lifelong therapy 
(often greater than 50 years). Where patients have access to treatment, morbidity and mortality 
are driven by non–AIDS-associated comorbidities, which are observed earlier than in 
HIV-uninfected age-matched controls despite the best available ART. The contribution of 
specific nucleos(t)ides, including abacavir and tenofovir disoproxil fumarate, to long-term 
morbidity and mortality is increasingly important in this context.  
The GS-9883/F/TAF FDC has the potential to offer a simple, once-daily regimen containing a 
second generation INSTI that provides a high barrier to resistance, does not require a boosting 
agent, and offers an effective and safer alternative to standard nucleos(t)ide based regimens, 
without the need for  HLA testing or close monitoring of renal or bone toxicities.  It could 
provide a FDC treatment that avoids the risk of hypersensitivity reactions, would not contribute 
to an increased risk of cardiovascular events, could be used in patients with chronic hepatitis B 
or C infection or renal impairment, and that could be continued as patients age and confront 
non-HIV-related comorbidities.

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The objective of this study is to evaluate the safety and efficacy of a FDC containing 
GS-9883/F/TAF versus DTG + a FDC of F/TAF.  Dolutegravir is a second generation, 
unboosted INSTI, providing a once daily unboosted option with rapid viral suppression, good 
tolerability, and a high barrier to resistance and is on the DHHS Treatment Guidelines as a 
preferred INSTI. By keeping the backbone of F/TAF constant in both arms, we will be able to 
compare GS-9883 with DTG in a single variable design trial. This design is an extension of the 
ongoing Phase 2 study, given that a single variable design is considered the best direct evidence 
of benefit.
1.8.
Risk/Benefit Assessment for the Study
All patients with HIV-1 infection should receive effective antiretroviral therapy. Potential risks 
associated with all classes of ARVs include immune reconstitution syndrome, lipodystrophy, and 
lactic acidosis with steatosis.  The risk of class effects is considered to be low.  Important 
identified risks appropriately managed by study inclusion/exclusion criteria as well as through 
close clinical and laboratory monitoring during the study, are as follows: hypersensitivity 
reaction to dolutegravir, including liver injury, and allergy to any components of the tablets.  
Interim data will also be reviewed by an independent data monitoring committee.  Potential 
benefits may include provision of a new antiretroviral therapy that is not currently available and 
which may have fewer side effects than alternative therapies.  Other potential benefits include 
provisions of fixed dose combination therapy, and the knowledge that patient participation will 
contribute to the body of knowledge of HIV therapies.  
Following a chronic 39 week study in monkeys, animals administered the highest dose of  
GS-9883 (1000 mg/kg/day) had bile duct hyperplasia (increased cell growth) and hypertrophy 
(increased cell size), and some increased cell growth and inflammation in nearby liver cells. 
These effects were not seen in monkeys administered the mid-level dose (200 mg/kg/day), and 
these animals had plasma GS-9883 exposures that were approximately 5-fold above human 
exposures when given the GS-9883/F/TAF FDC.  No adverse drug reactions associated with 
liver or bile duct problems have been identified in humans treated with GS-9883. Potential 
hepatobiliary toxicity is appropriately managed by study inclusion/exclusion criteria, close 
clinical and laboratory monitoring, as well as specific toxicity management guidance to 
investigators (Refer to Section 7.5.5.).
Potential benefits of GS-9883 may include provision of a new antiretroviral therapy that is not 
currently available and which may have fewer side effects than alternative therapies. Other 
potential benefits include provisions of fixed dose combination therapy, and the knowledge that 
patient participation will contribute to the body of knowledge of HIV therapies.
The overall benefit-risk assessment for GS-9883/F/TAF and DTG + F/TAF is favorable at this 
time.

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1.9.
Rationale for Dose Selection
FTC
The 200 mg dose of FTC represents the marketed dose for this agent that is currently available as 
single agent capsules (EMTRIVA) and as a component of a number of fixed-dose combination 
tablets, including: TRUVADA, ATRIPLA, COMPLERA (EVIPLERA), and STRIBILD.
TAF
Based upon results of the Phase 1 Study GS-US-120-0104, in which various doses of TAF 
(8 mg, 25 mg, and 40 mg) were administered to HIV-infected subjects in 10 days of 
monotherapy, the range of exposure achieved with TAF 25 mg was chosen as the reference 
exposure. In this study, TAF 25 mg resulted in near-maximal antiviral activity and plasma TFV 
exposure > 90% lower relative to TDF.
The recommended dose of TAF is based on ensuring that patients have a TAF systemic exposure 
that is within the range of the reference exposure achieved with TAF 25 mg, or with TAF 10 mg 
when administered with the boosting agent COBI as E/C/F/TAF, for which an extensive safety 
and efficacy database exists. Specifically, TAF 25 mg is recommended with third agents that do 
not have a clinically relevant effect on TAF exposure. Study GS-US-141-1418 showed that 
GS-9883 does not have a clinically relevant effect on TAF exposure. Therefore, the dose of TAF 
25 mg is appropriate for the GS-9883/F/TAF FDC.
GS-9883
The dose of GS-9883 for Phase 2 was selected based upon data from Study GS-US-141-1219 
(Table 1-5), in which HIV-1-infected subjects were administered 5, 25, 50, or 100 mg doses of 
GS-9883 monotherapy under fasting conditions for 10 days. 
Table 1-5.
GS-US-141-1219: Trough GS-9883 Plasma Concentrations at Steady 
State Following GS-9883 Administration Under Fasting Conditions 
and Corresponding Protein-Adjusted IQ95 Values
GS-9883 dose
n
Median (range) Ctau,SS (ng/mL)
Median (range) paIQ95a
5 mg
4
206.5 (146.0 – 342.0)
1.3 (0.9 – 2.1)
25 mg
4
797.5 (714.0 – 1900.0)
4.9 (4.4 – 11.7)
50 mg
4
2170.0 (852.0 – 3020.0)
13.4 (5.3 – 18.6)
100 mg
4
4190.0 (3730.0 – 5970.0)
25.9 (23 – 36.9)
a
The paIQ95 value is estimated based on steady-state Ctau values and the in vitro paIC95 value for wild-type HIV-1 
(162 ng/mL).
Source: Data on File

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Single-agent GS-9883 was well tolerated at all doses administered. The range of GS-9883 
plasma exposure at steady state (Ctau,SS) observed in the 50-mg cohort correlated with protein 
adjusted 95% inhibitory quotient (paIQ95) values ranging from 5.3 to 19, while the range of 
GS-9883 plasma exposure at steady state (Ctau,SS) observed in the 100-mg cohort correlated with 
paIQ95 values ranging from 23 to 37 (Table 1-5). 
Based on PK/PD analyses, exposure following a 75-mg dose of single-agent GS-9883 is 
expected to provide near-maximal virologic response, with a predicted paIQ95 of approximately 
20, providing considerable coverage above the target concentration of 162 ng/mL (paIC95).  
GS-9883 (75 mg) single agent coadministered with F/TAF (200/25 mg) is currently being 
evaluated in a Phase 2 study, GS-US-141-1475 (GS-9883+F/TAF vs DTG+F/TAF). The 
Week 24 data from this study support the safety and efficacy of GS-9883 exposures obtained 
with the 75 mg dose of the single agent.
GS-9883/F/TAF FDC Dose Selection
A fixed dose formulation of GS-9883/F/TAF was developed for use in Phase 3 studies. 
Preliminary results from the relative bioavailability (rBA) study (GS-US-141-1233) of 
GS-9883/F/TAF (75/200/25 mg) showed that GS-9883 plasma exposure was higher (with Cmax
and AUCinf increase of 31% and 27%, respectively) following administration of the FDC as 
compared with exposure following administration of GS-9883 (75 mg) + F/TAF (200/25 mg) 
under fasted conditions. The increase in GS-9883 exposures associated with the FDC 
formulation results in an estimated mean paIQ95 of 24.3, compared to an estimated mean paIQ95
of 19.2 for the GS-9883 (75 mg) single agent coadministered with F/TAF, in the fasted state. 
In order to bridge exposures of GS-9883 in the FDC to the exposure observed with GS-9883 
75 mg administered as a single agent, and to bridge to the safe and effective exposures observed 
in the Phase 2 study GS-US-141-1475, a lower strength GS-9883/F/TAF FDC was developed for 
use in the Phase 3 studies. Comparability of GS-9883 exposures was confirmed in an rBA study 
of GS-9883/F/TAF (50/200/25 mg) and GS-9883 (75 mg) + F/TAF prior to initiation of dosing 
in the Phase 3 studies.
1.10.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.

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2.
OBJECTIVES
The primary objective of this study is:

To evaluate the efficacy of a fixed dose combination (FDC) containing 
GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) versus dolutegravir (DTG)
+ a FDC containing emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, 
antiretroviral treatment-naïve adult subjects as determined by the achievement of 
HIV-1 RNA 50 copies/mL at Week 48
The secondary objective of this study is:

To evaluate the efficacy, safety and tolerability of the two treatment regimens through 
Weeks 48, 96, and 144
To evaluate the long term efficacy and safety of FDC GS-9883/F/TAF through OL Weeks 48 
and 96.

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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint is:

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 as defined 
by the US FDA-defined snapshot algorithm.
The secondary endpoints of this study include:

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 as 
defined by the US FDA-defined snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96, 
and 144 as defined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, 
and 144

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 48 OL and 96 
OL as defined by Missing = Excluded and Missing = Failure algorithm

The change from baseline in CD4+ cell count at Weeks 48 OL and 96 OL. 
3.2.
Study Design
This protocol describes a randomized, double-blind, multicenter, active-controlled study to 
evaluate the safety and efficacy of GS-9883/F/TAF FDC versus DTG + FDC of FTC/TAF in 
HIV-1 infected, antiretroviral treatment-naïve adult subjects.
3.3.
Study Treatments
Subjects who provide written informed consent and meet all eligibility criteria will be 
randomized in a 1:1 ratio to one of the following two treatment groups:
Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match dolutegravir 50 mg and Placebo to match FDC of 
emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF) administered orally, once daily, 
without regard to food (n=300)
Treatment Group 2: Dolutegravir 50 mg + FDC of emtricitabine 200 mg/tenofovir alafenamide 
25 mg (F/TAF) + Placebo to match FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food 
(n=300)
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 - 199 cells/μL, or ≥ 200 cells/μL) at screening, and region (US vs. Ex-US) at randomization.

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3.4.
Duration of Treatment
Subjects will be treated for at least 144 weeks during the blinded treatment phase. After 
Week 144, all subjects will continue to take their blinded study drug and attend visits every 
12 weeks until the End of Blinded Treatment Visit. Once the last subject completes the 
Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic 
(preferably within 30 days) for an End of Blinded Treatment Visit. At the End of Blinded 
Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension 
phase for 96 weeks (Week 96 OL). After Week 96 OL, subjects will discontinue the study drug, 
transition onto commercially available treatment and complete a 30-Day Follow-up Visit. In a 
country where GS-9883/F/TAF is not available, subjects will be given the option to continue OL 
GS-9883/F/TAF until the product becomes accessible to subjects through an access program, or 
until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.
All subjects participating in the open label extension phase, without regard to their blinded 
treatment regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for 
96 weeks. 
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension phase will be required to return to the 
clinic after the End of Blinded Treatment Visit for a 30-Day Follow-up visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.

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Figure 3-1.
Study Schema
a
Following the Day 1 visit, subjects will be required to return for study visits at Weeks 4, 8, 12, and then every 12 weeks 
through Week 144.
b
After Week 144, all subjects will continue to take their blinded study drug and attend visits every 12 weeks until the End of 
Blinded Treatment Visit. 
c
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to 
the clinic (preferably within 30 days) for an End of Blinded Treatment Visit. At the End of Blinded Treatment Visit, subjects 
will be given GS-9883/F/TAF FDC in an open label (OL) extension phase for 96 weeks (Week 96 OL). After Week 96 OL, 
subjects will discontinue the study drug, transition onto commercially available treatment and complete a 30-Day Follow-up 
Visit. In a country where GS-9883/F/TAF is not available, subjects will be given the option to continue OL GS-
9883/F/TAF until the product becomes accessible to subjects through an access program, or until Gilead Sciences elects to 
discontinue the study in that country, whichever occurs first.
3.5.
Biomarker Testing
 
 
 
 
 
 
 
 
 
 
 
 
CCI

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3.5.2.
Additional Sample Storage
 
 
CCI

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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 600 subjects who meet the eligibility criteria will be enrolled.
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) Age 18 years
3) Antiretroviral treatment naïve (≤ 10 days of prior therapy with any antiretroviral agent 
following a diagnosis of HIV-1 infection) except the use for PrEP (pre-exposure prophylaxis) 
or PEP (post-exposure prophylaxis), up to one month prior to screening
4) Plasma HIV-1 RNA levels 500 copies/mL at screening
5) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6) Adequate renal function:
Estimated glomerular filtration rate ≥30 mL/min (≥0.50 mL/sec) according to the 
Cockcroft-Gault formula {Cockcroft 1976}:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786  
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)
0.85  CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
7) Hepatic transaminases (AST and ALT) 5 upper limit of normal (ULN)
8) Total bilirubin 1.5 mg/dL (26 umol/L), or normal direct bilirubin

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9) Adequate hematologic function (absolute neutrophil count ≥750/mm3 (≥0.75 GI/L); 
platelets ≥50,000/mm3 (≥ 50 GI/L); hemoglobin ≥ 8.5 g/dL (≥85 g/L))
10) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if 
serum lipase is ≤5 × ULN)
11) Females of childbearing potential must agree to utilize protocol recommended highly 
effective contraceptive methods or be non-heterosexually active or practice sexual abstinence 
(as defined in Appendix 7) from screening, throughout the duration of the study period, and 
for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods 
must have used the same method for at least 3 months prior to study drug dosing.
12) Male subjects who engage in heterosexual intercourse must agree to use protocol specified 
method(s) of contraception (as described in Appendix 7) throughout the study period and for 
90 days following the last dose of study drug.
13) Male subjects must agree to refrain from sperm donation from first study drug dose until at 
least 90 days following the last study drug dose
14) Life expectancy ≥ 1 year
15) Screening genotype report must show sensitivity to FTC and TFV. This report will be 
provided by Gilead Sciences. Alternatively, if genotype results from a local laboratory 
obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype 
will be acceptable to fulfill this inclusion criterion in the event that the genotype obtained at 
screening is not yet available and all other inclusion/exclusion criteria have been confirmed
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 30 days prior to 
screening (refer to Appendix 6)
2) Subjects experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal 
bleeding)
3) Have been treated with immunosuppressant therapies or chemotherapeutic agents within 
3 months of study screening, or expected to receive these agents or systemic steroids during 
the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based 
therapies)
4) Current alcohol or substance use judged by the Investigator to potentially interfere with 
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5) A history of or ongoing malignancy (including untreated carcinoma in-situ) other than 
cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous 
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must 
not have received any systemic therapy for KS within 30 days of Day 1 and are not 
anticipated to require systemic therapy during the study
6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or 
antifungal therapy within 30 days prior to Day 1
7) Participation in any other clinical trial, including observational studies, without prior 
approval from the sponsor is prohibited while participating in this trial
8) 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 the dosing requirements
9) Any known allergies to the excipients of GS-9883/F/TAF FDC or DTG + F/TAF FDC
tablets
10) Females who are pregnant (as confirmed by positive serum pregnancy test)
11) Females who are breastfeeding
12) Subjects receiving ongoing therapy with any of the following medications in the table below, 
including drugs not to be used with FTC, TAF, GS-9883 and DTG
Drug Class
Agents Disallowed*
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural Supplements
St. John’s Wort, Echinacea
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the
duration of the study.
13) Acute hepatitis in the 30 days prior to study entry
14) Screening HBV DNA with HBV viral load > 9 log IU/mL, if determined to be HBV infected
15) Active tuberculosis infection

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
Subjects will be assigned a screening number at the time of consent. Randomization and Day 1 
visits cannot occur until the Investigator has received the results of the screening genotype 
report and subject eligibility has been confirmed.
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
Subjects will be randomized in a 1:1 ratio to Treatment Group 1 or Treatment Group 2. 
Randomization will be stratified by HIV-1 RNA level (≤100,000 copies/mL, > 100,000 to 
≤400,000 copies/mL, or > 400,000 copies/mL) at screening, CD4+ cell count (< 50 cells/μL, 
50 – 199 cells/μL, or ≥ 200 cells/μL) at screening and region (US vs. Ex-US) at randomization.
The IWRS will assign study drug bottle numbers of blinded FDC of GS-9883/F/TAF + Placebo 
to match DTG + F/TAF FDC, or DTG + F/TAF FDC + Placebo to match FDC of 
GS-9883/F/TAF at each study visit for each subject. 
At the End of Blinded Treatment Visit the IWRS will assign open label GS-9833/F/TAF/FDC
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 or in the case of pregnancy that occurs while on study drug, the investigator may 
obtain treatment assignment directly from the IWRS system for that subject. Gilead strongly 
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 emergency medical care or in the event of pregnancy that occurs 
while on study drug. 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 Pharmacovigilance and Epidemiology (PVE) may independently unblind cases for 
expedited reporting of suspected unexpected serious adverse reactions (SUSARs).

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5.2.
Description and Handling 
5.2.1.
Formulation
5.2.1.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg/25 mg and Placebo to Match Tablets
GS-9883 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets are capsule-shaped, 
film-coated purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the 
other side of the tablet. Each tablet core contains 50 mg of GS-9883, 200 mg of emtricitabine, 
and 25 mg of tenofovir alafenamide. In addition to the active ingredients, the GS-9883/F/TAF
tablets contain croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, polyvinyl 
alcohol, talc, and titanium dioxide.
The placebo to match (PTM) GS-9883/F/TAF tablets are capsule-shaped, film-coated 
purplish-brown, debossed with "GSI" on one side of the tablet and "9883" on the other side and 
are identical in physical appearance to GS-9883/F/TAF tablets. The placebo tablets contain 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. 
The tablet cores are film-coated with iron oxide red, iron oxide black, polyethylene glycol, 
polyvinyl alcohol, talc, and titanium dioxide.
5.2.1.2.
Dolutegravir (DTG) 50 mg and Placebo to Match Tablets
Dolutegravir 50 mg tablets are round, film-coated yellow, debossed with “50” on one side and 
debossed with “SV 572” on the other side. Each tablet core contains 50 mg of dolutegravir. In 
addition to the active ingredient, DTG tablets contain D-mannitol, microcrystalline cellulose, 
povidone K29/32, sodium starch glycolate and sodium stearyl fumarate. The tablet cores are 
film-coated with iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc and titanium 
dioxide.
The placebo to match (PTM) DTG tablets are round, film coated yellow, debossed with “50” on 
one side and debossed with “SV 572” on the other side.  PTM DTG tablets are identical in 
physical appearance to DTG 50 mg tablets. The placebo tablet cores contain microcrystalline 
cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. The tablet cores 
are film-coated with iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc and titanium 
dioxide.
5.2.1.3.
Emtricitabine/Tenofovir alafenamide (F/TAF) 200 mg/25 mg and Placebo to 
Match Tablets
Emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets are rectangular-shaped, film-coated 
blue, debossed with "GSI" on one side of the tablet and "225" on the other side of the tablet. 
Each tablet core contains 200 mg of emtricitabine and 25 mg of tenofovir alafenamide. In 
addition to the active ingredients, the F/TAF tablets contain croscarmellose sodium, magnesium 
stearate and microcrystalline cellulose. The tablet cores are film-coated with FD&C blue 
#2/indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc and titanium 
dioxide.

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The placebo to match (PTM) F/TAF tablets are rectangular-shaped, film-coated blue, debossed 
with "GSI" on one side of the tablet and "225" on the other side of the tablet.  PTM F/TAF 
tablets are identical in physical appearance to F/TAF 200 mg/25 mg tablets. The placebo tablet 
cores contain microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and 
magnesium stearate. The tablet cores are film-coated with FD&C blue #2/indigo carmine 
aluminum lake, polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide.
5.2.2.
Packaging and Labeling
5.2.2.1.
GS-9883/Emtricitabine/Tenofovir alafenamide (GS-9883/F/TAF) 
50 mg/200 mg /25 mg and Placebo to Match Tablets
GS-9883/F/TAF tablets and PTM GS-9883/F/TAF tablets are packaged in white, high density 
polyethylene (HDPE) bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester 
packing material.  Each bottle is enclosed with a white, continuous thread, child-resistant 
polypropylene screw cap with an induction-sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations. 
5.2.2.2.
Dolutegravir (DTG) 50 mg and Placebo to Match Tablets
Dolutegravir 50 mg tablets and PTM Dolutegravir 50 mg tablets are packaged in white, high
density polyethylene (HDPE) bottles. Each bottle contains 30 tablets.  Each bottle is enclosed 
with a white, continuous thread, child-resistant polypropylene screw cap with an induction-
sealed and aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.
5.2.2.3.
Emtricitabine/Tenofovir Alafenamide (F/TAF) 200 mg/25 mg and Placebo to 
Match Tablets
Emtricitabine/tenofovir alafenamide (F/TAF) 200 mg/25 mg and Placebo to Match tablets are 
packaged in white, high density polyethylene (HDPE) bottles. Each bottle contains 30 tablets, 
silica gel desiccant, and polyester packing material.  Each bottle is enclosed with a white, 
continuous thread, child-resistant polypropylene screw cap with an induction-sealed and 
aluminum-faced liner.
Study drug(s) to be distributed to centers in the US and other participating countries shall be 
labeled to meet applicable requirements of the US FDA, EU Guideline to Good Manufacturing 
Practice - Annex 13 (Investigational Medicinal Products), and/or other local regulations.

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5.2.3.
Storage and Handling
Study drugs should be stored at controlled room temperature of 25°C (77°F); excursions are 
permitted between 15°C and 30°C (59°F and 86°F).  Storage conditions are specified on the 
label.  Until dispensed to the subjects, all bottles of study drugs should be stored in a securely 
locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drug(s) should not be stored in a container 
other than the container in which they were supplied.
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 through inhalation when handling.
5.3.
Dosage and Administration of GS-9883/Emtricitabine/Tenofovir alafenamide 
and Dolutegravir + Emtricitabine/Tenofovir alafenamide
Study drugs GS-9883/F/TAF FDC, DTG + F/TAF FDC and placebo-to-match tablets will be 
provided by Gilead Sciences.
Treatment Group 1: FDC of GS-9883 50 mg/emtricitabine 200 mg/ tenofovir alafenamide 
25 mg (GS-9883/F/TAF) + Placebo to match dolutegravir 50 mg and Placebo to match FDC of 
emtricitabine 200 mg/tenofovir alafenamide 25 mg (F/TAF) administered orally, once daily, 
without regard to food 
Treatment Group 2: Dolutegravir 50 mg + FDC of emtricitabine 200 mg/tenofovir alafenamide 
25 mg (F/TAF) + Placebo to match FDC of GS-9883 50 mg/emtricitabine 200 mg/tenofovir 
alafenamide 25 mg (GS-9883/F/TAF) administered orally, once daily, without regard to food.
After the End of Blinded Treatment Visit, all subjects who choose to participate in the open label 
extension will receive GS-9883/F/TAF FDC once daily
Subjects will be instructed to bring all study medication in the original container at each clinic 
visit for drug accountability.  The Investigator will be responsible for maintaining accurate 
records for all study drug bottles dispensed and tablets returned. The inventory and dispensing 
logs must be available for inspection by the study monitor. Study medication supplies, including 
partially used or empty bottles, must be accounted for by the study monitor prior to destruction 
or return. 

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5.4.
Prior and Concomitant Medications
5.4.1.
Prior and Concomitant Medications (Blinded Phase through End of Blinded 
Treatment Visit)
The use of medications for the treatment of HIV, other than study drug, is prohibited.
Medications listed in the following table and use of herbal/natural supplements are excluded or 
should be used with caution while subjects are participating in the study.  Subjects will refrain 
from consumption of grapefruit juice and Seville orange juice throughout participation in the 
study. 
Table 5-1.
Prior and Concomitant Medications (Blinded Phase through End of 
Blinded Treatment Visit)
Drug Class
Agents Disallowed*
Use Discouraged and To Be Used With Caution
Acid Reducing Agents
Antacids
Buffered medications
Concentration of study drug may decrease with 
antacids. Subjects may not take antacids (eg, Tums or 
Rolaids); the ulcer medication sucralfate (Carafate); 
or vitamin or mineral supplements that contain 
calcium, iron or zinc for a minimum of 6 hours 
before and 2 hours after any dose of study drug.
Antiarrhythmic Agent
Dofetilide
Anticonvulsants
Phenobarbital, Phenytoin, 
Carbamazepine, Oxcarbazepine
Antimycobacterials
Rifampin, Rifapentine
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
GI Motility Agents
Cisapride
Herbal/Natural 
Supplements
St. John’s Wort, Echinaccea
Oral Hypoglycemic 
Agent
Metformin: close monitoring is recommended. A 
dose adjustment of Metformin may be necessary.  
Limit total daily doses of Metformin to 1000 mg 
when initiating study medication or if initiating 
metformin while on study drug.
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study. 
Should subjects have a need to initiate treatment with any excluded concomitant medication, the 
Gilead Sciences Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded medication is initiated prior to discussion with the Sponsor, the 
Investigator must notify Gilead Sciences as soon as he/she is aware of the use of the excluded 
medication.

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5.4.2.
Prior and Concomitant Medications (Open-Label Rollover Extension Phase)
The use of medications for the treatment of HIV-1 infection, other than GS-9883/F/TAF, is 
prohibited.
Medications listed in the following table and use of herbal/natural supplements are excluded or 
should be used with caution while participants are participating in the study.  This list should be 
utilized in jurisdictions in which GS-9883/F/TAF has NOT been approved.
Table 5-2.
Prior and Concomitant Medications (Open-Label Rollover Extension 
Phase)
Drug Class
Agents Disallowed*
To Be Used With Caution
Medications or oral 
supplements containing 
polyvalent cations 
(e.g., Mg, Al, Ca, Fe): 
Calcium or iron 
supplements 
Cation-containing antacids 
or laxatives 
Buffered medications
Antacids containing Al/Mg or Calcium:
GS-9883/F/TAF can be taken under fasting 
conditions 2 hours before antacids containing 
Al/Mg or calcium.
Routine administration of GS-9883/F/TAF 
simultaneously with, or 2 hours after, antacids 
containing Al/Mg or calcium is not 
recommended.
Supplements containing Calcium or Iron:
GS-9883/F/TAF and supplements containing
calcium or iron can be taken together with food. 
Routine administration of GS-9883/F/TAF under 
fasting conditions simultaneously with, or 
2 hours after, supplements containing calcium or 
iron is not recommended.
Antiarrhythmic Agent
dofetilide
Anticonvulsants
phenobarbital, phenytoin, 
carbamazepine, oxcarbazepine
Antimycobacterials
rifampin, rifapentine, rifabutin
Antiretrovirals
Any antiretroviral drug that is 
not part of the study regimen
Hypoglycemic agent
Metformin:
Refer to the prescribing information of 
metformin for assessing the benefit and risk of 
concomitant use of BIKTARVY and metformin.
Herbal/Natural 
Supplements
St. John’s Wort
*
Administration of any of the above medications must be discontinued at least 30 days prior to the Day 1 visit and for the 
duration of the study. 

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In jurisdictions in which GS-9883/F/TAF has been approved, consult the local prescribing 
information for GS-9883/F/TAF dose recommendations with concomitant medications.
Should participants have a need to initiate treatment with any excluded concomitant medication, 
the Gilead Medical Monitor must be consulted prior to initiation of the new medication. In 
instances where an excluded 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 excluded medication.
5.5.
Accountability for Investigational Medicinal Product (IMP)
The investigator is responsible for ensuring adequate accountability of all used and unused IMP. 
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.
Study drug 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
Study drug return and disposal will be performed as outlined in Section 9.1.7.

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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 6.3 for details about randomization and treatment assignment.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30-days before Day 1 to determine eligibility for participation in 
the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including history of HIV-1 disease-related events and prior 
medications within 30 days of the screening visit

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine

Height 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis

Blood sample collection for the following laboratory analyses:
Serum pregnancy test (females of childbearing potential only). If the test is positive, the 
subject will not be enrolled

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Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN) 
and TSH.
Estimated glomerular filtration rate according to the Cockcroft-Gault formula:
Male:
(140 – age in years) (wt in kg) CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)
CLcr (mL/sec)
72 (serum creatinine in umol/L) 0.6786  
Female:
(140 – age in years) (wt in kg) 0.85 CLcr (mL/min)
72 (serum creatinine in mg/dL)
(140 – age in years) (wt in kg)
0.85  CLcr (mL/sec)
72 (serum creatinine in umol/L) 0. 6786
Hematology profile: complete blood count (CBC) with differential and platelet count
CD4+ cell count
Plasma HIV-1 RNA 
Hepatitis B Virus (HBV) blood panel: Hepatitis B virus surface antigen serology
(HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core
antibody (HBcAb)
■
The following will be conducted by the central laboratory if the following criteria are 
met:
○
If positive HBsAg, reflex testing for plasma HBV DNA, HBeAg (if negative, 
reflex HBeAb) and quantitative HBsAg. 
○
If positive HBcAb with negative HBsAg and negative HBsAb, reflex testing for 
plasma HBV DNA (if positive, reflex HBeAg). If HBeAg is performed and found 
to be negative, reflex HBeAb.
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed.  
HIV-1 genotype testing (protease and reverse transcriptase). The HIV-1 PR/RT genotype 
testing may not be performed for subjects that fail to meet other screening criteria.

Review of adverse events and concomitant medications

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Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30-days after screening for the Day 1 Visit.
From the time of obtaining informed consent through the first administration of investigational 
medicinal product, record all serious adverse events (SAEs), as well as any adverse events 
related to protocol-mandated procedures on the adverse events case report form (eCRF).  All 
other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history are to be captured on the medical history eCRF.  See 
Section 7 Adverse Events and Toxicity Management for additional details.
6.2.2.
Day 1 Assessments
The following evaluations are to be completed at the Day 1 Visit. The Investigator must have 
received the results from the screening genotype report and confirmed eligibility before 
proceeding with the Day 1 visit. The subject must complete all study procedures before being 
administered the study drug:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject.  Subject is to read questionnaire by himself/herself and 
write/mark answers directly onto questionnaires.

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate
CCI

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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN) and TSH.
PT/INR (prothrombin time/international normalized ratio
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 glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA 
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Subjects who meet the definition of HBV infection at Screening Visit (positive serum 
HBsAg or Positive HBcAb with quantifiable HBV DNA), will have plasma HBV DNA 
tested.
 
 
 

Provide subject dosing diary to all subjects 

Dispense study drug  
CCI
CCI

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
Observed first dose administration of the assigned study drugs as described in Section 5.3

Subjects should be instructed to take study drugs without regard to food. The subject should 
be counseled regarding the importance of adherence and taking their study medications at 
approximately the same time each day as directed by the Investigator.
6.3.
Randomization
Once eligibility has been confirmed and prior to or during the Day 1 visit, the Investigator or 
designee will randomize the subject using the Interactive Web Response System (IWRS). Once a 
subject number has been assigned to a subject, it will not be reassigned to any other subject. The 
subject number assignment and randomization may be performed up to 3 days prior to the 
in-clinic Day 1 visit provided that all screening procedures have been completed and subject 
eligibility has been confirmed.
6.4.
Treatment Assessments (Week 4 -144)
The following evaluations are to be completed at the end of Weeks 4, 8, 12, 24, 36, 48, 60, 72, 
84, 96, 108, 120, 132, and 144 unless otherwise specified.  
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the 
Day 1 visit through Week 12 and completed within ± 6 days of the protocol-specified visit date 
through Week 144, unless otherwise specified.  The visit window at Weeks 48, 96 and 144 will 
be ± 6 weeks of the protocol-specified visit date, and these clinical visit windows coincide with 
the Weeks 48, 96 and 144 statistical analysis window for HIV-1 RNA.
Regularly scheduled evaluations will be made on all subjects whether or not they continue to 
receive study drug.

Review of AEs and changes in concomitant medications

Complete physical examination (Weeks 24, 48, 96, 144) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed 

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Weeks 24, 48, 96, 144)

Short Form 36 Health Survey (SF-36), HIV Symptoms Distress Module, Work Productivity 
and Activity Impairment Questionnaire (WPAI) and Pittsburgh Sleep Quality Index (PSQI) 
to be completed by the subject at Weeks 4, 12 and 48.  Subject is to read questionnaire by 
himself/herself and write/mark answers directly onto questionnaires.

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
Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 12, 24, 48, 72, 96, 120, and 144  analyses of glucose will be done as part of the 
fasting metabolic assessments and not as part of the chemistry profile. At Weeks 24, 48, 
72, 96, 120 and 144, TSH will also be analyzed.
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. (Weeks 12, 24, 48, 72, 96, 120, and 144)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula 
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
For subjects who meet the definition of HBV infection at any visit
■
The following will be conducted by the central laboratory: HBsAb, HBsAg 
(qualitative and quantitative) and HBeAg (if negative, reflex HBeAb) (Weeks 12, 24, 
48, 72, 96 and every 24 weeks post Week 96)
■
Plasma HBV DNA 
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For subjects who do NOT meet the definition of HBV infection at any visit
■
The following will be conducted by the central laboratory: Hepatitis B surface 
antibody (HBsAb), Hepatitis B virus core antibody (HBcAb), and Hepatitis B virus 
surface antigen serology (HBsAg). Subjects who are HBsAg and/or HBcAb positive 
will have a reflex test for HBV DNA (viral load) (Weeks 48, 96 and 144)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed (Weeks 48, 96 and 144)

Pharmacokinetic Blood Collection for subjects who are on study drug. Details of 
pharmacokinetic blood sampling procedures and sample management will be documented in 
the Pharmacokinetic Sample Collection, Processing, Storage, and Shipment Manual.
Single Anytime, Trough and Post Dose PK Samples for all subjects on study drug: 
■
Subjects will have a single anytime pre or post-dose PK blood at Weeks 8, 24 
and 36.
■
Observed dosing at the clinic: Subjects will have a trough PK blood sample collected 
between 20-28 hours following their last dose at Weeks 4 and 12. Subjects must be 
instructed to not take their study drugs on the morning of their visit for the trough 
sample collection. Subjects will then take an observed dose of study drug at the clinic. 
A single post dose PK blood sample will be collected between 1 and 4 hours post 
dose. If the subject has taken their dose of study drugs prior to the visit, the visit may 
proceed, but the subject must return within 72 hours for the trough PK blood sample 
collection. In the event a subject routinely takes their study drug in the evening, a 
single post dose sample may be drawn at Weeks 4 and 12 as the subject will not be 
instructed to change their dosing time to accommodate this trough PK draw.
■
Dosing diaries will be collected from subjects for the single anytime PK and trough 
PK collection. If a dosing diary is not returned the site may ask the subject for the 
time of the last dose and if it was taken with or without food.

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
Provide subject dosing diary to all subjects (Weeks 4, 8, 12, 24)

Document study drug dispensation and accountability for all study drugs dispensed.

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.12.1.
6.5.
Treatment Assessments (Post Week 144 until the Open Label Rollover 
Extension)
6.5.1.
Post Week 144 Assessments
After Week 144, all subjects will continue to take their blinded study drugs and attend visits 
every 12 weeks until the last subject completes the Week 144 Visit of the blinded phase. Study 
visits are to be completed within 6 days of the protocol-specified visit date unless otherwise 
specified.

Review of AEs and changes in concomitant medications

Complete physical examination (every 48 weeks) (urogenital/anorectal exams will be 
performed at the discretion of the Investigator) or symptom-directed physical examination as 
needed
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
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (every 48 weeks)

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Every 24 weeks, analyses of glucose will be done as part of the fasting metabolic 
assessments and not as part of the chemistry profile. In addition, TSH will also be 
analyzed every 24 weeks.
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. (Every 24 weeks)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
For subjects who meet the definition of HBV infection at any visit
■
The following will be conducted by the central laboratory: HBsAb, HBsAg 
(qualitative and quantitative) and HBeAg (if negative, reflex HBeAb). (every 
24 weeks)
■
Plasma HBV DNA 
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For subjects who do NOT meet the definition of HBV infection at any visit
■
The following will be conducted by the central laboratory: Hepatitis B surface 
antibody (HBsAb), Hepatitis B virus core antibody (HBcAb), and Hepatitis B virus 
surface antigen serology (HBsAg). Subjects who are HBsAg and/or HBcAb positive 
will have a reflex test for HBV DNA (viral load) (every 48 weeks)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed (every 48 weeks)

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Sections 6.12.1 and 6.12.2.

Document study drug dispensation and accountability for all study drugs dispensed.
6.5.2.
End of Blinded Treatment Visit
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, 
all subjects will return to the clinic (preferably within 30 days) for an End of Blinded Treatment 
Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an 
open label (OL) extension phase for 96 weeks (Week 96 OL). After Week 96 OL, subjects will 
discontinue the study drug, transition onto commercially available treatment and complete a 
30-Day Follow-up Visit. In a country where GS-9883/F/TAF is not available, subjects will be 
given the option to continue OL GS-9883/F/TAF until the product becomes accessible to 
subjects through an access program, or until Gilead Sciences elects to discontinue the study in 
that country, whichever occurs first. Subjects who receive the open-label GS-9883/F/TAF FDC 
will return for study visits every 12 weeks.
Subjects who complete the study through the End of Blinded Treatment Visit and do not 
continue on the open label GS-9883/F/TAF FDC extension will be required to return to the clinic 
for a 30-Day Follow-up visit. Subjects who have discontinued drug study prior to the End of 
Blinded Treatment Visit will not be eligible for the open-label rollover extension; these subjects 
will be asked to continue attending the scheduled study visits through the End of Blinded 
Treatment Visit and discontinue the study after the End of Blinded Treatment Visit.
Treatment assignments will be provided to the investigators within 30 days of the last subject 
completing the End of Blinded Treatment Visit.
The following will be performed at the End of Blinded Treatment Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
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
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will not be 
able to participate.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, phosphorus, magnesium, potassium, sodium, uric acid, and amylase 
(reflex lipase testing is performed in subjects with total amylase 1.5 ULN), and TSH
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 glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection)

Document study drug dispensation, if applicable, and accountability for all study drugs 
dispensed

Subjects who wish to continue in the Open-Label Rollover extension study will receive open 
label GS-9883/F/TAF.
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6.5.3.
Treatment Assessments (Open-Label Rollover Extension)
For purposes of study visit identification during the open-label rollover extension, study visits 
will be identified by the number of weeks that have elapsed between the End of Blinded 
Treatment Visit and the corresponding open-label study visit, and labeled with “OL” 
eg. Week 12 OL, Week 24 OL, etc.
All subjects participating in the open label extension phase, without regard to their blinded 
treatment regimen, will return for study visits at Week 12 OL and every 12 weeks thereafter for 
96 weeks.
Study visits are to be completed of the protocol-specified visit date based on the End of Blinded 
Treatment Visit through Week 12 OL and completed ± 6 days of the protocol-specified visit date 
every 12 weeks thereafter, unless otherwise specified.
The following will be performed at the Open-Label Extension Visits:

Review of AEs and changes in concomitant medications

Complete physical examination (Week 48 OL, Week 96 OL) (urogenital/anorectal exams 
will be performed at the discretion of the Investigator) or symptom-directed physical 
examination as needed

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

12-lead ECG performed supine (Week 48 OL, Week 96 OL)

Urine collection for the following laboratory procedures:
Urinalysis 
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test. If the test is positive, the subject will be 
discontinued.
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
Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN). 
At Weeks 24, 48, 72, and 96 OL, analyses of glucose will be done as part of the fasting 
metabolic assessments and not as part of the chemistry profile. In addition, TSH will also 
be analyzed at Week 24, 48, 72 and 96 OL.
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. (Week 24, 48, 72 and 96 OL)
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
For subjects who meet the definition of HBV infection at any visit
■
The following will be conducted by the central laboratory: HBsAb, HBsAg 
(qualitative and quantitative) and HBeAg (if negative, reflex HBeAb) (every 
24 weeks)
■
Plasma HBV DNA (every 12 weeks)
For subjects who do NOT meet the definition of HBV infection at any visit
■
The following will be conducted by the central laboratory: Hepatitis B surface 
antibody (HBsAb), Hepatitis B virus core antibody (HBcAb), and Hepatitis B virus 
surface antigen serology (HBsAg). Subjects who are HBsAg and/or HBcAb positive 
will have a reflex test for HBV DNA (viral load) (Week 48 and Week 96 OL)
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a 
HCV RNA test performed (Week 48 and Week 96 OL)

Plasma storage sample for safety, virology, or PK testing

Document study drug dispensation and accountability for all study drugs dispensed.

Subjects who meet the criteria for virologic failure will be managed according to the 
Management of Virologic Rebound Section 6.12.1.

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6.6.
Post-treatment Assessments
6.6.1.
Early Study Drugs Discontinuation Assessments
If the subject discontinues study drug prior to the End of Blinded Treatment Visit, the subject 
will be asked to return to the clinic within 72 hours of stopping study drugs for the Early Study 
Drugs Discontinuation Visit. The subject will be asked to continue attending the scheduled study 
visits through the End of Blinded Treatment Visit.
If the subject discontinues study drug during the Open Label rollover extension, the subject will 
be asked to return to the clinic within 72 hours of stopping the study drug for the Early Study 
Drugs Discontinuation Visit.
At the Early Study Drugs Discontinuation Visit, any evaluations showing abnormal results 
indicating that there is a possible or probable causal relationship with the study drug, will
be repeated weekly (or as often as deemed prudent by the Investigator) until the 
abnormality is resolved, returns toBaseline, or is otherwise explained.
The following evaluations are to be completed at the Early Study Drugs Discontinuation Visit:

Review of AEs and changes in concomitant medications

Complete physical examination (urogenital/anorectal exams will be performed at the 
discretion of the Investigator)

12-lead ECG performed supine (blinded treatment phase only)

Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN), 
and TSH
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Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
Plasma storage sample for safety, virology, or PK testing
Plasma HBV DNA (for subjects who meet the definition of HBV infection anytime)
HIV-1 genotype/phenotype testing for subjects with virologic failure

Drug accountability
6.6.2.
30 Day Follow Up
Subjects who prematurely discontinue study drug during the blinded phase and refuse to 
continue in the study through the End of Blinded Treatment Visit will be asked to return to the 
clinic 30 days after the completion of the Early Study Drugs Discontinuation Visit for the 
30-Day Follow-Up Visit.
Those subjects who prematurely discontinue study drug during the blinded phase and 
continue in the study through at least one subsequent visit after the Early Study Drug 
Discontinuation Visit will not be required to complete the 30-Day Follow-Up Visit.
Subjects who complete the study drugs through the End of Blinded Treatment Visit and who do 
not participate in the open-label rollover extension, will be required to return to the clinic 
30 days after the completion of study drug for the 30 Day Follow Up visit.
Subjects who prematurely discontinue study drug during the Open Label rollover extension will 
be asked to return to the clinic 30 days after the completion of the Early Study Drugs 
Discontinuation Visit for the 30-day Follow-Up Visit. The subject will not continue attending the 
scheduled study visits.
Subjects who complete the Open Label rollover extension will be asked to return to the clinic 
30 days after the completion of the study drugs for the 30-day Follow-Up Visit.
For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be used. 
The following evaluations are to be completed at the 30-Day Follow-Up Visit:

Review of AEs and changes in concomitant medications

Symptom-directed physical examination

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
Vital signs measurement (blood pressure, pulse, respiration rate, and temperature), including 
weight

Urine collection for the following laboratory procedures:
Urinalysis
Urine pregnancy test (females of childbearing potential only); positive urine pregnancy 
tests will be confirmed with a serum test.

Blood sample collection for the following laboratory analyses:
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and 
indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid, and 
amylase (reflex lipase testing is performed in subjects with total amylase 1.5 ULN).
Estimated glomerular filtration rate according to the Cockcroft-Gault formula
Hematology profile: complete blood count (CBC) with differential and platelet count
Plasma HIV-1 RNA
CD4+ cell count
At the 30-Day Follow-Up Visit, any evaluations showing abnormal results believed to be a 
reasonable possibility of a causal relationship with the study drugs will be repeated weekly (or as 
often as deemed prudent by the Investigator) until the abnormality is resolved, returns to 
baseline, or is otherwise explained. 
6.7.
Criteria for Discontinuation of Study Treatment
Study medication will be discontinued in the following instances:

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the subject’s best 
interest

Subject request to discontinue for any reason

Pregnancy during the study; refer to Appendix 7

Development of active tuberculosis infection

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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 intercurrent illness, the subject 
may resume study dosing at the discretion of the investigator

Lack of efficacy

Subject noncompliance

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)
6.8.
Blood and Urine Storage
 
 
 
 
 
6.9.
Assessments for Premature Discontinuation from Study
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.
6.10.
End of Study
The end of study will be the last patient’s last observation (or visit). 
6.11.
Post Study Care
After a subject has completed/terminated their participation in the study, long-term care for the 
subject will remain the responsibility of their primary treating physician.
6.12.
Virologic Failure
Virologic failure is defined as virologic rebound or having HIV-1 RNA ≥50 copies/mL at study
drug discontinuation, Week 48, Week 96, Week 144, Week 48 OL or Week 96 OL.
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6.12.1.
Management of Virologic Rebound
Subjects who meet the criteria listed below will be considered to have virologic rebound:

At any visit, after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA 
≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled 
visit; OR

At any visit, a 1 log10 increase in HIV-1 RNA from the nadir which is subsequently 
confirmed at the following scheduled or unscheduled visit
Following the unconfirmed virologic rebound, subjects will be asked to return to the clinic for a 
scheduled or unscheduled blood draw (2 to 3 weeks after the date of the original test that resulted 
in HIV-1 RNA virologic rebound) for confirmation of virologic rebound. If virologic rebound is 
confirmed at the scheduled or unscheduled visit and the HIV-1 RNA is ≥200 copies/mL, the 
blood sample from the confirmation visit will be the primary sample used for HIV-1 genotypic 
and phenotypic testing.  Subjects with documented non-adherence within 72 hours of the visit 
may not be tested for resistance. After a subject’s first post-baseline resistance test, additional 
testing will be conducted on a case-by-case basis. Any subject may be discontinued at 
Investigator’s discretion or per local treatment guidelines.
If no resistance is detected from the genotype or phenotype, the subject may remain on study 
drugs and a repeat HIV-1 RNA should be repeated (2 to 3 weeks after date of test with HIV-1 
RNA ≥ 50 copies/mL). Investigators should carefully evaluate the benefits and risks of 
remaining on study drug for each individual subject and document this assessment in the on-site 
medical record. 
Subjects who are noncompliant on an ongoing basis will be considered for discontinuation per 
the Investigator’s discretion or local treatment guidelines. Investigators who opt to discontinue 
study drugs for an individual subject must discuss with the Medical Monitor prior to study drug 
discontinuation. 
For subjects who are off study drug but remain on study, it will be the Investigator’s discretion to 
manage virologic rebound.
Please refer to Figure 6-1 for the management of subjects who meet the criteria for virologic 
rebound.

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Figure 6-1.
Virologic Rebound Schema
a
If virologic rebound is not confirmed, the subject will remain on their current regimen.
b
If virologic rebound is confirmed and the HIV-1 RNA is ≥ 200 copies/mL, the HIV-1 genotype and phenotype (reverse 
transcriptase, protease and integrase) will be analyzed.
c
Based on the results of the genotypic and phenotypic assays, the subject will remain on study drugs or study drugs will be 
discontinued. If genotyping or phenotyping assay fails, a new ARV regimen may be configured at the discretion of the 
Investigator.
d
If no resistance is detected, HIV-1 RNA will be repeated (2-3 weeks later).  Investigator reviews study drug 
continuation/discontinuation options and discusses with the Medical Monitor prior to study drug discontinuation
e
A new ARV regimen will be configured, at the Investigator’s discretion, and the subject will remain in the study.
6.12.2.
Subjects with HIV-1 RNA ≥ 50 copies/mL at Study Discontinuation, 
Week 48, 96, 144, Week 48 OL or Week 96 OL
Subjects with HIV-1 RNA ≥ 50 copies/mL at study discontinuation or last visit will be 
considered virologic failures. Subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48, Week 96, 
Week 144, Week 48 OL or Week 96 OL will be asked to return for an unscheduled visit within 
the visit window for a retest. 
Subjects with HIV-1 RNA ≥ 200 copies/mL at study drug discontinuation, last visit, 
Week 48, Week 96, Week 144, Week 48 OL or Week 96 OL will also have resistance testing 
conducted. 

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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 7.6.1)

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 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (SAE) is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is 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 subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to IMP
therapy using clinical judgment and the following considerations:

No: Evidence exists that the adverse event has an etiology other than the IMP. For SAEs, an 
alternative causality must be provided (eg, pre-existing condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.

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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
AE severity should be recorded and graded according to the GSI Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 5). 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.
The distinction between the seriousness and the severity of an adverse event should be noted. 
Severe is a measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For 
example, a headache may be severe in intensity, but would not be classified as serious unless it 
met one of the criteria for serious events.
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 eCRF:

all SAEs and adverse events related to protocol-mandated procedures.
7.3.1.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
until 30-days after last administration of study IMP 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.

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7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (i.e, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead Pharmacovigilance and Epidemiology (PVE) as instructed. This also 
includes any SAEs resulting from protocol-associated procedures performed after informed 
consent is signed.
Any SAEs and deaths that occur after the post treatment follow-up visit but within 30-days or 
4 weeks of the last dose of study IMP, regardless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after the protocol defined follow up period; 
however, if the investigator learns of any SAEs that occur after study participation has concluded 
and the event is deemed relevant to the use of IMP, he/she should promptly document and report 
the event to Gilead PVE.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to Gilead PVE within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study start), record the 
SAE on the paper serious adverse event report form and submit by fax or email within 
24 hours of the investigator’s knowledge of the event to:
Gilead PVE contact information:
Email:
Fax:

As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further 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 reports, autopsy reports, and other 
documents are also to be submitted by e-mail or fax only when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the traceability of a document to the subject identifiers.
PPD
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
Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form.
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 drug reactions (SADRs), or 
suspected unexpected serious adverse reactions (SUSARs). In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure, EU Summary of Product Characteristics
(SmPC), 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.
Toxicity Management 
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 4 as outlined below.

Clinical events and clinically significant laboratory abnormalities will be graded according to 
the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities 
(Appendix 5). 

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 discontinuation, unless such a delay is not consistent with good medical practice
Any questions regarding toxicity management should be directed to the Gilead Medical 
Monitor.
7.5.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the Investigator.

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7.5.2.
Grade 3 Laboratory Abnormality or Clinical Event

For Grade 3 clinically significant laboratory abnormality or clinical event, investigational 
medicinal product may be continued if the event is considered to be unrelated to
investigational medicinal product.

For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by 
repeat testing, that is considered to be related to investigational medicinal product, 
investigational medicinal product will be withheld until the toxicity returns to Grade 2. When
restarting investigational medicinal product following resolution of the adverse event, the 
investigational medicinal product should be restarted at full dose upon discussion with the 
Gilead Sciences Medical Monitor.

If a laboratory abnormality recurs to Grade 3 following rechallenge with investigational 
medicinal product and is considered related to investigational medicinal product, then 
investigational medicinal product will be permanently discontinued and the subject managed 
according to local practice. Recurrence of laboratory abnormalities considered unrelated to 
investigational medicinal product may not require permanent discontinuation but requires 
discussion with the Gilead Sciences Medical Monitor.
7.5.3.
Grade 4 Laboratory Abnormality or Clinical Event

For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality 
confirmed by repeat testing that is considered related to investigational medicinal product, 
investigational medicinal product will 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 Grade 4 laboratory abnormality (eg, Grade 4 CK after strenuous exercise, or 
triglyceride elevation that is nonfasting or that can be medically managed) or a clinical event 
considered unrelated to investigational medicinal product requires discussion with the Gilead 
Sciences Medical Monitor.
7.5.4.
On-Treatment ALT Flare and Post-Treatment Exacerbation of Hepatitis B
Management
In On-Treatment ALT Flare is defined as:

Confirmed (within 3 days of receipt of initial laboratory results) serum ALT > 2 ×Day 1 
value and >10 × ULN, with or without associated symptoms.

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7.5.4.1.
Management of ALT Flare in Subjects Receiving Study Medication
If laboratory results indicate elevation of ALT 2 × Day 1 value and 10 × ULN, the following 
is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally within 3 days after
initial laboratory results were drawn). During the visit, a clinical assessment of the subject 
will be performed. The assessment should include a physical examination and evaluation of 
the subject’s mental status.

If the ALT elevation is confirmed, request the central clinical laboratory to conduct reflex
testing for plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM, and 
HCV serology
Check the following laboratory parameters: serum ALT and AST, total bilirubin, INR, and serum 
albumin. Based on the results of the confirmatory tests, the following treatment modifications are 
recommended:
Elevated Liver Enzymes, Normal or Stable relative to Day 1 Liver Function Tests 
If ALT levels are elevated (i.e., 2 × Day 1 and 10 × ULN) with normal or stable total 
bilirubin and INR relative to Day 1, the subject may remain on study medication and should be 
monitored weekly as long as ALT levels return to normal or Day 1 level.  During monitoring, if 
the ALT values remain persistently elevated, the Investigator should discuss with the Gilead 
Medical Monitor whether the study drug should be discontinued.  
Elevated Liver Enzymes, Elevated Liver Function Tests
If ALT values are elevated (i.e., 2 × Day 1 and 10 × ULN), and total bilirubin is confirmed to 
be 2 x Day 1 value, and INR is 0.5 above Day 1, provided both are > ULN,  the investigator 
should consider discontinuing study medication (upon discussion with the Gilead Medical 
Monitor, unless the safety of the patient is of immediate concern).  The subject should be 
monitored weekly as long as ALT, total bilirubin, and INR values remain elevated or above 
Day 1 values.
During monitoring, if the ALT values and the liver function tests remain persistently elevated, 
the Investigator should discuss with the Gilead Medical Monitor whether the study drug should 
be discontinued.

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7.5.4.2.
Management of Exacerbation of Hepatitis B in Subjects who have Discontinued 
Study Medication
If laboratory results indicate (1) an ALT elevation 2 × Day 1 and 10 × ULN alone OR 
associated with (2) abnormal laboratory parameters suggestive of worsening hepatic function 
(total bilirubin 2 × Day 1, INR 0.5 above Day 1, provided both are > ULN) and the subject is on 
no post-study therapy for HBV, the following is recommended:

Schedule the subject to return to the clinic as soon as possible (ideally no later than 3 days 
after the initial laboratory values were drawn). During the visit, perform a clinical assessment 
of the subject.

Check the following laboratory parameters: serum ALT and AST, bilirubin, INR, and
albumin.

If the ALT elevation is confirmed, request the clinical laboratory to conduct reflex testing 
for plasma HBV DNA, HBV serology (HBsAg and HBsAb), HDV, HAV IgM and HCV. If 
serum HBV DNA is increasing, the investigator should consider immediate initiation of 
approved therapy.

The subject should be followed until laboratory parameters (ALT, total bilirubin, INR) return 
to normal or Day 1 up to a maximum of 6 months after the initial occurrence of the event.
7.5.5.
Management of Potential Hepatobiliary Toxicity
Monkeys given a high dose (1000 mg/kg/day) for 39 weeks had evidence of biliary hyperplasia 
and hepatocyte hypertrophy on histopathologic examination. The risk to humans given the 
clinical dose of GS-9883 (50 mg/day) is unknown. Investigators should be aware of this potential 
toxicity. Any study subject exhibiting signs/symptoms or laboratory abnormalities suggestive of 
possible hepatobiliary toxicity should undergo thorough examination and clinical workup as 
deemed appropriate by the Investigator, and the Investigator must communicate promptly with 
the Gilead Medical Monitor. Consideration should be given to appropriate imaging studies 
(for example, ultrasound of the liver and biliary tree) and potential consultation with a 
gastroenterologist with specialty training in hepatobiliary diseases. Management of graded 
laboratory and clinical abnormalities will be managed as outlined in Section 7.5.
7.5.6.
On-Treatment Hepatitis C Management 
If a subject tests positive for HCV RNA at screening or develops signs or symptoms of active 
Hepatitis C virus Gilead recommends that local medical practice is followed at the discretion of
the Investigator. Investigational medicinal product may be continued without dose 
interruption. Should the Investigator decide to initiate Hepatitis C treatment the Investigator 
must contact the Gilead Medical Monitor to confirm that no drug-drug interactions are expected. 
Subjects should return to the clinic for scheduled or unscheduled follow up visit(s) according to 
local medical practice for laboratory evaluations. If Hepatitis C treatment is initiated, 
Investigators should use the Gilead provided retest laboratory kits to manage the active 
Hepatitis C.

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7.6.
Special Situations Reports
7.6.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, reports 
of adverse events associated with product complaints, reports of adverse reactions in infants 
following exposure from breastfeeding, occupational exposure with an adverse event, and 
pregnancy reports regardless of an associated AE.  
Medication error is any unintentional error in the prescribing, dispensing, or administration of a 
medicinal product while in the control of the health care provider, subject, or consumer.
Abuse is defined as persistent or sporadic intentional excessive use of a medicinal product by a 
subject.
Misuse is defined as any intentional and inappropriate use of a medicinal product that is not in 
accordance with the protocol instructions or the local prescribing information.
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.  
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
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. 
The subject’s treatment assignment will be unblinded by the Investigator as described in Protocol 
Section 5.1.1.
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.

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Any premature termination of pregnancy (e.g., a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. 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. Any complications during pregnancy and 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: 
 
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead PVE using the 
pregnancy and pregnancy outcome forms within 24 hours. Monitoring of the subject should 
continue until the conclusion of the pregnancy. If the end of the pregnancy occurs after the study 
has been completed, the outcome should be reported directly to Gilead PVE, 
fax number
 or email 
 
Refer to Appendix 7 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
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 7.6.2.1 and the eCRF completion guidelines for full instructions on the 
mechanism of special situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
PPD
PPD
PPD
PPD

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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 to evaluate the efficacy of a FDC of GS-9883/F/TAF 
versus DTG + F/TAF in HIV-1 infected, antiretroviral treatment naïve-adult subjects as 
determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48

The secondary objectives of this study are to evaluate the efficacy, safety and tolerability of 
the two treatment groups through Weeks 48, 96, and 144.

To evaluate the long term efficacy and safety of FDC GS-9883/F/TAF through OL Weeks 48 
and 96. 
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at 
Week 48 as defined by the US FDA-defined snapshot algorithm.
8.1.3.
Secondary Endpoint
The secondary endpoints include:

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 as 
defined by the US FDA-defined snapshot algorithm

The proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96and 144 
as defined by the US FDA-defined snapshot algorithm

The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, 
and 144

The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 48 OL 
and 96 OL as defined by Missing = Excluded and Missing = Failure algorithm

The change from baseline in CD4+ cell count at Weeks 48 OL and 96 OL.
8.2.
Analysis Conventions
8.2.1.
Analysis Sets
8.2.1.1.
All Randomized
The randomized analysis set includes all subjects who are randomized into the study. This is the 
primary analysis set for by-subject listings.

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8.2.1.2.
Efficacy
8.2.1.2.1.
Full Analysis Set (FAS)
The primary analysis set for efficacy analyses is defined as full analysis set (FAS), which will 
include all subjects who (1) are randomized into the study and (2) have received at least 1 dose 
of study drug. Subjects will be grouped according to the treatment to which they were 
randomized.
8.2.1.2.2.
Per-Protocol (PP) Analysis Set
The secondary analysis set for efficacy analyses is defined as per-protocol (PP) analysis set, 
which will include all subjects who (1) are randomized into the study, (2) have received at least 
1 dose of study drug, and (3) have not committed any major protocol violation, including the 
violation of key entry criteria. Subjects will be grouped according to the treatment they actually 
received.
Subjects meeting any of the following criteria will be excluded from the Week 48 PP analysis
set:
1) Subjects who do not have on-treatment HIV-1 RNA in the Week 48 analysis window, except 
when missing data is due to discontinuation of study drug for lack of efficacy. 
2) Subjects who do not meet the inclusion criterion that the screening genotype report must 
show sensitivity to FTC, TFV.
3) Subjects who meet the exclusion criterion for receiving ongoing therapy with any of the 
medications listed in the table in protocol Section 4.3 including drugs not to be used with 
GS-9883, FTC, TAF, and DTG.
4) Nonadherence to study drug: subjects with adherence rate for active study drug up to the 
Week 48 Visit below the 2.5th percentile
8.2.1.3.
Safety
The primary analysis set for safety analyses is defined as safety analysis set, which will include 
all subjects who (1) are randomized into the study and (2) have received at least 1 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, unless specified otherwise. Subjects will be grouped 
according to the treatment they actually received.

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8.2.1.4.
Pharmacokinetics
 
 
 
8.2.1.4.2.
Pharmacokinetic (PK) Analysis Set
The primary analysis set for general PK analyses is defined as the PK analysis set, which will 
include all subjects who (1) are randomized into the study, (2) have received at least 1 dose, and 
(3) have at least 1 nonmissing PK concentration data for any the analyte of interest reported by 
the PK lab. 
8.2.1.5.
All GS-9883/F/TAF Analysis Set
All GS-9883/F/TAF analysis set will include all subjects who (1) are randomized into the study 
and (2) have received at least 1 dose of the blinded GS-9883/F/TAF or OL GS-9883/F/TAF. 
Subjects will be grouped into two groups: (1) All GS-9883/F/TAF group, including all subjects 
who randomized into GS-9883/F/TAF and received at least 1 dose of GS-9883/F/TAF; 
(2) DTG + F/TAF to GS-9883/F/TAF group, including all subjects who randomized to 
DTG + FTAF in the double-blinded phase and received at least 1 dose of OL GS-9883/F/TAF in 
the extension phase. This is the primary analysis set for the all GS-9883/F/TAF efficacy and 
safety analyses.
8.3.
Data Handling Conventions
HIV-1 RNA results of “No HIV-1 RNA detected” and “<20 cp/mL HIV-1 RNA Detected” will 
be imputed as 19 copies/mL for analysis purpose.  Logarithm (base 10) transformation will be 
applied to HIV-1 RNA levels for efficacy analysis. 
Natural logarithmic transformation of plasma concentrations and PK parameters will be applied 
for PK analysis.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit plus 
or minus one significant digit, respectively (eg, if the result of a continuous laboratory test is 
< 20, a value of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as normal (ie, no toxicity grade) for the laboratory abnormality summary.
All available data for subjects that do not complete the study will be included in data listings.
CCI

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8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline characteristics will be summarized using standard descriptive 
methods including sample size, mean, SD, median, Q1, Q3, minimum, and maximum for 
continuous variables and frequency and percentages for categorical variables.
Demographic data will include sex, race, ethnicity, and age. 
Baseline characteristics will include body weight, height, body mass index, eGFR, HIV-1 
infection, and enrollment distribution by randomization stratum will be summarized.
For categorical demographic and baseline characteristics, the Cochran–Mantel–Haenszel (CMH)
test will be used to compare treatment groups. For continuous demographic and baseline 
characteristics, the Wilcoxon rank sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
8.5.1.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is the proportion of subjects who achieve HIV-1 RNA 
50 copies/mL at Week 48 as determined by the US FDA-defined snapshot algorithm. The 
primary analysis of the efficacy endpoint will be based on the FAS.
8.5.1.2.
US FDA-defined Snapshot Algorithm
The analysis window at Week 48 is defined as from Study Day 295 to Study Day 378. All HIV-1 
RNA data collected on-treatment (ie, including data collected up to 1 day after the last dose date 
of study drug) will be used in the snapshot algorithm. Virologic outcome will be defined as the 
following categories:

HIV-1 RNA < 50 copies/mL: this includes subjects who have the last available HIV-1 RNA 
< 50 copies/mL in the Week 48 analysis window while on randomized treatment

HIV-1 RNA 50 copies/mL: this includes subjects
a) Who have the last available HIV-1 RNA 50 copies/mL in the Week 48 analysis 
window while on randomized treatment, or
b) Who do not have on-treatment HIV-1 RNA data in the Week 48 analysis window and 
i)
Who discontinue study drug prior to or in the Week 48 analysis window due to lack 
of efficacy, or
ii) Who discontinue study drug prior to or in the Week 48 analysis window due to 
reasons other than adverse event (AE), death, or lack of efficacy and have the last 
available HIV-1 RNA up to 1 day after the premature discontinuation of the study 
drug 50 copies/mL

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
No Virologic Data in the Week 48 analysis window: this includes subjects who do not 
have on-treatment HIV-1 RNA data in the Week 48 analysis window because of the 
following: 
a) Discontinuation of study drug prior to or in the Week 48 analysis window due to AE or 
death (regardless of whether the last available HIV-1 RNA up to 1 day after the 
premature discontinuation of the study drug < 50 copies/mL or not) or,
b) Discontinuation of study drug prior to or in the Week 48 analysis window due to reasons 
other than AE, death, or lack of efficacy (eg, withdrew consent and loss to follow-up) and 
the last available HIV-1 RNA up to 1 day after the premature discontinuation of the study 
drug < 50 copies/mL or,
c) Missing data during the window but on study drug.
8.5.1.3.
Analysis of Primary Efficacy Endpoint
The null hypothesis is that the proportion of subjects achieving HIV-1 RNA < 50 copies/mL 
(as defined by the US FDA-defined snapshot algorithm) at Week 48 in GS-9883/F/TAF is at 
least 12% lower than the response rate in DTG + F/TAF; the alternative hypothesis is that the 
response rate in GS-9883/F/TAF is less than 12% lower than that in DTG + F/TAF.
Non-inferiority will be assessed using the conventional confidence interval approach.  The point 
estimate of treatment difference (GS-9883/F/TAF group – DTG + F/TAF group) and the 
associated 2-sided 95% confidence interval will be constructed using a normal approximation 
method based on stratum-stratified Mantel-Haenszel proportions, where stratification factors 
include baseline HIV-1 RNA level (100,000 copies/mL, vs. 100,000 copies/mL) and region 
(US vs. Ex-US). Note that to avoid small or missing cells in analysis strata, CD4+ cell count is 
not stratified in the analysis because HIV-1 RNA and CD4+ cell count are highly correlated.
If non-inferiority of GS-9883/F/TAF to DTG + F/TAF is established, the lower bound of the 
95% CI will be compared to 0; if the lower bound of the 95% CI is greater than 0, then 
superiority of GS-9883/F/TAF over DTG + F/TAF will be established.
8.5.2.
Secondary Analyses
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 and 
the proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96 and 144, as 
defined by the US FDA-defined snapshot algorithm, will be analyzed using the same method as 
for the primary efficacy endpoint.

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The changes from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96, 
and 144 will be summarized by treatment using descriptive statistics. The differences in changes 
from baseline in log10 HIV-1 RNA and CD4+ cell count between 2 treatments groups and the 
associated 95% confidence intervals will be constructed using ANOVA models, including 
treatment (GS-9883/F/TAF vs. DTG + F/TAF), baseline HIV-1 RNA level 
(100,000 copies/mL vs. 100,000 copies/mL), and region (US vs. Ex-US) as fixed effects in 
the model.
In addition, missing CD4+ cell count will be imputed using Last Observation Carried Forward 
(LOCF) method and analyzed similarly.
8.5.3.
Efficacy Analyses for All GS-9883/F/TAF Analysis
The following analyses will be conducted for all GS-9883/F/TAF analysis using all 
GS-9883/F/TAF analysis set: (1) the proportion of subjects with HIV-1 RNA < 50 copies/mL by 
Missing = Excluded and Missing = Failure approaches by visit, (2) the change from baseline in 
CD4+ Cell Count by visits, and (3) the change from baseline in CD4 % by visits. No statistical 
comparison will be conducted for all GS-9883/F/TAF analysis. 
8.6.
Safety Analysis
All safety analyses will be performed using the safety analysis set for the double-blinded phase 
analysis and using all GS-9883/F/TAF analysis set for the all GS-9883/F/TAF analysis, unless 
specified otherwise.
All safety data collected on or after the date that the study drug was first administered up to the 
date of the last dose of study drug plus 30 days, unless specified otherwise, will be summarized 
for subjects in the safety analysis set 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 for all enrolled subjects.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug
administration page in eCRF. Exposure data will be summarized by treatment.
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.

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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.
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 (using conventional units) 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 attached in Appendix 5.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 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. If baseline data are missing, then 
any graded abnormality (i.e., at least a Grade 1) will be considered treatment emergent. The 
maximum post baseline toxicity grade will be summarized by laboratory parameter.
Laboratory abnormalities that occur before the first dose of study drug or after the last dose of 
study drug plus 30 days will be included in a data listing.
8.6.4.
Other Safety Evaluations
Vital signs and safety ECG data will be summarized as appropriate.

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8.7.
Pharmacokinetic Analysis
 
 
 
 
For the general PK analyses, the pharmacokinetics of GS-9883 may be evaluated using 
descriptive statistics or population approaches.
TAF and FTC concentrations may be analyzed and PK parameters summarized as applicable.  
8.8.
Patient Reported Outcomes (PRO)
The PRO measures based on questionnaires (e.g. SF-36 and HIV Symptoms Distress Module) 
may be summarized using descriptive statistics.
8.9.
Sample Size
A total of approximately 600 HIV-1 infected subjects, randomized in a 1:1 ratio to 2 treatment 
groups (300 subjects per treatment group), achieves at least 95% power to detect a 
non-inferiority margin of 12% in Week 48 response rate (HIV-1 RNA < 50 copies/mL as defined 
by the US FDA-defined snapshot algorithm) difference between the 2 treatment groups. For the 
sample size and power computations, it is assumed that both treatment groups have a response 
rate of 91% (based on Gilead Studies GS-US-292-0104 and GS-US-292-0111), that the
non-inferiority margin is 12%, and that the significance level of the test is at a one-sided 
0.025 level. Sample size and power calculations were made using the statistical software package 
nQuery Advisor (Version 6.0).
8.10.
Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) will review the progress, efficacy, 
and safety data of this study while the study is ongoing. The committee will convene after 
approximately the first 50% of subjects enrolled complete Week 12 visit or prematurely 
discontinue from the study drug, as well as after all subjects have completed their Week 24 visit 
or prematurely discontinued from the study drug. However, Gilead will defer to the IDMC for 
any decision to convene earlier or more frequently. The IDMC will examine the safety results of 
the trial and also focus on logistical issues such as accrual, retention, quality of clinical and 
laboratory data, and implications of results of external studies. Blinding will be preserved during 
the conduct of the study and access to unblinded data will be limited to designated parties.
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No formal stopping rules will be used by the IDMC for safety outcomes. Rather, a clinical 
assessment will be made to determine if the nature, frequency, and severity of adverse events 
associated with a study regimen warrant the early termination of the study in the best interest of 
the participants.
For each IDMC analysis performed prior to the analysis of the primary efficacy endpoint, an 
alpha penalty of 0.00001 will be applied for the primary analysis of the primary endpoint.
8.11.
Analysis Schedule
The Week 48 OL analyses will be conducted after all subjects either complete their Week 48 OL 
visits or prematurely discontinue from the study drug. Final analysis and/or Week 96 OL 
analyses will be performed after all subjects complete the study or prematurely discontinue 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.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The 

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

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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 IRBs or IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.

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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 or IEC 
in accordance with local requirements and receive documented IRB or 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. Gilead will 
ensure that the report meets the standards set out in the ICH Guideline for Structure and Content 
of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases. 
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:
the results of the study in their entirety have been publicly disclosed by or with the consent of 
Gilead in an abstract, manuscript, or presentation form or the study has been completed at all 
study sites for at least 2 years
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, e.g. attendance at Investigator's Meetings.  If required under the applicable statutory 
and regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.

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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
Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? 
Curr Med Res Opin 2014;30 (1):89-97.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
Costagliola D. Demographics of HIV and aging. Curr Opin HIV AIDS 2014;9 (4):294-301.
Department for Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral 
Agents in HIV-1-Infected Adults and Adolescents. Developed by the DHHS 
Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working 
Group of the Office of AIDS Research Advisory Council (OARAC). Downloaded 
from http://aidsinfo.nih.gov/guidelines on 5/11/2015. Last Updated 08 April, 
2015.
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.
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.
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.
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.
Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M. Self-reported adherence supports 
patient preference for the single tablet regimen (STR) in the current cART era. 
Patient preference and adherence 2012;6:427-33.

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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table (Blinded Phase)
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Appendix 5.
GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities
Appendix 6.
Definitions of Stage 3 Opportunistic Illnesses in HIV (CDC Guidelines)
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements

PPD
PPD
PPD
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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 
GS-9883/Emtricitabineffenofovir Alafenamide Versus 
Dolutegravir + Emtricitabine/Tenofovir AJafenamide in HIV-1 Infected, Antiretroviral 
Treatment-Naive Adults 
GS-US-380-1490 Amendment 3, 06 May 2019 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this a roval. 
.....__ ____ ___, (Printed) 
Date 
INVESTIGATOR STATEMENT 
l 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. f will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
f will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. l 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 
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Appendix 2.
Study Procedures Table (Blinded Phase)
Study Procedures
Screeninga
Day1b
4
8
12
24
36
End of Weeke, q
Post-
Week 
144e, r
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-upp
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12
Weeks
Informed Consent
X
Medical History
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Complete/Symptom-Directed 
Physical Exam
X
X
Xd
Xd
Xd
X
Xd
X
Xd
Xd
Xd
X
Xd
Xd
Xd
X
Xd
X
Xd,f
Xf
12-Lead ECG (performed 
supine)
X
X
X
X
X
X
Xw
X
X
Questionnaires
X
X
X
X
Height
X
Vital signs (blood pressure, 
pulse, respiration rate, and 
temperature), including 
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy Test
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
X
X
X
X
Xx
X
Estimated Glomerular 
Filtration Rate
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilej
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HCV Serologyu
X
X
X
X
X
HIV-1 Genotypek
X
HIV-1 Genotype/Phenotypee
Xe
CCI

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 100
06 May 2019
Study Procedures
Screeninga
Day1b
4
8
12
24
36
End of Weeke, q
Post-
Week 
144e, r
End of 
Blinded 
Treatment 
Visity
30-Day 
Follow-upp
Early 
Study 
Drugs 
DCc
48
60
72
84
96
108
120
132
144
Every 
12
Weeks
Single PK Samplel
X
X
X
Trough and Post Dose PK 
Samplem
X
X
Randomizationv
X
Provide subject dosing diary 
to subjects
X
X
X
X
X
HBV blood panelt
X
Xt
Xt
Xt
Xt
Xt
Xt
Xt
X
Plasma HBV DNAt
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug Dispensation
Xb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Study Drug Accountability
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a.
Evaluations to be completed within 30 days prior to Day 1. 
b.
Initiation of the first dose of study drug is to take place in-clinic following completion of study procedures at the Day 1 visit.
c.
Early Study Drugs Discontinuation visit to occur within 72 hours of last dose of study drug. Subjects will be asked to continue attending the scheduled study visits through the 
End of Blinded Treatment Visit even if the subject discontinues study drug.
d.
Symptom-directed physical examination as needed.
e.
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Section 6.12). 
f.
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to baseline, or is otherwise explained. 
g.
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN). At Day 1, Weeks 12, 24, 48, 72, 96, 120 and 144, every 24 weeks post Week 144, and End of Blinded Treatment Visit, analyses of glucose will be done as part 
of the fasting metabolic assessments every 24 weeks and not as part of the chemistry profile. Additionally: TSH will be analyzed at Screening, Day 1, Weeks 24, 48, 72, 96, 
120, and 144 followed by every 24 weeks post Week 144, End of Blinded Treatment Visit and Early Study Drugs Discontinuation visit. PT/INR to be performed at Day 1.
CCI
CCI

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 101
06 May 2019
i.
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.
j.
CBC with differential and platelet count.
k.
The Investigator must have received the results from the screening genotype report before proceeding with the Day 1 visit.  Screening genotype report must show sensitivity 
to TFV and FTC. If genotype results from a local laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype will be acceptable to 
fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been confirmed.
l.
A single PK blood sample will be collected at any time pre or post-dose 
m.
A trough PK blood sample will be collected between 20-28 hours following the last dose. Following an observed dose, a single post dose blood sample will be collected 
between 1 and 4 hours post dose.
 
p.
Only required for those subjects not enrolling in the open-label rollover extension, those subjects who prematurely discontinue study drugs and do not continue in the study 
through at least one subsequent visit after the Early Study Drugs Discontinuation Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a 6 days window may be 
used.
q.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the Day 1 visit through Week 12 and completed within ± 6 days through to 
Week 144, unless otherwise specified. The visit window at Weeks 48, 96, and 144 will be ± 6 weeks of the protocol-specified visit date. 
r.
After Week 144, all subjects will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit.  Visit window of 
6 days for study visits post Week 144.  
s.
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for 96 weeks.
t.
HBV blood panel will be performed at Screening (Hepatitis B virus surface antigen (HBsAg), Hepatitis B virus surface antibody (HBsAb) and Hepatitis B virus core antibody 
(HBcAb)). 
For subjects who meet the definition of HBV infection at any visit: The following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and quantitative) 
and HBeAg (if negative, reflex HBeAb) (Weeks 12, 24, 48, 72, 96 and every 24 weeks post Week 96) and Plasma HBV DNA (every visit)
For subjects who do NOT meet the definition of HBV infection at any visit: The following will be conducted by the central laboratory: Hepatitis B surface antibody 
(HBsAb), Hepatitis B virus core antibody (HBcAb), and Hepatitis B virus surface antigen serology (HBsAg). Subjects who are HBsAg and/or HBcAb positive will have a reflex 
test for HBV DNA (viral load) (Week 48, 96 and 144 and every 48 weeks post Week 144)
u.
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a HCV RNA test performed (Week 48, 96 and 144 and every 48 weeks post Week 144)
v.
Randomization may be performed up to 3 days prior to the in-clinic Day 1 visit provided that all screening procedures have been completed and subject eligibility has been 
confirmed.
w.
To be performed every 48 weeks.
x.
To be performed every 24 weeks.
y.
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (preferably within 30 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension phase for 96 weeks 
(Week 96 OL). After Week 96 OL, subjects will discontinue the study drug, transition onto commercially available treatment and complete a 30-Day Follow-up Visit. In a 
country where GS-9883/F/TAF is not available, subjects  will be given the option to continue OL GS-9883/F/TAF until the product becomes accessible to subjects through an
access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first..
CCI

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 102
06 May 2019
Appendix 3.
Study Procedures Table (Open Label Rollover Extension)
Study Procedures
End of 
Blinded 
Treatment 
Visita
End of Weeke, l, O
30-Day 
Follow-upk
Early Study Drugs DCc
12 OL
24 
OL
36 
OL
48 
OL
60
OL
72
OL
84
OL
96
OL
Adverse Events
X
X
X
X
X
X
X
X
X
Xf
Xf
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Complete/Symptom-Directed 
Physical Exam
X
Xd
Xd
Xd
X
Xd
Xd
Xd
X
Xd,f
Xf
12-Lead ECG (performed 
supine)
X
X
X
Vital signs (blood pressure, 
pulse, respiration rate, and 
temperature), including 
Weight
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
Xf
Xf
Urine Pregnancy Testg
X
X
X
X
X
X
X
X
X
X
X
Chemistry Profileh
X
X
X
X
X
X
X
X
X
Xf
Xf
Metabolic Assessmentsi
X
X
X
X
X
Estimated Glomerular 
Filtration Rate
X
X
X
X
X
X
X
X
X
Xf
X
Hematology Profilej
X
X
X
X
X
X
X
X
X
Xf
Xf
Plasma HIV-1 RNA
X
X
X
X
X
X
X
X
X
X
X
CD4+ Cell Count 
X
X
X
X
X
X
X
X
X
X
X
HBV Blood Panelm
X m
X m
X m
X m
Plasma HBV DNAm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
X m
HCV Serologyn
Xn
Xn
HIV-1 Genotype/Phenotypee
Xe
Study Drug Dispensationb
Xb
X
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
X
X
CCI

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 103
06 May 2019
a.
Once the last subject completes the Week 144 visit and Gilead completes the Week 144 analysis, all subjects will return to the clinic (within 30 days ± 6 days) for an End of 
Blinded Treatment Visit. At the End of Blinded Treatment Visit, subjects will be given GS-9883/F/TAF FDC in an open label (OL) extension phase for 96 weeks (Week 96 
OL). After Week 96 OL, subjects will discontinue the study drug, transition onto commercially available treatment and complete a 30-Day Follow-up Visit. In a country 
where GS-9883/F/TAF is not available, subjects will be given the option to continue OL GS-9883/F/TAF until the product becomes accessible to subjects through an access 
program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.
b.
Open label study drug, GS-9883/F/TAF FDC will be dispensed to subjects participating in the Open-Label Rollover extension for 96 weeks.
c.
Subjects who discontinue study drug during the open label rollover extension portion of the study will be asked to return to the clinic within 72 hours of stopping study drugs 
for the Early Study Drugs Discontinuation Visit followed by a 30-Day Follow-Up Visit.  The subject will not continue attending the scheduled study visits.
d.
Symptom-directed physical examination as needed.
e.
HIV-1 genotype and phenotype testing for subjects with virologic failure. Following virologic rebound, subjects will be asked to return to the clinic (2-3 weeks later) prior to 
the next scheduled visit or at the next scheduled study visit, for a HIV-1 RNA and HIV-1 genotype and phenotype (reverse transcriptase, protease, and integrase genotype and 
phenotype) blood draw. Based on the results of this testing, subjects should be managed according to the Virologic Rebound Schema (Section 6.12.1).
f.
Any adverse event or test showing abnormal results that is believed to have a possible or probable causal relationship with the study drug will be repeated weekly (or as often 
as deemed prudent by the Investigator) until the abnormality is resolved, returns to Day 1, or is otherwise explained. 
g.
Females of childbearing potential only. Positive urine pregnancy tests will be confirmed with a serum test.
h.
Chemistry profile: alkaline phosphatase, AST, ALT, GGT, total bilirubin, direct and indirect bilirubin, total protein, albumin, LDH, CPK, bicarbonate, BUN, calcium, 
chloride, creatinine, glucose, phosphorus, magnesium, potassium, sodium, uric acid and amylase (reflex lipase testing is performed in subjects with total amylase 
1.5 ULN). At Weeks 24 OL, 48 OL, 72 OL, 96 OL, and End of Blinded Treatment Visit, analyses of glucose will be done as part of the fasting metabolic assessments and 
not as part of the chemistry profile. For all subjects, TSH will be done at the End of Blinded Treatment Visit, Weeks 24 OL, 48 OL, 72 OL, 96 OL, and Early Study Drug 
Discontinuation Visit.
i.
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) every 24 weeks. 
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.
j.
CBC with differential and platelet count.
k.
Subjects who complete the open-label rollover extension will be required to return to the clinic 30 days after the completion of study drugs for the 30-Day Follow-Up Visit. 
Subjects who permanently discontinue study drugs during the open-label rollover extension will be asked to return to the clinic 30 days after the completion of the Early 
Study Drugs Discontinuation Visit for the 30-Day Follow-Up Visit. For the purpose of scheduling a 30-Day Follow-Up Visit, a ± 6 days window may be used.
l.
Study visits are to be completed within ± 2 days of the protocol-specified visit date based on the End of Blinded Treatment Visit date through Week 12 OL and completed 
within ± 6 days of the protocol-specified visit date every 12 weeks thereafter, unless otherwise specified
m.
For subjects who meet the definition of HBV infection at any visit: The following will be conducted by the central laboratory: HBsAb, HBsAg (qualitative and 
quantitative) and HBeAg (if negative, reflex HBeAb) (every 24 weeks) and Plasma HBV DNA (every 12 weeks). 
For subjects who do NOT meet the definition of HBV infection at any visit: The following will be conducted by the central laboratory: Hepatitis B surface antibody 
(HBsAb), Hepatitis B virus core antibody (HBcAb), and Hepatitis B virus surface antigen serology (HBsAg). Subjects who are HBsAg and/or HBcAb positive will have a reflex 
test for HBV DNA (viral load) (Weeks 48 OL and 96 OL)
n.
Hepatitis C virus (HCVAb) serology. Subjects who are HCVAb positive will have a HCV RNA test performed. (Weeks 48 OL and 96 OL)
o.
After Week 96 OL, if subject is in a country where GS-9883/F/TAF is not available, the study procedures completed by the subject will be the same at every 48 weeks (i.e. 
OL Weeks 48, 96) and at every 12 weeks (i.e. OL Weeks 12, 24. 36, 60, 72, 84) until the product becomes accessible to subjects through an access program, or until Gilead 
Sciences elects to discontinue the study in that country, whichever occurs first.

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 104
06 May 2019
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Grade 1 
May continue dosing 
Repeat lab to 
at the discretion of 
confirm toxicity 
the investigator 
grade 
If confirmed and possibly and/or probably related to investigational 
medicinal products: 
1. 
Withhold investigational medicinal products until 
Grade 2 
2. 
Restart all investigational medicinal products at full dose 
l 
If Grade 3 or 4 recurrence that is confirmed and possibly or probably 
related to investigational medicinal products, discontinue all 
investigational medicinal products dosing permanently 
l 
If c 
Repeat lab to 
confirm toxicity 
grade 
l 
mve 
onfirmed and unrelated to 
stigational medicinal products, 
ng may continue at the discretion 
he investigator 
dosi 
oft 
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 that is considered unrelated to 
investigational medicinal products, continue all investigational 
medicinal products at the same dose at the discretion of the 
investigator 

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 105
06 May 2019
Appendix 5.
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

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 106
06 May 2019
HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Absolute Lymphocyte Count
HIV NEGATIVE ONLY
Adult and Pediatric 
13 Years
600 to 650/mm3
0.60 to 0.65 GI/L
500 to 600/mm3
0.50 to 0.60 GI/L
350 to 500/mm3
0.35 to 0.50 GI/L
350/mm3
0.35 GI/L
Platelets 
100,000 to < 125,000/mm3
100 to 125 GI/L
50,000 to 100,000/mm3
50 to 100 GI/L
25,000 to 50,000/mm3
25 to 50 GI/L
25,000/mm3
25 GI/L
WBCs 
2000/mm3 to 2500/mm3
1,500 to 2,000/mm3
1000 to 1,500/mm3
1000/mm3
2.00 GI/L to 2.50 GI/L
1.50 to 2.00 GI/L
1.00 to 1.50 GI/L
1.00 GI/L
Hypofibrinogenemia
100 to 200 mg/dL
75 to 100 mg/dL
50 to 75 mg/dL
50 mg/dL
1.00 to 2.00 g/L
0.75 to 1.00 g/L
0.50 to 0.75 g/L
0.50 g/L
Hyperfibrinogenemia
ULN to 600 mg/dL
600 mg/dL
—
—
ULN  to 6.0 g/L
6.0 g/L
—
—
Fibrin Split Product 
20 to 40 μg/mL
40 to 50 μg/mL
50 to 60 μg/mL
60 μg/mL
20 to 40 mg/L
40 to 50 mg/L
50 to 60 mg/L
60 mg/L
Prothrombin Time (PT)
1.00 to 1.25 ULN
1.25 to 1.50 ULN 
1.50 to 3.00 ULN 
3.00 ULN 
International Normalized Ratio 
of prothrombin time (INR)
1.1 to 1.5 x ULN
>1.5 to 2.0 x ULN
>2.0 to 3.0 x ULN
>3.0 x ULN
Activated Partial
Thromboplastin Time (APTT)
1.00 to 1.66 ULN
1.66 to 2.33 ULN
2.33 to 3.00 ULN
3.00 ULN
Methemoglobin 
5.0 to 10.0%
10.0 to 15.0%
15.0 to 20.0%
20.0% 
#
An overlap between the Grade 1 scale and the Lab’s normal range for absolute neutrophils may result for pediatric subjects.  Please follow the Gilead convention of grading 
any result within the LLN and ULN a 0.

GS-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 107
06 May 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 t o <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

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Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 108
06 May 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-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 109
06 May 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-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 110
06 May 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.  

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Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 111
06 May 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-9883/F/TAF
Protocol GS-US-380-1490
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 112
06 May 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.

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Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 113
06 May 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Appendix 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

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23) Salmonella septicemia, recurrent
24) Toxoplasmosis of brain
25) Wasting syndrome attributed to HIV infection
CDC Stage-3-Defining Opportunistic Illnesses in HIV Infection - 2014 {Schneider 2008}

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Appendix 7.
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.  In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born subject is considered to be 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 data on GS-9883/F/TAF in pregnant women is limited or not available. There is no 
suspicion of human teratogenicity based on class effects or genotoxic potential. Relevant 
non-clinical reproductive studies for human pregnancy do not indicate a strong suspicion of 
human teratogenicity/fetotoxicity. Data from clinical pharmacokinetic interaction studies of 
GS-9883 and F/TAF have demonstrated that there is no reduction in the clinical efficacy of 
hormonal contraception or that the effect on hormonal contraception is insignificant. Please refer 
to the latest version of the GS-9883/F/TAF investigator’s brochure, the F/TAF investigator’s 
brochure and the current Prescribing Information and local product labeling for DTG 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 Day 1 visit prior to randomization.  At minimum a pregnancy test 
will be performed at the end of relevant systemic exposure. 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 true even for women of childbearing potential with infrequent or irregular 
periods.  Female subjects must agree to one of the following from Screening until 30 days 
following the end of relevant systemic exposure.

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
Complete abstinence from intercourse of reproductive potential.  Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle. 
Or

Consistent and correct use of 1 of the following methods of birth control listed below. 
Intrauterine device (IUD) with a failure rate of <1% per year
Intrauterine hormone-releasing system (IUS) with a failure rate of <1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Or

Consistent and correct use of one hormonal method and one barrier method
Barrier methods
■
Diaphragm with spermicide
■
Cervical cap with spermicide
■
Male condom (with or without spermicide)
Hormonal methods
■
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.

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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 
end of relevant systemic exposure.  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 end of relevant systemic exposure.
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 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 7.3.